3 Adrenal Adenomas and Carcinomas

Suggested citation:  Endocrine Society. Endocrine Facts and Figures: Cancers and Neoplasias. First Edition. 2017

The three major types of adrenal tumors are adrenal adenomas, adrenal hyperplasias, and adrenocortical carcinomas. Adrenal adenomas included in this chapter are non-functioning (non-hormone secreting), cortisol-producing (Cushing’s syndrome), and aldosterone-producing (including Conn’s adenoma) adenomas. Adrenal hyperplasias, technically referring to increased ACTH-independent cell growth of parts of the adrenal cortex, included are cortisol-producing (macronodular and micronodular) and aldosterone-producing (familial hyperaldosteronism types I, II and III). Both unilateral aldosterone-producing adenomas and bilateral adrenal hyperplasias can give rise to primary aldosteronism. Adrenocortocol carcinomas can arise in patients with hereditay predisposition such as Lynch syndrome, Li-Fraumeni syndrome, Multiple Endocrine Neoplasia type 1, Beckwith-Wiedemann syndrome and Familial Adenomatous Polyposis.

3.1    PREVALENCE AND INCIDENCE

Estimates of the prevalence of adrenal tumors vary greatly according to the screening method and the population examined. Most adrenal tumors are incidentally discovered by imaging procedures, conducted for different purposes, and are therefore termed incidentalomas. Adrenal incidentalomas can cover a range of phenotypes from non-functioning adenomas or functioning (hormone-secreting), associated with primary aldosteronism or autonomous cortisol production to carcinomas.100-102 The prevalence of adrenal incidentalomas by subtypes is shown in Table 3.1.

Table 3.1. Prevalence of adrenal tumor subtypes determined by computed tomography (CT) scans from literature reviews, worldwide.
Adrenal incidentaloma types Adrenal incidentaloma subtypes Proportion of all adrenal incidentalomas (%) References
Adrenal adenomas Non-functioning adenomas 58.3-86 Anagnostis et al. 2009100; Giordano et al. 2010102 Di Dalmazi et al. 2012103; Vassilatou et al. 2009104; Akehi et. al. 2013105; Libe et al. 2002106
Cortisol-producing adenomas

(subclinical Cushing’s syndrome)

1-41
Aldosterone-producing adenomas 1.6-3.3 Anagnostis et al. 2009100; Amar et al. 2010107
Adrenal hyperplasias N/A 7-17 Anagnostis et al. 2009100; Barzon et al. 2003101;
Adrenocortical carcinomas N/A 1.2-11 Anagnostis et al. 2009100; Barzon et al. 2003101;Bilimoria et al. 2008108

Abbreviations: N/A, not applicable.

Detection frequency of adrenal tumors has increased in recent years with increasing use of sensitive imaging methods: computed tomography (CT) scans, magnetic resonance imaging (MRI), and ultrasonography (Table 3.2).101 Adrenal incidentalomas are among the most prevalent tumors in humans, being detected in 0.1% of the normal population by ultrasound, and in 1-4% by abdominal imaging analysis (CT scans, MRI and ultrasound).109,110 Worldwide studies roughly estimate the same prevalence at autopsy (1.4 to 6%) and in CT scans (0.35 to 6%).100-102 In a systemic review, adenomas and adrenocortical carcinomas comprised 41% and up to 10% of all incidentalomas, respectively.109 However, these numbers likely overestimate the presence of adrenocortical cancer, which is a very rare disease.111

An estimated 10% of subjects with adrenal incidentalomas secrete excess cortisol in the absence of clinically overt Cushing’s syndrome, defined as subclinical Cushing’s syndrome; and while most cases may undergo extensive screening, an adrenalectomy may be performed in some. However, the incidence of subclinical Cushing’s syndrome is 79 per 100,000 persons, while clinical adrenal Cushing’s syndrome is very rare (~1 person per 100,000).112 As the majority of incidentalomas will never progress to clinical Cushing’s syndrome, some authors suggest that extensive screening and adrenalectomy are unnecessary.113

Aldosterone-producing adenomas (Conn’s adenoma or aldosternoma) are most commonly small (<2cm) tumors, arising sporadically. It is thought to comprise 33-67% of primary aldosteronism, which itself accounts for up to 10% of all hypertension patients.114 In a study of 71 adrenal glands removed from unilateral primary aldosteronism cases in Italy, 77.5% of patients had a single nodule and 22.5% had multinodular hyperplasia.115

Adrenocortical carcinomas are rare, aggressive malignancies (Table 3.2), with an estimated incidence of 0.5-2.0 per million (300 cases per year) in the US, and 0.7-2.0 million worldwide.116-118  According to the SEER database (1973 and 2000), the age-adjusted incidence of adrenocortical carcinoma in the US was 0.72 per million, accounting for only a small fraction of all adrenal incidentalomas, and comprising 0.02% – 0.2% of all cancers reported annually in adults.119-121 Childhood adrenocortical carcinomas have a worldwide incidence of 0.2-0.3 per million and represent 0.2-1.3% of all childhood cancers.122,123

Table 3.2. Prevalence of adrenal adenomas and adrenocortical carcinomas.
Data source Method Population Patients Prevalence

(%)

Proportion of  subtypes (%) References
Adrenal incidentalomas Literature review Worldwide, n=71,206 patients Abdominal CT scan in patients

 

0.5 – 2 Barzon et al. 2003101
Autopsy studies  1 – 8.7

(avg. 2.3)

 

High-resolution CT scan of chest in patients in a screening program for lung cancer Prospective study Italy, adults, age 50-79 years, median age 58 years, no adrenal hyperfunction

(n=520)

Benign adrenal mass 4.2 Bovio et al. 2006116

 

Malignant adrenal mass 0.2
CT scans and biochemical function analysis on adrenal masses Retrospective study US,

Adrenal incidentalomas >1cm,

1985-1989  (n=172)

 

Cortisol-producing tumors

 

0.01 Herrera et al. 1991

124

Adrenal carcinomas 0.029
Incidentalomas discovered by CT scan Retrospective study Korea, adults, age 20-86 years, 55.2% females,

2005-2012  (n=834)

 

 

Non-functioning incidentalomas 82.2 Kim et al. 2013125
Subclinical Cushing’s syndrome 6.0
Aldosterone-producing adenomas 4.6
Pheochromocytoma 7.2
Adrenal incidentalomas (ultrasound, CT scan or MRI) Prospective study Turkey, age 29-78 years, mean age 54.5 years, 71% female  (n=70) Non-functioning incidentalomas 94.3 Emral et al. 2003126
Subclinical Cushing’s syndrome 5.7

TEMPORAL INCREASE

A temporal increase in the prevalence of incidentalomas and adrenocortical carcinomas has been observed, probably due to increased use of advanced imaging analysis (CT scan, MRI, ultrasonography), and progression towards use of high-resolution imaging techniques (Table 3.3).119

Table 3.3. Temporal increase in the prevalence of adrenocortical carcinomas – time of diagnosis of 725 Adrenocortical carcinomas in the SEER database, US. 
Condition Data source Method Population Time period Prevalence (%)
Adrenocortical carcinomas

 

SEER 12 registries database,

1973-2000

Retrospective study US, 54.1% females, age 1-97 years, average age at diagnosis 51.2 years (n=725) 1973-1979 14.1
1980-1986 20.0
1987-1993 25.9
1994-2000 40
Abbreviations: SEER, Surveillance, Epidemiology, and End Results.

Source: Kebebew et al. 2006119

In a 2013 report of adrenocortical carcinomas (n=359, 55% female, age 1-91 years, median age 56 years), in the Netherlands Cancer Registry (1993-2010), incidence appeared to be decreasing over time from 1.3 per million in 1993 to 1.0 per million in 2010. However, the authors suggested that individuals with pre-malignant tumors might have undergone early surgery.127

AGE

The prevalence of adrenal tumors is reported to increase with age (Table 3.4). Pooled studies of deceased individuals estimate the incidence of adrenal incidentalomas to be <1% for age <30 years and 7-10% for age ³70 years. 116,128 Overall the prevalence is estimated to be 3% of the population at middle-age and up to 10% in the elderly.116,128,129 In a worldwide literature review (1952-1992, n=1,330) of adrenocortical carcinomas, 62.3% of patients were >30 years of age. Several large series (>50 patients) suggest a bimodal age distribution for peak of incidence (<5 years and at 40-50 years) (Table 3.5).121

 Table 3.4. Incidence rate of adrenocortical carcinomas according to age, US.
Data source Population Age range (years) Incidence of adrenocortical carcinomas per 100,000 individuals
Male Female
SEER, Cancer statistics review, 1975-2012 US, age-adjusted, all races 0-14 NC 0.0
15-39 0.0 0.1
³40 0.2 0.3
Abbreviations: SEER, Surveillance, Epidemiology, and End Results; NC, statistic not calculated as rate based on <16 cases.

Source: National Cancer Institute.130

 Table 3.5. Peak age of adrenal tumors, worldwide.
Condition Peak age (years) Mean or median age at diagnosis (years) References
Adrenal incidentalomas 40-60 (range) 55 (mean) Barzon et al. 2003101
Adrenocortical carcinomas <5

 

4 (median) Fassnacht et al. 2013118; Wajchenberg et al. 2000131; Wooten et al. 1993121
40-50 (range) 44 (median)

Pediatric adrenal carcinomas are rare, with an estimated incidence of 0.3 per million children (<15 years) in the US, with ~25 new cases diagnosed each year, representing 0.2% of childhood tumors.132,133 The main presenting symptoms are hormonal excess (61%), abdominal pain (13%) and abdominal mass (26%).133  A very significant proportion of adrenocortical carcinoma (50-80%) is associated with TP53 germline mutations and the diagnosis of Li Fraumeni syndrome. Childhood ACC can also occur as part of Beckwith Wiedemann syndrome.134

TUMOR LOCATION

While a left- or right-located adrenal lesion is not linked to any particular disease state, bilateral lesions can indicate metastasis, congenital adrenal hyperplasia, bilateral cortical adenomas, or infiltrative disease.100 In a prospective evaluation in Italy, Bovio and colleagues suggested that the right-side dominance of adrenal tumors in earlier studies may be explained by ultrasonography being less accurate in detecting left-side adrenal masses.116 More recent imaging with CT and MRI scans shows left adrenal gland tumors to be slightly higher than right adrenal tumors (Table 3.6).108,116

 Table 3.6. Prevalence of adrenal mass location.
Diagnosis Population Data source Prevalence of adrenal mass lesion location in patients (%) References
Right Left Bilateral
Adrenocortical carcinomas

 

Worldwide, females 58.6%,

1952-1992 (n=1891)

Review of English literature from 87 studies 44.8 52.8 2.4 Wooten et al. 1993121
Adrenal incidentalomas Worldwide CT scan, MRI, or ultrasonography (if confirmed by CT scan or MRI) 50-60 30-40 10-15 Anagnostics et al. 2009100; Barzon et al. 2003101; Mantero et al. 2000135
Adrenocortical carcinomas

 

US, median age 55 years, females 58.2%,

1985-2005 (n=3982)

National Cancer Data Base (NCDB)

 

41.3 49.6 1.1 Bilimoria, et al. 2008108
Lung cancer metastasis Italy, adults age 50-79 years, median age 58 years, no adrenal hyperfunction (n=520) Chest CT scan in a screening program for lung cancer 26 60.8 13.2 Bovio et al. 2006116

 

Adrenal incidentalomas Korea, adults, age 20-86, 55.2% females (n=348) CT scan, 2005-2012 30.2 62.0 7.8 Kim et al. 2013125

TUMOR SIZE AND STAGE

Despite some overlap, adrenal adenomas are generally smaller (usually £4cm) than adrenal carcinomas (Table 3.7), with 5-25% of adrenal adenomas increasing in size during follow-up.101 Reinhard and colleagues analyzed 498 consecutive autopsies in Germany, and identified 0.3-8 mm nodules in 53.7% of cases, and 3.2-28 mm adenomas in 5% of cases.136 In a large study of adrenal incidentalomas, tumor mass size was the most reliable variable to distinguish adenomas and carcinomas.135 In a US report of 166 non-functional unilateral benign adrenal incidentalomas identified by CT scan (between 1976 and 1994) in 100% of patients, masses were £3cm, while 89% were £2cm, and 52% were £1cm.137 Contrary to these findings in benign incidentalomas, adrenocortical carcinomas are larger in size. In a US study of 392 adrenocortical carcinomas, only 4.2% were £6cm and in another single center study, only 3% of 391 adrenocortical carcinomas were <5cm.119,138 In a US SEER database study (1988-2000) of 457 adrenocortical carcinomas compared to 47 benign adrenal tumors, the risk of malignancy increased with tumor size: 52% for tumors ³4cm, 80% for those ³6cm, 95% for ³8cm, and 98% for ³10cm.139

Table 3.7. Size of tumors in adrenal adenomas and adrenocortical carcinomas, worldwide.
Condition Population Average (cm) ±SEM References
Adrenal adenomas

 

US, children, age <19 years (n=7) 3.3 ±0.6 Hanna et al. 2008133
Italy, age 15-86 years (n=1004) 3.5

(range 1-15)

Mantero et al. 2000135
Adrenocorticol carcinoma US, children, age <19 years (, n=16) 8.5±1.2 Hanna et al. 2008133
Italy, age 15-86 years (n=1004) 7.5

(range 2.6-25)

Mantero et al. 2000135
US, age 1-97 years, average age 51.2 years, 54.1% female, SEER 12 registries database, 1973-2000 (n=725) 12

(range 2-36)

Kebebew et al. 2006119

Abbreviation: SEER, Surveillance, Epidemiology, and End Results; SEM, standard error of mean.

At diagnosis, the majority of adrenocortical carcinomas are already at the advanced stages III and IV (Table 3.8).119,133,138,140

Table 3.8. Adrenocortical carcinoma characteristics, US.
Data source Method Population Characteristics Percentage References
SEER 12 registries database,

1973-2000, 26% of the US population

Retrospective study US, adrenocortical carcinomas, 54.1% females, age at diagnosis 1-97 years, average 51.2 years (n=725) Localized 40.6 Kebebew et al. 2006119
Distant 34.8
Regional 17.9
Unstaged 6.7
Stage I 19.3
Stage II 20.3
Stage III 34.3
Stage IV 25.9
Mayo Clinic, review of charts from histologically confirmed cases of adrenocortical carcinomas, Retrospective review US, children, avg. age 9 years, female:male 1.9:1, adrenocortical carcinomas,

1976-2005 (n=16)

Stage I 8 Hanna et al. 2008133
Stage II 13
Stage III 4
Stage IV 43
Michigan Endocrine Oncology Repository Retrospective single-center study US, adult, female:male 1:1.15,  adrenocortical carcinoma, Dec. 1979-Jan. 2013, (n=391) Stage I 3 Else et al. 2014138
Stage II 43
Stage III 28
Stage IV 26

Abbreviations: SEER, Surveillance, Epidemiology, and End Results.

METASTASES

Adrenal masses discovered during abdominal imaging are not generally considered to be adrenal incidentaloma, however, in patients with known malignancies, the risk of an adrenal mass being a metastasis is high (45-73%) and increases with tumor size (43-100% for >3cm tumors). In patients with extra-adrenal malignancies (lung, breast, kidney cancers; melanoma and lymphoma), adrenal metastases were identified in 3-40% at autopsy, and 6-20% of patients in radiological studies.101 Cancer in an unknown primary site can occasionally involve the adrenal glands, but metastatic cancer presenting as a true incidentaloma is rare. A 1998 US retrospective review of 1,639 cancer patients with an occult primary malignancy identified involvement of the adrenal gland (original site or metastasis) in 5.8% of patients, and tumors solely in the adrenal gland in 0.2% of patients.141.

HORMONE EXCESS SYNDROMES

Most adrenal incidentalomas are non-functioning, while ~15% show secretion of cortisol, aldosterone or medullary hormones.101 The most common disorder in incidentalomas (1-29%, average 9%) is the development of autonomous cortisol secretion, which remains subclinical in two-thirds of cases.101 Less than 1 in every 1000 adrenal masses, originally identified as benign, eventually became malignant, and 1.7% developed hyperfunction, usually involving cortisol.101 Although most adrenal adenomas are benign and non-functioning, there is still a concern that subclinical levels of autonomous hormone secretion cause metabolic abnormalities, which represent well known risk factors for example cardiovascular morbidity (e.g. hypertension, diabetes, dyslipidemia)  (Table 3.9).142,143

A study of adrenal incidentalomas (n=94, 1995-2005, Turkey) identified hypertension in 63%, obesity in 55%, diabetes mellitus in 36%, hypercholesterolemia in 36%, and low HDL cholesterol in 36% of cases, with similar frequencies to those in clinical Cushing’s syndrome.144 The risk of autonomous hormone secretion is higher with larger (>3cm) lesions.101,108 A 2011 report by Muscoguri and colleagues identified a direct correlation between mass size and insulin resistance, and in 2010, Kolanska and colleagues reported a higher prevalence (40%) of obesity in a cohort with non-functioning adenomas than in the general population.145 146

A number of worldwide studies indicate a higher prevalence (average 10%; range 6-23%) of subclinical Cushing’s syndrome in adrenal incidentalomas.147 Sub-clinical Cushing’s syndrome is associated with metabolic syndrome, hypertension, and dyslipidemias, but without overt clinical symptoms or signs of Cushing syndrome (Table 3.9).100,101,103 Patients with subclinical Cushing’s syndrome showed increased risks of cardiovascular disease and of developing overt Cushing’s disease (12.5% after 1 year).101,126,148 It was reported to be higher in patients with resistant hypertension (8%, 423 patients, age 1-80 years, Brazil), in young subjects (7.5%, 80 hypertensive patients, age 12-40 years, Romania), and in patients with osteoporosis and vertebral fractures (4.8%), relative to those with secondary hypertension (1%, 4,429 patients at a hypertension referral center, US).147,149-151 However, not all of the patients in these studies had a proven adrenal mass, but rather biochemical evidence for some degree of autonomous cortisol production. In the hypertensive population, the prevalence of primary hyperaldosteronism is estimated to be up to 10%; (60% of which is caused by aldosterone-producing adenomas).

Table 3.9. Prevalence of co-morbidities in non-functioning adrenal adenomas and sub-clinical Cushing’s syndrome, worldwide.
Co-morbidities Prevalence of co-morbidities in non-functioning adrenal adenomas (%)

(Muth et al. 2013152)

Prevalence of co-morbidities in subclinical Cushing’s syndrome (%)

(Barzon et al. 2003101 and Anagnostis et al. 2009100)

Hypertension 48 40-90
Cardiovascular disease 23 N/A
Diabetes/glucose intolerance 9 25-75
Hyperlipidemia 12 50
Osteopenia N/G 40-50
Osteoporosis 5 N/A
Obesity 40 35–50

Abbreviations: N/G, not given; N/A, not available.

Primary aldosteronism is a diverse group of adrenal disorders, usually arising due to either sporadic aldosterone-producing adenoma (Conn adenoma or aldosteronoma) or sporadic uni- or bilateral adrenal hyperplasia, and very rarely as familial form of bilateral adrenal hyperplasia.115 In primary aldosteronism, the adrenal gland produces aldosterone in an autonomous fashion, resulting in secondary hypertension with detrimental effects on the cardiovascular and renal systems.107,153-155 Even moderate increases in aldosterone are implicated in increased cardiovascular morbidity and mortality.156 Studies indicate that aldosterone-producing adenomas exist in 3.3-11.2% of the hypertensive population.153,157 Conn adenomas represent ~30-60% of the primary aldosteronism population.158 Mulatero and colleagues reported a higher risk for cardiovascular events in aldosterone-producing adenoma patients compared to patients with essential hypertension. During follow-up, aldosterone-producing adenoma patients had more strokes and arrhythmias and a higher percentage developed type-2 diabetes than did patients with essential hypertension.159

MUTATIONS

Table 3.10 presents data on the prevalence of somatic mutations associated with aldosterone-producing adenomas (Conn’s adenoma). Another cause of primary aldosteronism is bilateral adrenal hyperplasia, which can arise sporadically or in the setting of germline mutations.160 Table 3.11 summarizes prevalence data of the different types of adrenal hyperplasia and their associated mutations.

In one study TP53 germline mutations were found in 67% of individuals with adrenocortical carcinoma (n=21), of which 80% were children (<18 years).161 In a German report the TP53 mutation was identified in 3.9% of Caucasians with adult-onset adrenocortical carcinoma.162 In a US series, the prevalence of TP53 mutations was 5.8% in the adult population.163 The prevalence of the TP53 germline mutation R337H was reported to be 15-times higher (0.3%) in children in southern Brazil than other areas, with prevalence of 97% in childhood adrenocortical tumors.118,164,165

Li-Fraumeni syndrome is rare, autosomal dominant cancer disorder often caused by gene mutations that inactivate the tumor suppressor TP53 gene. Li-Fraumeni syndrome patients are at high risk of developing different types of cancers including breast, bone, brain and adrenal cancer (Table 3.12). Another fairly prevalent syndrome in adrenal cancer patients is Lynch syndrome, which is responsible for 3-5% of all adrenal cancers.163 Individuals with Beckwith-Wiedemann Syndrome are at a high risk of developing cancers of the liver, kidney and occasionally the adrenal cortex. Described as a complex of myxomas, spotted skin pigmentation and endocrine overactivity, Carney complex, caused by PRKAR1A, is a multiple neoplasia syndrome, mostly associated with micronodular hyperplasia. Two cases of adrenal cancer have also been described.166-168 Germline mutations in a related gene, PRKACA has been found mutated in patients with adrenal hyperplasia, and somatic mutations are found in 30% of cortisol-producing adenomas.169

Table 3.10. Prevalence of the most common somatic mutations causing aldosterone-producing adenomas.
Data source Population Mutation Prevalence in patients with aldosterone-producing adenoma (%)
European Network for the Study of Adrenal Tumors Patients across 7 centers (n=474) all somatic mutations 54
KCNJ5 38
CACNA1D 9.3
ATP1A1 5.3
ATP2B3 1.7

Source: Zennaro et al. 2015160

Table 3.11. Subtypes of adrenal hyperplasia and associated mutations, worldwide.
Subtype of Adrenal hyperplasia Data source Population Associated germline mutations Hormone secreted References
Macronodular adrenal hyperplasia Not stated Not stated ARMC5, PDE11A, PDE8B, PRKACA

 

Cortisol Louis et al. 2014170
Familial hyperaldosteronism-I

(FH-I)

University of Turino, Italy Primary aldosteronism diagnosis (n=300) CYP11B2/CYP11B1 chimera Aldosterone under adrenocorticotropic hormone control Mulatero et al. 2011171
Familial hyperaldosteronism-II

(FH-II)

Genetic linkage to chromosome #7p22, but mutations(s) unknown Aldosterone
Familial hyperaldosteronism-III

(FH-III)

KCNJ5 Aldosterone

 

Table 3.12. Hereditary syndromes associated with adrenocortical carcinoma.
Syndrome Prevalence in Patients Prevalence in General Population Gene Mutation References
Li-Fraumeni syndrome 3-6% of adults with adrenocortical carcinoma; 50–80% of children with adrenocortical carcinoma 1:20,000 to 1:1,000,000 TP53 Fassnacht et al. 2013118; Wasserman et al. 2015134 Raymond et al. 2013163; Else et al. 2014122
Multiple endocrine neoplasia type 1 (MEN1) 1–2% of adults with adrenocortical carcinoma 1:30,000 MENIN

 

Else et al. 2014122
Lynch syndrome 3.2% of adults with adrenocortical carcinoma 1:440 MSH2;

MSH6;

MLH1;

PMS2

Raymond et al. 2013163; Else et al. 2014122
Beckwith-Wiedemann syndrome Very rare, only found in children with adrenocortical carcinoma 1:13,000 IGF2;

H19;

CDKN1C

(gene locus 11p15)

Else et al. 2014122
Familial adenomatous polyposis Very rare: <1% of adults with adrenocortical carcinoma 1:30,000 APC Else et al. 2014122
Carney complex Very rare (2 case reports) in adrenocortical carcinoma. More than 700 patients worldwide PRKAR1A Else et al. 2014122; Kirschner et al. 2000172; Anselmo et al. 2012167; Morin et al. 2012173

 

3.2    COST BURDEN OF DISEASE

In the treatment of primary aldosteronism, some clinicians advocate oral therapy with mineralcorticoid-receptor antagonists to be more cost-effective than operative resection, while others have determined that surgery is more cost-effective than a pharmacological approach (Table 3.13). Based on 2009 treatment costs, a laparoscopic adrenalectomy in a hospital setting is expected to cost $8,378.63.114 The authors estimated that if adrenalectomy costs rose 2.5-fold to $22,524.59, or the cost of selective venus sampling quadrupled from $2,171 to $9,041, or the surgical failure in improving blood pressure increased six-fold to affect 32% of patients, then the pharmacological option would be the least costly strategy. However, treatment costs vary significantly, even within the United States, and there is no conclusive study suggesting a cost-benefit of strategy, surgery or pharmacotherapy.

 Table 3.13. Comparison of discounted expected costs of two treatment regimes for aldosterone-producing adenoma in primary hyperaldosteronism.
Method Population Treatment Cost ($)
Markov state transition model 40-year old (female) reference patient with 41 years of life remaining Endocrine Society’s Practice Guidelines:

selective venus sampling and laparoscopic  adrenalectomy.

27,821
Long-term pharmacological therapy: (daily spironolactone at $219 annually, plus eplerenone in 52% of cases) with 48% success of controlling hypertension, 46.9% of improving blood pressure but still requiring a single hypertensive. 34,691
Note: The cost estimates are based on 2009 US treatments costs. All cost estimates included physician’s visits, laboratory radiologic evaluation, medications, procedures, Medicare costs, and reimbursement but excluded costs outside the healthcare system (transporation, lost-productivity). Only costs that differed between the two treatment regimens were included.

Source: Reimel et al. 2010114

3.3    DEMOGRAPHIC DIFFERENCES

In a literature review of 6 worldwide studies (n=71,206), no overall sex differences in incidentalomas were identified at autopsy.101 However, two studies reported a high female-to-male ratio in adrenal masses.101,174 Both studies hypothesized that the increased incidence in females could be entirely due to the higher rates of abdominal scans in females than males (Table 3.14).101,103 Barzon and colleagues also reported an increase in prevalence of autopsy incidentalomas with age: 0.2% in young patients and 6.9% in patients of age >70 years.101 In adults with adrenocortical carcinomas, a lower median age-at-diagnosis was reported for females vs. males (30 vs. 39 years). In males, adrenocortical carcinoma tumors were found more often in patients age >30 years (71.7%) than age <30 years (28.4%).121 In several studies, adrenocortical carcinoma (n=1891) is more common in females than males with a ratio of 1.5:1.121,138

No significant differences were identified in the incidence of adrenocortical carcinoma between races.130

Table 3.14. Female-to-male sex ratios in adenomas and adrenocortical carcinoma.
Data source Method Population Condition Overall Female: Male sex ratio References
Literature review Literature reviews n=71,206 Adenomas at autopsy 1.0 Barzon et al. 2003101
Literature review Literature reviews Adrenal lesions Adenomas 1.2-1.6

 

Barzon et al. 2003101; Di Dimalzi et al. 2014175; Audenet et al. 2013174; Mantero et al. 2000135
International Pediatric Adrenocortical Tumor Registry,

1990-2001

Descriptive analysis US, children, age <20 years (60% <4 years, 14% >13 years); 61.4% female (n=254)

 

Childhood adrenocortical tumors Overall:                1.6 Michalkiewicz et al. 2004176
Age <4 years:      1.7
Age 4-12 years:  0.8
Age ³13 years:   6.2
1976-2005 Retrospective review US, children, age <19 years, average age 9.0 ±1.6 years  (n=23) Childhood adrenocortical carcinomas n=16), and

adenomas (n=7)

1.9

 

Hanna et al. 2008133
SEER 12 registries database,

1973-2000

Retrospective study 54.1% females, age 1-97 years, average age at diagnosis 51.2 years US, (n=725) Adrenocortical carcinoma 1.2

 

Kebebew et al. 2006119
International Pediatric Adrenocortical Tumor Registry, 1990-2001 Descriptive analysis US, children <20 years, (n-254) Adrenocortical carcinoma (pediatric) 1.6 Michalkiewicz et al. 2004176
Endocrine Department of the Hospital Cochin,

1963-1987

Retrospective study France, n=105, females n=75, mean age 46 years, range 6-81 years Adrenocortical carcinomas 2.5 Luton et al. 1990177
Michigan Endocrine Oncology repository, diagnosed December 1979 to January 2013 Retrospective single-center study US, n=391 Adrenocortical carcinomas 1.5 Else et al. 2014138

 

3.4    LIFE EXPECTANCY AND MORTALITY

Autonomous cortisol production bears an increased mortality in patients with adrenal incidentalomas. In one study analysing 206 patients, 18 patients had died and of these 17 had cortisol level >1.8 mg/dL.178 No statistics on mortality were available for nodular hyperplasias or adrenal familial hyperplasias. However, Li and Yang reported that in a retrospective review of 23 cases of bilateral adrenal macronodular hyperplasias (and the associated Cushing’s syndrome) in China, 20 showed elevated cortisol levels (associated with high morbidity and mortality).179 Zenarro and colleagues stated that familial hyperaldosteronism-I (in France) was associated with hypertension from an early age (family history of hypertension <50 years, history of hypertension <20 years, hypertension that is difficult to control), resulting in high morbidity and mortality at an early age.160

Adrenocortical carcinoma is a malignancy with a poor prognosis with median 5-year survival rates (range 25-54%).176,180 Data from a number of studies suggests that tumor size does not appear to correlate with metastatic disease or survival.108,180,181 In a 2008 review by Bilimoria and colleagues of 3,982 adrenocortical carcinoma cases diagnosed between 1985 and 2005 in the US, survival was significantly diminished with increasing age (>55 years), high-grade tumors (HR, 2.26), incomplete surgery (HR, 2.06), nodal metastases (HR, 1.56), distant metastasis (HR, 2.20), or in patients who had undergone surgery with resection of a contiguous organ (HR, 1.23).108 Microscopically complete resection was associated with lower recurrence rates in a 2013 study.182 Several studies also showed that disease stage correlated with poor outcomes.122,138,176,183 Table 3.15 presents the relationship between disease stage and median survival.

Table 3.15. Adrenocortical carcinoma disease stage and median survival times, US.
Data source Method Population Stage Median overall survival times (years) References
Adrenocortical carcinoma patients, University of Texas MD Anderson Cancer Center, 1998-2011 Retrospective review, 2013 Age 0-86 years, median age at diagnosis 48.5 years, 3.6% age <18 years, 85% Caucasian, 64.2% female (n=330) I 24.1 Ayala-Ramirez et al. 2013183
II 6.08
III 3.47
IV 0.89
Adrenocortical carcinoma patients, Michigan Endocrine Oncology repository, diagnosed December 1979 to January 2013 Restrospective single-center study Adults age >16 years, mean age at diagnosis 47.4 years, 86% Caucasian male:female ration 1:1.5 (n=391) I 4.77 Else et al. 2014138
II 6.14
III 2.50
IV 1.12

In a US study of 3,982 adrenocortical carcinomas, 26.5% of patients had nodal metastasis and 21.6% had distant metastasis. The 5-year survival for patients who had undergone resection was 38.6% (median 31.9 months).108 The risk of death was higher in older patients (>55 years), high-grade tumors (HR, 2.3), involved margins (HR, 2.1), nodal (HR, 1.6) or distant metastasis (HR, 2.2), or surgery with resection of a contiguous organ (HR, 1.2).108 Distant metastasis was mostly found in liver, lung and bone in 10.9%, 9.0% and 3.1% of cases, respectively.108 The adjusted HR for death increased with age: 1.0, 1.1, 1.5 and 2.3 for age 18-35 years, 36-55 years, 56-75 years, and >75 years respectively; and the 5-year observed survival rate decreased with age 14.6%, 42.1%, 35.8%, and 23.7% respectively.108  In a Netherlands study of adrenocortical carcinoma patients, the survival time decreased with advanced disease stage (Table 3.16). The relative-survival decreased with increasing age-at-diagnosis (5-year survival: 44% 0-44 years, 36% 45-59 years, 23% 60-74 years, and 37% >75 years).108

Table 3.16. Survival in months for adrenocortical carcinoma patients according to disease stage, Netherlands.
Data source Population Adrenocortical carcinoma disease stage Median survival, months (range)
Netherlands Cancer Registry,

1993-2010

Netherlands, 55% female, age 1-91 years, median age 56 years (n=359) I-II (33%) 159  (93-225)
III (10%) 26    (4-48)
IV (35%) 5      (2-7)
Note: 22% had unknown disease stage; Stage I-II: carcinoma in situ or localized in tissue of origin; Stage III: tumor infiltration into surrounding tissue or at least 1 positive lymph node or tumor infiltration into surrounding tissue and at least 1 positive lymph node; Stage IV: presence of distant metastasis.

Source: Bilimoria et al. 2008108

In pediatric adrenal tumors, complete tumor excision was associated with significantly better outcome. Outcome for ACC was better at earlier disease stages (Table 3.17).133

Table 3.17. Survival rates in pediatric adrenal tumors, US.
Data source Method Population Disease characteristics 5-year survival rate References
Pediatric adrenocortical tumors examined by histology Mayo Clinic

1976-2005

Retrospective analysis US, children age 34 days-19 years, mean age 9 years, 15 females, 8 males, n=7 adenomas, n=16 adrenocortical carcinomas (n=23), all >2.5cm Excised adenomas 100% Hanna et al. 2008133
Excised adrenocortical carcinomas 34%
Adrenocortical carcinomas stages I and II:
5-year survival 100%
Adrenocortical carcinomas stages III and IV:
5-year survival 0%
Median survival 21 months
Pediatric adrenocortical tumors, International Pediatric Adrenocortical Tumor Registry, 1990-2001 Descriptive analysis US, children <20 years, (n-254), overall male:female ratio 1:1.6, vitrilization in 84.2%, Cushing’s syndrome without viriization 5.5%. Tumors  completelyresected in 83%. Disseminated/residual disease treated with mitotane, cisplatin, etopside, and/or doxorubicin, or radiation therapy. Median follow up 2 years 5 months. Survived without evidence of disease (follow-up of 2 years 5 months) 61.8% Michalkiewicz et al. 2004176
Died (Follow-up of 2 years 5 months) 38.2%
5-year event-free survival estimate 54.2% (48.2-60.2%)

 

3.5    KEY TRENDS AND HEALTH OUTCOMES

Surgery is the mainstay of treatment for carcinomas and most hormone producing adrenal adenomas. Laparoscopic adrenalectomy (first described in 1992) is preferred over open adrenalectomy for small-to-medium size (<8cm), benign, functioning and non-functioning adrenal tumors.184 Tumors with a presurgical suspicion for adrenocortical carcinomas are best approached with an open adrenalectomy, following oncological principles. In two US studies comparing the two surgeries, the recurrence rate was 86% in 156 adrenocortical carcinoma patients who had undergone open adrenalectomy and 100% in 6 patients who had undergone laparoscopic adrenalectomy, although 2 other studies suggested there was no significant difference between the two surgeries at Stages 1 and 2.122 Contraindications for laparoscopic adrenalectomy include large benign tumors (>8 cm) and adrenocortical carcinomas. Robot-assisted adrenalectomy (introduced early 2000s) is becoming increasingly popular as it can overcome technical limitations of laparoscopic adrenalectomy, and is shown to consistently reduce blood loss during and after surgery. In a 2011 report from Italy of cortical adenomas (n=19), aldosteronomas (n=2), hyperplasias (n=2), adrenal carcinoma (n=1), others (n=18); robot-assisted adrenolectomies led to minimal blood loss (median 27ml) and short operative times (118±46 mins). Differences in surgery time between right and left side (125 min vs. 110 min) and blood loss (86 ml vs. 35 ml) were not statistically significant.185 In a 2014 retrospective study (n=76, 2000-2010) of US medical charts by Brandao and colleagues, a significantly lower surgery-related blood loss was reported for robot-assisted adrenolectomies than for laparoscopic adrenalectomy (median 50ml vs. 100ml) performed by the same surgeon, but the authors identified no significant differences in the length of hospital stay.186

A 2008 study by Brunaud and colleagues, reported operating times were determined by the surgeon’s experience; the longer operation times with robot-assisted adrenalectomies compared with laparoscopic adrenalectomy did not apply after a surgeon’s learning curve of 20 cases. The mean operating time in laparoscopic adrenalectomies was higher in obese patients (body mass index >30 kg/m2) than those with a lower BMI (90 vs. 78 min respectively), and for patients with tumor size >5.5cm, than those with smaller tumors (100 vs. 80 min, respectively).  These difference did not apply to robot-assisted adrenalectomies.187

In a 4-study review of robot-assisted adrenalectomies, the morbidity rate was 0-20% and the mortality rate was 0%; in a single study for laparoscopic adrenalectomy, the reported mortality rate was 0%. 185 From a review of 100 laparoscopic adrenalectomies from 19 publications, the most commonly reported complications of surgery were bleeding (40%) and injury to peritoneal and retroperitoneal organs (4.2%), with an overall mortality rate of 0.2% 30 days post surgery (0.8-1.2% deaths in 4 centers, and zero deaths in 15 centers).184,188 Bilateral surgery can lead to higher blood loss, higher mortality (4/7 deaths) and lower success rates of disease management (50-100%) than unilateral adrenalectomies, which can achieve endocrinolgical cure.188

Non-functioning adrenal incidentalomas

Conservative management is recommended over surgery in cases of stable non-functioning adrenal incidentalomas that lack autonomous hormone production. A quality-of-life survey of non-functioning adrenal incidentaloma patients (released from surveillance after 24 months of stable disease) found that although the follow-up program was well tolerated, 30% of cases showed signs of depression, possibly related to the significant hypertension and metabolic co-morbidities, as outlined earlier in Table 3.9.152

Conn’s syndrome

Complication rates for aldosterone-producing adenomas are reported to be 7%.184,188 Post-surgery studies of laparoscopic adrenalectomies for Conn’s syndrome showed 95-100% success in achieving normokalaemia, with hypertension cured or significantly improved in 88-100% of surgeries.188 Persistant hypertension was reported in 0-12% of patients post-adrenalectomy.184 A worldwide review of 13 studies with respect to outcome of laparoscopic adrenalectomies is shown in Table 3.18.

Table 3.18. Patient outcome after laparoscopic adrenalectomies in aldosteronoma, worldwide.
Condition Population Procedures Operating time (minutes), mean (range) Blood loss (milliliters), mean (range) Length of stay (days), mean (range)
Aldosteronomas or Conn’s syndrome Review of 13 worldwide studies (n=323) Laparoscopic adrenalectomies

 

164

(38-295)

177

(35-297)

3.4

(1-10.4)

Source: Gumbs and Gagner. 2006184

Subclinical Cushing’s syndrome

Subclinical Cushing’s syndrome is detected at low rates in the course of surveillance of non-functioning adrenal adenomas. In a retrospective study of conservatively managed non-functioning adrenal incidentalomas, Morelli and colleagues reported that 8.2% of patients progressed to subclinical Cushing’s syndrome during 5 years of follow-up.189 Giordano and colleagues reported this to be the case in just 5.1% of patients.102

In 2014 Morelli and colleagues reported that at diagnosis, patients with subclinical Cushing’s syndrome had higher rates of diabetes mellitus and cardiovascular incidents than patients without subclinical Cushing’s syndrome. After a 5-year follow-up, subclinical Cushing’s syndrome correlated with worsening metabolic symptoms and cardiovascular incidents.189 These studies contradicted data from Giordano and colleagues, who reported finding no differences in hypertension and metabolic diseases between non-functioning adrenal incidentalomas and subclinical Cushing’s syndrome.102

While some studies recommend simply monitoring subclinical Cushing’s syndrome, others suggest the higher prevalence of cardiovascular disorders warrants surgery in both subclinical Cushing’s and non-functioning tumors, especially in patients exhibiting hypertension, obesity, and diabetes.144 A study of 45 subclinical Cushing’s syndrome cases, by Toniato and colleagues, reported that surgery relieved hypercortisolism and co-morbidities (Table 3.19); while conservative management only led to a worsening of certain conditions (diabetes mellitus, hypertension, hyperlipidemia).190 The improvement in comorbidities post surgery from another study, a systemic review by lacobone and colleagues, are also shown in Table 3.19.191 However, subclinical Cushing’s syndrome poses a particular challenge as there is no consensus, whether it needs to be treated or whether treatment of co-morbidities is favorable.

Table 3.19. Percent improvement in subclinical Cushing’s syndrome co-morbidities with surgery or conservative management.
Co-morbidities Percentage improvement in comorbidities in subclinical Cushing’s syndrome patients (%)
Laparoscopic adrenalectomies performed over a 15-year period by the same surgeon, n=45

(Toniato et al. 2009190)

Systematic review, MEDLINE, Embase and Cochrane Databases (1980-2013) searched for outcomes of unilateral adrenalectomy; 7 papers, 6 retrospective studies, 1 clinical trial, n=230

(Iacobone et al. 2015191)

Diabetes Mellitus 62.5 46
Hypertension 67 72
Hyperlipidemia 37.5 Inconclusive
Obesity 50 29
Osteoporosis No change No change

 Adrenal hyperplasia

Macronodular adrenal hyperplasia can present with or without hormone excess; patients with hypercortisolism can present with subclinical Cushing syndrome or clinical Cushing syndrome. Unilateral adrenalectomy addressing the larger adrenal gland is often the treatment of choice and often normalizes the clinical symptoms.179 Familial macronodular adrenal hyperplasias with a predisposition to cortisol production is caused by ARMC5 mutations in a significant number of patients. Adrenocortical hyperplasias can also lead to primary aldosteronism, particulalrly in the setting of KCNJ5 germline mutations. However, sporadic hyperplasia of the zona glomerulosa is rarely evident on imaging, but can be observed microscopically. If untreated, adrenal hyperplasias with primary aldosteronism results in the early onset of hypertension and cerebral hemorrhage.192 Untreated familial hyperaldosteronism also results in left ventricular hypertrophy.192,193

Surgery for sporadic unilateral hyperplasia causing primary aldosteornism usually reduces hypertension and improves cardiovascular outcomes, similar to aldosterone-producing adenomas. Bilateral disease requires pharmacological management.155,192

Adrenocortical carcinoma

More adrenocortical carcinomas are detected as a result of increased adrenal hormone production rather than as an incidental finding on a CT scan (Table 3.20).122

Table 3.20. Detection of adrenocortical carcinomas, US.
Data source Method Population Detection method Percentage of adrenocortical carcinomas detected (%)
University of Michigan Health Systems, over 10 years Retrospective review

 

Adrenocortical cases Incidental CT scan 20–30
Increased adrenal hormone production: 45–70
Cortisol 50–80
Androgens 40–60
Cortisol and androgens 50

Source: Else et al. 2014122

The mainstay of a curative approach for ACC is complete oncological surgery, with consideration of an open surgical approach.

The adrenolytic medication, Mitotane, is used as standard care in advanced adrenocortical carcinomas. The first-line therapy for metastatic cancer includes Mitotane with etoposide, doxorubicin and cisplatin.118 Mitotane has been shown to improve 5-year survival rates in several studies (Table 3.21).122,180

Radiation therapy improves local control, but has not been shown to significantly improve survival times.194 Furthermore, it is recommended that radiation not be used when TP53 mutations are present.122

A study by Fassnacht and colleagues, argued for specialized centers with multidisciplinary teams for treatment and follow-up of adrenocortical carcinoma patients.122,195 Adrenocortical carcinoma patients appear to have better outcomes when patients are treated at specialized centers.195

Table 3.21. Recent studies of adrenocortical carcinoma treatments, risk factors, and outcomes.
Year Data source Population Results References
2014 Prospective study: does tumor size predict outcome n=37 patients with tumors >8 cm (n=207) Tumor size not predictive of outcome; 5-year survival rate 25% vs. 50% with addition of Mitotane Abdel-Aziz et al. 2014180
2013 National Cancer Database: impact of tumor size Patients with staging information, 1985-2000 (n=2,248) Tumor size not predictive of metastasis and does not correlate with survival. However, patient age was a predictor of overall survival after resection. Canter et al. 2013181
2014 Review of 8 retrospective studies,

1989 -2010

Advanced adrenocortical carcinoma; patients without mitotane (n=527); patients with mitotane (n=212) Mitotane as adjuvant therapy in 8 studies: disease-free survival was significantly better in 2 studies, not significant in 4, favorable in 1, and significantly worse in 1 study. Overall survival was significantly better/favorable in 1 study.122 Else et al. 2014.122
2014

 

 

 

 

 

2013

Review of 10 studies (3 prospective and 7 retrospective),

1984-2007

Advanced adrenocortical carcinoma; 359 patients; 102 responders Mitotane as a therapeutic agent (nonadjuvant): all 10 studies showed some cases of partial remission (n=73), stable disease (n-14) and complete remission (n=15) were reported in 3 studies each. Else et al. 2014122 ; Ayala-Ramirez et al. 2013183
Retrospective single center: clinical outcomes Median age 48.5 (n=330) For surgical resection median local recurrence time 1.04 years. Median survival 3.21 years. Poor survival: older age, functional tumors; higher disease stage
2013 Retrospective cohort, single center study: impact of adjuvant radiotherapy on adrenocortcal carcinomas post surgery US, 16 received radiation therapy, 32 did not; 1998-2011 (n=48) Radiation therapy did not improve outcomes after initial surgery. Local recurrence in 43.8% receiving radiation therapy vs. 31.3% in control group. At 5-year, local recurrence rate 53% in radiation therapy group and 67% in non-radiation therapy group. Habra et al. 2013194
2013 Retrospective study German Adrenocortical Carcinoma Registry: Survival n=101 who underwent repeated surgery, of which 99 received additional therapies post-surgery 94% experienced progression (median 6 months); shorter progression-free-survival if both (i) time to first recurrence was >12 months and (ii) microscopically complete resection of recurrent tumors (n = 22; median progression-free-survival 24 months; median overall survival >60 months). Erdogan et al. 2013182
2010 Single center prospective study for stage II at specialized center Adults, Stage II (n=149) Prospective follow-up group (n=30): 30% recurrence rate; 5-year survival 96%; risk of death HR, 0.19.

Retrospective group (n=119): 74% recurrence rate, 5-year survival 55%; risk of death HR, 0.03-1.39.

Overall 5-year survival in study 58% (n=149).

Fassnacht et al. 2010195
2004 Worldwide Pediatric Adrenocortical Tumor Registry Age <20 years (n=254) 5-year survival 54.2%. Disease stage, endocrine dysfunction and age correlated with poor prognosis Michalkiewicz et al. 2004176

References

  1. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program stat fact sheets: thyroid cancer. 2012; http://seer.cancer.gov/statfacts/html/thyro.html. Accessed February, 6, 2016.
  2. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. SEER Cancer Statistics Review, 1975-2012. 2014; http://seer.cancer.gov/csr/1975_2012/. Accessed February, 2016.
  3. National Institute of Health. Surveillance, Epidemiology, and End Results (SEER) Program Cancer Statistics. 2012; http://seer.cancer.gov/faststats/selections.php? – Output. Accessed February 6, 2016.
  4. Kilfoy BA, Devesa SS, Ward MH, Zhang Y, Rosenberg PS, Holford TR, Anderson WF. Gender is an age-specific effect modifier for papillary cancers of the thyroid gland. Cancer Epidemiol Biomarkers Prev. 2009;Apr;18(4):1092-1100.
  5. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006;May 10;295(18):2164-2167.
  6. Aschebrook-Kilfoy B, Schechter RB, Shih YC, Kaplan EL, Chiu BC, Angelos P, Grogan RH. The clinical and economic burden of a sustained increase in thyroid cancer incidence. Cancer Epidemiol Biomarkers, Prev. 2013;Jul;22(7):1252-1259.
  7. Aschebrook-Kilfoy B, Grogan RH, Ward MH, Kaplan E, Devesa SS. Follicular thyroid cancer incidence patterns in the United States, 1980-2009. Thyroid. 2013;Aug;23(8):1015-1021.
  8. Zheng T, Holford TR, Chen Y, Ma JZ, Flannery J, Liu W, Russi M, Boyle P. Time trend and age-period-cohort effect on incidence of thyroid cancer in Connecticut, 1935-1992. Int, J. Cancer. 1996;Aug 7;67(4):504-509.
  9. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E. Cancer treatment and survivorship statistics, 2012. CA: a cancer journal for clinicians. Jul-Aug 2012;62(4):220-241.
  10. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. C. A. Cancer J Clin. 2016;Jan;66(1):7-30.
  11. O’Grady TJ, Gates MA, Bosccoe FP. Thyroid cancer incidence attributable to overdiagnosis in the United States 1981-2011. Int J Cancer. 2015;Dec 1;137(11):2664-2673.
  12. Morris LGT, Tuttle RM, Davies L. Changing Trends in the Incidence of Thyroid Cancer in the United States. JAMA otolaryngology– head & neck surgery. 2016;142(7):709-711.
  13. Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. C. A. Cancer J Clin. 2012;Mar-Apr;62(2):118-128.
  14. Enewold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Devesa SS. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol Biomarkers, Prev. 2009;Mar;18 (3):784-791.
  15. Aschebrook-Kilfoy B, Ward MHS, M.M. S, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Thyroid. 2011;Feb;21(2):125-134.
  16. Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988-2005. Cancer. 2009;Aug 15;115(16):3801-3807.
  17. Morris LG, Sikora AG, Tosteson TD, Davies L. The increasing incidence of thyroid cancer: the influence of access to care. Thyroid. Jul 2013;23(7):885-891.
  18. Yu GP, Li JC, Branovan D, McCormick S, Schantz SP. Thyroid cancer incidence and survival in the national cancer institute surveillance, epidemiology, and end results race/ethnicity groups. Thyroid. May 2010;20(5):465-473.
  19. Li N, Du XL, Reitzel LR, Xu L, Sturgis EM. Impact of enhanced detection on the increase in thyroid cancer incidence in the United States: review of incidence trends by socioeconomic status within the surveillance, epidemiology, and end results registry, 1980-2008. Thyroid. 2013;Jan;23(1):103-110.
  20. Vanderlaan WP. The occurrence of carcinoma of the thyroid gland in autopsy material. N. Engl J Med. 1947;Aug 14;237(7):221.
  21. Arem R, Padayatty SJ, Saliby AH, Sherman SI, Sherman SI. Thyroid microcarcinoma: prevalence, prognosis, and management. Endocr Pract. 1999;May-Jun;5(3):148-156.
  22. Dean DS, Gharib H. Epidemiology of thyroid nodules. Best Pract Res Clin Endocrinol, Metab. 2008;Dec;22(6):901-911.
  23. Ezzat S, D.A. S, Cain DR, Braunstein GD. Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch Intern, Med. 1994;Aug 22;154(16):1838-1840.
  24. Ahmed S, Johnson PT, Horton KM, Lai H, Zaheer A, Tsai S, Fishman EK. Prevalence of unsuspected thyroid nodules in adults on contrast enhanced 16- and 64-MDCT of the chest. World Journal of Radiology. 2012;4(7):311-317.
  25. Frates MC, Benson CB, Charboneau JW, Cibas ES, Clark OH, Coleman BG, Cronan JJ, Doubilet PM, Evans DB, Goellner JR, Hay ID, Herzberg BS, Intenzo CM, Jeffrey RB, Langer JE, Larsen PR, Mandel SJ, Middleton WD, Reading CC, Sherman SI, Tessler FN. Management of thyroid nodules detected at US: Society of Radilogists in Ultrasound Consensus Conference Statement. Radiology. 2005;237:794-800.
  26. Scopa CD. Histopathology of thyroid tumors. An overview. Hormones (Athens, Greece). Apr-Jun 2004;3(2):100-110.
  27. Kalezic NK, Zivaljevic VR, Slijepcevic NA, Paunovic IR, Diklic AD, Sipetic SB. Risk factors for sporadic medullary thyroid carcinoma. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). May 2013;22(3):262-267.
  28. Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA, Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565-612.
  29. Are C, Shaha AR. Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches. Annals of surgical oncology. Apr 2006;13(4):453-464.
  30. Nagaiah G, Hossain A, Mooney CJ, Parmentier J, Remick SC. Anaplastic thyroid cancer: a review of epidemiology, pathogenesis, and treatment. Journal of oncology. 2011;2011:542358.
  31. Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, Kebebew E, Lee NY, Nikiforov YE, Rosenthal MS, Shah MH, Shaha AR, Tuttle RM. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. Nov 2012;22(11):1104-1139.
  32. Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA. Mutational Profile Of Advanced Primary and Metastatic Radioactive Iodine-Refractory Thyroid Cancers Reveals Distinct Pathogenetic Roles for BRAF, PIK3CA and AKT1. Cancer research. 2009;69(11):4885-4893.
  33. Agrawal N, Akbani R, Aksoy BA, Ally A, Arachchi H, Asa SL, Auman JT, Balasundaram M, Balu S, Baylin SB, Behera M, Bernard B, Beroukhim R, Bishop JA, Black AD, Bodenheimer T, Boice L, Bootwalla MS, Bowen J, Bowlby R, Bristow CA, Brookens R, Brooks D, Bryant R, Buda E, Butterfield YSN, Carling T, Carlsen R, Carter SL, Carty SE, Chan TA, Chen AY, Cherniack AD, Cheung D, Chin L, Cho J, Chu A, Chuah E, Cibulskis K, Ciriello G, Clarke A, Clayman GL, Cope L, Copland J, Covington K, Danilova L, Davidsen T, Demchok JA, DiCara D, Dhalla N, Dhir R, Dookran SS, Dresdner G, Eldridge J, Eley G, El-Naggar AK, Eng S, Fagin JA, Fennell T, Ferris RL, Fisher S, Frazer S, Frick J, Gabriel SB, Ganly I, Gao J, Garraway LA, Gastier-Foster JM, Getz G, Gehlenborg N, Ghossein R, Gibbs RA, Giordano TJ, Gomez-Hernandez K, Grimsby J, Gross B, Guin R, Hadjipanayis A, Harper HA, Hayes DN, Heiman DI, Herman JG, Hoadley KA, Hofree M, Holt RA, Hoyle AP, Huang FW, Huang M, Hutter CM, Ideker T, Iype L, Jacobsen A, Jefferys SR, Jones CD, Jones SJM, Kasaian K, Kebebew E, Khuri FR, Kim J, Kramer R, Kreisberg R, Kucherlapati R, Kwiatkowski DJ, Ladanyi M, Lai PH, Laird PW, Lander E, Lawrence MS, Lee D, Lee E, Lee S, Lee W, Leraas KM, Lichtenberg TM, Lichtenstein L, Lin P, Ling S, Liu J, Liu W, Liu Y, LiVolsi VA, Lu Y, Ma Y, Mahadeshwar HS, Marra MA, Mayo M, McFadden DG, Meng S, Meyerson M, Mieczkowski PA, Miller M, Mills G, Moore RA, Mose LE, Mungall AJ, Murray BA, Nikiforov YE, Noble MS, Ojesina AI, Owonikoko TK, Ozenberger BA, Pantazi A, Parfenov M, Park PJ, Parker JS, Paull EO, Pedamallu CS, Perou CM, Prins JF, Protopopov A, Ramalingam SS, Ramirez NC, Ramirez R, Raphael BJ, Rathmell WK, Ren X, Reynolds SM, Rheinbay E, Ringel MD, Rivera M, Roach J, Robertson AG, Rosenberg MW, Rosenthall M, Sadeghi S, Saksena G, Sander C, Santoso N, Schein JE, Schultz N, Schumacher SE, Seethala RR, Seidman J, Senbabaoglu Y, Seth S, Sharpe S, Mills Shaw KR, Shen JP, Shen R, Sherman S, Sheth M, Shi Y, Shmulevich I, Sica GL, Simons JV, Sipahimalani P, Smallridge RC, Sofia HJ, Soloway MG, Song X, Sougnez C, Stewart C, Stojanov P, Stuart JM, Tabak B, Tam A, Tan D, Tang J, Tarnuzzer R, Taylor BS, Thiessen N, Thorne L, Thorsson V, Tuttle RM, Umbricht CB, Van Den Berg DJ, Vandin F, Veluvolu U, Verhaak RGW, Vinco M, Voet D, Walter V, Wang Z, Waring S, Weinberger PM, Weinstein JN, Weisenberger DJ, Wheeler D, Wilkerson MD, Wilson J, Williams M, Winer DA, Wise L, Wu J, Xi L, Xu AW, Yang L, Yang L, Zack TI, Zeiger MA, Zeng D, Zenklusen JC, Zhao N, Zhang H, Zhang J, Zhang J, Zhang W, Zmuda E, Zou L. Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell. 2014;159(3):676-690.
  34. Costa V, Esposito R, Ziviello C, Sepe R, Bim LV, Cacciola NA, Decaussin-Petrucci M, Pallante P, Fusco A, Ciccodicola A. New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma. Oncotarget. 2015;6(13):11242-11251.
  35. Erler P, Keutgen XM, Crowley MJ, Zetoune T, Kundel A, Kleiman D, Beninato T, Scognamiglio T, Elemento O, Zarnegar R, Fahey TJ, 3rd. Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer. Surgery. 2014;Dec;156(6):1342-1350.
  36. Pringle DR, Yin Z, Lee AA, Manchanda PK, Yu L, Parlow AF, Jarjoura D, La Perle KMD, Kirschner LS. Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer. Endocr Relat, Cancer. 2012;May 24;19(3):435-446.
  37. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. 2016(1557-9077 (Electronic)).
  38. Yip L, Nikiforova MN, Yoo JY, McCoy KI, Stang MT, Armstrong MJ, Nicholson KJ, Ohori NP, Coyne C, Hodak SP, Ferris Rl, LeBeau SO, Nikiforov YE, Carty SE. Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: a study of 1510 patients. Ann, Surg. 2015;Sep;262(3):519-525.
  39. Henke LE, Pfeifer JD, Ma C, Perkins SM, DeWees T, El-Mofty S, Moley JF, Nussenbaum B, Haughey BH, Baranski TJ, Schwarz JK, Grigsby PW. BRAF mutation is not predictive of long-term outcome in papillary thyroid carcinoma. Cancer, Med. 20150610 2015;Jun;4(6):791-799.
  40. Nikiforov YE. Molecular diagnostics of thyroid tumors. Arch Pathol Lab, Med. 20110429 DCOM- 20110628 2011;May;135(5):569-577.
  41. Afkhami M, Karunamurthy A, Chiosea S, Nikiforova MN, Seethala R, Nikiforov YE, Coyne C. Histopathologic and Clinical Characterization of Thyroid Tumors Carrying the BRAF(K601E) Mutation. Thyroid. 2016;Feb;26(2):242-247.
  42. Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El-Naggar AK, Xing M. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocrine-related cancer. 2013;20(4):603-610.
  43. Liu R, Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat, Cancer. 2016;Mar;23(3):R143-155.
  44. Richards ML. Familial syndromes associated with thyroid cancer in the era of personalized medicine. Thyroid. 2010;Jul;20(7):707-713.
  45. Phay JE, Moley JF, Lairmore TC. Multiple endocrine neoplasias. Semin Surg, Oncol. 2000;18:324-332.
  46. Feldman GL, Edmonds MW, Ainsworth PJ, Schuffenecker I, Lenoir GM, Saxe AW, Talpos GB, Roberson J, Petrucelli N, Jackson CE. Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG→ATG) mutation. Surgery. 2000;128(1):93-98.
  47. Prasad ML, Vyas M, Horne MJ, Virk RK, Morotti R, Liu Z, Tallini G, Nikiforova MN, Christison-Lagay ER, Udelsman R, Dinauer CA, Nikiforov YE. NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States. Cancer. 2016;Apr 1;122(7):1097-1107.
  48. Tufano RP, Teixeira GV, Bishop J, Carson KA, Xing M. BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis. Medicine,. 2012;Sep;91(5):274-282.
  49. Xing M. BRAF Mutation in Papillary Thyroid Cancer: Pathogenic Role, Molecular Bases, and Clinical Implications. Endocrine reviews. 2007;28(7):742-762.
  50. Karunamurthy A, Panebianco F, Hsiao S, Vorhauer J, Nikiforova M, Chiosea SI, Nikiforov Y. Prevalence and phenotypic characteristics of EIF1AX mutations in thyroid nodules. Endocr Relat, Cancer. 2016;Apr;23(4):295-301.
  51. Wojcicka A, Kolanowska M, Jazdzewski K. MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer. Eur, J. Endocrinol. 2016;Mar;174(3):R89-98.
  52. Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(20):7269-7274.
  53. Lubitz CC, Kong CY, McMahon PM, Daniels GH, Chen Y, Economopoulos KP, Gazelle GS, Weinstein MC. Annual financial impact of well-differentiated thyroid cancer care in the United States. Cancer. May 1 2014;120(9):1345-1352.
  54. Sun GH, DeMonner S, Davis MM. Epidemiological and economic trends in inpatient and outpatient thyroidectomy in the United States, 1996-2006. Thyroid. Jun 2013;23(6):727-733.
  55. Stack BC, Jr., Moore E, Spencer H, Medvedev S, Bodenner DL. Outpatient thyroid surgery data from the University Health System (UHC) Consortium. Otolaryngol Head Neck Surg. Vol 148. England, 2013:740-745.
  56. Sosa JA, Mehta PJ, Wang TS, Yeo HI, Roman SA. Racial disparities in clinical and economic outcomes from thyroidectomy. Ann, Surg. 2007;Dec;246(6):1083-1091.
  57. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. Nov 2009;19(11):1167-1214.
  58. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;Apr;140(4):317-322.
  59. Haddow JE, McClain MR, Palomaki GE, Kloza EM, Williams J. Screening for thyroid disorders during pregnancy: results of a survey in Maine. Am, J. Obstet Gynecol. 2006;Feb;194(2):471-474.
  60. Jin H, Pinheiro PS, Xu J, Amei A. Cancer incidence among Asian American populations in the United States, 2009-2011. Int, J. Cancer. 2016;May 1;138(9):2136-2145.
  61. Horn-Ross PL, McClure LA, Chang ET, Clarke CA, Keegan TH, Rull RP, Quach T, Gomez SL. Papillary thyroid cancer incidence rates vary significantly by birthplace in Asian American women. Cancer Causes, Control. 2011;Mar;22(3):479-485.
  62. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Annals of surgical oncology. Jun 2010;17(6):1471-1474.
  63. Holmes L, Hossain J, Opara F. Pediatric Thyroid Carcinoma Incidence and Temporal Trends in the USA (1973–2007): Race or Shifting Diagnostic Paradigm? ISRN Oncology. 2012;2012:906197.
  64. Siegel DA, King J, Tai E, Buchanan N, Ajani UA, Li J. Cancer Incidence Rates and Trends Among Children and Adolescents in the United States, 2001–2009. Pediatrics. 2014;134(4):e945-e955.
  65. de Moor JS, Mariotto AB, Parry C, Alfano CM, Padgett L, Kent EE, Forsythe L, Scoppa S, Hachey M, Rowland JH. Cancer survivors in the United States: prevalence across the survivorship trajectory and implications for care. Cancer Epidemiol Biomarkers Prev. Apr 2013;22(4):561-570.
  66. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments]. Cancer,. 1998;Dec 15;83(12):2638-2648.
  67. Hollenbeak CS, Wang L, Schneider P, Goldenberg D. Outcomes of thyroid cancer in African Americans. Ethn, Dis. 2011;Spring;21(2):210-215.
  68. Orosco RK, Hussain T, Brumund KT, Oh DK, Chang DC, Bouvet M. Analysis of age and disease status as predictors of thyroid cancer-specific mortality using the Surveillance, Epidemiology, and End Results database. Thyroid. 2015;Jan;25(1):125-132.
  69. Nilubol N, Kebebew E. Should small papillary thyroid cancer be observed? A population-based study. Cancer. 2015;121(7):1017-1024.
  70. Ganly I, Nixon IJ, Wang LY, Palmer FL, Migliacci JC, Aniss A, Sywak M, Eskander AE, Freeman JL, Campbell MJ, Shen WT, Vaisman F, Momesso D, Corbo R, Vaisman M, Shaha A, Tuttle RM, Shah JP, Patel SG. Survival from Differentiated Thyroid Cancer: What Has Age Got to Do with It? Thyroid,. 2015;Oct;25(10):1106-1114.
  71. Henke LE, Perkins SM, Pfeifer JD, Ma C, Chen Y, DeWees T, Grigsby PW. BRAF V600E mutational status in pediatric thyroid cancer. Pediatric Blood & Cancer. 2014;61(7):1168-1172.
  72. Esfandiari NH, Hughes DT, Yin H, Banerjee M, Haymart MR. The effect of extent of surgery and number of lymph node metastases on overall survival in patients with medullary thyroid cancer. J. Clin Endocrinol Metab. 2014;Feb;99(2):448-454.
  73. Glaser SM, Mandish SF, Gill BS, Balasubramani GK, Clump DA, Beriwal S. Anaplastic thyroid cancer: Prognostic factors, patterns of care, and overall survival. Head, Neck. 2016;Apr;38(Suppl 1:E2083-90).
  74. Hay ID, McConahey WM, Goellner JR. Managing patients with papillary thyroid carcinoma: insights gained from the Mayo Clinic’s experience of treating 2,512 consecutive patients during 1940 through 2000. Trans Am Clin Climatol Assoc. 2002;113:241-260.
  75. Sosa JA, M. BH, Tielsch JM, Powe NR, Gordon TA, Udelsman R. The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Ann, Surg. 1998;Sept;228(3):320-330.
  76. National Institute of Health, Drugs Approved for Thyroid Cancer. 2012; http://www.cancer.gov/about-cancer/treatment/drugs/thyroid. Accessed March 13, 2016.
  77. Busaidy NL, Cabanillas ME. Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease. Journal of Thyroid Research. 2012;2012:618985.
  78. Shoup M, Stojadinovic A, Nissan A, Ghossein RA, Freedman S, Brennan MF, Shah JP, Shaha AR. Prognostic indicators of outcomes in patients with distant metastases from differentiated thyroid carcinoma. Journal of the American College of Surgeons. 2003;197(2):191-197.
  79. Dadu R, Devine C, Hernandez M, Waguespack SG, Busaidy NL, Hu MI, Jimenez C, Habra MA, Sellin RV, Ying AK, Cote GJ, Sherman SI, Cabanillas ME. Role of Salvage Targeted Therapy in Differentiated Thyroid Cancer Patients Who Failed First-Line Sorafenib. The Journal of Clinical Endocrinology & Metabolism. 2014;99(6):2086-2094.
  80. National Comprehensive Cancer Network (NCCN) Guidelines. 2016; https://http://www.nccn.org/professionals/physician_gls/f_guidelines.asp – site. Accessed 9/26/2016, 2016.
  81. Perez CA, Santos ES, Arango BA, Raez LE, Cohen EE. Novel molecular targeted therapies for refractory thyroid cancer. Head, Neck. 2012;May;34(5):736-745.
  82. Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, Elisei R, Bendlova B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O’Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Clifton-Bligh R, Tallini G, Holt EH, Sykorova V. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J. Clin Oncol. 2015;Jan 1;33(1):42-50.
  83. Yarchoan M, LiVolsi VA, Brose MS. BRAF mutation and thyroid cancer recurrence. J. Clin Oncol. 2015;Jan 1;33(1):7-8.
  84. Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, KeeShong Y, Sherman SI, Smit JWA, Chung J, Kappeler C, Pena C, Molnár I, Schlumberger MJ, on behalf of the DI. Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial. Lancet. 2014;384(9940):319-328.
  85. Maia AL, Siqueira DR, Kulcsar MA, Tincani AJ, Mazeto GM, Maciel LM. Diagnosis, treatment, and follow-up of medullary thyroid carcinoma: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism. Arquivos brasileiros de endocrinologia e metabologia. Oct 2014;58(7):667-700.
  86. Lodish MB, Stratakis CA. RET oncogene in MEN2, MEN2B, MTC and other forms of thyroid cancer. Expert Rev Anticancer, Ther. 2008;Apr;8(4):625-632.
  87. Schlumberger M, Tahara M, Wirth LJ, Robinson BF, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N. Engl J Med. 2015;Feb 12;372(7):621-630.
  88. White PT, Cohen MS. The discovery and development of sorafenib for the treatment of thyroid cancer. Expert Opin Drug Discov. 20150320 DCOM- 20151203 2015;Apr;10(4):427-439.
  89. Cabanillas ME, Habra MA. Lenvatinib: Role in thyroid cancer and other solid tumors. Cancer Treat, Rev. 2016;Jan(Jan;42):47-55.
  90. Elisei R, Schlumberger MJ, Muller SP, Schoffski P, Brose MS, Shah MH, Licitra L, Jarzab B, Medvedev V, Kreissl MC, Niederle B, Cohen EE, Wirth LJ, Ali H, Hessel C, Yaron Y, Ball D, Nelkin B, Sherman SI. Cabozantinib in progressive medullary thyroid cancer. J. Clin Oncol. 2013;Oct 10;31(29):3639-3646.
  91. Hart CD, De Boer RH. Profile of cabozantinib and its potential in the treatment of advanced medullary thyroid cancer. OncoTargets and therapy. 2013;6:1-7.
  92. Gruber JJ, Colevas AD. Differentiated Thyroid Cancer: Focus on Emerging Treatments for Radioactive Iodine-Refractory Patients. The oncologist. 2015;20(2):113-126.
  93. Carhill AA, Litofsky DR, Ross DS, Jonklaas J, Cooper DS, Brierley JD, Ladenson PW, Ain KB, Fein HG, Haugen BR, Magner J, Skarulis MC, Steward DL, Xing M, Maxon HR, Sherman SI. Long-Term Outcomes Following Therapy in Differentiated Thyroid Carcinoma: NTCTCS Registry Analysis 1987–2012. The Journal of Clinical Endocrinology & Metabolism. 2015;100(9):3270-3279.
  94. Kloos RT, Ringel MD, Knopp MV, Hall NC, King M, Stevens R, Liang J, Wakely PE, Vasko VV, Saji M, Rittenberry J, Wei L, Arbogast D, Collamore M, Wright JJ, Grever M, Shah MH. Phase II Trial of Sorafenib in Metastatic Thyroid Cancer. Journal of Clinical Oncology. 2009;27(10):1675-1684.
  95. Thomas L, Lai SY, Dong W, Feng L, Dadu R, Regone RM, Cabanillas ME. Sorafenib in Metastatic Thyroid Cancer: A Systematic Review. The oncologist. 2014;19(3):251-258.
  96. Wells SA, Jr., Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J. Clin Oncol. 2012;Jan 10;30(2):134-141.
  97. Fox E, Widemann BC, Chuk MK, Marcus L, Aikin A, Whitcomb PO, Merino MJ, Lodish M, Dombi E, Steinberg SM, Wells SA, Balis FM. Vandetanib in Children and Adolescents with Multiple Endocrine Neoplasia Type 2B Associated Medullary Thyroid Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2013;19(15):4239-4248.
  98. Goffredo P, Thomas SM, Adam MA, Sosa JA, Roman SA. Impact of Timeliness of Resection and Thyroidectomy Margin Status on Survival for Patients with Anaplastic Thyroid Cancer: An Analysis of 335 Cases. Ann Surg, Oncol. 20151114 2015;Dec;22(13):4166-4174.
  99. Smallridge RC, Copland JA, Brose MS, Wadsworth JT, Houvras Y, Menefee ME, Bible KC, Shah MH, Gramza AW, Klopper JP, Marlow LA, Heckman MG, Von Roemeling R. Efatutazone, an Oral PPAR-γ Agonist, in Combination With Paclitaxel in Anaplastic Thyroid Cancer: Results of a Multicenter Phase 1 Trial. The Journal of Clinical Endocrinology and Metabolism. 2013;98(6):2392-2400.
  100. Anagnostis P, Karagiannis A, Tziomalos K, Kakafika AI, Athyros VG, Mikhailidis DP. Adrenal incidentaloma: a diagnostic challenge. Hormones (Athens, Greece). Jul-Sep 2009;8(3):163-184.
  101. Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. European journal of endocrinology / European Federation of Endocrine Societies. 2003;149(4):273-285.
  102. Giordano R, Marinazzo E, Berardelli R, Picu A, Maccario M, Ghigo E, Arvat E. Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas. European journal of endocrinology / European Federation of Endocrine Societies. Apr 2010;162(4):779-785.
  103. Di Dalmazi G, Vicennati V, Rinaldi E, Morselli-Labate AM, Giampalma E, Mosconi C, Pagotto U, Pasquali R. Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study. European journal of endocrinology / European Federation of Endocrine Societies. Apr 2012;166(4):669-677.
  104. Vassilatou E, Vryonidou A, Michalopoulou S, Manolis J, Caratzas J, Phenekos C, Tzavara I. Hormonal activity of adrenal incidentalomas: results from a long-term follow-up study. Clinical endocrinology. May 2009;70(5):674-679.
  105. Akehi Y, Kawate H, Murase K, Nagaishi R, Nomiyama T, Nomura M, Takayanagi R, Yanase T. Proposed diagnostic criteria for subclinical Cushing’s syndrome associated with adrenal incidentaloma. Endocrine journal. 2013;60(7):903-912.
  106. Libe R, Dall’Asta C, Barbetta L, Baccarelli A, Beck-Peccoz P, Ambrosi B. Long-term follow-up study of patients with adrenal incidentalomas. European journal of endocrinology / European Federation of Endocrine Societies. Oct 2002;147(4):489-494.
  107. Amar L, Plouin PF, Steichen O. Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism. Orphanet journal of rare diseases. 2010;5:9.
  108. Bilimoria KY, Shen WT, Elaraj D, Bentrem DJ, Winchester DJ, Kebebew E, Sturgeon C. Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer. Dec 1 2008;113(11):3130-3136.
  109. Aron D, Terzolo M, Cawood TJ. Adrenal incidentalomas. Best Practice & Research Clinical Endocrinology & Metabolism. 2012;26(1):69-82.
  110. Duh QY. Functioning and non-functioning adrenal tumors. In: Bland KI, ed. The practice of general surgery. 1 ed: W.B. Saunders; 2002:1077-1082.
  111. Cawood TJ, Hunt PJ, O’Shea D, Cole D, Soule S. Recommended evaluation of adrenal incidentalomas is costly, has high false-positive rates and confers a risk of fatal cancer that is similar to the risk of the adrenal lesion becoming malignant; time for a rethink? Eur, J. Endocrinol. 2009;Oct;161(4):513-527.
  112. Reincke M. Subclinical Cushing’s syndrome. Endocrinol Metab Clin North, Am. 2000;Mar;29(1):43-56.
  113. Ross NS. Epidemiology of Cushing’s syndrome and subclinical disease. Endocrinol Metab Clin North, Am. 1994;Sept;23(3):539-546.
  114. Reimel B, Zanocco K, Russo MJ, Zarnegar R, Clark OH, Allendorf JD, Chabot JA, Duh Q-Y, Lee JA, Sturgeon C. The management of aldosterone-producing adrenal adenomas—does adrenalectomy increase costs? Surgery. 2010;148(6):1178-1185.
  115. Monticone S, Hattangady NG, Penton D, Isales CM, Edwards MA, Williams TA, Sterner C, Warth R, Mulatero P, Rainey WE. a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism type III. J Clin Endocrinol Metab. Nov 2013;98(11):E1861-1865.
  116. Bovio S, Cataldi A, Reimondo G, Sperone P, Novello S, Berruti A, Borasio P, Fava C, Dogliotti L, Scagliotti GV, Angeli A, Terzolo M. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J. Endocrinol Invest. 2006;Apr;29(4):298-302.
  117. Kutikov A, Mallin K, Canter D, Wong Y-N, Uzzo RG. Effects of Increased Cross Sectional Imaging on the Diagnosis and Prognosis of Adrenocortical Carcinoma: Analysis of the National Cancer Data Base. The Journal of urology. 2011;186(3):805-810.
  118. Fassnacht M, Kroiss M, Allolio B. Update in adrenocortical carcinoma. J Clin Endocrinol Metab. Dec 2013;98(12):4551-4564.
  119. Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World, J. Surg. 2006;May;30(5):872-878.
  120. Roman S. Adrenocortical carcinoma. Curr Opin, Oncol. 2006;Jan;18(1):36-42.
  121. Wooten MD, King DK. Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature. Cancer. 1993;72(11):3145-3155.
  122. Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM, Jolly S, Miller BS, Giordano TJ, Hammer GD. Adrenocortical carcinoma. Endocrine reviews. 2014;35(2):282-326.
  123. Multiple endocrine neoplasia type 1. 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=652. Accessed August 2016, 2015.
  124. Herrera MF, Grant CS, van Heerden JA, van Heerden JA, Sheedy PF, Ilstrup DM. Incidentally discovered adrenal tumors: an institutional perspective. Surgery. 1991;Dec;110(6):1014-1021.
  125. Kim J, Bae KH, Choi YK, Jeong JY, Park KG, Kim JG, Lee IK. Clinical Characteristics for 348 Patients with Adrenal Incidentaloma. Endocrinology and Metabolism. 2013;28(1):20-25.
  126. Emral R, Uysal AR, Asik M, Gullu S, Corapcioglu D, Tonyukuk V, Erdogan G. Prevalence of subclinical Cushing’s syndrome in 70 patients with adrenal incidentaloma: clinical, biochemical and surgical outcomes. Endocr, J. 2003;Aug;50(4):399-408.
  127. Kerkhofs TMA, Verhoeven RHA, Van der Zwan JM, Dieleman J, Kerstens MN, Links TP, Van de Poll-Franse LV, Haak HR. Adrenocortical carcinoma: A population-based study on incidence and survival in the Netherlands since 1993. European Journal of Cancer. 2013;49(11):2579-2586.
  128. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally Discovered Adrenal Masses. Endocrine reviews. 1995;16(4):460-484.
  129. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr, Rev. 2004;Apr;25(2):309-340.
  130. SEER. 1975-2012; http://seer.cancer.gov/csr/1975_2012/browse_csr.php?sectionSEL=32&pageSEL=sect_32_table.01.html. Accessed March,6, 2016.
  131. Wajchenberg BL, Albergaria PMA, Medonca BB, Latronico AC, Campos CP, Alves VA, Zerbini MC, Liberman B, Carlos GG, Kirschner MA. Adrenocortical carcinoma: clinical and laboratory observations. Cancer. 2000;Feb 15;88(4):711-736.
  132. Ross NS, Aron DC. Hormonal Evaluation of the Patient with an Incidentally Discovered Adrenal Mass. New England Journal of Medicine. 1990;323(20):1401-1405.
  133. Hanna AM, Pham TH, Askegard-Giesmann JR, Grams JM, Iqbal CW, Stavlo P, Moir CR. Outcome of adrenocortical tumors in children. Journal of pediatric surgery. 2008;43(5):843-849.
  134. Wasserman JD, Novokmet A, Eichler-Jonsson C, Ribeiro RC, Rodriguez-Galindo C, Zambetti GP, Malkin D. Prevalence and Functional Consequence of TP53 Mutations in Pediatric Adrenocortical Carcinoma: A Children’s Oncology Group Study. Journal of Clinical Oncology. 2015;33(6):602-609.
  135. Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G, Angeli A. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J. Clin Endocrinol Metab. 2000;85:637-644.
  136. Reinhard C, Saeger W Fau – Schubert B, Schubert B. Adrenocortical nodules in post-mortem series. Development, functional significance, and differentiation from adenomas. Gen Diagn, Pathol. 1996;Mar;141(3-4):203-208.
  137. Kloos RT, Gross MD, Shapiro B, Francis IR, Korobkin M, Thompson NW. Diagnostic dilemma of small incidentally discovered adrenal masses: role for 131I-6beta-iodomethyl-norcholesterol scintigraphy. World, J. Surg. 1997;Jan;21(1):36-40.
  138. Else T, Williams AR, Sabolch A, Jolly S, Miller BS, Hammer GD. Adjuvant therapies and patient and tumor characteristics associated with survival of adult patients with adrenocortical carcinoma. J. Clin Endocrinol Metab. 2014;Feb;99(2):455-461.
  139. Sturgeon C, Shen WT, Clark OH, Duh Q-Y, Kebebew E. Risk Assessment in 457 Adrenal Cortical Carcinomas: How Much Does Tumor Size Predict the Likelihood of Malignancy? Journal of the American College of Surgeons. 2006;202(3):423-430.
  140. Sullivan M, Boileau M, Hodges CV. Adrenal cortical carcinoma. J. Urol. 1978;Dec;120(6):660-665.
  141. Lee JE, Evans DB, Hickey RC, Sherman SI, Gagel RF, Abbruzzese MC, Abbruzzese JL. Unknown primary cancer presenting as an adrenal mass: frequency and implications for diagnostic evaluation of adrenal incidentalomas. Surgery. 1998;Dec;124(6):1115-1122.
  142. Shen WT, Sturgeon C, Duh QY. From incidentaloma to adrenocortical carcinoma: the surgical management of adrenal tumors. J. Surg Oncol. 2005;Mar;189(3):186-192.
  143. Peppa M, Boutati E, Koliaki C, Papaefstathiou N, Garoflos E, Economopoulos T, Hadjidakis D, Raptis SA. Insulin resistance and metabolic syndrome in patients with nonfunctioning adrenal incidentalomas: a cause-effect relationship? Metabolism: clinical and experimental. Oct 2010;59(10):1435-1441.
  144. Erbil Y, Ademoglu E, Ozbey N, Barbaros U, Yanik BT, Salmaslioglu A, Bozbora A, Ozarmagan S. Evaluation of the cardiovascular risk in patients with subclinical Cushing syndrome before and after surgery. World, J. Surg. 2006;Sep;30(9):1665-1671.
  145. Muscogiuri G, Sorice GP, Prioletta A, Mezza T, Cipolla C, Salomone E, Giaccari A, Pontecorvi A, Della Casa S. The size of adrenal incidentalomas correlates with insulin resistance. Is there a cause-effect relationship? Clinical endocrinology. Mar 2011;74(3):300-305.
  146. Kolanska K, Owecki M, Nikisch E, Sowinski J. High prevalence of obesity in patients with non-functioning adrenal incidentalomas. Neuro endocrinology letters. 2010;31(3):418-422.
  147. Shimon I. Screening for Cushing’s syndrome: is it worthwhile? Pituitary. 2015;Apr;18(2):201-205.
  148. Tauchmanova L, Rossi R, Biondi B, Pulcrano M, Nuzzo V, Palmieri EA, Fazio S, Lombardi G. Patients with subclinical Cushing’s syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab. Nov 2002;87(11):4872-4878.
  149. Martins LC, Conceicao FL, Muxfeldt ES, Salles GF. Prevalence and associated factors of subclinical hypercortisolism in patients with resistant hypertension. J. Hypertens. 2012;May;30(5):967-973.
  150. Trifanescu R, Carsote M, Caragheorgheopol A, Hortopan D, Dumitrascu A, Dobrescu M, Poiana C. Screening for secondary endocrine hypertension in young patients. Mædica. 2013;8(2):108-115.
  151. Anderson GH, Jr., Blakeman N, Streeten DH. The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients. J. Hypertens. 1994;May;12(5):609-615.
  152. Muth A, Taft C, Hammarstedt L, Bjorneld L, Hellstrom M, Wangberg B. Patient-reported impacts of a conservative management programme for the clinically inapparent adrenal mass. Endocrine. Aug 2013;44(1):228-236.
  153. Arlt W. A detour guide to the Endocrine Society Clinical Practice Guideline on case detection, diagnosis and treatment of patients with primary aldosteronism. European journal of endocrinology / European Federation of Endocrine Societies. Mar 2009;162:435-438.
  154. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. Journal of the American College of Cardiology. Dec 5 2006;48(11):2293-2300.
  155. Miyake Y, Tanaka K, Nishikawa T, Naruse M, Takayanagi R, Sasano H, Takeda Y, Shibata H, Sone M, Satoh F, Yamada M, Ueshiba H, Katabami T, Iwasaki Y, Tanaka H, Tanahashi Y, Suzuki S, Hasegawa T, Katsumata N, Tajima T, Yanase T. Prognosis of primary aldosteronism in Japan: results from a nationwide epidemiological study. Endocrine journal. 2014;61(1):35-40.
  156. Piaditis G, Markou A, Papanastasiou L, Androulakis I, Kaltsas G. PROGRESS IN PRIMARY ALDOSTERONISM: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension. European journal of endocrinology / European Federation of Endocrine Societies. Dec 23 2015;May;172(5):R191-203.
  157. Lu ZH, Zhu XX, Tang ZQ, Yang GQ, Du J, Wang XL, Yang JZ, Gu WJ, Guo QH, Jin N, Yang LJ, Ba JM, Dou JT, Mu YM. Female sex hormones are associated with the reduction of serum sodium and hypertension complications in patients with aldosterone-producing adenoma. Endocrine journal. 2013;60(11):1261-1268.
  158. Choi M, Scholl UI, Yue P, Bjorklund P, Zhao B, Nelson-Williams C, Ji W, Cho Y, Patel A, Men CJ, Lolis E, Wisgerhof MV, Geller DS, Mane S, Hellman P, Westin G, Akerstrom G, Wang W, Carling T, Lifton RP. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science (New York, N.Y.). Feb 11 2011;331(6018):768-772.
  159. Mulatero P, Monticone S, Bertello C, Viola A, Tizzani D, Iannaccone A, Crudo V, Burrello J, Milan A, Rabbia F, Veglio F. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab. Dec 2013;98(12):4826-4833.
  160. Zennaro MC, Boulkroun S, Fernandes-Rosa F. An update on novel mechanisms of primary aldosteronism. J Endocrinol. Vol 224: (c) 2015 Society for Endocrinology.; 2015:R63-r77.
  161. Gonzalez KD, Noltner KA, Buzin CH, Gu D, Wen-Fong CY, Nguyen VQ, Han JH, Lowstuter K, Longmate J, Sommer SS, Weitzel JN. Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J. Clin Oncol. 2009;Mar 10;27(8):1250-1256.
  162. Herrmann LJM, Heinze B, Fassnacht M, Willenberg HS, Quinkler M, Reisch N, Zink M, Allolio B, Hahner S. TP53 Germline Mutations in Adult Patients with Adrenocortical Carcinoma. The Journal of Clinical Endocrinology & Metabolism. 2011;97(3):E476-E485.
  163. Raymond VM, Else T, Everett JN, Long JM, Gruber SB, Hammer GD. Prevalence of Germline TP53 Mutations in a Prospective Series of Unselected Patients with Adrenocortical Carcinoma. The Journal of Clinical Endocrinology and Metabolism. 2013;98(1):E119-E125.
  164. Sabbaga CC, Avilla SG, Schulz C, Garbers JC, Blucher D. Adrenocortical carcinoma in children: clinical aspects and prognosis. J. Pediatr Surg. 1993;Jun;28(6):841-843.
  165. Ribeiro RC, Sandrini F, Figueiredo B, Zambetti GP, Michalkiewicz E, Lafferty AR, DeLacerda L, Rabin M, Cadwell C, Sampaio G, Cat I, Stratakis CA, Sandrini R. An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(16):9330-9335.
  166. Elfiky AA, Krishnan Nair HK. Assessment and management of advanced adrenocortical carcinoma using a precision oncology care model. Discov, Med. 20160221 2016;Jan;21(113):49-56.
  167. Anselmo J, Medeiros S, Carneiro V, Greene E, Levy I, Nesterova M, Lyssikatos C, Horvath A, Carney JA, Stratakis CA. A large family with Carney complex caused by the S147G PRKAR1A mutation shows a unique spectrum of disease including adrenocortical cancer. J. Clin Endocrinol Metab. 2012;Feb;97(2):351-359.
  168. Morin E, Mete O, Wasserman JD, Joshua AM, Asa SL, Ezzat S. Carney complex with adrenal cortical carcinoma. J. Clin Endocrinol Metab. 2012;Feb;97(2):E202-206.
  169. Beuschlein F, Fassnacht M, Assie G, Calebiro D, Stratakis CA, Osswald A, Ronchi CL, Wieland T, Sbiera S, Faucz FR, Schaak K, Schmittfull A, Schwarzmayr T, Barreau O, Vezzosi D, Rizk-Rabin M, Zabel U, Szarek E, Salpea P, Forlino A, Vetro A, Zuffardi O, Kisker C, Diener S, Meitinger T, Lohse MJ, Reincke M, Bertherat J, Strom TM, Allolio B. Constitutive activation of PKA catalytic subunit in adrenal Cushing’s syndrome. N. Engl J Med. 2014;Mar 13;370(11):1019-1028.
  170. Louiset E, Lefebvre H. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia. The New England journal of medicine. Mar 13 2014;370(11):1071-1072.
  171. Mulatero P, Tizzani D, Viola A, Bertello C, Monticone S, Mengozzi G, Schiavone D, Williams TA, Einaudi S, La Grotta A, Rabbia F, Veglio F. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms). Hypertension. Nov 2011;58(5):797-803.
  172. Kirschner LS, Sandrini F, Monbo J, Lin JP, Carney JA, Stratakis CA. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the Carney complex. Human Molecular Genetics. 2000;9(20):3037-3046.
  173. Morin E, Mete O, Wasserman JD, Joshua AM, Asa SL, Ezzat S. Carney complex with adrenal cortical carcinoma. J. Clin Endocrinol Metab. 2012;Feb;97(2):E202-E206.
  174. Audenet F, Mejean A, Chartier-Kastler E, Roupret M. Adrenal tumours are more predominant in females regardless of their histological subtype: a review. World journal of urology. Oct 2013;31(5):1037-1043.
  175. Di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E, Mosconi C, Golfieri R, Paccapelo A, Pagotto U, Pasquali R. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing’s syndrome: a 15-year retrospective study. The lancet. Diabetes & endocrinology. May 2014;2(5):396-405.
  176. Michalkiewicz E, Sandrini R, Figueiredo B, Miranda EC, Caran E, Oliveira-Filho AG, Marques R, Pianovski MA, Lacerda L, Cristofani LM, Jenkins J, Rodriguez-Galindo C, Ribeiro RC. Clinical and outcome characteristics of children with adrenocortical tumors: a report from the International Pediatric Adrenocortical Tumor Registry. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004;22(5):838-845.
  177. Luton J-P, Cerdas S, Billaud L, Thomas G, Guilhaume B, Bertagna X, Laudat M-H, Louvel A, Chapuis Y, Blondeau P, Bonnin A, Bricaire H. Clinical Features of Adrenocortical Carcinoma, Prognostic Factors, and the Effect of Mitotane Therapy. New England Journal of Medicine. 1990;322(17):1195-1201.
  178. Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol Metab. Dec 2014;99(12):4462-4470.
  179. Li J, Yang CH. Diagnosis and treatment of adrenocorticotrophic hormone-independent macronodular adrenocortical hyperplasia: A report of 23 cases in a single center. Experimental and therapeutic medicine. Feb 2015;9(2):507-512.
  180. Abdel-Aziz TE, Rajeev P, Sadler G, Weaver A, Mihai R. Risk of Adrenocortical Carcinoma in Adrenal Tumours Greater than 8 cm. World journal of surgery. 2014;May;39(5):1268-1273.
  181. Canter DJ, Mallin K, Uzzo RG, Egleston BL, Simhan J, Walton J, Smaldone MC, Master VA, Bratslavsky G, Kutikov A. Association of tumor size with metastatic potential and survival in patients with adrenocortical carcinoma: an analysis of the National Cancer Database. The Canadian journal of urology. Oct 2013;20(5):6915-6921.
  182. Erdogan I, Deutschbein T, Jurowich C, Kroiss M, Ronchi C, Quinkler M, Waldmann J, Willenberg HS, Beuschlein F, Fottner C, Klose S, Heidemeier A, Brix D, Fenske W, Hahner S, Reibetanz J, Allolio B, Fassnacht M. The role of surgery in the management of recurrent adrenocortical carcinoma. J Clin Endocrinol Metab. Jan 2013;98(1):181-191.
  183. Ayala-Ramirez M, Jasim S, Feng L, Ejaz S, Deniz F, Busaidy N, Waguespack SG, Naing A, Sircar K, Wood CG, Pagliaro L, Jimenez C, Vassilopoulou-Sellin R, Habra MA. Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center. European journal of endocrinology / European Federation of Endocrine Societies. Dec 2013;169(6):891-899.
  184. Gumbs AA, Gagner M. Laparoscopic adrenalectomy. Best Practice & Research Clinical Endocrinology & Metabolism. 2006;20(3):483-499.
  185. Giulianotti PC, Buchs NC, Addeo P, Bianco FM, Ayloo SM, Caravaglios G, Coratti A. Robot-assisted adrenalectomy: a technical option for the surgeon? The International Journal of Medical Robotics and Computer Assisted Surgery. 2011;7(1):27-32.
  186. Brandao LF, Autorino R, Zargar H, Krishnan J, Laydner H, Akca O, Mir MC, Samarasekera D, Stein R, Kaouk J. Robot-assisted Laparoscopic Adrenalectomy: Step-by-Step Technique and Comparative Outcomes. European Urology. 2014;66(5):898-905.
  187. Brunaud L, Bresler L, Ayav A, Zarnegar R, Raphoz A-L, Levan T, Weryha G, Boissel P. Robotic-assisted adrenalectomy: what advantages compared to lateral transperitoneal laparoscopic adrenalectomy? The American Journal of Surgery. 2008;195(4):433-438.
  188. Assalia A, Gagner M. Laparoscopic adrenalectomy. Br, J. Surg. 2004;Oct;91(10):1259-1274.
  189. Morelli V, Reimondo G, Giordano R, Della Casa S, Policola C, Palmieri S, Salcuni AS, Dolci A, Mendola M, Arosio M, Ambrosi B, Scillitani A, Ghigo E, Beck-Peccoz P, Terzolo M, Chiodini I. Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J Clin Endocrinol Metab. Mar 2014;99(3):827-834.
  190. Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E. Surgical versus conservative management for subclinical Cushing syndrome in adrenal incidentalomas: a prospective randomized study. Annals of surgery. Mar 2009;249(3):388-391.
  191. Iacobone M, Citton M, Scarpa M, Viel G, Boscaro M, Nitti D. Systematic review of surgical treatment of subclinical Cushing’s syndrome. The British journal of surgery. 2015;Mar;102(4):318-320.
  192. Stowasser M, Taylor PJ, Pimenta E, Ahmed AH, Gordon RD. Laboratory investigation of primary aldosteronism. The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists. May 2010;31(2):39-56.
  193. Scholl UI, Goh G, Stölting G, de Oliveira RC, Choi M, Overton JD, Fonseca AL, Korah R, Starker LF, Kunstman JW, Prasad ML, Hartung EA, Mauras N, Benson MR, Brady T, Shapiro JR, Loring E, Nelson-Williams C, Libutti SK, Mane S, Hellman P, Westin G, Åkerström G, Björklund P, Carling T, Fahlke C, Hidalgo P, Lifton RP. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet. Sep 2013;45:1050-1054.
  194. Habra MA, Ejaz S, Feng L, Das P, Deniz F, Grubbs EG, Phan A, Waguespack SG, Ayala-Ramirez M, Jimenez C, Perrier ND, Lee JE, Vassilopoulou-Sellin R. A retrospective cohort analysis of the efficacy of adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma. J Clin Endocrinol Metab. Jan 2013;98(1):192-197.
  195. Fassnacht M, Johanssen S, Fenske W, Weismann D, Agha A, Beuschlein F, Fuhrer D, Jurowich C, Quinkler M, Petersenn S, Spahn M, Hahner S, Allolio B. Improved survival in patients with stage II adrenocortical carcinoma followed up prospectively by specialized centers. J Clin Endocrinol Metab. Nov 2010;95(11):4925-4932.
  196. Salpea P, Stratakis CA. Carney complex and McCune Albright syndrome: an overview of clinical manifestations and human molecular genetics. Molecular and cellular endocrinology. 2014;386(1-2):85-91.
  197. Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Molecular and cellular endocrinology. 2014;386(1-2):2-15.
  198. Brito JP, Asi N, Bancos I, Gionfriddo MR, Zeballos-Palacios CL, Leppin AL, Undavalli C, Wang Z, Domecq JP, Prustsky G, Elraiyah TA, Prokop LJ, Montori VM, Murad MH. Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review. Clinical endocrinology. 2015;82(3):338-345.
  199. Almeida MQ, Stratakis CA. Solid tumors associated with multiple endocrine neoplasias. Cancer genetics and cytogenetics. Nov 2010;203(1):30-36.
  200. Lee M, Pellegata NS. Multiple Endocrine Neoplasia Type 4. In: Stratakis C, ed. Endocrine Tumor Syndromes and Their Genetics. Vol 41. Basel, Switzerland: Karger; 2013:63-78.
  201. Marinoni I, Pellegata NS. p27kip1: a new multiple endocrine neoplasia gene? Neuroendocrinology. 2011;93(1):19-28.
  202. Favier J, Amar L, Gimenez-Roqueplo AP. Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol. 2015;11(2):101-111.
  203. Persu A, Hamoir M, Gregoire V, Garin P, Duvivier E, Reychler H, Chantrain G, Mortier G, Mourad M, Maiter D, Vikkula M. High prevalence of SDHB mutations in head and neck paraganglioma in Belgium. Journal of hypertension. 2008;26(7):1395-1401.
  204. King KS, Prodanov T, Kantorovich V, Fojo T, Hewitt JK, Zacharin M, Wesley R, Lodish M, Raygada M, Gimenez-Roqueplo AP, McCormack S, Eisenhofer G, Milosevic D, Kebebew E, Stratakis CA, Pacak K. Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Nov 1 2011;29(31):4137-4142.
  205. Tsirlin A, Oo Y, Sharma R, Kansara A, Gliwa A, Banerji MA. Pheochromocytoma: A review. Maturitas. 2014;77(3):229-238.
  206. Bausch B, Borozdin W, Mautner VF, Hoffmann MM, Boehm D, Robledo M, Cascon A, Harenberg T, Schiavi F, Pawlu C, Peczkowska M, Letizia C, Calvieri S, Arnaldi G, Klingenberg-Noftz RD, Reisch N, Fassina A, Brunaud L, Walter MA, Mannelli M, MacGregor G, Palazzo FF, Barontini M, Walz MK, Kremens B, Brabant G, Pfäffle R, Koschker A-C, Lohoefner F, Mohaupt M, Gimm O, Jarzab B, McWhinney SR, Opocher G, Januszewicz A, Kohlhase J, Eng C, Neumann HPH. Germline NF1 Mutational Spectra and Loss-of-Heterozygosity Analyses in Patients with Pheochromocytoma and Neurofibromatosis Type 1. The Journal of Clinical Endocrinology & Metabolism. 2007;92(7):2784-2792.
  207. Hes FJ, Höppener JWM, Lips CJM. Pheochromocytoma in Von Hippel-Lindau Disease. The Journal of Clinical Endocrinology & Metabolism. 2003;88(3):969-974.
  208. Karasek D, Shah U, Frysak Z, Stratakis C, Pacak K. An update on the genetics of pheochromocytoma. Journal of human hypertension. Mar 2013;27(3):141-147.
  209. Kantorovich V, King KS, Pacak K. SDH-related Pheochromocytoma and paraganglioma. Best practice & research. Clinical endocrinology & metabolism. 2010;24(3):415-424.
  210. Lefebvre M, Foulkes WD. Pheochromocytoma and paraganglioma syndromes: genetics and management update. Curr Oncol. Vol 21. Canada, 2014:e8-e17.
  211. Kirmani S, Young WF. Hereditary Paraganglioma-Pheochromocytoma Syndromes – GeneReviews® – NCBI Bookshelf. 2008; http://www.ncbi.nlm.nih.gov/books/NBK1548/.
  212. Stratakis CA, Carney JA. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney–Stratakis syndrome): molecular genetics and clinical implications. J Intern Med. Jul 2009;266:43-52.
  213. Carney JA. Carney triad: a syndrome featuring paraganglionic, adrenocortical, and possibly other endocrine tumors. J Clin Endocrinol Metab. Oct 2009;94(10):3656-3662.
  214. Xekouki P, Szarek E, Bullova P, Giubellino A, Quezado M, Mastroyannis SA, Mastorakos P, Wassif CA, Raygada M, Rentia N, Dye L, Cougnoux A, Koziol D, Sierra MdL, Lyssikatos C, Belyavskaya E, Malchoff C, Moline J, Eng C, Maher LJ, 3rd, Pacak K, Lodish M, Stratakis CA. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice. J. Clin Endocrinol Metab. 2015;May;100(5):E710-719.
  215. Burnichon N, Vescovo L, Amar L, Libe R, de Reynies A, Venisse A, Jouanno E, Laurendeau I, Parfait B, Bertherat J, Plouin PF, Jeunemaitre X, Favier J, Gimenez-Roqueplo AP. Integrative genomic analysis reveals somatic mutations in pheochromocytoma and paraganglioma. Hum Mol Genet. Oct 15 2011;20(20):3974-3985.
  216. Neumann HPH, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peçzkowska M, Szmigielski C, Eng C. Germ-Line Mutations in Nonsyndromic Pheochromocytoma. New England Journal of Medicine. 2002;346(19):1459-1466.
  217. Patocs A, Lendvai NK, Butz H, Liko I, Sapi Z, Szucs N, Toth G, Grolmusz VK, Igaz P, Toth M, Racz K. Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome. Pathol Oncol, Res.Oct;22(4):673-679.
  218. Thosani S, Ayala-Ramirez M, Palmer L, Hu MI, Rich T, Gagel RF, Cote G, Waguespack SG, Habra MA, Jimenez C. The Characterization of Pheochromocytoma and Its Impact on Overall Survival in Multiple Endocrine Neoplasia Type 2. The Journal of Clinical Endocrinology & Metabolism. 2013;98(11):E1813-E1819.
  219. Burnichon N, Cascon A, Schiavi F, Morales NP, Comino-Mendez I, Abermil N, Inglada-Perez L, de Cubas AA, Amar L, Barontini M, de Quiros SB, Bertherat J, Bignon YJ, Blok MJ, Bobisse S, Borrego S, Castellano M, Chanson P, Chiara MD, Corssmit EP, Giacche M, de Krijger RR, Ercolino T, Girerd X, Gomez-Garcia EB, Gomez-Grana A, Guilhem I, Hes FJ, Honrado E, Korpershoek E, Lenders JW, Leton R, Mensenkamp AR, Merlo A, Mori L, Murat A, Pierre P, Plouin PF, Prodanov T, Quesada-Charneco M, Qin N, Rapizzi E, Raymond V, Reisch N, Roncador G, Ruiz-Ferrer M, Schillo F, Stegmann AP, Suarez C, Taschin E, Timmers HJ, Tops CM, Urioste M, Beuschlein F, Pacak K, Mannelli M, Dahia PL, Opocher G, Eisenhofer G, Gimenez-Roqueplo AP, Robledo M. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clinical cancer research : an official journal of the American Association for Cancer Research. May 15 2012;18(10):2828-2837.
  220. Boikos SA, Xekouki P, Fumagalli E, Faucz FR, Raygada M, Szarek E, Ball E, Kim SY, Miettinen M, Helman LJ, Carney JA, Pacak K, Stratakis CA. Carney triad can be (rarely) associated with germline succinate dehydrogenase defects. Eur, J. Hum Genet. 2016;Apr;24(4):569-573.
  221. Haller F, Moskalev EA, Faucz FR, Barthelmess S, Wiemann S, Bieg M, Assie G, Bertherat J, Schaefer IM, Otto C, Rattenberry E, Maher ER, Strobel P, Werner M, Carney JA, Hartmann A, Stratakis CA, Agaimy A. Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in Carney triad. Endocr Relat, Cancer. 2014;Aug;21(4):567-577.
  222. Bertherat J. Carney complex (CNC). Orphanet Journal of Rare Diseases. 2006;1:21.
  223. Stratakis C, Salpea P, Raygada M. Carney Complex – GeneReviews® – NCBI Bookshelf. 2015; http://www.ncbi.nlm.nih.gov/books/NBK1286/.
  224. Almeida MQ, Stratakis CA. Carney complex and other conditions associated with micronodular adrenal hyperplasias. Best practice & research. Clinical endocrinology & metabolism. Dec 2010;24(6):907-914.
  225. Gaujoux S, Tissier F, Ragazzon B, Rebours V, Saloustros E, Perlemoine K, Vincent-Dejean C, Meurette G, Cassagnau E, Dousset B, Bertagna X, Horvath A, Terris B, Carney JA, Stratakis CA, Bertherat J. Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new association. J Clin Endocrinol Metab. 2011;96(11):E1888-1895.
  226. Goudet P, Bonithon-Kopp C, Murat A, Ruszniewski P, Niccoli P, Menegaux F, Chabrier G, Borson-Chazot F, Tabarin A, Bouchard P, Cadiot G, Beckers A, Guilhem I, Chabre O, Caron P, Du Boullay H, Verges B, Cardot-Bauters C. Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d’etude des Tumeurs Endocrines. European journal of endocrinology / European Federation of Endocrine Societies. Jul 2011;165(1):97-105.
  227. Jochmanova I, Wolf KI, King KS, Nambuba J, Wesley R, Martucci V, Raygada M, Adams KT, Prodanov T, Fojo AT, Lazurova I, Pacak K. SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations. J. Cancer Res Clin Oncol. 2017;Apr 3.
  228. Giusti F, Marini F, Brandi ML. Multiple Endocrine Neoplasia Type 1. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews(R). Seattle WA: University of Washington, Seattle; 1993.
  229. Moline J, Eng C. Multiple Endocrine Neoplasia Type 2. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews(R). Seattle (WA): University of Washington, Seattle. All rights reserved.; 1993.
  230. Marini F, Falchetti A, Del Monte F, Carbonell Sala S, Tognarini I, Luzi E, Brandi ML. Multiple endocrine neoplasia type 2. Orphanet J Rare Dis. Vol 1. England, 2006:45.
  231. Schovanek J, Martucci V, Wesley R, Fojo T, Del Rivero J, Huynh T, Adams K, Kebebew E, Frysak Z, Stratakis CA, Pacak K. The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study. BMC cancer. 2014;Jul 21;14:523.
  232. Turkova H, Prodanov T, Maly M, Martucci V, Adams K, Widimsky JJ, Chen CC, Ling A, Kebebew E, Stratakis CA, Fojo T, Pacak K. Charateristics and Outcomes of Metastatic SDHB and Sporadic Pheochromocytoma/Paragaglioma: An National Institutes of Health Study Endocr Pract. 2016;Mar;22(3):302-314.
  233. Kantorovich V, King KS, Pacak K. SDH-related pheochromocytoma and paraganglioma. Best Pract Res Clin Endocrinol Metab. Vol 24. Netherlands: Published by Elsevier Ltd.; 2010:415-424.
  234. Chetty R. Familial paraganglioma syndromes. Journal of clinical pathology. Jun 2010;63(6):488-491.
  235. Qin Y, Yao L, King EE, Buddavarapu K, Lenci RE, Chocron ES, Lechleiter JD, Sass M, Aronin N, Schiavi F, Boaretto F, Opocher G, Toledo RA, Toledo SP, Stiles C, Aguiar RC, Dahia PL. Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Nat Genet. 2010;Mar;42(3):229-233.
  236. Schiavi F, Boedeker CC, Bausch B, Peczkowska M, Gomez CF, Strassburg T, Pawlu C, Buchta M, Salzmann M, Hoffmann MM, Berlis A, Brink I, Cybulla M, Muresan M, Walter MA, Forrer F, Valimaki M, Kawecki A, Szutkowski Z, Schipper J, Walz MK, Pigny P, Bauters C, Willet-Brozick JE, Baysal BE, Januszewicz A, Eng C, Opocher G, Neumann HP. Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. Jama. Oct 26 2005;294(16):2057-2063.
  237. Persu A, Lannoy N, Maiter D, Mendola A, Montigny P, Oriot P, Vinck W, Garin P, Hamoir M, Vikkula M. Prevalence and spectrum of SDHx mutations in pheochromocytoma and paraganglioma in patients from Belgium: an update. Horm Metab Res. May 2012;44(5):349-353.
  238. Zhang L, Smyrk TC, Young WF, Stratakis CA, Carney JA. Gastric Stromal Tumors in Carney Triad Are Different Clinically, Pathologically, and Behaviorally From Sporadic Gastric Gastrointestinal Stromal Tumors: Findings in 104 Cases. The American journal of surgical pathology. 2010;34(1):53-64.
  239. Christakis I, Qiu W, Silva Figueroa AM, Hyde S, Cote GJ, Busaidy NL, Williams M, Grubbs E, Lee JE, Perrier ND. Clinical Features, Treatments, and Outcomes of Patients with Thymic Carcinoids and Multiple Endocrine Neoplasia Type 1 Syndrome at MD Anderson Cancer Center. Hormones and Cancer. 2016;7(4):279-287.
  240. Dy BM, Que FG, Thompson GB, Young WF, Rowse P, Strajina V, Richards ML. Metastasectomy of neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. The American Journal of Surgery.208(6):1047-1053.
  241. Baudin E, Habra MA, Deschamps F, Cote G, Dumont F, Cabanillas M, Arfi-Roufe J, Berdelou A, Moon B, Al Ghuzlan A, Patel S, Leboulleux S, Jimenez C. Therapy of endocrine disease: treatment of malignant pheochromocytoma and paraganglioma. Eur, J. Endocrinol. 2014;Sep; 171(3):R111-122.
  242. Petri BJ, van Eijck CH, de Herder WW, Wagner A, de Krijger RR. Phaeochromocytomas and sympathetic paragangliomas. Br J Surg. 2009;Dec;96(12):1381-1392.
  243. Hadoux J, Favier J, Scoazec J-Y, Leboulleux S, Al Ghuzlan A, Caramella C, Deandreis D, Borget I, Loriot C, Chougnet C, Letouze E, Young J, Amar L, Bertherat J, Libe R, Dumont F, Deschamps F, Schlumberger M, Gimenez-Roqueplo AP, Baudin E. SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma. Int, J. Cancer. 2014;Dec 1;135(11):2711-2720.
  244. Kiriakopoulos A, Petralias A, Linos D. Posterior retroperitoneoscopic versus laparoscopic adrenalectomy in sporadic and MENIIA pheochromocytomas. Surg, Endosc. 2015;Aug;29(8):2164-2170.
  245. Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML. Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1). The Journal of Clinical Endocrinology & Metabolism. 2012;97(9):2990-3011.
  246. Moley JF, Skinner M, Gillanders WE, Lairmore TC, Rowland KJ, Traugott AL, Jin LX, Wells SA. Management of the Parathyroid Glands During Preventive Thyroidectomy in Patients with Multiple Endocrine Neoplasia Type 2. Annals of surgery. 2015;262(4):641-646.
  247. Tonelli F, Fratini G, Falchetti A, Nesi G, Brandi ML. Surgery for gastroenteropancreatic tumours in multiple endocrine neoplasia type 1: review and personal experience. Journal of Internal Medicine. 2005;257(1):38-49.
  248. Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, Ayala-Ramirez M, Jimenez C. A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2010;95(5):2023-2037.
  249. Tomassetti P, Migliori M, Caletti GC, Fusaroli P, Corinaldesi R, Gullo L. Treatment of Type II Gastric Carcinoid Tumors with Somatostatin Analogues. New England Journal of Medicine. 2000;343(8):551-554.
  250. Jensen. Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1. Journal of Internal Medicine. 1998;243(6):477-488.
  251. Kazanjian KK, Reber HA, Hines OJ. Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch Surg. 2006;Aug; 141(8):765-769.
  252. Grubbs EG, Rich TA, Ng C, Bhosale PR, Jimenez C, Evans DB, Lee JE, Perrier ND. Long-term outcomes of surgical treatment for hereditary pheochromocytoma. J. Am Coll Surg. 2013;Feb;216(2):280-290.
  253. Reynen K. Cardiac Myxomas. New England Journal of Medicine. 1995;333(24):1610-1617.
  254. NIH. Parathyroid Cancer Treatment-Health Professional Version (PDQ). 2013; http://www.cancer.gov/cancertopics/pdq/treatment/parathyroid/HealthProfessional/page1. Accessed April 2016, 2015.
  255. Ospina NS, Sebo TJ, Thompson GB, Clarke BL, Young WF, Jr. Prevalence of Parathyroid Carcinoma in 348 Patients with Multiple Endocrine Neoplasia Type 1- Case Report and Review of the Literature. Clinical endocrinology. 2015;84(2):244-249.
  256. Kassahun WT, Jonas S. Focus on parathyroid carcinoma. International journal of surgery (London, England). 2011;9(1):13-19.
  257. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985–1995. Cancer. 1999;86(3):538-544.
  258. Chow E, Tsang RW, Brierley JD, Filice S. Parathyroid carcinoma—the Princess Margaret Hospital experience. International Journal of Radiation Oncology Biology Physics. 1998;41(3):569-572.
  259. Hsu KT, Sippel RS, Chen H, Schneider DF. Is central lymph node dissection necessary for parathyroid carcinoma? Surgery. 2014;156(6):1336-1341.
  260. Wei CH, Harari A. Parathyroid carcinoma: update and guidelines for management. Current treatment options in oncology. Mar 2012;13(1):11-23.
  261. Harari A, Waring A, Fernandez-Ranvier G, Hwang J, Suh I, Mitmaker E, Shen W, Gosnell J, Duh Q-Y, Clark O. Parathyroid Carcinoma: A 43-Year Outcome and Survival Analysis. The Journal of Clinical Endocrinology & Metabolism. 2011;96(12):3679-3686.
  262. Allen ME, Semrad A, Yang AD, Martinez SR. Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring? Rare tumors. Feb 11 2013;5(1):e12.
  263. Sadler C, Gow KW, Beierle EA, Doski JJ, Langer M, Nuchtern JG, Vasudevan SA, Goldfarb M. Parathyroid carcinoma in more than 1,000 patients: A population-level analysis. Surgery. Dec 2014;156(6):1622-1630.
  264. Lee PK, Jarosek SL, Virnig BA, Evasovich M, Tuttle TM. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer. 2007;109(9):1736-1741.
  265. Schaapveld M, Jorna FH, Aben KK, Haak HR, Plukker JT, Links TP. Incidence and prognosis of parathyroid gland carcinoma: a population-based study in The Netherlands estimating the preoperative diagnosis. American journal of surgery. Nov 2011;202(5):590-597.
  266. Brown S, O’Neill C, Suliburk J, Sidhu S, Sywak M, Gill A, Robinson B, Delbridge L. Parathyroid carcinoma: increasing incidence and changing presentation. ANZ journal of surgery. 2011;81(7-8):528-532.
  267. Witteveen JE, Haak HR, Kievit J, Morreau H, Romijn JA, Hamdy NAT. Challenges and Pitfalls in the Management of Parathyroid Carcinoma: 17-Year Follow-Up of a Case and Review of the Literature. Hormones & Cancer. 2010;1(4):205-214.
  268. Vellanki P, Lange K, Elaraj D, Kopp PA, El Muayed M. Denosumab for management of parathyroid carcinoma-mediated hypercalcemia. J. Clin Endocrinol Metab. 2014;Feb’99(2):387-390.
  269. McClenaghan F, Qureshi YA. Parathyroid cancer. Gland Surgery. 2015;4(4):329-338.
  270. Shane E. Parathyroid Carcinoma. The Journal of Clinical Endocrinology & Metabolism. 2001;86(2):485-493.
  271. Wiseman SM, Rigual NR, Hicks WL, Jr., Popat SR, Lore JM, Jr., Douglas WG, Jacobson MJ, Tan D, Loree TR. Parathyroid carcinoma: a multicenter review of clinicopathologic features and treatment outcomes. Ear, nose, & throat journal. Jul 2004;83(7):491-494.
  272. Munson ND, Foote RL, Northcutt RC, Tiegs RD, Fitzpatrick LA, Grant CS, van Heerden JA, Thompson GB, Lloyd RV. Parathyroid carcinoma: Is there a role for adjuvant radiation therapy? Cancer. 2003;98(11):2378-2384.
  273. Wilkins BJ, Lewis JS. Non-Functional Parathyroid Carcinoma: A Review of the Literature and Report of a Case Requiring Extensive Surgery. Head and Neck Pathology. 2009;3(2):140-149.
  274. Koea JB, Shaw JHF. Parathyroid cancer: biology and management. Surgical Oncology. 1999;8(3):155-165.
  275. Shortell CK, Andrus CH, Phillips CE, Jr., Schwartz SI. Carcinoma of the parathyroid gland: a 30-year experience. Surgery. 1991;Oct;110(4):704-708.
  276. Villar-Del-Moral J, Jimenez-Garcia A, Salvador-Egea P, Martos-Martinez JM, Nuno-Vazquez-Garza JM, Serradilla-Martin M, Gomez-Palacios A, Moreno-Llorente P, Ortega-Serrano J, de la Quintana-Basarrate A. Prognostic factors and staging systems in parathyroid cancer: A multicenter cohort study. Surgery. Nov 2014;156(5):1132-1144.
  277. Mehta A, Patel D, Rosenberg A, Boufraqech M, Ellis RJ, Nilubol N, Quezado MM, Marx SJ, Simonds WF, Kebebew E. Hyperparathyroidism-jaw tumor syndrome: Results of operative management. Surgery. 2014;156(6):1315-1325.
  278. Crona J, Delgado Verdugo A, Maharjan R, Stålberg P, Granberg D, Hellman P, Björklund P. Somatic Mutations in H-RAS in Sporadic Pheochromocytoma and Paraganglioma Identified by Exome Sequencing. The Journal of Clinical Endocrinology & Metabolism. 2013;98(7):E1266-E1271.
  279. Chen H, Sippel RS, O’Dorisio MS, Vinik AI, Lloyd RV, Pacak K. The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010;39(6):775-783.
  280. Dannenberg H, Speel EJM, Zhao J, Saremaslani P, van der Harst E, Roth J, Heitz PU, Bonjer HJ, Dinjens WNM, Mooi WJ, Komminoth P, de Krijger RR. Losses of Chromosomes 1p and 3q Are Early Genetic Events in the Development of Sporadic Pheochromocytomas. The American Journal of Pathology. 2000;157(2):353-359.
  281. Aarts M, Dannenberg H, deLeeuw RJ, van Nederveen FH, Verhofstad AA, Lenders JW, Dinjens WN, Speel EJ, Lam Wl, de Krijger RR. Microarray-based CGH of sporadic and syndrome-related pheochromocytomas using a 0.1-0.2 Mb bacterial artificial chromosome array spanning chromosome arm 1p. Genes Chromosomes, Cancer. 2006;Jan;45(1):83-93.
  282. Jarbo C, Buckley PG, Piotrowski A, Mantripragada KK, Benetkiewicz M, Diaz de Stahl T, Langford CF, Gregory SG, Dralle H, Gimm O, Backdahl M, Geli J, Larsson C, Westin G, Akerstrom G, Dumanski JP. Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH. Mar 1. 2006;118(5):1159-1164.
  283. van Nederveen FH, Korpershoek E, deLeeuw RJ, Verhofstad AA, Lenders JW, Dinjens WNM, Dinjens WN, Lam WL, de Krijger RR. Array-comparative genomic hybridization in sporadic benign pheochromocytomas. Endocr Relat, Cancer. 2009;16(2):505-513.
  284. Prodanov T, Havekes B, Nathanson KL, Adams KT, Pacak K. Malignant paraganglioma associated with succinate dehydrogenase subunit B in an 8-year-old child: the age of first screening? Pediatric nephrology (Berlin, Germany). 02/03 2009;24(6):1239-1242.
  285. Plouin P-F, Gimenez-Roqueplo A-P. Pheochromocytomas and secreting paragangliomas. Orphanet Journal of Rare Diseases. 2006;Dec 8;1:49.
  286. Iacobone M, Schiavi F, Bottussi M, Taschin E, Bobisse S, Fassina A, Opocher G, Favia G. Is genetic screening indicated in apparently sporadic pheochromocytomas and paragangliomas? Surgery. 2011;150(6):1194-1201.
  287. Curras-Freixes M, Inglada-Perez L, Mancikova V, Montero-Conde C, Leton R, Comino-Mendez I, Apellaniz-Ruiz M, Sanchez-Barroso L, Aguirre Sanchez-Covisa M, Alcazar V, Aller J, Alvarez-Escola C, Andia-Melero VM, Azriel-Mira S, Calatayud-Gutierrez M, Diaz JA, Diez-Hernandez A, Lamas-Oliveira C, Marazuela M, Matias-Guiu X, Meoro-Aviles A, Patino-Garcia A, Pedrinaci S, Riesco-Eizaguirre G, Sabado-Alvarez C, Saez-Villaverde R, Sainz de Los Terreros A, Sanz Guadarrama O, Sastre-Marcos J, Scola-Yurrita B, Segura-Huerta A, Serrano-Corredor Mde L, Villar-Vicente MR, Rodriguez-Antona C, Korpershoek E, Cascon A, Robledo M. Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients. J Med Genetics. 2015;Oct;52(10):647-656.
  288. Santos P, Pimenta T, Taveira-Gomes A. Hereditary Pheochromocytoma. Int J Surg Pathol. Vol 222014:393-400.
  289. Luchetti A, Walsh D, Rodger F, Clark G, Martin T, Irving R, Sanna M, Yao M, Robledo M, Neumann HPH, Woodward ER, Latif F, Abbs S, Martin H, Maher ER. Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis. International journal of endocrinology. 2015;2015:138573.
  290. Oudijk L, de Krijger RR, Rapa I, Beuschlein F, de Cubas AA, Dei Tos AP, Dinjens WNM, Korpershoek E, Mancikova V, Mannelli M, Papotti M, Vatrano S, Robledo M, Volante M. H-RAS Mutations Are Restricted to Sporadic Pheochromocytomas Lacking Specific Clinical or Pathological Features: Data From a Multi-Institutional Series. The Journal of Clinical Endocrinology & Metabolism. 2014;99(7):E1376-E1380.
  291. Pomares FJ, Canas R, Rodriguez JM, Hernandez AM, Parrilla P, Tebar FJ. Differences between sporadic and multiple endocrine neoplasia type 2A phaeochromocytoma. Feb;48. 1998;2(195-200).
  292. van der Harst E, de Krijger RR, Bruining HA, Lamberts SW, Bonjer HJ, Dinjes WN, Proye C, Koper JW, Bosman FT, Roth J, Heitz PU, Komminoth P. Prognostic value of RET proto-oncogene point mutations in malignant and benign, sporadic phaeochromocytomas. Int, J. Cancer. 1998;Oct 23;79(5):537-540.
  293. Lai EW, Perera SM, Havekes B, Timmers HJ, Brouwers FM, McElroy B, Adams KT, Ohta S, Wesley RA, Eisenhofer G, Pacak K. Gender-related differences in the clinical presentation of malignant and benign pheochromocytoma. Endocrine. 2008;Aug-Dec;34(1-3):96-100.
  294. Zelinka T, Widimsky J, Weisserova J. Diminished circadian blood pressure rhythm in patients with asymptomatic normotensive pheochromocytoma. Physiol, Res. 2001;2001;50(6):631-634.
  295. Adler JT, G.Y. M-R, Chen H, Benn DE, Robinson BG, Sippel RS, Sidhu SB. Pheochromocytoma: current approaches and future directions. Oncologist,. 2008;Jul;13(7):779-793.
  296. Goffredo P, Sosa JA, Roman SA. Malignant pheochromocytoma and paraganglioma: A population level analysis of long-term survival over two decades. Journal of Surgical Oncology. 2013;107(6):659-664.
  297. Amar L, Servais A, Gimenez-Roqueplo AP, Zinzindohoue F, Chatellier G, Plouin PF. Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J. Clin Endocrinol Metab. 2005;Apr;90(4):2110-2116.
  298. Mannelli M. Management and treatment of pheochromocytomas and paragangliomas. Ann, N. Y. Acad Sci.Aug;1073:405-416.
  299. Van Slycke S, Caiazzo R, Pigny P, Cardot-Bauters C, Arnalsteen L, D’Herbomez M, Leteurtre E, Rouaix-Emery N, Ernst O, Huglo D, Vantyghem MC, Wemeau JL, Carnaille B, Pattou F. Local-regional recurrence of sporadic or syndromic abdominal extra-adrenal paraganglioma: incidence, characteristics, and outcome. Surgery. Dec 2009;146(6):986-992.
  300. Garnier S, Reguerre Y, Orbach D, Brugieres L, Kalfa N. [Pediatric pheochromocytoma and paraganglioma: an update]. Bull Cancer. Vol 101. France, 2014:966-975.
  301. Hammond PJ, Murphy D, Carachi R, Davidson DF, McIntosh D. Childhood phaeochromocytoma and paraganglioma: 100% incidence of genetic mutations and 100% survival. Journal of pediatric surgery. Feb 2010;45(2):383-386.
  302. Ayala-Ramirez M, Chougnet CN, Habra MA, Palmer JL, Leboulleux S, Cabanillas ME, Caramella C, Anderson P, Al Ghuzlan A, Waguespack SG, Deandreis D, Baudin E, Jimenez C. Treatment with Sunitinib for Patients with Progressive Metastatic Pheochromocytomas and Sympathetic Paragangliomas. The Journal of Clinical Endocrinology and Metabolism. 2012;97(11):4040-4050.
  303. Nomura K, Kimura H, Shimizu S, Kodama H, Okamoto T, Obara T, Takano K. Survival of patients with metastatic malignant pheochromocytoma and efficacy of combined cyclophosphamide, vincristine, and dacarbazine chemotherapy. J. Clin Endocrinol Metab. 2009;Aug;94(8):2850-2856.
  304. Khorram-Manesh A, Ahlman H, Nilsson O, Friberg P, Odén A, Stenström G, Hansson G, Stenquist O, Wängberg B, Tisell LE, Jansson S. Long-term outcome of a large series of patients surgically treated for pheochromocytoma. Journal of Internal Medicine. 2005;258(1):55-66.
  305. Gedik GK, Hoefnagel CA, Bais E, Olmos RA. 131I-MIBG therapy in metastatic phaeochromocytoma and paraganglioma. Eur, J. Nucl Med Mol Imaging. 2008;Apr;35(4):725-733.
  306. Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R, Keiser HR. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern, Med. 1988;Aug 15;109(4):267-273.
  307. Ayala-Ramirez M, Feng L, Habra MA, Rich T, Dickson PV, Perrier ND, Phan A, Waguespack S, Patel S, Jimenez C. Clinical Benefits of Systemic Chemotherapy for Patients with Metastatic Pheochromocytomas or Sympathetic Extra-Adrenal Paragangliomas: Insights from the Largest Single Institutional Experience. Cancer. 2012;118(11):2804-2812.
  308. Agarwal G, Sadacharan D, Aggarwal V, Chand G, Mishra A, Agarwal A, Verma AK, Mishra SK. Surgical management of organ-contained unilateral pheochromocytoma: comparative outcomes of laparoscopic and conventional open surgical procedures in a large single-institution series. Langenbecks Arch, Surg. 2012;Oct;397(7):1109-1116.
  309. Ito T, Igarashi H, Jensen RT. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances. Best practice & research. Clinical gastroenterology. 2012;26(6):737-753.
  310. Halfdanarson TR, Rubin J, Farnell MB, Grant CS, Petersen GM. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors. Endocrine-related cancer. 2008;15(2):409-427.
  311. McKenna LR, Edil BH. Update on pancreatic neuroendocrine tumors. Gland Surg. 2014;3(4):258-275.
  312. D’Haese JG, Tosolini C, Ceyhan GO, Kong B, Esposito I, Michalski CW, Kleeff J. Update on surgical treatment of pancreatic neuroendocrine neoplasms. World journal of gastroenterology : WJG. Oct 14 2014;20(38):13893-13898.
  313. Milan SA, Yeo CJ. Neuroendocrine tumors of the pancreas. Current opinion in oncology. Jan 2012;24(1):46-55.
  314. Berge T, Linell F. Carcinoid tumours. Frequency in a defined population during a 12-year period. Acta Pathol Microbiol Scand, A. 1976;Jul;84(4):322-330.
  315. Ito Y, Hirokawa M, Masuoka H, Yabuta T, Kihara M, Higashiyama T, Takamura Y, Kobayashi K, Miya A, Miyauchi A. Prognostic factors of minimally invasive follicular thyroid carcinoma: extensive vascular invasion significantly affects patient prognosis. Endocrine journal. 2013;60(5):637-642.
  316. Sadowski SM, Triponez F. Management of pancreatic neuroendocrine tumors in patients with MEN 1. Gland Surg. Vol 4. China Republic : 1949-2015:63-68.
  317. Ro C, Chai W, Yu VE, Yu R. Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment. Chinese Journal of Cancer. 2013;32(6):312-324.
  318. Halfdanarson TR, Rabe KG, Rubin J, Petersen GM. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Annals of Oncology. 2008;19(10):1727-1733.
  319. Ter-Minassian M, Chan JA, Hooshmand SM, Brais LK, Daskalova A, Heafield R, Buchanan L, Qian ZR, Fuchs CS, Lin X, Christiani DC, Kulke MH. Clinical presentation, recurrence, and survival in patients with neuroendocrine tumors: results from a prospective institutional database. Endocrine-related cancer. Apr 2013;20(2):187-196.
  320. Kuo JH, Lee JA, Chabot JA. Nonfunctional pancreatic neuroendocrine tumors. The Surgical clinics of North America. Jun 2014;94(3):689-708.
  321. Ekeblad S, Skogseid B, Dunder K, Oberg K, Eriksson B. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clinical cancer research : an official journal of the American Association for Cancer Research. Dec 1 2008;14(23):7798-7803.
  322. Wang SE, Su CH, Kuo YJ, Shyr YM, Li AF, Chen TH, Wu CW, Lee CH. Comparison of functional and nonfunctional neuroendocrine tumors in the pancreas and peripancreatic region. Pancreas. Mar 2011;40:253-259.
  323. Ehehalt F, Saeger HD, Schmidt CM, Grutzmann R. Neuroendocrine tumors of the pancreas. The oncologist. May 2009;14(5):456-467.
  324. Service FJ, M. MM, O’Brien PC, Ballard DJ. Functioning insulinoma-incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin, Proc. 1991;Jul;66(7):711-719.
  325. Schindl M, Kaczirek K, Kaserer K, Niederle B. Is the new classification of neuroendocrine pancreatic tumors of clinical help? World, J. Surg. 2000;Nov;24(11):1312-1318.
  326. Norton JA, Fraker DL, Alexander HR, Venzon DJ, Doppman JL, Serrano J, Goebel SU, Peghini PL, Roy PK, Gibril F, Jensen RT. Surgery to Cure the Zollinger–Ellison Syndrome. New England Journal of Medicine. 1999/08/26 1999;341(9):635-644.
  327. Mansour JC, Chen H. Pancreatic endocrine tumors. Journal of Surgical Research. 2004;120(1):139-161.
  328. Navalkele P, O’Dorisio MS, O’Dorisio TM, Zamba GKD, Lynch CF. Incidence, Survival and Prevalence of Neuroendocrine Tumors versus Neuroblastoma in Children and Young Adults: Nine Standard SEER Registries, 1975–2006. Pediatric blood & cancer. 2011;56(1):50-57.
  329. Ramage JK, Ahmed A, Ardill J, Bax N, Breen DJ, Caplin ME, Corrie P, Davar J, Davies AH, Lewington V, Meyer T, Newell-Price J, Poston G, Reed N, Rockall A, Steward W, Thakker RV, Toubanakis C, Valle J, Verbeke C, Grossman AB. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. Jan 2012;61(1):6-32.
  330. Burns WR, Edil BH. Neuroendocrine pancreatic tumors: guidelines for management and update. Current treatment options in oncology. Mar 2012;13(1):24-34.
  331. FDA. Everolimus (Afinitor). 2016; http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm488028.htm. Accessed April 22, 2016.
  332. Highlights of Prescribing Information: Afinitor (everolimus) http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022334s036lbl.pdf.
  333. Kouvaraki MA, J.A. A, Hoff P, Wolff R, Evans DB, Lozano R, Yao JC. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J. Clin Oncol. 2004;Dec 1;22(23):4762-4771.
  334. Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen D-T, Helm J, Kvols L. First-Line Chemotherapy With Capecitabine and Temozolomide in Patients With Metastatic Pancreatic Endocrine Carcinomas. Cancer. 2011;117(2):268-275.
  335. Kwekkeboom DJ, W dHW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J. Clin Oncol. 2008;May 1;26(13):2124-2130.
  336. Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EGE, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K. Everolimus for Advanced Pancreatic Neuroendocrine Tumors. The New England journal of medicine. 2011;364(6):514-523.
  337. Raymond E, Dahan L, Raoul J-L, Bang Y-J, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen J-S, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. New England Journal of Medicine. 2011;364(6):501-513.
  338. Broder MS, Beenhouwer D, Strosberg JR, Neary MP, Cherepanov D. Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR: A systematic literature review. World Journal of Gastroenterology. 2015;21(6):1945-1955.
  339. Caplin ME, Baudin E, Ferolla P, Filosso P, Garcia-Yuste M, Lim E, Oberg K, Pelosi G, Perren A, Rossi RE, Travis WD. Pulmonary Neuroendocrine (Carcinoid) Tumors: European Neuroendocrine Tumor Society Expert Consensus and Recommendations for Best Practice for Typical and Atypical Pulmonary Carcinoid. Annals of Oncology. 2015;Aug;26(8):1604-1620.
  340. Howell DL, O’Dorisio MS. Management of neuroendocrine tumors in children, adolescents, and young adults. J. Pediatr Hematol Oncol. 2012;May;34(Suppl2):S64-68.

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