4 Familial Neoplasia Syndromes

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

Endocrine neoplasia syndromes are inborn conditions predisposing to the development of one or more endocrine tumors, either benign or malignant.196,197 In addition, endocrine tumors can also be part of other hereditary syndromes, primarily dominated by non-endocrine neoplasias. On the other hand, sporadic disease is diagnosed in the absence of: pathogenic predisposing mutation, a family history, or syndromic features.198

Multiple endocrine neoplasia (MEN) syndromes are characterized by tumors in multiple endocrine organs (Table 4.1).197 All core endocrine tumor syndromes are inherited in an autosomal dominant fashion. The specific gene mutations and the primary characteristics associated with hereditary neoplasia syndromes are shown in Table 4.1.

Table 4.1. Primary characteristics and genetic mutations linked to familial neoplasia syndromes.
Familial endocrine neoplasias Primary characteristics Genetic mutations References
MEN1 (Wermer’s syndrome)
Multiple endocrine neoplasia type 1 (MEN1) Parathyroid four gland hyperplasia,

entero-pancreatic neuroendocrine tumors and pituitary adenoma

MEN1 Thakker. 2014197; Almeida and Stratakis. 2010199
MEN2 (Sipple syndrome)
Familial medullary thyroid carcinoma (FMTC)** Medullary thyroid carcinoma RET Lee and Pellegata. 2013200; Thakker. 2014197
Multiple endocrine neoplasia type 2 (MEN2), also known as type 2A (MEN2A) Medullary thyroid carcinoma, PHEO, and

parathyroid adenoma

RET Thakker. 2014197; Almeida and Stratakis. 2010199
MEN2B
Multiple endocrine neoplasia type 2B Medullary thyroid carcinoma, and

PHEO

RET Thakker. 2014197; Almeida and Stratakis. 2010199
CDKN1B-related MEN*
CDKN1B-related MEN Parathyroid adenoma,

Pituitary adenoma, reproductive organ tumors, and adrenal tumors

CDKN1B Thakker. 2014197; Marinoni and Pellegata. 2011201
Neurofibromatosis Type I (NF1) (von Recklinghausen disease) and von Hippel-Lindau (VHL) disease
NF1 PHEO, and extra-adrenal PGL, neural sheath tumors, neurofibromas, and other manifestations NF1 Almeida and Stratakis. 2010199
VHL PHEO, pNET, RCC, HBL VHL
Abbreviations: PHEO, Pheochromocytoma; PGL, Paraganglioma.

Note: *, Insufficient numbers to estimate penetrance; **, Familial medullary thyroid cancer (FMTC) can either occur alone or as part of the MEN2 phenotype.

 

4.1 PREVALENCE AND INCIDENCE

4.1.1 Multiple Endocrine Neoplasia syndromes

Each MEN syndrome subtype is characterized by a number of specific endocrine cancers, and their prevalence is presented in Table 4.2. Approximately 75-95% of MEN1 is due to a genetic mutation in the MEN1 gene.197

Table 4.2. Prevalence of cancers in Multiple Endocrine Neoplasia (MEN) syndromes, literature reviews, worldwide.
Multiple endocrine neoplasia subtype Endocrine cancer Life-time risk (%) References
MEN1 Parathyroid hyperplasia 90 Thakker. 2014197; Almeida and Stratakis. 2010199
Entero-pancreatic neuroendocrine tumor 30-70 in patients;

80 at autopsy

Pituitary adenoma 30-40
MEN2/MEN2A Medullary thyroid carcinoma (MTC) 90
PHEO 50
Parathyroid adenoma 20-30
MEN2B Medullary thyroid carcinoma >90
PHEO 40-50
CDKN1B-related MEN Parathyroid adenoma 81 Thakker. 2014197; Lee and Pellegata. 2013200; Marinoni and Pellegata. 2011201
Pituitary adenoma 41.6
Reproductive organ tumors Insufficient data
Adrenal and renal tumors

4.1.2 Pheochromocytoma (PHEO) and Paraganglioma (PGL) syndromes

Between 25% and 52.8% of PGL/PHEO cases are linked to germline mutations causing hereditary PGL/PHEO.199,202-204 Approximately 2-7% of patients with NF1 develop catacholmine-secreting tumors, usually solitary, benign, adrenal PHEO.205,206 VHL-associated tumors, are often bilateral and are most often benign, but can be malignant.202,205,207 The prevalence of diseases associated with PGL and PHEO syndromes are shown in Table 4.3. The most common of these are SDHx-related hereditary PGLs.

Table 4.3. Prevalence and incidence of PGL and PHEO in associated diseases, from literature reviews, worldwide.
Diseases associated with PGL and PHEO syndromes PHEO/PGL Penetrance References
MEN2A 50 Almeida and Stratakis. 2010199; Karasek et al. 2013208
MEN2B 40–50 Almeida and Stratakis. 2010199
SDHx-related PGL Up to 70% Kantorovich et al. 2010209
VHL 1–20 Almeida and Stratakis. 2010199; Karaskek et al. 2013208; Lefebvre and Foulkes. 2014210; Kirmani and Young. 2008211
NF1 0.1–5.7 Almeida and Stratakis. 2010199; Lefebvre and Foulkes. 2014202,210
Carney-Stratakis syndrome or dyad Very rare Carney and Stratakis. 2009212
Carney triad Very rare Carney. 2009213
3PAS Very rare Xekouki et al. 2015214

Abbreviations: MEN, Medullary Endocrine Neoplasia; NF1, Neurofibromatosis type 1; PAS, pituitary adenoma with paraganglioma/pheochromocytoma.

In 190 PHEO/PGL cases (1993-2008), germline or somatic mutations in one of the major PHEO/PGL-associated genes were identified in 45.5% of the tumors. Germline mutations were identified in 57 patients (13.2% VHL, 11.6% SDHA-D, 4.7% RET, 4.7% NF1, 0.5% TMEM127).215

Due to the high levels of familial cases among apparently sporadic tumor cases, genetic counseling and testing in all cases of PHEO or PGL is recommended. In 2002 it was estimated that up to 24% of apparently sporadic cases could have germline mutations.216 In 2016, Patocs and colleagues reported that 1 of 15 gene mutations could be present in up to 30% of apparently sporadic PHEO/PGL cases.217

In a database search1of 31 studies involving 5,031 patients (mean age 44 years) genetically tested for mutations in any of 11 genes (NF1 and RET, VHL, SDHD and SDHC, SDHB, SDHAF2, SDHC and TMEM127, MAX, IDH), the frequency of germline mutations was 11-13%, and the most common of these mutations was SDHB (4.6%).198 However, the true number of patients with apparently sporadic PHEO/PGL with an underlying germline mutation is likely even higher as the study also included patients with only partial genetic testing.

Sequencing showed that ~70% of skull base and neck PGL (HNPGL) cases carried mutations in the genes SDHB, SDHC and SDHD.211 In a series of PGL and PHEO cases in France (n=202), 45.5% of the tumors had a germline or somatic mutation.215

In a retrospective review of 85 patients with MEN2-associated PHEO (81% Caucasian, 68% with family history of Medullary thyroid carcinoma (MTC), 67% family history of PHEO; in one cancer center (1960-2012, US), 82% had MEN2A and the remaining 18% had MEN2B. Five germline RET mutations were identified in 73% of patients, of which the most common were in codons 634 (69%) and 918 (8%). The most common MEN2-PHEO associated mutation (codon 634), was not associated with advanced stage MTC at diagnosis or a shorter survival.218

A study in 17 independent referral centers (in Europe and US) identified germline MAX mutations by DNA screening in 1.12% of PGL and/or PHEO patients with no other known mutations (genetic screenings n=1,694; frozen tumors n=245).219

The age at onset for sporadic cases is later in life at ~40-50 years compared to before 40 years in inherited PHEO cases.  In a 2002 study of registries in Germany and Poland, of 271 non-syndromic (assumed sporadic) cases of PHEO (155 female, 116 male, age range 4-81 years, mean age 40 years) with no family history of the disease, 24% (n=66) of patients were identified as having a germ-line mutation in 1 of 4 genes screened (VHL, RET, SDHD, and SDHB). The mean age at onset at tumor presentation for sporadic cases was later in life than for hereditary disease (Table 4.4).216 In later studies, the number was estimated to be even higher (~30%).

Table 4.4. Prevalence of sporadic and inherited cases presenting with non-syndromic Pheochromocytoma (PHEO), Europe.
Data source Population Disease phenotype Mutations Proportion (%) Age at presentation (years) No. patients with age at onset ≤18 yr
PHEO patients from population registries in Freiburg, Germany and Warsaw, Poland. Total assumed sporadic cases (n=271); PHEO (n=241), PGL (n=22), PHEO+PGL (n=8); female (n=155), male (n=116), age range 4-80 years, mean age 40 years Total (n=271) 39.3 48
Actual non-syndromic (sporadic) (n=205) 76 43.9 21
Hereditary predisposition to VHL, MEN2, PHEO, PGL (n=66) Deleterious germline mutations in VHL, RET, SDHD, SDHB 24 24.9 27
Hereditary cases with germline mutations (n=66)
Von Hippel-Lindau (n=30) VHL 45 18.3 20
MEN2 (n=13) RET 20 36.4 0
PHEO-PGL (n=11) SDHD 17 28.7 3
PHEO-PGL (n=12) SDHB 18 25.6 4
Abbreviations: PGL, paraganglioma; PHEO, pheochromocytoma. MEN2, multiple endocrine neoplasia.

 Source: Neumann et al. 2002216

Several specific subtypes of SDHx-related hereditary PGL and related syndromes have been subclassified. Carney-Stratakis syndrome is a subcategory of SDHx-related, inherited tumor syndromes predominantly presenting with the dyad of PGL and gastrointestinal stromal tumor (GIST). The annual worldwide incidence of Carney-Stratakis (dyad) syndrome is <1 per million.213 The syndrome was identified in fewer than 20 families, some with germline mutations in SDHA, SDHD, SDHC and SDHB.211,212 The third condition is Carney triad, where tumors affect at least five organs, including stomach, lungs, the paraganglionic system, the adrenal system, and the oesophagus. The prevalence of tumors in Carney triad patients is outlined in Table 4.5. The hereditary basis of most Carney triad remains unknown, with the exception of a few cases that have been linked to SDHx (SDHA, SDHB, SDHC, SDHD) mutations.220 All cases, however, share abnormal methylation of the SDHC promoter. Both subtypes can also be caused by somatic methylation of, for example, the SDHC locus.221

Table 4.5. Prevalence of tumors in Carney triad, worldwide.
Data source Clinical manifestation of Carney triad Prevalence in Carney triad patients (%)
Among 77 patients with Carney triad, Worldwide Gastric stromal tumor 75
Pulmonary chondroma 15
Extra-adrenal PGL 10
Adrenocortical adenoma 20
Esophageal leiomyoma 10

Source: Carney. 2009213

4.1.3 Carney complex

The annual worldwide incidence of Carney complex is <1 per million, of which ~70% of cases are inherited and due to a genetic variants in PRKAR1A.222,223 The Carney complex is a rare, dominantly inherited syndrome associated with spotty skin pigmentation, myxomas, and endocrine overactivity. The most common endocrine tumor associated with Carney complex is primary pigmented nodular adrenocortical disease.224 The prevalence of the most common clinical symptoms of Carney complex is presented in Table 4.6.

Table 4.6. Prevalence of clinical symptoms associated with Carney complex from literature reviews, worldwide.
Clinical symptoms of Carney complex Prevalence in Carney complex (%) References
Spotty skin pigmentation >80 Almeida and Stratakis. 2010224
Cardiac myxomas 30-60 Almeida and Stratakis. 2010224; Bertherat. 2006222
Primary pigmented nodular adrenocortical disease (PPNAD) 25-60
Testicular tumors 33-56 Bertherat. 2006222
Growth-hormone producing pituitary adenoma 12 Almeida and Stratakis. 2010224
Thyroid tumors/cancer 10-25/2.5 Almeida and Stratakis. 2010224; Bertherat. 2006222
Psammomatous melanotic scwannoma 8-18
Pancreatic cancer 2.5 Gaujoux et al. 2011225

 

4.2 COST BURDEN OF DISEASE

Due to the rarity of all hereditary endocrine neoplasia syndromes, cost benefit and cost-effectiveness analyses are not available. In general, as evidenced in other hereditary diseases, such as Lynch syndrome, it is likely that there is a benefit in genetic testing and screening certainly with regards to morbidity and mortality and possibly with regards to cost-effectiveness.

 

4.3 DEMOGRAPHIC DIFFERENCES

In general, it is important to note that although gender differences exist with regards to associated tumor risks, most studies are small and may be influenced by small sample sizes and ascertainment bias.

4.3.1 Multiple Endocrine Neoplasias

In 2011, Goudet and colleagues in France reported that females diagnosed with MEN1 had a greater probability of developing pituitary tumors, and males had a greater probability of developing the ZES/gastrinomas type of duodeno-pancreatic tumors. While no sex differences were identified in other duodeno-pancreatic tumors, thymic tumors were found exclusively in males (Table 4.7). A family history of MEN1 was found more frequently in males at the time of diagnosis.226

Table 4.7. Significant differences in the prevalence of MEN1 characteristics by sex.
Data source Study Population Disease characteristics of MEN1 Prevalence (%)
Females Males
Multicenter ‘Groupe d’etude des Tumeurs Endocrines’,

22 regions, 1956-1991

Cohort study France and Belgium, MEN1 (57.8% female) (n=734) Pituitary tumors 46.5 30.3
Pituitary tumors: patients diagnosed with MEN1 at time of 1st lesion 44.2 67.3
Thymic tumors 0 6.1
Duodeno-pancreatic: ZES/gastrinomas 24.3 36.5
Pituitary tumors (patients diagnosed with MEN1 at time of 1st lesion); n=55 44.2 67.3

Source: Goudet et al. 2011226

 4.3.2 SDHB-related PHEO and PGL

A 2017 report of 241 mutation carriers (asymptomatic relatives of patients) showed 16.6% (n=40) developed PHEO/PGL during the study with a penetrance of 49.8% at 85 years. Males had a higher age-related penetrance of disease with 50% penetrance at 74 years vs. not reached. There was no association between mutation and gender or tumor location.227

4.3.3 Carney complex

The female to male ratio of Carney complex is 2.4:1.224 Carney triad is by far more likely to be seen in females (85%) than males (15%).213

 

4.4 LIFE EXPECTANCY AND MORTALITY

4.4.1 Multiple endocrine neoplasias

The care of patients with MEN1 can be challenging, often requiring a multidisciplinary team of healthcare workers.197,199 Studies indicate that between 28% and 70% of deaths in MEN1 patients are a direct result of MEN1, often due to malignant pancreatic neuroendocrine tumors (pNETs), gastrinomas, and foregut carcinoids.197 Improved knowledge, early diagnosis due to screening for genetic mutations, as well as routine surveillance and biochemical testing and imaging in asymptomatic relatives, has improved patient outcome in MEN syndromes.228

In 85 MEN2 patients with PHEO (retrospective review between 1960-2012 at one cancer center in the US), there had been deaths in 24% of cases (median age at death 38 years), which had been mostly linked to PHEO (10%), or MTC (85%). Of 107 patients with the most common mutation (codon 634), all had MTC and 55% had PHEO. Of the patients with PHEO, survival after MEN2 diagnosis was 100% at 5 years, 98% at 10 years, and 90% at 15 years. For patients without PHEO, the survival rates were lower, at 98%, 85%, and 78%, respectively. The median survival times were 499 months with PHEO, and 444 months with MTC only.  Each year of delay in MTC diagnosis increased the chance of death by 6%, and each 1-cm increase in PHEO size at time of diagnosis was associated with an HR for death by 1.5.  MTC-patients without PHEO had three-times higher risk-of-death than patients with PHEO.218

In MEN2B, medullary thyroid carcinoma is often early onset. Prior to the availability of early diagnosis, patients did not survive beyond age 21 years, but with early diagnosis and thyroidectomy by age 1 year, patients can live a more normal life span.229,230

4.4.2. Hereditary Pheochromocytoma and paraganglioma syndromes

Germline mutations in the SDHB gene are likely to be associated with a higher morbidity and mortality than mutations in other SDH genes. Furthermore, PGLs associated with the SDHB mutation have a higher risk of becoming malignant (34-71%), than those associated with SDHD (<5%) or SDHC (low risk) germline mutations.211

In a 2014 retrospective US study of 106 PHEO/PGL patients with SDHB mutations, there were no significant differences in survival based on specific SDHB mutations or patient sex. However, the study found metastatic disease developed significantly earlier in patients with larger (≥4.5cm) tumors, and those with primary tumors larger than 5.5cm had significantly worse overall survival than those with smaller tumors. In PGL, the size of the tumor was an age-independent predictor of patient survival and metastases development, and in both PHEO and PGL, age at diagnosis was found to be an independent predictor of patient survival.231

Approximately 10-20% of PGLs/PHEOs are metastatic. A higher potential for metastasis was observed in succinate dehydrogenase subunit B/fumarate hydratase (SDHB/FH)-associated tumors, and the age of onset of primary tumors was earlier for those with SDHB mutations (Table 4.8).

Table 4.8. Metastatic PGL/PHEO diagnosed and treated between 2000 to 2014, US.
Data source

 

 

Population

 

 

Characteristics Tumor type
SDHB mutations Apparently sporadic tumors (AST)
Retrospective study at the National Institute of Health (NIH, 2000-2014 US (n=132); children (n=27), adults (n=105); 58% males, 42% females Prevalence (%) 55 45
Age at primary tumor (years) 31 ± 16 40 ± 15
Metastatic tumors at 1st diagnosis (%) 23+ 15

Source: Turkova et al. 2016232

Mutations in SDHB are linked to more aggressive tumors, with a higher metastatic rate (34-71%) than other PGLs/PHEOs (Table 4.9).231 The overall 5-year survival of PGL or PHEO patients with SDHB mutations was 75.7%. The 5-year survival probability from initial diagnosis for patients with or without synchronous metastasis was 74.5% and 96.4% respectively. The authors also reported that an increase in tumor size predicted a decrease in survival, and an increase in metastasis.  For tumor sizes ≤4cm, 4-6cm, 6-9cm, and >9cm, the probability of 5-year survival was 94.1%, 95%, 83.4% and 88% respectively, and the median years to death were >55, >25, 12, and 20, and the survival HR was 1.0, 4.6, 12.2 and 5.8 respectively for PGL/PHEO cases.231

Table 4.9. Differences in tumor size and survival probability in SDHB-associated PGL and PHEO, US.
Study Population Measurement PGL PHEO
Retrospective study, National Institute of Health referral center US, n=106 PHEO/PGL patients with SDHB mutations; n=39 females, n=67 males; metastatic disease in n=106 (72.6%) Number of patients (n) 89 17
Median age at initial diagnosis (years) 29 31
Median sizes of primary tumors (cm) 6 8
5-year survival probability without synchronous metastasis (%) 97.9 88.9
5-year survival probability with synchronous metastasis (%) 73.2 80.0

Source: Schovanek et al. 2014231

The phenotypes, malignancy rates, and survival rates of genes linked to familial PGL/PHEO are outlined in Table 4.10.

Table 4.10. Phenotype associated with gene mutations for PGL/PHEO from literature reviews, worldwide.
Genetic mutation Phenotype Mean age at diagnosis (years) Malignancy rate (%) 5-year survival rate (%) Reference
Sporadic PGL/ PHEO 40-50 N/A N/A Lefevbre and Foulkes. 2014210
RET PHEO 30-40 1–5 N/A Karasek et al. 2013208
VHL PHEO and rarely PGLs 30 <5 N/A
NF1 PHEO and rarely extra-adrenal PGLs 40-42 0-12 N/A Lefevbre and Foulkes. 2014210; Karasek et al. 2013208
SDHAF2 PGL 30-40 rare N/A Lefevbre and Foulkes. 2014210; Karasek et al. 2013208; Kantorovich et al. 2010233; Kirmani and Young. 2008211
SDHA PGL N/A 0-14 N/A Kirmani and Young. 2008211; Karasek et al. 2013208
SDHB PGL and PHEO 25-30 34-71 36 Almeida and Stratakis. 2010199; Kantorovich et al. 2010233; Chetty. 2010234; Karasek et al. 2013208; Lefebvre and Foulkes. 2014210
SDHC PGL 35-38 Rarely N/A Almeida and Stratakis. 2010199; Kantorovich et al. 2010233; Chetty. 2010234; Else et al. 2014122; Karasek et al. 2013208; Lefebvre and Foulkes. 2014210; Kirmani and Young. 2008211
SDHD PGL, PHEO 40-50 <5 N/A Alameida and Stratakis. 2010199; Kantorovich et al. 2010233; Chetty. 2010234; Lefebvre and Foulkes. 2014210; Kirmani and Young. 2008211;
MAX Predisposed to PHEO; possibly PGL 32 25 N/A Kirmani and Young. 2008211; Karasek et al. 2013208
TMEM127 PHEO only 42-45 <5 N/A Kirmani and Young. 2008211; Qin et al. 2010235; Karasek et al. 2013208; Lefebvre and Foukes. 2014210

Abbreviations: N/A, not available.

In an international study, SDHC mutations were reported in 4% of head and neck PGL (HNPGL) cases and were absent in PHEO index cases (Table 4.11). The authors also reported that patients with SDHC mutations had a younger age at diagnosis than patients with sporadic PGL (45 and 52 years, respectively).236

Table 4.11. Tumors associated with mutations in SHD gene family in PHEO syndrome, worldwide.
Data source Population Percentage of patients with cartoid body tumors (%) Percentage of patients with multiple tumors (%) Percentage of patients with malignant tumors
PHEO registry,

January 2001 – December 2004

Unrelated index cases (n=121), sporadic cases (n=371) SDHC  (n=22) 59 9 0
Sporadic HNP (n=90) 32
SDHB (n=15) 40
SDHD (n=42) 57

Source: Schiavi et al. 2005236

The rate of metastatic disease in children with PHEO/PGL has been described to be between 9% and 47%, and up to 70% in children age <10 years. In a study of 263 cases of PHEO/PGL (2000-2010), metastatic disease was described in 125 (47.5%) of cases.  Of these patients, 49 (39%) presented with a tumor before age 20 years, and 32 (65%) of these 49 cases had metastatic disease, with the latter showing a high prevalence of SDHB germline mutations (Table 4.12).204

Table 4.12. Metastatic disease in PHEO/PGL cases in individuals developing tumors age <20 years, US.
Data source Population Mutation Prevalence (%)
tumor age <20 yrs
Metastatic

n=32

Non-metastatic n=17
National Institutes of Health, 2000-2010 PGL/ PHEO (n=263), metastatic disease (n=32) age <20 years, non-metastatic disease (age <20 years) SDHB 71.9 23.5
SDHD 9.4 5.9
VHL 6.3 23.5
NF1 0 11.8
No mutation (sporadic) 12.5 35.3

Source: King et al. 2011204

The 5-, 10- and 20-year survival rates for the children (n=49) were 97.6%, 97.6%, and 83.7% respectively.204

In a recent retrospective US study of PGL/PHEO cases (n=106) associated with SDHB mutations, the 5-year survival rates for primary tumors were 94.1% for £4cm, 83.4% for 6-9cm, and 88% for >9cm. Of the patients that developed metastatic disease (72.6%), for tumors ³5.5cm, the 5-year survival rates with or without metastatic disease were 65.8% and 97.1%.231

In a 2008 study from Belgium of 56 cases of PHEO and/or PGL (Table 4.13), mutations were identified in 41% of cases. Of the 23 familial cases, 19 were of HNPGL and 4 were abdominal PHEO/PGL.203  Surprisingly, the normally malignant SDHB mutations in sympathetic PGL showed unilateral, late onset symptoms, and no evidence of recurrence or malignancy. In 2012, the authors provided an update of 59 HNPGL, and 53 PHEO cases (between May 2003 to May 2011). The prevalence of mutations in SDHx genes was 44% in all HNPGLs, and 37% in apparently sporadic cases. In the latter group, SDHB and SDHD mutations were detected in 20% and 18% of cases respectively.237

Table 4.13. Prevalence of SDHD and SDHB mutations in head and neck PGL, Belgium.
Data source Population Disease type mutation Prevalence (%)
Cliniques Universitaires Saint Luc, May 2003 – May 2006 Belgium, PHEO and/or PGL patients (n=56), head and neck PGL (familial n=6, sporadic n=30), abdominal PHEO/PGL (n=18), PGL of the cauda equine (n=2) Familial head & neck PGL cases SDHD 100
Sporadic cases SDHD 13
SDHB 27

Source: Persu et al. 2008203

4.4.3. Carney complex

Most individuals with Carney complex have a normal lifespan, but some die at an early age, resulting in an estimated average life expectancy of 50 years.223 However, this estimate is based on historic data, and regular screening and improvement in care is expected to reduce associated morbidity and mortality.

Carney triad is chronic, persistent and frequently indolent.199 In a US study of 104 cases, patients commonly presented with gastric bleeding, 47% showed metastasis, and 13% died of metastatic GIST at a mean age of 45 years. The 40-year survival was 73%, and the 10-year survival was 100%.238

 

4.5 KEY TRENDS AND HEALTH OUTCOMES

A 2016 retrospective review of 291 MEN1 patients at a tertiary referral centre (1980-2014), reported a 10-year overall survival rate of 45% and a 10-year disease-free survival rate of 42%.239 In 2014, Dy and colleagues reported that for 30 MEN1 patients who underwent resection for neuroendocrine tumors at a single tertiary care center (1994-2010), the estimated 10-year survival was 86.4%, and the disease-free interval was 89% for 1 year, 50% for 5 years, and 19% for 10 years.240

Approximately 20% of sporadic PGL/PHEO cases carry somatic mutations in NF1 and approximately 10% of these are metastatic.241 In metastatic PHEO/PGL, the 5- and 10-year survival rates were significantly better in patients with apparently sporadic tumors (AST) than those with SDHB mutations (p value 0.01). In individuals with SDHB mutations, children had significantly longer survival than adults.232

Inherited, bilateral PHEO tumors can be treated by open total bilateral adrenalectomy, although patients may suffer from permanent adrenal insufficiency, requiring lifelong steroid replacement. Cortex-sparing adrenalectomy is the preferred option although it presents a higher chance of recurrence.242

Patients with SDHB mutations have a higher response rate to targeted therapy with 123I-metaiodobenzylguanidine (MIBG). In malignant PGL and PHEO patients treated with MIGB, the tumor response rate ranged from 22 to 48%. Of those responding to MIBG treatment, between 35 and 67% exhibited a biochemical response.241 Targeted radiotherapy with 90Y-DOTATOC and 177Lu-DOTATOC results in <10% response rates, but overall has not been well explored.  Malignant tumors associated with SDHB mutations are often deficient in O6-methylguanine-DNA methyltransferase (MGMT), and so respond better to cyclophosphamide-vincristine-decarbazine (CVD) regimen or to the less toxic temozolomide (TMZ) therapy than non- SDHB such as sporadic cases.241 In one study (n=18), a complete/partial response was detected in 55% of patients. A modified CVD regimen with doxorubicin in malignant PGL/PHEO patients (n=13) showed a 46% partial response rate. TMZ therapy resulted in response rates that were partial (33%), stable (47%), and progressive (20%) in 15 malignant PGL/PHEO cases where 67% of patients (n=10) carried an SDHB mutation.243

Between May 2008 and January 2013 in Greece, 17 patients (11 sporadic, 6 MEN2A-associated PHEO) with a mean tumor size of 3.7cm had undergone retroperitoneal adrenalectomy (PRA) and 17 patients (13 sporadic PHEO, 4 MEN2A syndrome) with a mean tumor size of 5.1cm had undergone the laparoscopic technique.  There was no mortality and no blood transfusions were needed for either group. PRA proved to have better clinical results than laparoscopic techniques for sporadic and inherited PHEO: mean hospital stay was 2.1 days for PRA and 4 days for the laparoscopic group; mean operative times were 105.6 and 137 minutes respectively.244

The treatment and outcome of a number of endocrine cancers are shown in Table 4.14. Subtotal parathyroidectomy is the initial treatment of choice for primary hyperparathyroidism in MEN1 patients, while total parathyroidectomy with autotransplantation may be used in cases of extensive disease at initial or repeat surgery.245

Table 4.14. Outcomes of treatments for familial endocrine cancers.
Endocrine Cancer Treatment Outcome References
Parathyroid tumors
MEN1 Subtotal parathyroidectomy (removal of £3.5 glands) 40-60% of patients had persistent or recurrent hypercalcemia within 10-12 years post surgery Thakker et al. 2012245; Giusti et al. 2005
10-30% of patients had hypocalcemia requiring long-term therapy with Vitamin D or calcitriol.
Total parathyroidectomy with autotranplantation >50% of patients had recurrent hypercalcemia
MEN2A Preventative thyroidectomies in 50 patients in group A involving central neck dissection with total parathroidectomy and autotransplantation of parathyroid slivers to forearm or neck (1993-2000); compared to group B of 97 MEN2A (5 MEN2B) patients with preventative thyroidectomies, preserving parathyroid glands (2003-2015). Permanent hypoparathyroidism occurred in 6% of group A and 1% of group B. After total thyroidectomy, no patient in either group developed permanent recurrent laryngeal nerve injury or hyperparathyroidism. Moley et al. 2015246
Well-differentiated tumors of the gastro-entero-pancreatic (GEP) tract
a) Gastrin-secreting tumors gastrinomas (60-80% of cases)
MEN1 Surgery recommended for tumors at pancreatic islet, stomach endocrine cells, or duodenum.  Medications can be used to control some of the gastro-entero-pancreatic hormone excess. Surgery: 77% cure rate by pancreatoduodenectomy in 12 MEN1-associated hypergastrinomas. Tonelli et al. 2005247
Surgery 15% of MEN1 patients were free of disease immediately after surgery; 5% were free of disease 5 years after surgery. Thakker et al. 2012245
Long-term administration of Somatostatin analogues: octreotide, and lanreotide Type II gastric carcinoid tumors in patients with combined MEN 1 and the Zollinger-Ellison syndrome, 2 patients treated with lanreotide (30mg every 10 days) and 1 patient with octreotide (20mg every 28 days) with follow up at 6 months and 1 year. Tumor regression (with reduction in size and number) in all 3 patients after 6 months and complete disappearance after 1 year of treatment. Waguespack et al. 2010248; Tomassetti et al. 2000249
Gastric carcinoid tumors in Zollinger-Ellison syndrome (ZES) patients (n=231); and in patients with both ZES and MEN1 (n=45). Proton-pump inhibitors (eg. omeprazole or lasoprazole) to treat gastric acid hypersecretion; some may also require histamine H2 receptor antagonists (cimetidine or ranitidine). Gastric carcinoid tumors in 13-30% ZES with MEN1 and ZES and 0-0.6% in ZES without MEN1. Acid secretion controlled with Omeprazole (65mg/day) for up to 14 years (mean 6.2 years); with Ranitidine, (2700mg/day) for up to 15 years (mean 5.9 years).  Once acid secretion is controlled, patients with MEN1 have better long-term survival than those without MEN1. Jensen. 1998250
Insulinomas (20% of cases)
Pancreatic neuroendocrine tumors Resection in 70 patients, 50 had non-functional tumors (37 carcinomas, 13 benign islet cell neoplasms); 20 had functional tumors (16 insulinomas mostly <2cm at diagnosis, 2 gastrinomas, 2 glucagonomas);

US,

1990-2005

Post-opertaive complications: 48.1% of pancreaticoduodenectomies, 12.5% of pancreatectomies or 0% of ennucleations (mainly functional tumors). With a median follow-up of 50 months, 100% of those that had functional tumors were alive, while 77% of those with carcinomas were alive. Kazanjian et al. 2006251
Hereditary PHEO
Hereditary PHEO Adrenalectomy in 96 patients (47 with bilateral disease). Originally unilateral adrenalectomy was performed in 30% of patients, and PHEO developed in contralateral gland after 1-20 years post diagnosis (median 8.2 years) Cortical-sparing adrenalectomy avoided long-term corticosteroid dependence in most cases. 7% (4/55) recurrences in cortical-sparring remnants, 3% (3/101) recurrences in adrenal bed after total adrenal resections. Acute adrenal insufficiency developed in 20% (5/25) of patients who underwent total bilateral adrenalectomy. Acute adrenal insufficiency developed in 3% (1/39) who underwent cortical-sparring adrenalectomy. Of these with adequate follow-up, 78% (21/27) were steroid independent at 3-year follow-up. Grubbs et al. 2013252
Carney complex
Cardiac myxomas Surgery of myxomas of the heart 35% recurrence, most diagnosed in first 4 years post surgery. Recurrence risk: 12-22% for familial and 1-3% for sporadic tumors. Reynen. 1995253

Abbreviations: PGL, Paraganglioma; PHEO, Pheochromocytoma.

 

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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