3 Cushing’s

Suggested citation: Endocrine Society. Endocrine Facts and Figures: Adrenal. First Edition. 2016.

Cushing’s Syndrome (CS) refers to the clinical manifestations induced by chronic exposure to excess glucocorticoids and may have exogenous causes (e.g., excess glucocorticoid intake for the treatment of inflammatory conditions) or endogenous. There are three pathological conditions that can result in the chronic overproduction of endogenous cortisol. The most common condition is Cushing’s Disease (CD), where pituitary corticotroph adenoma overproduces ACTH. Secondly, and more rare, a non-pituitary tumor can produce ACTH in an “ectopic” manner. Finally, one or (rarely) both two adrenals that have tumors (benign or malignant) can directly over-secrete cortisol. Adrenocortical or exogenous adenomas and carcinomas cause primary hypercortisolism, which accounts for 20% of endogenous CS cases.5,53,54 Chronic hyperproduction of ACTH causes secondary hypercortisolism, which accounts for roughly 80% of endogenous CS,54 and ACTH-secreting pituitary or exogenous adenomas causes CD, which is the most common form of secondary hypercortisolism. CD accounts for 70% of CS cases.55

CS may follow over administration of prednisone, dexamethasone, or prednisolone. CS manifestations typically are nonspecific, which complicates the initial diagnosis.4

Commonly recommended initial testing are urinary free cortisol, late-night salivary cortisol, and 1-mg overnight dexamethasone suppression test (DST). Imaging is the key to diagnosis. CS continues to pose diagnostic and therapeutic challenges; life-long follow-up is mandatory.56

Untreated, it has significant morbidity and mortality. The syndrome remains a challenge to diagnose and manage.57,58


CS is a rare condition that, according to one estimate, affects fewer than five in 10,000 individuals.59  Table 6 summarizes data on the prevalence and incidence of CS and CD.

Table 6. The prevalence and incidence of Cushing’s syndrome and Cushing’s disease.
Population Data Source Prevalence (cases per million) Incidence rates (cases per million per year) Reference
US, aged ≤ 65 from 2007 to 2010* Commercial database of patients N/A
CS, 48.6 in 2009 and 39.5 in 2010**
CD, 7.6 in 2009 and 6.2 in 2010***
Broder et al. 201460
Medline database, 2000-2005 Systematic review CS, 20,000-50,000 in patients with diabetes CS, 0.7 to 2.4 (researchers acknowledged that this estimate probably was too low) Newell et al. 200657
166 Danish patients diagnosed with CS, 1985-1995 Data from the National Patient Register of the Danish National Board of Health N/A CD, 1.2-1.7 Lindholm et al. 200161
49 CD patients in Vizcaya (Spain) between 1975 and 1992 Epidemiological study CD, 39.1 CD, 2.4 (15 times more frequent in women vs. men) Extabe et al. 199462
Abbreviations: N/A, data not available; CS, Cushing’s syndrome; CD, Cushing’s disease; US, United States
Note: *, The authors defined CS as ≥ 2 claims of CS diagnosis in 1 year and defined CD as CS plus a diagnosis of benign pituitary adenoma or hypophysectomy during the same year.60 **, The authors noted that their estimates of US cases of CS and CD were somewhat higher than previous estimates from Europe. The lowest rates of CS were in ≤ 17-year-olds and highest rates were in 35- to 44-year-olds.60 ***,The lowest rates of CD were in ≤ 17-year-olds and highest rates were in 18- to 24-year-olds. The rates varied by sex (2.3-2.7 in males, 9.8-12.1 in females). In females, lowest rates ranged 2.5-4.0 in ≤ 17-year-olds and highest 16.7-27.2 in 18-24 year olds. In males, there were too few cases to report estimates by age.60


Initial diagnosis of CD typically is made in adults—mostly women—aged 30-50, and pediatric cases are rare.63 Table 7 shows the age distribution among CD patients. Endogenous CS has been divided into corticotropin-dependent and corticotropin-independent types; the former may account for 80-85% of instances, of which an estimated 80% are caused by pituitary adenomas.57

Table 7. Age distribution among United States Cushing’s disease patients in 2010.
Age (years) Number (%)
≤ 17 29 (4.2)
18–24 65 (9.5)
25–34 108 (15.8)
35–44 175 (25.5)
45–54 186 (27.2)
55–64 114 (16.6)
≥ 65 8 (1.2)

Source: Broder et al. 201517


CS is rare and is associated with increased mortality in patients with no concurrent malignancy; also, the excess mortality usually occurs during the first year of disease. However, data on mortality associated with CD and CS are scarce, and the impaired quality of health in long-term survivors of CD is not fully explained.61,64   Table 8 presents mortality data related to CD and CS.

Table 8. Mortality associated with Cushing’s disease and Cushing’s syndrome.
Population Data Source SMR References
166 Danish patients diagnosed with CS from 1985-1995. Data from the National Patient Register of the Danish National Board of Health
Of 139 patients with nonmalignant disease, SMR=3.68.
In 45 patients with CD who had been cured through transsphenoidal neurosurgery, SMR=0.31.
Of 20 patients with persistent hypercortisolism after initial neurosurgery, SMR=5.06.
In patients with adrenal adenoma, SMR=3.95.
Lindholm et al. 200161
N/A Systematic review and meta-analysis of mortality studies in patients with CD and CS secondary to a benign adrenal adenoma
In patients with CD, SMR=1.84.
In CD patients with persistent disease after initial surgery, SMR=3.73.
In CD patients with initial remission, SMR=1.23.
In patients with a benign adrenal adenoma, SMR=1.90.*
Graversen et al. 201264
Spain, N=49, 1975-1992 Epidemiological study
Overall, SMR=3.8.
In patients with vascular disease, SMR=5.**
Extabe et al. 199462
UK 1967-2009, Greece 1962-2009, N=418, all with endogenous CS (311 with CD, 74 with adrenal CS and 33 with ectopic CS) Systematic analysis of a large series with prolonged follow-up
In CD overall, SMR=9.3. In adrenal CS, SMR=5.3. ***
In ectopic CS, SMR=68.5.
Ntali et al. 201365
N=33, CS patients Columbia Presbyterian Medical Center Records, 1932-1951 5-year survival rate was 50%; life expectancy generally was limited by cardiovascular events, but over time mortality rates have decreased. Plotz et al. 195266
N=60, UK, 51 female, median age 36-46 years, median follow-up 15 years SMR for 60 CD patients was compared with general UK. A meta-analysis of SMRs from seven studies (including this study) was performed for overall mortality in CD.
Overall, SMR=4.8
For vascular disease, SMR=13.8.
For persistent disease (n = 6), SMR=16 vs. remission (n = 54) SMR=3.3. After adjustment for age and sex, relative risk of death for persistent disease was 10.7. Hypertension and diabetes mellitus were associated with significantly worse survival.
Clayton et al. 201167
N=248 Dutch patients with pituitary adenomas treated by transsphenoidal surgery for NFMAs (N = 174) and ACTH-producing adenomas (N = 74). Clinical study.
For the entire cohort, SMR=1.41.
For NFMA patients, SMR=1.24 vs. 2.39 in CD.
In patients with CD vs. NFMAs, the age-adjusted mortality was significantly increased.
Dekkers et al. 200768
Abbreviations: N/A, data not available; UK, United Kingdom; SMR, standard mortality ratio, CS, Cushing’s syndrome; CD Cushing’s disease; N, number; NFMA, nonfunctioning pituitary macroadenomas  
Note: *, Age, sex and observation time did not significantly impact mortality.64 **, Higher age, persistence of hypertension and abnormalities of glucose metabolism after treatment, were independent predictors of mortality (multivariate analyses, P < 0.01).62 ***, SMR was high overall as well as in all subgroups of patients irrespective of their remission status. In CD, the probability of 10-year survival was 95.3% with 71.4% of the deaths attributed to cardiovascular causes or infection/sepsis. In adrenal CD, the probability of 10-year survival was 95.5%. Patients with ectopic CD had the worst outcome with 77.6% probability of 5-year survival.65



Clinical presentation can be highly variable, and establishing the diagnosis can often be difficult.58

A positive diagnosis of CS requires that chronic hypercortisolism is unequivocally demonstrated biologically using tests such as the 24-hour urinary cortisol, late-evening plasma or salivary cortisol, diurnal cortisol test, midnight 1-mg, or the classic 48-hour-low-dose DST. All of which have essentially the same diagnosis potencies. The search for the responsible cause then relies on the assessment of corticotroph function and imaging. Suppressed ACTH plasma levels indicate adrenal CS, and the responsible unilateral adrenocortical tumor is always visible on computed tomography scans. However, its benign or malignant nature may be difficult to diagnose before surgery. Imaging can suspect bilateral adrenal CS, when the two adrenals are small, as in the primary pigmented nodular adrenal dysplasia associated with Carney complex, or enlarged, as in the ACTH-independent macronodular adrenocortical hyperplasia (or primary macronodular adrenal hyperplasia). Measurable or increased ACTH plasma levels indicate either CD or the ectopic ACTH syndrome. When the dynamics of the corticotroph function (high-dose DST, the CRH test) are equivocal, and/or the imaging is non-contributive, it may be difficult to distinguish between the two. This is a situation where sampling ACTH plasma levels in the inferior petrosal sinus may be necessary.53

Biochemical diagnosis of CS is complicated by the cyclical nature of cortisol secretions. First-line biochemical tests include late-night salivary cortisol and urinary free cortisol tests.57 Researchers have compared these two diagnostic approaches in a group of patients who presented with CS, CD, or obesity; each patient provided three samples for both tests.69 The two approaches had similar variability, but late-night salivary cortisol testing demonstrated better diagnostic performance.69

Dexamethasone extinction testing is another approach to confirm a CS diagnosis, but it requires careful controls and may not provide sufficient diagnostic accuracy to be used alone.57 Thus, a differential CS diagnosis often relies on biochemical assays.70 The dexamethasone extinction test followed by the CRH extinction test71,72 has provided a single measurement of cortisol from late-night serum or saliva samples. The desmopressin test may facilitate a rapid diagnosis of cyclical CD.73 Researchers are studying tests and strategies that may enable more accurate and more convenient diagnosis of CS and CD.74,75

Imaging studies for the diagnosis of CS and CD have been challenging: MRI has been estimated to detect only 60-70% of CD adenomas.76-78 Moreover, positive MRI results may be confounding because incidental pituitary adenomas may exist in 10% of the population.79 Further, microadenomas may be difficult to image, and full-body scans have been used for differential diagnosis.53

Bilateral intrapetrosal sinus sampling may help physicians to distinguish between pituitary and ectopic sources of increased ACTH levels,80,81 but the procedure has been termed invasive and elaborate.77,78,81,82

Authors of a later study suggested that because adrenal lesions are relatively common place and are easily detected by advanced imaging technologies, clinicians may be tempted to test all patients with such lesions for excess cortisol secretion that is indicative of CS.83 However, since most such lesions rarely lead to frank disease, one author suggested that routine screening in unselected populations is clinically ineffective and potentially deleterious if unaffected patients undergo invasive surgery.83

One report suggested that the probability of finding an adrenal incidentaloma in a patient 20-29 years old was 0.2%, but the probability of such a finding in a patient > 70 years was 6.9%.84

Some authors suggested that CS should be included in the differential diagnoses of certain high-risk patient populations, including patients who present with diabetes mellitus, hypertension, and early-onset osteoporosis.85

Quality of Life

CS of any etiology (adrenal, pituitary, or ectopic) impacts negatively on health-related QOL, especially in active hypercortisolism but also after an endocrine cure. Generic questionnaires (e.g., the short-form 36 health survey SF-36, the derived SF-12, and the Hospital Anxiety and Depression Scale), as well as disease-specific measures (e.g., the Cushing QOL and the Tuebingen CD-25 questionnaires) have provided information on the impact of CS on patients perceived health.86 Patients may experience severe fatigue, physical changes, emotional instability, depression, and cognitive impairment.87

Treating CS improves patient-perceived QOL, but it often takes many months and often never normalizes. In addition to persistent decreased QOL in cured CS patients, brain and cerebellar volume are also reduced. Depression, anxiety, and cognitive dysfunction are common. Pediatric patients with CS also have worse QOL than normal children, and they have delayed growth and pubertal development and sub-normal body composition and psychological and cognitive maturation. Fluoxetine has been suggested as a neuroprotectant and antidepressant for patients with CS, although no prospective studies are yet available.86

The initial onset of CD is insidious and can involve nonspecific, highly variable, and often cyclical presentations of clinical signs (Table 9). Reports about the time required for CD diagnosis vary widely. A study that included 19 patients with ACTH-secreting tumors reported an average of 4.3 years from initial presentation to diagnosis.88 A study that included 49 patients reported an average time from symptom onset to diagnosis of 45.8 ± 2.7 months (range 6-144 months).62 The European Registry on CS identified 481 CS patients (66% of whom presented with CD) and reported a median diagnostic delay of 2 years.89

Table 9. Comorbidities that may present with Cushing’s syndrome.
Symptom Prevalence in All CS patients
Hypertension 58-85%
Obesity 32-41%
Diabetes mellitus 50-81%
Major depression 31-50%
Osteoporosis 31-50%
Dyslipidemia 38-71%

Source: Feelders et al. 201287


The therapeutic goal is to normalize tissue exposure to cortisol to reverse increased morbidity and mortality. Optimum treatment consisting of selective and complete resection of the causative tumor is necessary to allow eventual normalization of the hypothalamic-pituitary-adrenal axis, maintenance of pituitary function, and avoidance of tumor recurrence. The development of new drugs offers clinicians several choices to treat patients with residual cortisol excess. However, for patients affected by this challenging syndrome, the long-term effects and comorbidities associated with hypercortisolism require ongoing care.90


Surgery (resection of the pituitary or ectopic source of ACTH, or unilateral or bilateral adrenalectomy) remains the optimal treatment in all forms of CS, but may not always lead to remission. Bilateral adrenalectomy is reserved for recurrent cases of CD and can be performed laparoscopically.91

The best treatment option of CD is total removal of the responsible corticotroph adenoma  using a transsphenoidal approach, while preserving the normal anterior pituitary function. If this fails, all other options directed towards the pituitary (radiation therapies) or the adrenals (medications or surgery) have numerous side effects. There is at present no recognized efficient medical treatment for corticotroph adenomas.53

Medical therapy (steroidogenesis inhibitors, agents that decrease ACTH levels, or glucocorticoid receptor antagonists) and pituitary radiotherapy may be needed as an adjunct. A multidisciplinary approach, long-term follow-up, and treatment modalities customized to each individual are essential for controlling hypercortisolemia and managing comorbidities.58

A study that examined two US claims databases between 2008 and 2010 and reported that among 228 newly treated CD patients, 180 (78.9%) underwent surgery, 42 (18.4%) received pharmacotherapy, and 6 (2.6%) were administered radiotherapy.92

Table 10 presents outcomes data of surgical/radiation treatments for CD and CS.

Table 10. Surgical/radiation treatments for Cushing’s syndrome and Cushing’s disease.
Treatment Outcomes Reference
Transsphenoidal surgery Remission rates were between 60-80% (< 15% for microadenomas), but relapse rates were as high as 20%. Newell-Price et al. 200657


Transsphenoidal surgery


Remission rates were between 65-90% (65% for macroadenomas > 1 cm). Aghi et al. 200893
Transsphenoidal surgery Remission occurred in 60-90% of CD patients with microadenomas and slightly fewer (50-70%) in cases with macroadenomas. Hofman et al. 200894; Hoybye et al. 200495; Shimon et al. 200296
Transsphenoidal surgery Experienced neurosurgeons reportedly have achieved perioperative mortality rates between 0-1.5% with low overall complication rates. Barker et al. 200397
Transsphenoidal surgery Recurrence was as high as 25% at 45 months. Patil et al. 2008 98
Transsphenoidal surgery Recurrence occurred in 20-25% of patients. Barbetta et al. 200199; Sonino et al. 1996100; Patil et al. 200898
Repeat transsphenoidal surgery


Treatment resulted in remission in 50-60% of patients, along with corresponding increases in the incidence of complications. Biller et al., 2008101; Tritos et al., 2011102
Laparoscopic surgery Prognosis was good except for adrenocortical carcinomas. Newell-Price et al. 200657
Conventional fractionated radiotherapy Treatment was effective but was associated with long-term hypopituitarism. Newell-Price et al. 200657
Proton stereotactic radiation therapy Treatment led to remission in 17 cases (52%). Petot et al. 2008103
Laparoscopic adrenalectomy All patients resolved signs/symptoms of CS, maintained weight, improved glucose tolerance and blood pressure control, and had no residual cortisol secretion. Vella et al. 2001104
Bilateral adrenalectomy


50% of patients experienced tumor progression within 3 years. Assie et al. 2007105

Abbreviations: CD, Cushing’s disease; CS, Cushing’s syndrome

Drug Therapies

Pharmaceutical therapies for CD can be divided into two groups: steroidogenesis inhibitors (drugs that act on the corticotrophic cells of the adenoma) and glucocorticoid receptor antagonists.106

Steroidogenesis inhibitors currently used for the treatment of CD include ketoconazole, metyrapone, mitotane, and etomidate.106

Ketoconazole and metyrapone are enzyme inhibitors that have a rapid onset but diminished control following corticotropin oversecretion in CD.57 Both these agents are used off-label to treat CS.107 The long-term use of ketoconazole may be limited by liver toxicity.108,109

Mitotane has been used to treat relatively benign CD, and etomidate, which is the only drug approved for intravenous treatment of CD, rapidly reduces cortisol levels.108,110

In 2012, the FDA approved pasireotide and mifepristone as pharmacological alternatives for treating CD patients who are not eligible for surgery.106,111-113 Pasireotide targets the somatostatin receptor subtype 5, which is overexpressed in corticotrophic adenomas.114 Ongoing phase III trials are further investigating pasireotide’s safety and efficacy in new, persistent, or recurring cases of CD, and another clinical trial is evaluating an extended-release formulation of pasireotide for once-a-month dosing.113 Pasireotide’s safety profile is similar to that of other somatostatin analogs but has been associated with elevated incidences of hyperglycemia.108,114

Mifepristone is a glucorticoid receptor antagonist that reportedly improved glucose tolerance with patients and showed long-term safety.115

A proof-of-concept study is currently underway for the treatment of CD with LCI699, a potent 11b-hydroxylase inhibitor.110,116,117  Table 11 summarizes outcome data on a variety of drug therapies for CD and CS.

Table 11. Studies on drug therapies for Cushing’s syndrome and Cushing’s disease.
Treatment Outcomes Reference
Mifepristone (Phase 3) Treatment improved glycemic control in 60% and reduced hypertension in some subgroups; the overall clinical status of 87% of patients improved. Fleseriu et al. 2012118
LCI699 (phase 2) Treatment reduced plasma aldosterone and ACTH-stimulated cortisol response at all doses administered with no increased side effects compared with placebo. Wang et al. 2015119
Ketoconazole One study reported that 50% of patients taking ketoconazole achieved biochemical control and clinical improvement, but 20% of the patients discontinued the drug because of poor tolerability. Fleseriu et al. 2015110
Cabergoline Treatment has been reported to suppress cortisol production in 50-70% of patients over a 12-month period, but only 30-40% of patients remain in remission after 2 to 3 years. Pivonello et al. 1999120; Pivonello et al. 2009121; Godbout et al. 2010122
Cabergoline Treatment was well tolerated, but normalized cortisol levels in only one-third of patients. Molitch et al. 2014108
Pasireotide Treatment decreased cortisol levels in 88% of patients in a recent phase 3 study. Colao et al. 2012123
Pasireotide Treatment normalized cortisol levels in 25% of patients who received the drug and worsened glucose tolerance in most patients. Molitch et al. 2014108

Abbreviations: CS, Cushing’s syndrome; ACTH, adrenocorticotropic hormone

Genetic Approaches

Studies are examining genetics-based approaches for treating CD. One author reasoned that disruptions of cell signaling were associated with ACTH-producing adenomas and suggested investigating epithelial growth factor receptors, cyclins, and cyclin-dependent kinases.124

Subclinical Cushing’s Syndrome

Abstract clinically unapparent adrenal masses have become a common in everyday practice. These are usually incidentally detected, mostly due to the routine use of imaging techniques, such as ultrasound and computed tomography. A substantial percentage of these incidentalomas are hormonally active, with 5-20% of the tumors producing glucocorticoids. Autonomous glucocorticoid production without specific signs and symptoms of CS is termed subclinical CS.125,126

With an estimated prevalence of 79 cases per 100,000 persons, subclinical CS is much more common than classic CS. Depending on the amounts of glucocorticoids secreted by the tumor, the clinical spectrum ranges from slightly attenuated diurnal cortisol rhythm to complete atrophy of the contralateral adrenal gland with lasting AI after unilateral adrenalectomy.125

Patients with subclinical CS lack the classical stigmata of hypercortisolism but have a high prevalence of obesity, hypertension, type 2 diabetes and cardiovascular complications. All patients with incidentally detected adrenal masses scheduled for surgery must undergo testing for subclinical CS to avoid postoperative adrenal crisis.125

The diagnosis of subclinical CS is based on biochemical evaluation; however, there is still no consensus regarding diagnostic criteria. Many experts agree that an abnormal 1mg DST initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis is sufficient to diagnose subclinical CS. Although some recommend a higher dexamethasone dose (3 mg instead of 1 mg) to reduce false-positive results.125

The optimal management of patients with subclinical CS is not yet defined. The conservative approach of observation and medical treatment of morbidities is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. Surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2, or abnormal glucose tolerance and obesity.126 Some researchers also recommend surgery in patients < 50 years and those with suppressed plasma ACTH.125


  1. Bishop PM. The history of the discovery of Addison’s disease. Proc R Soc Med. 1950;43(1):35-42.
  2. NIDDK. Adrenal Insufficiency and Addison’s Disease. Bethesda, MD: NIH; 2014:1-16.
  3. Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. Jama. 2002;287(2):236-240.
  4. Aron DC. Cushing’s syndrome: why is diagnosis so difficult? Rev Endocr Metab Disord. 2010;11(2):105-116.
  5. Society TP. Cushing’s Syndrome and Cushing’s Disease. New York, NY: The Pituitary Society; 2013.
  6. Betterle C, Morlin L. Autoimmune Addison’s disease. Endocr Dev. 2011;20:161-172.
  7. Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014;383(9935):2152-2167.
  8. Lovas K, Loge JH, Husebye ES. Subjective health status in Norwegian patients with Addison’s disease. Clin Endocrinol (Oxf). 2002;56(5):581-588.
  9. Thomsen AF, Kvist TK, Andersen PK, Kessing LV. The risk of affective disorders in patients with adrenocortical insufficiency. Psychoneuroendocrinology. 2006;31(5):614-622.
  10. Hahner S, Loeffler M, Fassnacht M, Weismann D, Koschker AC, Quinkler M, Decker O, Arlt W, Allolio B. Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis. J Clin Endocrinol Metab. 2007;92(10):3912-3922.
  11. Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adrenal insufficiency is common: a cross-sectional study in 216 patients. Am J Med Sci. 2010;339(6):525-531.
  12. Forss M, Batcheller G, Skrtic S, Johannsson G. Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency – a worldwide patient survey. BMC Endocr Disord. 2012;12:8.
  13. Tiemensma J, Andela CD, Kaptein AA, Romijn JA, van der Mast RC, Biermasz NR, Pereira AM. Psychological morbidity and impaired quality of life in patients with stable treatment for primary adrenal insufficiency: cross-sectional study and review of the literature. Eur J Endocrinol. 2014;171(2):171-182.
  14. Andela CD, Scharloo M, Pereira AM, Kaptein AA, Biermasz NR. Quality of life (QoL) impairments in patients with a pituitary adenoma: a systematic review of QoL studies. Pituitary. 2015.
  15. Chauhan. Adrenal Insufficiency: Burden Of Disease And Cost Of Illness. http://www.ispor.org/research_pdfs/45/pdffiles/PDB30.pdf. Accessed May 22, 2016.
  16. 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;161(4):513-527.
  17. Broder MS, Neary MP, Chang E, Cherepanov D, Ludlam WH. Burden of illness, annual healthcare utilization, and costs associated with commercially insured patients with cushing disease in the United States. Endocr Pract. 2015;21(1):77-86.
  18. Erichsen MM, Lovas K, Skinningsrud B, Wolff AB, Undlien DE, Svartberg J, Fougner KJ, Berg TJ, Bollerslev J, Mella B, Carlson JA, Erlich H, Husebye ES. Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry. J Clin Endocrinol Metab. 2009;94(12):4882-4890.
  19. Kong MF, Jeffcoate W. Eighty-six cases of Addison’s disease. Clin Endocrinol (Oxf). 1994;41(6):757-761.
  20. Willis AC, Vince FP. The prevalence of Addison’s disease in Coventry, UK. Postgrad Med J. 1997;73(859):286-288.
  21. Mason AS, Meade TW, Lee JA, Morris JN. Epidemiological and clinical picture of Addison’s disease. Lancet. 1968;2(7571):744-747.
  22. Lovas K, Husebye ES. High prevalence and increasing incidence of Addison’s disease in western Norway. Clin Endocrinol (Oxf). 2002;56(6):787-791.
  23. Ekman B, Fitts D, Marelli C, Murray RD, Quinkler M, Zelissen PM. European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy. BMC Endocrine Disorders. 2014;14(1):1-7.
  24. Nilsson B, Gustavasson-Kadaka E, Bengtsson BA, Jonsson B. Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab. 2000;85(4):1420-1425.
  25. Regal M, Paramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001;55(6):735-740.
  26. Rushworth RL, Torpy DJ. A descriptive study of adrenal crises in adults with adrenal insufficiency: increased risk with age and in those with bacterial infections. BMC Endocrine Disorders. 2014;14(1):1-8.
  27. Broersen LH, Pereira AM, Jorgensen JO, Dekkers OM. Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endocrinol Metab. 2015:jc20151218.
  28. Spinner MW, Blizzard RM, Childs B. Clinical and genetic heterogeneity in idiopathic Addison’s disease and hypoparathyroidism. J Clin Endocrinol Metab. 1968;28(6):795-804.
  29. Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361(9372):1881-1893.
  30. Wallace I, Cunningham S, Lindsay J. The diagnosis and investigation of adrenal insufficiency in adults. Ann Clin Biochem. 2009;46(Pt 5):351-367.
  31. Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, Johannsson G. Premature mortality in patients with Addison’s disease: a population-based study. J Clin Endocrinol Metab. 2006;91(12):4849-4853.
  32. Bensing S, Brandt L, Tabaroj F, Sjoberg O, Nilsson B, Ekbom A, Blomqvist P, Kampe O. Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clin Endocrinol (Oxf). 2008;69(5):697-704.
  33. Erichsen MM, Lovas K, Fougner KJ, Svartberg J, Hauge ER, Bollerslev J, Berg JP, Mella B, Husebye ES. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur J Endocrinol. 2009;160(2):233-237.
  34. Johannsson G, Falorni A, Skrtic S, Lennernas H, Quinkler M, Monson JP, Stewart PM. Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy. Clin Endocrinol (Oxf). 2015;82(1):2-11.
  35. Nieman LK, Chanco Turner ML. Addison’s disease. Clin Dermatol. 2006;24(4):276-280.
  36. Bouillon R. Acute adrenal insufficiency. Endocrinol Metab Clin North Am. 2006;35(4):767-775, ix.
  37. Neary N, Nieman L. Adrenal insufficiency: etiology, diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes. 2010;17(3):217-223.
  38. Hillier SG. Diamonds are forever: the cortisone legacy. J Endocrinol. 2007;195(1):1-6.
  39. Napier C, Pearce SH. Current and emerging therapies for Addison’s disease. Curr Opin Endocrinol Diabetes Obes. 2014;21(3):147-153.
  40. Aulinas A, Webb SM. Health-related quality of life in primary and secondary adrenal insufficiency. Expert Rev Pharmacoecon Outcomes Res. 2014;14(6):873-888.
  41. Raff H, Sharma ST, Nieman LK. Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing’s syndrome, adrenal insufficiency, and congenital adrenal hyperplasia. Compr Physiol. 2014;4(2):739-769.
  42. Wood BR, Lacy JM, Johnston C, Weigle DS, Dhanireddy S. Adrenal Insufficiency as a Result of Ritonavir and Exogenous Steroid Exposure: Report of 6 Cases and Recommendation for Management. J Int Assoc Provid AIDS Care. 2015.
  43. Song Y, Schroeder JR, Bush LM. Iatrogenic Cushing syndrome and secondary adrenal insufficiency related to concomitant triamcinolone and ritonavir administration: a case report and review. J Int Assoc Provid AIDS Care. 2014;13(6):511-514.
  44. Sannarangappa V, Jalleh R. Inhaled corticosteroids and secondary adrenal insufficiency. Open Respir Med J. 2014;8:93-100.
  45. Lang K, Burger-Stritt S, Hahner S. Is DHEA replacement beneficial in chronic adrenal failure? Best Pract Res Clin Endocrinol Metab. 2015;29(1):25-32.
  46. Bjornsdottir S, Oksnes M, Isaksson M, Methlie P, Nilsen RM, Hustad S, Kampe O, Hulting AL, Husebye ES, Lovas K, Nystrom T, Bensing S. Circadian hormone profiles and insulin sensitivity in patients with Addison’s disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy. Clin Endocrinol (Oxf). 2014.
  47. Oksnes M, Bjornsdottir S, Isaksson M, Methlie P, Carlsen S, Nilsen RM, Broman JE, Triebner K, Kampe O, Hulting AL, Bensing S, Husebye ES, Lovas K. Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of addison’s disease: a randomized clinical trial. J Clin Endocrinol Metab. 2014;99(5):1665-1674.
  48. Gagliardi L, Nenke MA, Thynne TR, von der Borch J, Rankin WA, Henley DE, Sorbello J, Inder WJ, Torpy DJ. Continuous subcutaneous hydrocortisone infusion therapy in Addison’s disease: a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014;99(11):4149-4157.
  49. Nilsson AG, Marelli C, Fitts D, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engstrom BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Lennernas H, Skrtic S, Johannsson G. Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency. Eur J Endocrinol. 2014;171(3):369-377.
  50. Quinkler M, Nilsen RM, Zopf K, Ventz M, Oksnes M. Modified release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency. Eur J Endocrinol. 2015.
  51. White K, Arlt W. Adrenal crisis in treated Addison’s disease: a predictable but under-managed event. Eur J Endocrinol. 2010;162(1):115-120.
  52. Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015;100(2):407-416.
  53. Bertagna X, Guignat L, Groussin L, Bertherat J. Cushing’s disease. Best Pract Res Clin Endocrinol Metab. 2009;23(5):607-623.
  54. Bourdeau I, Lampron A, Costa MH, Tadjine M, Lacroix A. Adrenocorticotropic hormone-independent Cushing’s syndrome. Curr Opin Endocrinol Diabetes Obes. 2007;14(3):219-225.
  55. Lake MG, Krook LS, Cruz SV. Pituitary adenomas: an overview. Am Fam Physician. 2013;88(5):319-327.
  56. Hatipoglu BA. Cushing’s syndrome. J Surg Oncol. 2012;106(5):565-571.
  57. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet. 2006;367(9522):1605-1617.
  58. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clin Epidemiol. 2015;7:281-293.
  59. Eckstein N, Haas B, Hass MD, Pfeifer V. Systemic therapy of Cushing’s syndrome. Orphanet J Rare Dis. 2014;9:122.
  60. Broder MS, Neary MP, Chang E, Cherepanov D, Ludlam WH. Incidence of Cushing’s syndrome and Cushing’s disease in commercially-insured patients <65 years old in the United States. Pituitary. 2014.
  61. Lindholm J, Juul S, Jorgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, Hagen C, Jorgensen J, Kosteljanetz M, Kristensen L, Laurberg P, Schmidt K, Weeke J. Incidence and late prognosis of cushing’s syndrome: a population-based study. J Clin Endocrinol Metab. 2001;86(1):117-123.
  62. Etxabe J, Vazquez JA. Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol (Oxf). 1994;40(4):479-484.
  63. Steffensen C, Bak AM, Rubeck KZ, Jorgensen JO. Epidemiology of Cushing’s syndrome. Neuroendocrinology. 2010;92 Suppl 1:1-5.
  64. Graversen D, Vestergaard P, Stochholm K, Gravholt CH, Jorgensen JO. Mortality in Cushing’s syndrome: a systematic review and meta-analysis. Eur J Intern Med. 2012;23(3):278-282.
  65. Ntali G, Asimakopoulou A, Siamatras T, Komninos J, Vassiliadi D, Tzanela M, Tsagarakis S, Grossman AB, Wass JA, Karavitaki N. Mortality in Cushing’s syndrome: systematic analysis of a large series with prolonged follow-up. Eur J Endocrinol. 2013;169(5):715-723.
  66. Plotz CM, Knowlton AI, Ragan C. The natural history of Cushing’s syndrome. Am J Med. 1952;13(5):597-614.
  67. Clayton RN, Raskauskiene D, Reulen RC, Jones PW. Mortality and morbidity in Cushing’s disease over 50 years in Stoke-on-Trent, UK: audit and meta-analysis of literature. J Clin Endocrinol Metab. 2011;96(3):632-642.
  68. Dekkers OM, Biermasz NR, Pereira AM, Roelfsema F, van Aken MO, Voormolen JH, Romijn JA. Mortality in patients treated for Cushing’s disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab. 2007;92(3):976-981.
  69. Elias PC, Martinez EZ, Barone BF, Mermejo LM, Castro M, Moreira AC. Late-night salivary cortisol has a better performance than urinary free cortisol in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 2014;99(6):2045-2051.
  70. Bruno OD, Juarez-Allen L, Rossi MA, Longobardi V. In what clinical settings should Cushing’s syndrome be suspected? Medicina (B Aires). 2009;69(6):674-680.
  71. Heuser I, Yassouridis A, Holsboer F. The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res. 1994;28(4):341-356.
  72. Alwani RA, Schmit Jongbloed LW, de Jong FH, van der Lely AJ, de Herder WW, Feelders RA. Differentiating between Cushing’s disease and pseudo-Cushing’s syndrome: comparison of four tests. Eur J Endocrinol. 2014;170(4):477-486.
  73. Leal-Cerro A, Martin-Rodriguez JF, Ibanez-Costa A, Madrazo-Atutxa A, Venegas-Moreno E, Leon-Justel A, Garcia-Hernandez N, Luque RM, Castano JP, Cano DA, Soto-Moreno A. Desmopressin test in the diagnosis and follow-up of cyclical Cushing’s disease. Endocrinol Nutr. 2014;61(2):69-76.
  74. Friedman TC, Ghods DE, Shahinian HK, Zachery L, Shayesteh N, Seasholtz S, Zuckerbraun E, Lee ML, McCutcheon IE. High prevalence of normal tests assessing hypercortisolism in subjects with mild and episodic Cushing’s syndrome suggests that the paradigm for diagnosis and exclusion of Cushing’s syndrome requires multiple testing. Horm Metab Res. 2010;42(12):874-881.
  75. Odeniyi IA, Fasanmade OA. Urinary free cortisol in the diagnosis of Cushing’s syndrome: how useful? Niger J Clin Pract. 2013;16(3):269-272.
  76. Doppman JL, Oldfield EH, Nieman LK. Bilateral sampling of the internal jugular vein to distinguish between mechanisms of adrenocorticotropic hormone-dependent Cushing syndrome. Ann Intern Med. 1998;128(1):33-36.
  77. Raff H, Findling JW. A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med. 2003;138(12):980-991.
  78. Nieman LK, Ilias I. Evaluation and treatment of Cushing’s syndrome. Am J Med. 2005;118(12):1340-1346.
  79. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med. 1994;120(10):817-820.
  80. Castinetti F, Morange I, Dufour H, Jaquet P, Conte-Devolx B, Girard N, Brue T. Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing’s syndrome. Eur J Endocrinol. 2007;157(3):271-277.
  81. Kaskarelis IS, Tsatalou EG, Benakis SV, Malagari K, Komninos I, Vassiliadi D, Tsagarakis S, Thalassinos N. Bilateral inferior petrosal sinuses sampling in the routine investigation of Cushing’s syndrome: a comparison with MRI. AJR Am J Roentgenol. 2006;187(2):562-570.
  82. Bonelli FS, Huston J, 3rd, Carpenter PC, Erickson D, Young WF, Jr., Meyer FB. Adrenocorticotropic hormone-dependent Cushing’s syndrome: sensitivity and specificity of inferior petrosal sinus sampling. AJNR Am J Neuroradiol. 2000;21(4):690-696.
  83. Ross NS. Epidemiology of Cushing’s syndrome and subclinical disease. Endocrinol Metab Clin North Am. 1994;23(3):539-546.
  84. Aron DC. The adrenal incidentaloma: disease of modern technology and public health problem. Rev Endocr Metab Disord. 2001;2(3):335-342.
  85. Guaraldi F, Salvatori R. Cushing syndrome: maybe not so uncommon of an endocrine disease. J Am Board Fam Med. 2012;25(2):199-208.
  86. Santos A, Crespo I, Aulinas A, Resmini E, Valassi E, Webb SM. Quality of life in Cushing’s syndrome. Pituitary. 2015;18(2):195-200.
  87. Feelders RA, Pulgar SJ, Kempel A, Pereira AM. The burden of Cushing’s disease: clinical and health-related quality of life aspects. Eur J Endocrinol. 2012;167(3):311-326.
  88. Flitsch J, Spitzner S, Ludecke DK. Emotional disorders in patients with different types of pituitary adenomas and factors affecting the diagnostic process. Exp Clin Endocrinol Diabetes. 2000;108(7):480-485.
  89. Valassi E, Santos A, Yaneva M, Toth M, Strasburger CJ, Chanson P, Wass JA, Chabre O, Pfeifer M, Feelders RA, Tsagarakis S, Trainer PJ, Franz H, Zopf K, Zacharieva S, Lamberts SW, Tabarin A, Webb SM, Group ES. The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur J Endocrinol. 2011;165(3):383-392.
  90. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet. 2015;386(9996):913-927.
  91. Thompson SK, Hayman AV, Ludlam WH, Deveney CW, Loriaux DL, Sheppard BC. Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing’s disease: a 10-year experience. Ann Surg. 2007;245(5):790-794.
  92. Broder MS, Neary MP, Chang E, Cherepanov D, Sun GH, Ludlam WH. Treatment patterns in Cushing’s disease patients in two large United States nationwide databases: application of a novel, graphical methodology. Pituitary. 2014.
  93. Aghi MK. Management of recurrent and refractory Cushing disease. Nat Clin Pract Endocrinol Metab. 2008;4(10):560-568.
  94. Hofmann BM, Hlavac M, Martinez R, Buchfelder M, Muller OA, Fahlbusch R. Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years. J Neurosurg. 2008;108(1):9-18.
  95. Hoybye C, Grenback E, Thoren M, Hulting AL, Lundblad L, von Holst H, Anggard A. Transsphenoidal surgery in Cushing disease: 10 years of experience in 34 consecutive cases. J Neurosurg. 2004;100(4):634-638.
  96. Shimon I, Ram Z, Cohen ZR, Hadani M. Transsphenoidal surgery for Cushing’s disease: endocrinological follow-up monitoring of 82 patients. Neurosurgery. 2002;51(1):57-61; discussion 61-52.
  97. Barker FG, 2nd, Klibanski A, Swearingen B. Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab. 2003;88(10):4709-4719.
  98. Patil CG, Prevedello DM, Lad SP, Vance ML, Thorner MO, Katznelson L, Laws ER, Jr. Late recurrences of Cushing’s disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab. 2008;93(2):358-362.
  99. Barbetta L, Dall’Asta C, Tomei G, Locatelli M, Giovanelli M, Ambrosi B. Assessment of cure and recurrence after pituitary surgery for Cushing’s disease. Acta Neurochir (Wien). 2001;143(5):477-481; discussion 481-472.
  100. Sonino N, Zielezny M, Fava GA, Fallo F, Boscaro M. Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. J Clin Endocrinol Metab. 1996;81(7):2647-2652.
  101. Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stalla GK, Swearingen B, Vance ML, Wass JA, Boscaro M. Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2008;93(7):2454-2462.
  102. Tritos NA, Biller BM, Swearingen B. Management of Cushing disease. Nat Rev Endocrinol. 2011;7(5):279-289.
  103. Petit JH, Biller BM, Yock TI, Swearingen B, Coen JJ, Chapman P, Ancukiewicz M, Bussiere M, Klibanski A, Loeffler JS. Proton stereotactic radiotherapy for persistent adrenocorticotropin-producing adenomas. J Clin Endocrinol Metab. 2008;93(2):393-399.
  104. Vella A, Thompson GB, Grant CS, van Heerden JA, Farley DR, Young WF, Jr. Laparoscopic adrenalectomy for adrenocorticotropin-dependent Cushing’s syndrome. The Journal of clinical endocrinology and metabolism. 2001;86(4):1596-1599.
  105. Assie G, Bahurel H, Coste J, Silvera S, Kujas M, Dugue MA, Karray F, Dousset B, Bertherat J, Legmann P, Bertagna X. Corticotroph tumor progression after adrenalectomy in Cushing’s Disease: A reappraisal of Nelson’s Syndrome. J Clin Endocrinol Metab. 2007;92(1):172-179.
  106. Tritos NA, Biller BM. Cushing’s disease. Handb Clin Neurol. 2014;124:221-234.
  107. Daniel E, Newell-Price J. THERAPY OF ENDOCRINE DISEASE: Steroidogenesis enzyme inhibitors in Cushing’s syndrome. Eur J Endocrinol. 2015.
  108. Molitch ME. Current approaches to the pharmacological management of Cushing’s disease. Mol Cell Endocrinol. 2014.
  109. Castinetti F, Guignat L, Giraud P, Muller M, Kamenicky P, Drui D, Caron P, Luca F, Donadille B, Vantyghem MC, Bihan H, Delemer B, Raverot G, Motte E, Philippon M, Morange I, Conte-Devolx B, Quinquis L, Martinie M, Vezzosi D, Le Bras M, Baudry C, Christin-Maitre S, Goichot B, Chanson P, Young J, Chabre O, Tabarin A, Bertherat J, Brue T. Ketoconazole in Cushing’s disease: is it worth a try? J Clin Endocrinol Metab. 2014;99(5):1623-1630.
  110. Fleseriu M, Petersenn S. Medical therapy for Cushing’s disease: adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers. Pituitary. 2015.
  111. Lau D, Rutledge C, Aghi MK. Cushing’s disease: current medical therapies and molecular insights guiding future therapies. Neurosurg Focus. 2015;38(2):E11.
  112. Castinetti F, Fassnacht M, Johanssen S, Terzolo M, Bouchard P, Chanson P, Do Cao C, Morange I, Pico A, Ouzounian S, Young J, Hahner S, Brue T, Allolio B, Conte-Devolx B. Merits and pitfalls of mifepristone in Cushing’s syndrome. Eur J Endocrinol. 2009;160(6):1003-1010.
  113. van der Pas R, de Herder WW, Hofland LJ, Feelders RA. Recent developments in drug therapy for Cushing’s disease. Drugs. 2013;73(9):907-918.
  114. McKeage K. Pasireotide: a review of its use in Cushing’s disease. Drugs. 2013;73(6):563-574.
  115. Wallia A, Colleran K, Purnell JQ, Gross C, Molitch ME. Improvement in insulin sensitivity during mifepristone treatment of Cushing syndrome: early and late effects. Diabetes Care. 2013;36(9):e147-148.
  116. Bertagna X, Pivonello R, Fleseriu M, Zhang Y, Robinson P, Taylor A, Watson CE, Maldonado M, Hamrahian AH, Boscaro M, Biller BM. LCI699, a potent 11beta-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing’s disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab. 2014;99(4):1375-1383.
  117. Calhoun DA, White WB, Krum H, Guo W, Bermann G, Trapani A, Lefkowitz MP, Menard J. Effects of a novel aldosterone synthase inhibitor for treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-controlled phase 2 trial. Circulation. 2011;124(18):1945-1955.
  118. Fleseriu M, Petersenn S. Medical management of Cushing’s disease: what is the future? Pituitary. 2012;15(3):330-341.
  119. Wang HZ, Tian JB, Yang KH. Efficacy and safety of LCI699 for hypertension: a meta-analysis of randomized controlled trials and systematic review. Eur Rev Med Pharmacol Sci. 2015;19(2):296-304.
  120. Pivonello R, Faggiano A, Di Salle F, Filippella M, Lombardi G, Colao A. Complete remission of Nelson’s syndrome after 1-year treatment with cabergoline. J Endocrinol Invest. 1999;22(11):860-865.
  121. Pivonello R, De Martino MC, Cappabianca P, De Leo M, Faggiano A, Lombardi G, Hofland LJ, Lamberts SW, Colao A. The medical treatment of Cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab. 2009;94(1):223-230.
  122. Godbout A, Manavela M, Danilowicz K, Beauregard H, Bruno OD, Lacroix A. Cabergoline monotherapy in the long-term treatment of Cushing’s disease. Eur J Endocrinol. 2010;163(5):709-716.
  123. Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, Biller BM, Pasireotide BSG. A 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med. 2012;366(10):914-924.
  124. Fukuoka H. New potential targets for treatment of Cushing’s disease: epithelial growth factor receptor and cyclin-dependent kinases. Pituitary. 2015.
  125. Reincke M. Subclinical Cushing’s syndrome. Endocrinol Metab Clin North Am. 2000;29(1):43-56.
  126. Zografos GN, Perysinakis I, Vassilatou E. Subclinical Cushing’s syndrome: current concepts and trends. Hormones (Athens). 2014;13(3):323-337.

Back to Top