Whom Should We Screen for Cushing Syndrome? The Endocrine Society Practice Guideline Recommendations 2008 Revisited

Abstract

Background Cushing’s syndrome (CS) is a rare and serious disease with high mortality. Patients are often diagnosed late in the course of the disease. Whether defined patient populations should be screened outside the at risk populations defined in current guidelines remains a topic of discussion. Patients and methods As part of the prospective German Cushing’s registry, we studied 377 patients with suspected CS. The chief complaint for CS referral was documented. Using urinary free cortisol, late-night salivary cortisol, and the 1 mg dexamethasone suppression test as well as long-term clinical observation, CS was confirmed in 93 patients, and ruled out for the remaining 284. Results Patients were referred for 18 key symptoms, of which five were more common in patients with CS than in those where CS was ruled out: Osteoporosis (8% vs. 2%, p = 0.02), adrenal incidentaloma (17% vs. 8%, p = 0.01), metabolic syndrome (11% vs. 4%, p = 0.02), myopathy (10% vs. 2%, p <0.001) and presence of multiple symptoms (16% vs. 1%, p < 0.001). Obesity was more common in patients where CS was ruled out (30% vs. 4%, p <0.001), but recent weight gain was prominent in those with CS. 68 of 93 patients with CS (73%) had typical chief complaints, as did 106 of 284 of patients with rule-out CS status (37%) according to the Endocrine Society practice guideline 2008. Conclusions The 2008 Endocrine Society Practice guideline for screening and diagnosis of CS defined at-risk populations that should undergo testing. These recommendations are still valid in 2022.

Localization diagnosis of adrenocorticotrophic hormone-dependent Cushing’s syndrome: two case reports and literature review

“…Some authors investigated 18 key symptoms of CS in CS patients and non-CS patients, and 5 of them were more common in CS patients than those excluding CS: osteoporosis incompatible with age, adrenal incidentaloma, metabolic syndrome, myopathy, and multiple symptoms such as hypertension, diabetes, and sleep disorders. Obesity was more common in patients excluding CS, while recent significant weight gain was more common in patients with CS (34). The female patient of case 1 complained of irregular menstruation, short-term weight gain, and purple striae, while the young female patient of case 2 presented with facial plethora, acne, and new-onset refractory hypertension.…”

A unique gene expression signature in visceral adipose tissue identifies a high blood pressure group in patients with Cushing’s syndrome

“…All patients with adrenal CS had typical signs and symptoms at the time of diagnosis. Diagnosis and subtype differentiation were based on the criteria recommended by current clinical practice guidelines [1, 25], following standard operational procedures as reported previously [18, 26]. NFAT was confirmed by at least one normal biochemical test for endogenous hypercortisolism and the absence of typical hypercortisolism-associated signs and symptoms.…”

The promising role of risk scoring system for Cushing syndrome: Time to reconsider current screening recommendations

“…There are several well-established characteristic phenotypes associated with chronic hypercortisolism such as weight gain, menstrual irregularities, hirsutism, muscle weakness, bruisability, skin atrophy, and buffalo hump; however, the independent contribution of each factor is not well understood or defined (60). In addition, comorbidities including hypertension, hypercholesterolemia, T2D, and osteoporosis are likely to be present in patients with hypercortisolism, but systematic screening recommendation for CS is questioned (9,(61)(62)(63)(64). The combination of these clinical data into tools to estimate the risk and, therefore, to screen for CS, is still in its infancy (15).…”

“…The Endocrine Society’s Clinical Practice Guideline for the diagnosis of CS recommends that exogenous glucocorticoids intake should be rule out before performing screening tests ( 1 , 9 ). It also states that hypercortisolism should be tested in patients in whom a diagnosis is most likely with signs and symptoms that include weight gain, abnormal glucose tolerance, and hypertension ( 1 , 9 , 10 ). Global prevalence of type 2 diabetes (T2D) and obesity is becoming more common, and these, in turn, are commonly associated with mild increased cortisol levels ( 11 , 12 ).…”

“…Moreover, other conditions with secondarily activated hypothalamic–pituitary–adrenal such as depression, alcohol dependence, and glucocorticoid resistance offer even more difficulties in discriminating CS ( 1 , 13 ). Even in highly specialized center, half of the patients submitted for screening of CS did not belong to the recommended groups for screening ( 9 ). As the lifetime experience to diagnose CS for a physician is very low ( 14 , 15 ), we can only speculate that the screening tests for hypercortisolism might be unnecessary used, leading to false-positive results.…”