Cushing's Syndrome Diagnosis and Management

Cushing's Syndrome Diagnosis and Management

• Cushing's syndrome is a potentially life-threatening disorder caused by high levels of cortisol.
• Early diagnosis is crucial to prevent further health problems and reduce mortality.
• It can be difficult to recognize as symptoms are common, such as weight gain and hypertension.
• Diagnosis involves screening tests such as timed measurement of urine, serum or salivary cortisol, before and after dexamethasone administration. Each test has limitations, thus the choice of tests must be tailored to individual patient needs.
• Once diagnosed, surgical removal of the abnormal tumor or tissue is often the optimal treatment.
• Medical treatment or bilateral adrenalectomy is necessary if surgery is not possible or in case of recurrence or metastasis to normalize cortisol levels.
• Clinical features often suggest the syndrome (see Table 1 in the article). These include fatigue, weight gain in specific areas, and skin changes.
• The features may cluster in one diagnosis, so subspecialists should look for features outside their area of expertise.
• The diagnosis is more likely in individuals showing early-onset symptoms of osteoporosis, fractures or hypertension.
• Cushing's syndrome needs to be considered if symptoms occur together within a few months or if signs and symptoms increase over time.
• Important to rule out exogenous steroid use (medications/products) which can cause similar symptoms.
• Screening tests include 24-hour urine free cortisol (UFC) excretion, late-night/bedtime salivary cortisol, and the 1 mg overnight dexamethasone suppression test (DST).
• Cortisol measurement can be via immunoassay (e.g., radioimmunoassay [RIA]) or structurally-based assay (e.g., high performance liquid chromatography or mass spectrometry [MS/MS]). The latter are more specific.
• Mild cases of the syndrome may be detected with bedtime salivary cortisol when other tests are normal.
• Mildly abnormal results may be found in other conditions, leading to misdiagnosis if not carefully considered.
• The causes of Cushing's syndrome are ACTH excess (from pituitary or non-pituitary tumors) and ACTH-independent primary adrenal overproduction. This is determined via ACTH measurements.
• Treatment in severe cases may involve combination therapy for quicker symptom improvement.
• Surgical removal of an abnormal tumor is the preferred approach.
• Alternative treatments (e.g., steroidogenesis inhibitors or glucocorticoid antagonists) aim to block cortisol action or synthesis.