Clinical Manifestation

The signs and symptoms of Cushing's syndrome may be subtle and nonspecific. These clinical manifestations vary depending on the severity and duration of hypercortisolism. Cushing's syndrome

Figure 11-1. Hypothalamus-pituitary-adrenal axis. ACTH = adreno-corticotropic hormone; CRH = corticotropin-releasing hormone.


Exogenous: iatrogenic (the most common cause)


ACTH dependent

Pituitary adenoma, Cushing's syndrome (70%) Ectopic Cushing's syndrome (15%) Bronchial carcinoid (25-49%) Occult (12-16%)

Small cell carcinoma of the lung (10%) Pancreatic islet cell tumors (4-16%) Medullary carcinoma of the thyroid gland (8%) Thymic carcinoid (5-16%) Pheochromocytoma (3%) ACTH independent

Adrenal neoplasms (15%) Nodular adrenal hyperplasia (rare) Pseudo-Cushing's syndrome Alcohol Depression

Others: stress, pregnancy, chronic renal failure, and HIV infection

ACTH = adrenocorticotropic hormone; HIV = human immunodeficiency virus.

may be unrecognized when patients are being treated in rheumatology, psychiatry, and orthopedic clinics. Progressive central weight gain (truncal obesity) is the most universal symptom of patients with Cushing's syndrome. Certain features, such as proximal muscle weakness and purple striae wider than 1 cm, are reliable clues to the diagnosis (Figure 11—2).16,17 Particular attention should be paid to worsening of signs or symptoms over time and findings atypical for age, such as thinning skin in young men or osteoporosis in children. The hallmark of Cushing's syndrome in a child is growth failure, and timely diagnosis is important to ensure normal growth and puberty.218-20 Certain clinical and biochemical features may suggest a specific cause of Cushing's syndrome (Table 11—2).8,10,21-24

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