normal gland, the diurnal pattern of cortisol secretion is lost. Ectopic ACTH syndrome most often is caused by malignant tumors (155). About one-half of these tumors are small-cell carcinomas of the lung (156). Other tumors include bronchial and thymic carcinomas, carcinoid tumors of the pancreas, and medullary carcinoma of the thyroid.
Ectopic corticotropin-releasing hormone (CRH) tumors are rare and include such tumors as bronchial carcinoids, medullary thyroid carcinoma, and metastatic prostatic carcinoma (156). The presence of an ectopic CRH-secreting tumor should be suspected in patients whose dynamic testing suggests pituitary ACTH-dependent disease but who have rapid disease progression and very high plasma ACTH levels.
The most common cause of ACTH-independent Cushing syndrome is exogenous or iatrogenic (i.e., superphysiologic therapy with corticosteroids) or factitious (self-induced). Corticosteroids are used in pharmacologic quantities to treat a variety of diseases with an inﬂammatory component. Over time, such therapy will result in Cushing syndrome. When corticosteroids are taken by the patient but not prescribed by a physician, the diagnosis may be especially challenging. The diagnostic workup for Cushing syndrome focuses on the ability to suppress autonomous cortisol secretion and whether ACTH is elevated or suppressed. According to the 2008 Endocrine Society’s clinical practice guidelines for the diagnosis of Cushing syndrome, the initial use of one test with high diagnostic accuracy (24-hour urine free cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-hour dexamethasone suppression test) is recommended. The 24-hour urine-free cortisol (UFC) should be used to diagnose Cushing syndrome in pregnant women and in patients with epilepsy, whereas the 1-mg overnight dexamethasone suppression test, rather than UFC, should be used for initial testing for Cushing syndrome in patients with severe renal failure and adrenal incidentaloma. The 2-mg 48-hour dexamethasone suppression test is the optimal test in conditions that are associated with overactivation of the hypothalamic–pituitary–adrenal (HPA) axis: depression, morbid obesity, alcoholism, and diabetes mellitus.
Patients with an abnormal result should see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone CRH test. These guidelines are summarized in (Fig. 31.7) (154).
Evaluation of suspected Cushing Syndrome Hirsutism, moon facies, striae, dorsocervical/supraclavicular fat pads,proximal muscle weakness, with no exogenous glucocorticoid use Endocrine consult exclude physiologic causes of hypercortisolism re-perform 1 or 2 of studies above,additional testing as needed Overnight dexamethasone suppression 1 mg Late night salivary cortisol (≥≥2 tests) 24 hr Urinary free cortisol