TAILIEUCHUNG - Chapter 096. Paraneoplastic Syndromes: Endocrinologic/Hematologic (Part 5)

Rarely, corticotropin-releasing hormone (CRH) is produced by pancreatic islet tumors, SCLC, medullary thyroid cancer, carcinoids, or prostate cancer. When levels are high enough, CRH can cause pituitary corticotrope hyperplasia and Cushing's syndrome. Tumors that produce CRH sometimes also produce ACTH, raising the possibility of a paracrine mechanism for ACTH production. A distinct mechanism for ACTH-independent Cushing's syndrome involves ectopic expression of various G protein–coupled receptors in the adrenal nodules. Ectopic expression of the gastric inhibitory peptide (GIP) receptor is the bestcharacterized example of this mechanism. In this case, meals induce GIP secretion, which inappropriately stimulates adrenal growth and glucocorticoid production | Chapter 096. Paraneoplastic Syndromes Endocrinologic Hematologic Part 5 Rarely corticotropin-releasing hormone CRH is produced by pancreatic islet tumors SCLC medullary thyroid cancer carcinoids or prostate cancer. When levels are high enough CRH can cause pituitary corticotrope hyperplasia and Cushing s syndrome. Tumors that produce CRH sometimes also produce ACTH raising the possibility of a paracrine mechanism for ACTH production. A distinct mechanism for ACTH-independent Cushing s syndrome involves ectopic expression of various G protein-coupled receptors in the adrenal nodules. Ectopic expression of the gastric inhibitory peptide GIP receptor is the best-characterized example of this mechanism. In this case meals induce GIP secretion which inappropriately stimulates adrenal growth and glucocorticoid production. Clinical Manifestations The clinical features of hypercortisolemia are detected in only a small fraction of patients with documented ectopic ACTH production. Patients with ectopic ACTH syndrome generally exhibit less marked weight gain and centripetal fat redistribution probably because the exposure to excess glucocorticoids is relatively short and because cachexia reduces the propensity for weight gain and fat deposition. The ectopic ACTH syndrome is associated with several clinical features that distinguish it from other causes of Cushing s syndrome . pituitary adenomas adrenal adenomas iatrogenic glucocorticoid excess . The metabolic manifestations of ectopic ACTH syndrome are dominated by fluid retention and hypertension hypokalemia metabolic alkalosis glucose intolerance and often steroid psychosis. The very high ACTH levels often cause increased pigmentation and melanotrope-stimulating hormone MSH activity derived from the POMC precursor peptide is also increased. The extraordinarily high glucocorticoid levels in patients with ectopic sources of ACTH can lead to marked skin fragility and easy bruising. In addition the high cortisol levels often

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