Hypothalamic, pituitary, and adrenal cortical relationships Hypothalamic, pituitary, and adrenal cortical relationships. Solid arrows indicate stimulation; dashed arrows, inhibition. Normal: Corticotropin-releasing hormone (CRH) elaborated by the median eminence of the hypothalamus stimulates secretion of adrenocorticotropic hormone (ACTH) by the anterior pituitary (AP). ACTH triggers the synthesis and release of cortisol, the principal glucocorticoid of the adrenal cortex. A rising level of cortisol inhibits the stimulatory action of CRH on ACTH release (or cortisol may inhibit CRH release), completing a negative feedback loop. Addison disease: In primary destructive disease of the adrenal cortex, the level of plasma cortisol is very low, and the effect of CRH on the anterior pituitary proceeds without inhibition, causing a marked increase in the secretion of ACTH. High levels of ACTH produce characteristic skin pigmentary changes. Cushing disease: The primary lesion may be at the level of the pituitary or hypothalamus. In either case, production of ACTH and cortisol is excessive. The former causes bilateral adrenal hyperplasia and the latter causes clinical manifestations of hypercortisolism. Cells of the anterior pituitary are relatively resistant to the high levels of circulating cortisol. Ectopic ACTH: In this syndrome, ACTH or an ACTH-like peptide is elaborated by a tumor such as carcinoma of the lung. The adrenals are stimulated, circulating cortisol is increased, and pituitary ACTH secretion is inhibited. Ectopic CRH: In this rare syndrome, CRH is elaborated by a tumor such as a bronchial carcinoid. The pituitary is stimulated, and there is elaboration of excess ACTH. The adrenals are stimulated, and circulating cortisol is increased. The hypercortisolism causes diminished hypothalamic CRH production; however, the negative feedback on the pituitary production of ACTH is overcome by the ectopic CRH. Adrenal adenoma or carcinoma: An adenoma or carcinoma of the adrenal cortex may produce cortisol autonomously. When the rate of production exceeds physiologic quantities, Cushing syndrome results; the effect of CRH on the anterior pituitary is inhibited by the high levels of circulating cortisol, with resultant diminished ACTH secretion and atrophy of normal adrenal tissue. Iatrogenic Cushing syndrome: Exogenous corticosteroid administration in excess of physiologic quantities of cortisol leads directly to peripheral manifestations of hypercortisolism and inhibits the effect of CRH on the anterior pituitary, with resultant diminished ACTH secretion, diminished cortisol production, and atrophy of normal adrenal tissue. (Redrawn and modified, with permission, from Burns TW, Carlson HE. Endocrinology. In: Sodeman WA et al, eds. Pathologic Physiology: Mechanisms of Disease. Saunders, 1985.) Source: Disorders of the Adrenal Cortex, Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e Citation: Hammer GD, McPhee SJ. Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e; 2013 Available at: http://accesspharmacy.mhmedical.com/DownloadImage.aspx?image=/data/books/961/ham007_fig_21-12.png&sec=53633542&BookID=961&ChapterSecID=53555702&imagename= Accessed: November 09, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved