Pathophysiologic Mechanisms of Familial or Sporadic Generalized Glucocorticoid Resistance (Chrousos) Syndrome. In this syndrome, hypothalamic corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) and pituitary adrenocorticotropic hormone (ACTH) are hypersecreted to compensate for the target tissue sensitivity defect, because of decreased glucocorticoid negative feedback. In response, the adrenal cortices hypertrophy and hypersecrete cortisol, adrenal androgens and steroid precursors, such as deoxy-corticosterone (DOC) and corticosterone (B) with mineralocorticod activity. The increased adrenal androgens may cause acne, hirsutism, male pattern baldness, oligo-amenorrhea and hypofertility in women and precocious puberty and ambiguous genitalia in children. The increased cortisol, DOC and B can cause hypertension with or without concurrent hypokalemic alkalosis. The increased hypothalamic CRH and AVP may cause anxiety and/or depression. The increased levels of ACTH may stimulate growth of adrenal rests in the testes of male patients causing oligospermia and infertility. (Modified from Chrousos GP, Detera-Wadleigh S, Karl M: Syndromes of Glucocorticoid Resistance. Ann Int Med 1993, 119:1113-1124).