Fig. 20.38 ). Cortisol also has diverse effects on calcium metabolism that lead to resorption of bone, which results in the development of osteoporosis, with consequent increased susceptibility to fractures. Because glucocorticoids suppress the immune response, patients with Cushing syndrome also are at increased risk for a variety of infections. Additional manifestations include hirsutism and menstrual abnormalities, as well as a number of psychiatric symptoms including mood swings, depression, and frank psychosis. Extraadrenal Cushing syndrome caused by pituitary or ectopic ACTH secretion usually is associated with increased skin pigmentation secondary to melanocyte-stimulating activity in the ACTH precursor molecule.
Fig.20.37Adrenocorticaladenoma.(A)Theadenomaisdistinguishedfromnodularhyperplasiabyitssolitary,circumscribednature.Thefunctionalstatusofanadrenocorticaladenomacannotbepredictedfromitsgrossormicroscopicappearance.(B)Histologicfeaturesofanadrenalcorticaladenoma.Theneoplasticcellsarevacuolatedbecauseofthepresenceofintracytoplasmiclipid.Thereismildnuclearpleomorphism.Mitoticactivityandnecrosisarenotseen.
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Fig.20.38ApatientwithCushingsyndrome.Characteristicfeaturesincludecentralobesity,“moonfacies,”andabdominalstriae.(Reproduced with permis-sion from Lloyd RV, et al: Atlasofnontumorpathology:endocrinediseases.Washington, DC, American Registry of Pathology, 2002.)
In pituitary and ectopic Cushing syndrome, ACTH levels are elevated and the urine is characterized by high levels of excreted corticosteroids. In contrast, ACTH levels are low in Cushing syndrome secondary to adrenal tumors.
Themostcommoncauseofhypercortisolismisexogenousadministrationofsteroids.
EndogenoushypercortisolismmostoftenissecondarytoanACTH-producingpituitarymicroadenoma(Cushing disease), followedbyprimaryadrenalneoplasms(ACTH-independent hypercortisolism)andparaneoplasticACTHproductionbytumors(e.g.,small-celllungcancer).
Themorphologicfeaturesintheadrenalincludebilateralcorticalatrophy(inexogenoussteroid-induceddisease),bilateraldiffuseornodularhyperplasia(mostcommonfindinginendogenousCushingsyndrome),oranadrenocorticalneoplasm.
Hyperaldosteronism is the generic term for a group of closely related conditions characterized by chronic excess aldosterone secretion. Hyperaldosteronism may be primary, or it may be secondary to an extraadrenal cause.
Primary hyperaldosteronism refers to autonomous overproduction of aldosterone with resultant suppression of the renin-angiotensin system and decreased plasma renin activity. The causes of primary hyperaldosteronism are as follows (
Fig. 20.39
Bilateral idiopathic hyperaldosteronism, characterized by bilateral nodular hyperplasia of the adrenal glands. This is the most common underlying cause of primary hyperaldosteronism, accounting for about 60% of cases. The pathogenesis of idiopathic hyperaldosteronism is unclear, although a subset harbors germ line mutations in the KCNJ5 gene, which encodes a potassium channel protein that is expressed in the adrenal gland.