Adrenocortical neoplasm, either an aldosterone-producing adenoma (the most common cause) or, rarely, an adrenocortical carcinoma. In approximately 35% of cases, primary hyperaldosteronism is caused by a solitary aldosterone-secreting adenoma, a condition referred to as Conn syndrome. Somatic mutations of KCNJ5 (see earlier) are also present in a subset of aldosteronesecreting adenomas.
Rarely, familial hyperaldosteronism may result from a genetic defect that leads to overactivity of the aldosterone synthase gene, CYP11B2.
Na is reabsorbed from tubular urine back into bloodstream
K moves from bloodstream into tubule and is excreted
Fig.20.39Themajorcausesofprimaryhyperaldosteronismanditsprincipaleffectsonthekidney.
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In secondary hyperaldosteronism, aldosterone release occurs in response to activation of the renin-angiotensin system. This condition is characterized by increased levels of plasma renin and is encountered in association with the following:
Decreased renal perfusion (arteriolar nephrosclerosis, renal artery stenosis)
Arterial hypovolemia and edema (congestive heart failure, cirrhosis, nephrotic syndrome)
MORPHOLOGYAldosterone-producingadenomasarealmostalwayssolitary,small(<2cmindiameter),well-circumscribedlesions.Theyarebrightyellowoncutsectionand,surprisingly,arecomposedoflipid-ladencorticalcellsmorecloselyresemblingfasciculatacellsthanglomerulosacells(thenormalsourceofaldosterone).Ingeneral,thecellstendtobeuniforminsizeandshape;occasionallythereissomenuclearandcellularpleomorphism.Acharacteristicfeatureofaldosterone-producingadenomasisthepresenceofeosinophilic,laminatedcytoplasmicinclusions,knownasspironolactone bodies. Thesetypicallyarefoundaftertreatmentwiththeanti-hypertensiveagentspironolactone,whichisthedrugofchoiceinprimaryhyperaldosteronism.IncontrastwithcorticaladenomasassociatedwithCushingsyndrome,thoseassociatedwithhyperaldosteronismdonotusuallysuppressACTHsecretion.Therefore,theadjacentadrenalcortexandthatofthecontralateralglandarenotatrophic.Bilateralidiopathichyperplasiaismarkedbydiffuseorfocalhyperplasiaofcellsresemblingthoseofthenormalzonaglomerulosa.
The most important clinical consequence of hyperaldosteronism is hypertension. With an estimated prevalence rate of 5% to 10% among unselected hypertensive patients, primary hyperaldosteronism may be the most common cause of secondary hypertension (i.e., hypertension secondary to an identifiable cause). The long-term effects of hyperaldosteronism-induced hypertension are cardiovascular compromise (e.g., left ventricular hypertrophy and reduced diastolic volumes) and an increase in the prevalence of adverse events such as stroke and myocardial infarction. Hypokalemia results from renal potassium wasting and, when present, can cause a variety of neuromuscular manifestations, including weakness, paresthesias, visual disturbances, and occasionally frank tetany. Hypokalemia was considered a mandatory feature of primary hyperaldosteronism, but almost 50% of normokalemic patients are now being diagnosed largely due to early detection.