Primary Hyperaldosteronism

Hyperaldosteronism is the generic term for a small group of closely related, uncommon syndromes, all characterized by chronic excess aldosterone secretion. Excessive levels of

aldosterone cause sodium retention and potassium excretion, with resultant hypertension and hypokalemia. Hyperaldosteronism may be primary, or it may be a secondary event

resulting from an extra-adrenal cause.

Primary hyperaldosteronism indicates an autonomous overproduction of aldosterone, with resultant suppression of the renin-angiotensin system and decreased plasma renin activity.

Primary hyperaldosteronism is caused by one of three mechanisms[115] ( Fig. 24-44 ):

• Adrenocortical neoplasm, either an aldosterone-producing adrenocortical adenoma (the most common cause) or, rarely, an adrenocortical carcinoma. In approximately 80% of

cases, primary hyperaldosteronism is caused by a solitary aldosterone-secreting adenoma, a condition referred to as Conn syndrome. This syndrome occurs most frequently in

adult middle life and is more common in women than in men (2:1). Multiple adenomas may be present in an occasional patient.

• Primary adrenocortical hyperplasia (idiopathic hyperaldosteronism), characterized by bilateral nodular hyperplasia of the adrenal glands, highly reminiscent of those found in

the nodular hyperplasia of Cushing syndrome. The genetic basis of idiopathic hyperaldosteronism is not clear, although it is possibly caused by an overactivity of the aldosterone

synthase gene, CYP11B2. [116]

• Glucocorticoid-remediable hyperaldosteronism is an uncommon cause of primary hyperaldosteronism that is familial and genetic. In some families, it is caused by a chimeric

gene resulting from fusion between CYP11B1 (the 11b-hydroxylase gene) and CYP11B2 (the aldosterone synthase gene).[117] This leads to a sustained production of hybrid

steroids in addition to both cortisol and aldosterone. The activation of aldosterone secretion is under the influence of ACTH and hence is suppressible by exogenous

administration of dexamethasone.

In secondary hyperaldosteronism, in contrast, aldosterone release occurs in response to activation of the renin-angiotensin system ( Chapter 4 ). It is characterized by increased levels of

plasma renin and is encountered in conditions such as the following:

• Decreased renal perfusion (arteriolar nephrosclerosis, renal artery stenosis)

• Arterial hypovolemia and edema (congestive heart failure, cirrhosis, nephrotic syndrome)

• Pregnancy (due to estrogen-induced increases in plasma renin substrate).

Morphology.

Aldosterone-producing adenomasare almost always solitary, small (<2 cm in diameter), well-circumscribed lesions, more often found on the left than on the right. They tend to occur

in the thirties and forties, and in women more often than in men. These lesions are often buried within the gland and do not produce visible enlargement, a point to be remembered in

interpreting sonographic or scanning images. They are bright yellow on cut section ( Fig. 24-45 ) and, surprisingly, are composed of lipid-laden cortical cells that more closely resemble

fasciculata cells than glomerulosa cells (the normal source of aldosterone). In general, the cells tend to be uniform in size and shape and resemble mature cortical cells; occasionally,

there is some nuclear and cellular pleomorphism but no evidence of anaplasia ( Fig. 24-46 ). A characteristic feature of aldesterone-producing adenomas is the presence of eosinophilic,

laminated cytoplasmic inclusions, known as spironolactone bodies, found after treatment with the anti-hypertensive drug spironolactone. In contrast to cortical adenomas associated

with Cushing syndrome, those associated with hyperaldosteronism do not usually suppress ACTH secretion. Therefore, the adjacent adrenal cortex and that of the contralateral gland are

not atrophic.

Bilateral idiopathic hyperplasia( Fig. 24-47 ) is marked by diffuse and focal hyperplasia of cells resembling those of the normal zona glomerulosa. The hyperplasia is often wedgeshaped,

extending from the periphery toward the center of the gland. Bilateral enlargement can be subtle in idiopathic hyperplasia, and as a rule, an adrenocortical adenoma should be

carefully excluded as the cause for hyperaldosteronism.

Clinical Course.

The clinical manifestations of primary hyperaldosteronism are hypertension and hypokalemia. Serum renin, as was mentioned previously, is low. Hypokalemia results from renal

potassium wasting and can cause a variety of neuromuscular manifestations, including weakness, paresthesias, visual disturbances, and occasionally frank tetany. Sodium retention

increases the total body sodium and

Figure 24-44The major causes of primary hyperaldosteronism and its principal effects on the kidney.

Figure 24-45Adrenal cortical adenoma. The adenoma is distinguished from nodular hyperplasia by its solitary, circumscribed nature. The functional status of an adrenal cortical

adenoma cannot be predicted from its gross or microscopic appearance.

Figure 24-46Histologic features of an adrenal cortical adenoma. The neoplastic cells are vacuolated because of the presence of intracytoplasmic lipid. There is mild nuclear

pleomorphism. Mitotic activity and necrosis are not seen.

Figure 24-47Nodular hyperplasia of the adrenal contrasted with normal adrenal gland. In cross-section, the adrenal cortex is yellow, thickened, and multinodular, owing to hypertrophy

and hyperplasia of the lipid-rich zonae fasciculata and reticularis.

Figure 24-48Consequences of C-21 hydroxylase deficiency. 21-Hydroxylase deficiency impairs the synthesis of both cortisol and aldosterone. The resultant decrease in feedback

inhibition (dashed line) causes increased secretion of adrenocorticotropic hormone, resulting ultimately in adrenal hyperplasia and increased synthesis of testosterone. The sites of action

of 11-, 17-, and 21-hydroxylase are shown by the numbers in circles.

TABLE 24-10-- Adrenocortical Insufficiency

Date: 2016-04-22; view: 807