Conn Syndrome 

Conn syndrome is characterized by increased aldosterone secretion from the adrenal glands, suppressed plasma renin activity (PRA), hypertension, and hypokalemia. It was first described in 1955 by JW Conn in a patient who, as in the image below, had an aldosterone-producing adenoma (ie, Conn syndrome). (See Etiology and Pathophysiology and Workup.)

Later, many other cases of adrenal hyperplasia with increased aldosterone secretion were described, and now the term primary hyperaldosteronism is used to describe Conn syndrome and other etiologies of primary hypersecretion of aldosterone (eg, adrenal hyperplasia). Currently, primary hyperaldosteronism, especially Conn syndrome, seems to be the most common form of secondary hypertension. (See Etiology and Pathophysiology.)

Classification

Primary hyperaldosteronism can be divided into many subtypes. The most common subtype is Conn syndrome, a unilateral aldosterone-producing adenoma (APA) that is usually small (< 3cm), unilateral, and renin-unresponsive. This means that aldosterone secretion is not affected by changes in posture. Conn syndrome occurs in 50-60% of cases of primary hyperaldosteronism. (See Workup.)

The remaining 40-50% of cases are due to bilateral adrenal hyperplasia, or idiopathic hyperaldosteronism (IHA), in which aldosterone increases in response to postural studies. (Rarely, aldosterone can be secreted by adrenocortical carcinomas and ovarian tumors.)

A rare subtype is renin-responsive adenoma. Morphologically and in response to adrenalectomy it appears as an APA, but it responds to physiologic maneuvers (aldosterone levels increase with standing), as do hyperplastic glands of IHA.

Another rare subtype is primary adrenal hyperplasia, in which a hyperplastic adrenal morphologically resembles that in IHA but mimics the APA response to physiologic maneuvers and unilateral adrenalectomy.

The last rare subtype is glucocorticoid-remediable aldosteronism (GRA), which is autosomal dominant in inheritance and is associated with variable degrees of hyperaldosteronism that are suppressible with exogenous glucocorticoids.

Epidemiology

Prevalence estimates in the United States for primary hyperaldosteronism and, specifically, Conn syndrome are, respectively, 0.05-2% and 0.03-1.2% of the population with hypertension.

Primary hyperaldosteronism is twice as common in women as in men. Peak incidence of the condition occurs in the third to sixth decades of life.

Etiology

Primary hyperaldosteronism is caused by increased aldosterone excretion from the adrenals, which results primarily from 2 major subtypes: (1) unilateral APA, or Conn syndrome (50-60% of cases), and (2) IHA, or bilateral adrenal hyperplasia (40-50% of cases).

Primary hyperaldosteronism can be inherited in an autosomal dominant fashion in patients with GRA, in whom activation of aldosterone secretion is induced by corticotropin and is suppressible with glucocorticoids. The involved gene is on chromosome 8.

Rarely, adrenocortical carcinomas secrete aldosterone. Usually, the tumors are large (>4cm). Aldosterone can be ectopically secreted by adrenal embryologic rest neoplasms within the kidney and ovary.

Pathophysiology

Aldosterone, by inducing renal distal tubular reabsorption of sodium, enhances secretion of potassium and hydrogen ions, causing hypernatremia, hypokalemia, and alkalosis.

The morbidity and mortality associated with primary hyperaldosteronism, especially Conn syndrome, are primarily related to hypokalemia and hypertension.^{[1, 2]} Hypokalemia, especially if severe, causes cardiac arrhythmias, which can be fatal.

Hypertension, especially if left untreated for many years, can lead to many complications, including heart disease (eg, coronary artery disease, congestive heart failure), stroke, and intracerebral hemorrhage (with very high blood pressure).