Hyperaldosteronism is a condition in which the adrenal gland releases excess aldosterone due to primary or secondary causes.1 The condition is now considered common, affecting more than 1 million people worldwide, but is markedly underdiagnosed.1 Primary hyperaldosteronism occurs when 1 or both of the adrenal glands produce an excess of aldosterone and is a leading cause of hypertension.1 Secondary aldosteronism occurs when aldosterone production increases due to extra-adrenal stimuli, such as irregularity in pituitary or renin-angiotensin-aldosterone (RAA) axis function or as a result of ectopic hormone production.2

Strategies for management of aldosterone hypersecretion vary depending on the inciting factor, degree of severity, and clinical presentation of the specific patient. On one side of the clinical spectrum are asymptomatic patients in whom aldosteronism may only be detected incidentally through abnormal electrolyte levels on routine blood work. On the other side of the spectrum are patients with severe symptoms including hypertension, hypokalemia, nausea, fatigue, headache, edema, hyperactive deep tendon reflexes, paresthesia, and muscle weakness.2

Primary causes of the hormone imbalance may be treated quickly and effectively with invasive intervention by way of surgical removal of the hyperactive gland.3 More complex manifestations and bilateral anomalies that extend beyond the scope of surgical resolution call for long-term pharmaceutical regimens and lifestyle modifications.4


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Etiology of Aldosteronism

Aldosterone is a mineralocorticoid produced in the zona glomerulosa of the adrenal gland and is responsible for sodium and fluid retention.2 Aldosterone acts on mineralocorticoid receptors in the distal tubule of the kidneys to maintain homeostasis of both anatomical fluid volume as well as electrolyte levels.2,6

Pathology within the adrenal glands causing primary aldosteronism include adrenocortical hyperplasia, adrenal adenomas (Conn Syndrome), and adrenocortical carcinomas.3 Hyperplasia is typically bilateral whereas adenomas are typically unilateral.3 Adrenocortical hyperplasia is the most common cause of primary aldosteronism and accounts for nearly two-thirds of reported primary cases.3 Adenomas account for the majority of the remaining one-third while adrenocortical carcinoma is found in only 1% of primary aldosteronism cases.3 Autonomous adrenal production of aldosterone could be caused by independent transcription and utilization of aldosterone synthase, the enzyme responsible for the production of aldosterone in the zona glomerulosa.6 In cases of adrenal hyperplasia, aldosterone-producing cell clusters (APCCs) can be found, unilaterally or bilaterally, creating aldosterone autonomously independent of RAA axis input.6

The true prevalence of primary aldosteronism has only recently been recognized due to inclusion of aldosterone-to-renin ratio (ARR) in serum analysis. Primary aldosteronism is now recognized as the most common cause of secondary hypertension accounting for 5% to 10% of patients with hypertension and 20% of those with resistant hypertension.1 Measurement of ARR allows for recognition of excess aldosterone independent of increased demand from the RAA axis. A ratio of ARR that exceeds 20:1 is considered indicative of renin-independent aldosteronism, suggesting pathology of the adrenal glands.2

In secondary aldosteronism, healthy adrenal glands overproduce aldosterone to compensate for extra-adrenal stimuli, such as an irregularity in pituitary or RAA axis function or ectopic hormone production.2 Renin is normally produced in the kidneys in response to diminished volume supply that leads to production of angiotensin II and, in turn, aldosterone.2 Pathologies that increase renin production in spite of systemic fluid normality include congestive heart failure, nephrotic syndrome, renal artery stenosis, coarctation of the aorta, and renin-secreting tumors.Congestive heart failure and nephrotic syndrome are edematous conditions that result in reduced active fluid volume in circulation, prompting the body to produce more aldosterone in response to perceived fluid reduction.2 Renal artery stenosis and coarctation of the aorta also result in renal hypoperfusion leading to increased renin production and secondary promotion of aldosteronism.2

Aldosteronism is largely considered a condition of sporadic occurrence, with manifestations attributable to genetic background making up only a small minority of all reported cases. There are 4 recognized forms of familial aldosteronism, all of which are largely outnumbered by aldosteronism caused by somatic mutation.2,4

Aldosteronism is uncommon in children and more common in women than men. There is no racial or geographic predisposition to aldosteronism in the United States or worldwide.8 It is understood however that a severe degree of underdiagnosis makes epidemiologic correlations difficult to ascertain.8 The epidemiology of secondary aldosteronism varies based on the underlying condition.

This article originally appeared on Clinical Advisor