Description

• Clinical syndrome of excess aldosterone production, independent of renin secretion, and nonsuppressible by sodium (Na⁺) loading
• Classically manifested by hypertension (HTN) and hypokalemia (about half of the patients are normokalemic)
• Systems affected: cardiovascular, endocrine, renal
• Synonym(s): hyperaldosteronism, Conn syndrome

Epidemiology

• Since the initial case by Dr. Jerome Conn in 1954, the epidemiology has changed significantly.
• Previously considered a rare cause of HTN
• Currently considered the most common cause of secondary HTN

Prevalence

• Affects 5–10% of patients with HTN
• Up to 10–30% in certain groups: moderate/severe HTN, resistant HTN, HTN plus hypokalemia, HTN plus adrenal incidentaloma, HTN plus sleep apnea
• Commonly diagnosed in the 3rd to 5th decade of life

Etiology and Pathophysiology

• Bilateral idiopathic hyperplasia (BIH): 60%
• Aldosterone-producing adenoma (APA): 30–40%
• Unilateral adrenal hyperplasia, adrenocortical carcinoma (ACC), and familial hyperaldosteronism (FH): rare <1%
• Aldosterone excess results in:
  • Renin suppression via feedback mechanism
  • HTN due to volume expansion and Na⁺ retention
  • Low potassium (K+) due to increased renal losses
  • Metabolic alkalosis due to renal hydrogen losses

Genetics

• FH syndromes
  • Type I: autosomal dominant, ACTH-induced aldosterone secretion, glucocorticoid-remediable aldosteronism (GRA)
  • Type II: autosomal dominant, familial APA or BIH type, not suppressible by glucocorticoids
  • Type III: germline mutation in the K+ channel gene KCNJ5, increased aldosterone production, not suppressible by glucocorticoids; concurrence with Cushing syndrome has been reported.
• Sporadic cases
  • Somatic KCNJ5 mutations (female predominance) found in 10–68% of sporadic APAs
  • Somatic ATP1A1 and ATP2B3 mutations (male predominance) and CACNA1D mutations are also found in sporadic APA.
• APA may rarely be seen in multiple endocrine neoplasia type 1 (MEN-1).

Commonly Associated Conditions

Aldosterone excess may independently increase the risk of coronary artery disease, stroke, left ventricular hypertrophy, atrial fibrillation, heart failure, diabetes mellitus type 2, obstructive sleep apnea, renal disease, and bone loss.

Pregnancy Considerations

• Increases in aldosterone production and plasma renin activity (PRA) are physiologic during pregnancy; confirmation tests are not recommended.
• The diagnosis of PA during pregnancy relies on a repeatedly suppressed plasma renin level.
• Avoid spironolactone and ACE inhibitors.