• Clinical science

Primary hyperaldosteronism (Conn syndrome)

Summary

Primary hyperaldosteronism, sometimes referred to as Conn syndrome, is an excess of aldosterone caused by autonomous overproduction, usually at the adrenal cortex. It is typically due to adrenal hyperplasia or adrenal adenoma. Primary hyperaldosteronism is one of the common causes of secondary hypertension. High systemic aldosterone levels result in increased sodium reabsorption and potassium secretion in the collecting ducts of the kidney, which leads to the retention of water along with sodium, as well as hypokalemia. Patients are often asymptomatic and found to have hypertension at routine health checks. It will often emerge that the patient's hypertension is resistant to pharmaceutical therapy, and they may have other signs suggestive of secondary hypertension, such as an age of onset below 30 years or above 55 years. If symptoms are present, they typically include headache, muscle weakness, and polyuria. Initial labs in primary hyperaldosteronism classically show a hypertensive patient with hypokalemia and metabolic alkalosis, and high plasma aldosterone concentration (PAC) and low plasma renin activity (PRA) (PAC/PRA ratio increased). Following biochemical confirmation of primary hyperaldosteronism with oral or intravenous sodium loading tests, imaging modalities such as CT and adrenal venous sampling are used to locate the source of autonomous aldosterone secretion. Treatment of primary hyperaldosteronism consists of surgical resection of adrenal adenoma or pharmaceutical therapy with aldosterone antagonists (e.g., spironolactone, eplerenone) in cases of bilateral adrenal hyperplasia.

Epidemiology

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[2][3][4]

Pathophysiology

Autonomous aldosterone secretion and hypertension

Hypokalemia and metabolic alkalosis

  • Increased sodium reabsorption leads to hypokalemia: ↑ Na+ reabsorption → electronegative lumen → K+ follows the electrical gradient through open K+ channels↑ K+ secretionhypokalemia
  • Hypokalemia causes metabolic alkalosis via two mechanisms (both of which decrease extracellular H+, thereby increasing extracellular pH):
    • Efflux of K+ from intracellular to extracellular space in exchange for H+
    • ↑ H+ secretion in the kidney in order to enable ↑ K+ reabsorption
  • Diabetes insipidus: hypokalemia → desensitization of renal tubules to antidiuretic hormone (ADH) → increased water excretion (polyuria) and excessive thirst (polydipsia)

References:[4]

Clinical features

The classic clinical picture of primary hyperaldosteronism: a young patient with hypokalemia and drug-resistant hypertension!

References:[3][5][6][7][8]

Diagnostics

Screening tests

Confirmatory tests: several alternatives

Subtype identification: imaging

  • Adrenal CT: initial test to identify the cause of primary hyperaldosteronism already confirmed biochemically
  • Adrenal venous sampling
    • Criterion standard for differentiating between unilateral adenoma and bilateral hyperplasia
    • Administered if surgical treatment of primary hyperaldosteronism is desired
    • Procedure: PAC measured via catheter in blood from right adrenal vein, left adrenal vein, and inferior vena cava
      • Unilateral disease → four-fold increase in PAC compared with the contralateral side
      • Bilateral hyperplasia → small or no difference in PAC between the two sides (i.e. PAC is bilaterally elevated)

The PAC/PRA ratio is used to detect primary hyperaldosteronism.

References:[9][1][2][3][5][10][11]

Differential diagnoses

References:[12][442;323]

The differential diagnoses listed here are not exhaustive.

Treatment

Bilateral adrenal hyperplasia

Unilateral autonomous aldosterone secretion (adenoma, unilateral hyperplasia, carcinoma)

References:[1][2][13]