Makindo Medical Notes

Aldosterone induces sodium and water retention, but this is followed within a few days by a spontaneous diuresis called aldosterone escape. This process returns excretion to the level of intake and partially lowers the extracellular fluid volume toward normal, thus avoiding any clinically significant edema.

About

• Excess production of aldosterone may cause up to 5% of cases of hypertension (HTN).

Aetiology

• High levels of aldosterone suppress renin production, leading to sodium retention and increased excretion of potassium (K⁺) and hydrogen (H⁺) ions.
• The main clinical clues are hypertension, hypokalemia, and metabolic alkalosis.

Causes of Primary Hyperaldosteronism

Clinical Features

• Hypertension, often resistant to usual treatments.
• Headaches and generalized weakness.
• Muscle weakness, myopathy, and cramps due to hypokalemia.

Indications for Screening

• Hypertension with hypokalemia (not diuretic-induced).
• Resistant hypertension (uncontrolled on three antihypertensive medications).
• Hypertension with an adrenal incidentaloma.
• Severe hypertension (systolic BP >160 mmHg, diastolic BP >100 mmHg).

Investigations (Test Off Diuretics, ACE Inhibitors, and ARBs)

An aldosterone (pmol/L) to renin (mIU/L) ratio greater than 30, where the aldosterone level is greater than 300 pmol/L, suggests primary aldosteronism (99% sensitivity, 79% specificity).

• Electrolyte Analysis:
  • Mild hypernatremia, hypokalemia, hypomagnesemia.
  • Metabolic alkalosis due to hydrogen ion excretion.
  • Note: More than 50% of patients may be normokalemic.
• Plasma Renin and Aldosterone Levels:
  • Measure seated, resting, mid-morning plasma renin activity and aldosterone concentration.
  • Correct hypokalemia before testing.
  • Use medications like doxazosin to control blood pressure without affecting the renin-angiotensin system.
  • High aldosterone levels (normal up to 630 pmol/L) with low or undetectable plasma renin suggest primary hyperaldosteronism.
  • An aldosterone to renin ratio (ARR) greater than 20-30 is diagnostic.
• Saline Suppression Test:
  • Confirmatory test involving infusion of 2000 ml of normal saline over 4 hours.
  • Aldosterone levels are checked at the start and finish.
  • In normal individuals, aldosterone levels fall below 200 pmol/L.
  • Failure to suppress indicates primary hyperaldosteronism.
• 131-Iodocholesterol Scanning: May help localize aldosterone-producing adenomas.
• Echocardiogram: May show left ventricular hypertrophy due to long-standing hypertension.
• Imaging Studies: CT or MRI of the adrenal glands to localize adenomas or hyperplasia.
• Adrenal Venous Sampling: May be necessary to distinguish unilateral from bilateral disease.
• Genetic Testing: Consider for glucocorticoid-remediable hyperaldosteronism.

Differential Diagnosis

• Glucocorticoid-Remediable Hyperaldosteronism: Genetic condition causing early-onset hypertension.
• Apparent Mineralocorticoid Excess: Can be due to licorice or glycyrrhizic acid ingestion.
• Liddle's Syndrome: Presents with hypertension, hypokalemia, metabolic alkalosis, but low aldosterone levels.
• Congenital Adrenal Hyperplasia: Enzyme defects leading to overproduction of mineralocorticoids.
• Gordon's Syndrome: Pseudohypoaldosteronism type II; characterized by hypertension and hyperkalemia.

Management

• Screening:
  • Patients with suspected primary hyperaldosteronism should be screened with serum aldosterone levels and plasma renin activity, ideally at 8 am when aldosterone secretion is highest.
  • A positive screening test warrants referral to a hypertension specialist for confirmatory testing.
• Surgical Management:
  • Conn's Adenoma (Unilateral Disease):
    • Laparoscopic adrenalectomy is the treatment of choice.
    • Hypertension is cured or significantly improved in approximately 70% of patients post-surgery.
    • The response to spironolactone preoperatively can help predict surgical outcomes.
  • Adrenal Carcinoma:
    • Surgical resection if feasible.
    • Postoperative adrenolytic therapy with mitotane may be required.
    • Prognosis is generally poor due to aggressive nature.
• Medical Management:
  • Bilateral Adrenal Hyperplasia or Non-surgical Candidates:
    • Mineralocorticoid receptor antagonists:
      • Spironolactone: 25–100 mg/day.
      • Eplerenone: 50–100 mg/day; more selective with fewer side effects.
      • Amiloride: Can also be used as an alternative.
  • Glucocorticoid-Remediable Hyperaldosteronism:
    • Treated with low-dose dexamethasone to suppress ACTH and reduce aldosterone production.
    • Also responds to mineralocorticoid receptor antagonists and amiloride.

References

• Screening for Conn's Syndrome (Primary Aldosteronism)