Hyperaldosteronism

Hyperaldosteronism

Hyperaldosteronism describes an excess of the mineralocorticoid hormone aldosterone.

Classical exam presentation

Patient with treatment-resistant hypertension and features of hypokalemia, such as muscle weakness, paraesthesia and constipation.

Definitions

Primary hyperaldosteronism - excess aldosterone secondary to increased production from the zona glomerulus in the adrenal cortex, the glands act autonomously.

Conn’s syndrome - Another eponym; this refers to primary hyperaldosteronism caused by an aldosterone-producing adrenal adenoma.

Secondary hyperaldosteronism - excess aldosterone production due to increased activation of the RAAS system. The problem is not with the adrenal glands.

Aetiology

Primary:

• Bilateral adrenal hyperplasia – most common cause (60%)
• Adrenal adenoma – that secretes aldosterone, also known as an aldosteronoma (Conn’s syndrome).
• Unilateral adrenal hyperplasia.

Secondary:

• Renal artery stenosis – low perfusion leads to increased stimulation of the baroreceptors in the wall of the afferent arteriole; RAAS system is activated leading to increased aldosterone.
• Renin-secreting tumour.

Pathophysiology

Hypertension:

1. Aldosterone stimulates Na+ channels in the collecting ducts to reabsorb Na+
2. With this comes Increased water retention
3. Leading to increased intravascular volume
   

Hypokalaemia:

1. Aldosterone acts on the principal cells in the collecting duct, upregulating the secretion of K+.

Clinical features

Patients may initially be asymptomatic and may be picked up on routine health checks with hypertension.

Features of hypokalemia

• Neuromuscular - cramps, paraesthesia, weakness
• Palpitations
• Fatigue
• Headaches

Diabetes insipidus

Polyuria (dilute urine), nocturia and polydipsia.

• Patients may develop nephrogenic DI due to desensitization of ADH receptors from prolonged hypokalaemia.

Diagnostics

Hyperaldosteronism should be suspected in patients with treatment-resistant hypertension, especially if signs of hypokalaemia are present.

1st line Ix: plasma aldosterone/renin (ARR) ratio

• Primary - elevated
• Secondary - reduced

If ARR is elevated, consider confirmatory testing with either

• Oral sodium loading test
• Saline infusion test
  

Both tests should show suppression of aldosterone production.

If high suspicion - i.e. biochemical evidence of hypokalemia, low plasma renin levels and high aldosterone levels; no confirmatory testing is required.

Localisation tests

Primary:

CT of the abdomen should be the initial Ix ordered to assess these patients.

• Crucial to exclude an adrenal carcinoma.

Adrenal vein sampling should then be used to distinguish between unilateral/bilateral disease.

Secondary:

Ultrasound of the kidneys to assess for renal artery stenosis.

CT of the abdomen may be ordered to rule out a renin secreting tumour.

General findings

• ABG - may show a metabolic alkalosis*.
• Plasma renin - low in primary disease, elevated in secondary.
• U&Es - hypernatraemia, hypokalaemia

*aldosterone stimulates secretion of H+ via H+/ATPase in the intercalated cells of the collecting tubules.

Genetic testing

Primary hyperaldosteronism in a patient aged <20 → test for familial hyperaldosteronism type I (also known as glucocorticoid remediable aldosteronism, GRA).

In very young patients → test for familial hyperaldosteronism type III (KCNJ5 mutation).

Management

Unilateral disease (adenoma/hyperplasia) - laparoscopic adrenalectomy.

• If surgery is not an option, then treat with spironolactone.

Bilateral disease (hyperplasia) – spironolactone 1st line, eplerenone is an alternative.

GRA - low dose glucocorticoid; aim is to suppress ACTH.*

*These patients have a mutation which increases the sensitivity of aldosterone synthase to ACTH.

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References:

https://www.ncbi.nlm.nih.gov/books/NBK279065/

https://academic.oup.com/jcem/article/101/5/1889/2804729#97177950