Conn’s syndrome - Adrenal axis

Conn’s syndrome

Definition

Conn’s syndrome is a condition of primary hyperaldosteronism.

Incidence/prevalence

Rare. Accounts for 1% patients with hypertension.

Aetiology

Eighty per cent of cases are due to an adrenal adenoma. In the remainder, there is diffuse hyperplasia of the zona glomerulosa. Very rarely it is caused by an adrenal carcinoma. Raised aldosterone is much more commonly a physiological response to reduced renal perfusion as in renal artery stenosis or congestive cardiac failure.

Pathophysiology

Aldosterone is the most important mineralocorticoid produced by the zona glomerulosa. It acts on the Na+ / K+ pump in renal tubular epithelial cells in the collecting tubules, distal tubule and collecting duct increasing the absorption of sodium and hence water with increased loss of potassium. The rise in blood volume increases renal perfusion and arterial blood pressure. However there is a significant loss of K+ leading to hypokalaemia and resistance to antidiuretic hormone. This causes increased urinary volumes and hence increased thirst.

Clinical features

Hypertension and symptoms resulting from the hypokalaemia such as cardiac arrhythmias, muscle weakness, cramps, latent tetany and paraesthesiae. The muscle weakness may present with paralysis. Polydipsia and polyuria may be a feature.

Macroscopy/microscopy

Adrenal cortical adenomas are well-circumscribed, yellow lipid laden tumours within the adrenal cortex. Adrenal cortical carcinomas are larger, with local invasion and metastatic spread. In hyperplasia, the glands are enlarged, with increased number, size and secretory activity of the cells within the zona glomerulosa.

Investigations

Urea and electrolytes demonstrate the hypokalaemia and may show a mild rise in sodium. Hypokalaemia may lead to a mild metabolic alkalosis (H+ /K+ exchange in the kidney). However, the use of diuretics to treat hypertension may mimic or mask these features. A high urinary K+ (>30 mmol/24 h) suggests primary aldosteronism.

The definitive test is to measure aldosterone and renin baselines after a night’s rest (low in 1â—¦ aldosteronism, high in 2â—¦ aldosteronism) and after being upright (stimulates renin in normal individuals, but aldosteronism suppresses renin).

CT scan of the adrenal glands. If negative, selective blood sampling may be required to find the source of aldosterone.

Management

Bilateral adrenal hyperplasia is usually treated with spironalactone (inhibits the Na+ /K+ pump, i.e. antagonises aldosterone) to control the blood pressure. Adenomas and carcinomas should be removed surgically. Spironalactone may be used prior to surgery.

Prognosis

30% have persistent hypertension after treatment, thought to be due to irreversible renal damage.