Hyperaldosteronism

Contents
Introduction
Pathology
Clinical Features
Investigations
Treatment

Introduction

The term mineralcorticoid excess is applied to diseases that feature an inappropriate increase in mineralocorticoid levels or activity. Various causes exist.

• Primary adrenal hyperplasia
• Aldosterone secreting adrenal adenoma (Conn's syndrome)
• Aldosterone secreting adrenal carcinoma
• Glucocorticoid suppressible hyperaldosteronism
• Congenital adrenal hyperplasia (rare forms)
• Congenital syndrome of apparent mineralocorticoid excess
• Acquired syndrome of apparent mineralocorticoid excess
• Exogenous mineralocorticoids
• Liddle's syndrome

Pathology

Primary adrenal hyperplasia is the commonest cause of mineralocorticoid excess and may be either bilateral or unilateral.

An aldesterone-secreting adenoma is the next commonest cause of hyperaldosteronism and is referred to as Conn's syndrome. The tumour tends to present between the ages of 30-50 years and has a male to female ratio of 1 : 2.

Aldosterone-producing carcinomas account for approximately 3-5% of cases of mineralocorticoid excess.

The hyperplasia, adenoma, carcinoma set mirrors the three causes of hyperparathyroidism.

Glucocorticoid suppressible hyperaldosteronism is an autosomal dominant disorder that is found on chromosome 8. It is a form of translocation in which the coding sequence for the enzyme aldosterone synthetase is placed fused with the regulatory sequence for the 11-beta-hydroxylase enzyme. This enzyme is involved in the production of cortisol and corticosterone and is normally under the control of ACTH. This means that the synthesis of aldotserone synthetase and therefore aldosterone is determined by ACTH and this results in excessive production of aldosterone that is unrelated to blood pressure, blood volume and the blood potassium level. However, sufficiently high doses of glucocorticoids will suppress the release of ACTH by the pituitary gland and therefore reduce the manufacture of aldosterone.

Both the congenital and acquired forms of the syndrome of apparent mineralocorticoid excess (SAME) share a basis in a nuance of steroid metabolism, although the precise mechanism that makes use of this basis differs. The renal mineralocorticoid receptor has a similar affinity for aldosterone and cortisol. However, the kidney possesses the steroid manipulating enzyme 11-beta-hydroxysteroid dehydrogenase. This enzyme interconverts cortisol and cortisone. In the kidney it serves to convert cortisol to cortisone. Cortisone is ineffective at the mineralocorticoid receptor and thus the enzyme protects the kidney against the unwanted mineralocorticoid aspirations of cortisol.

In congenital SAME, there is a deficiency of the enzyme 11-beta-hydroxysteroid dehydrogenase. Acquired SAME is caused by the ingestion of substances that inhibit 11-beta-hydroxysteroid dehydrogenase, such as liquorice and carbenoxolone.

Liddle's syndrome is a rare inherited disease in which a mutation in the beta subunit of the highly selective renal type 1 sodium channel causes the kidney to behave as if it was being bombarded by an excess of aldosterone although in fact aldosterone levels are suppressed by the consequences of the aberrant behaviour of this sodium channel.

Clinical Features

Many patients are asymptomatic but even then they tend to have hypertension, particularly diastolic hypertension; hyperaldosteronism is one of the commonest causes of secondary hypertension.

If symptoms are present they are likely to relate to the hypokalaemia that often develops in hyperaldosteronism and include muscle weakness and polyuria and polydipsia (due to the nephrogenic diabetes insipidus that can occur in hypokalaemia). The hypokalaemia can be accompanied by a metabolic alkalosis and this in turn can reduce the ionised calcium, resulting in the symptoms of hypocalcaemia.

Investigations

The urea and electrolytes should be checked. Hypokalaemia can occur.

Blood and urine aldosterone levels can be measured, as can blood renin. The renin levels should be suppressed by the high aldosterone levels. The ratio of aldosterone to renin can exceed 400 in hyperaldosteronism.

The adrenal glands should be imaged with CT or MRI scans.

Treatment

Spironolactone is an aldosterone antagonist and can negate the effects of the endogenous aldosterone. Nevertheless, patients who have an adenoma or carcinoma require surgery (both to control the disease and to try to determine if the tumour is an adenoma or a carcinoma); the five year survival for a carcinoma is only 25%. Surgery is also used for primary hyperplasia.