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Hypoadrenalism (underactivity of the adrenal glands)

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Hypoadrenalism (underactivity of the adrenal glands)

Written by Shern Chew, consultant endocrinologist

What is hypoadrenalism?

The adrenal glands are two small but very important glands, situated one above each kidney, which produce a range of hormones, or 'chemical messengers'. Underactivity of the adrenal glands is called hypoadrenalism.

Many of the symptoms of hypoadrenalism are due to a deficiency of the steroid hormone cortisol, which is a potentially fatal deficiency if left uncorrected. Each adrenal gland consists of two parts:

an outer ring - the cortex

an inner core - the medulla.

The two parts have separate hormone functions and control mechanisms. The production of cortisol in the cortex is controlled by the hormone adrenocorticotropin (ACTH), which is produced by the pituitary gland at the base of the brain.

The role of the pituitary gland in adrenal function

The way in which the pituitary gland regulates the normal production of steroid hormones by the adrenal gland is through the secretion of ACTH.

If the adrenal gland produces too little cortisol, then there will be a lower level of cortisol in the blood. This is sensed by the pituitary, which therefore will increase the release of ACTH, which in turn stimulates the adrenal cortex to produce more cortisol.

Conversely, too much circulating steroid hormone will switch off the release of ACTH from the pituitary gland, which in turn reduces the adrenal gland production of steroids.

What causes hypoadrenalism?

Primary hypoadrenalism or Addison's disease Primary hypoadrenalism, or Addison's disease, results from failure of the adrenal glands themselves. This is usually an 'autoimmune' disease, where the immune system produces antibodies that attack tissues of the body rather than a virus or bacteria.

In Addison's disease, antibodies attack the adrenal cortex, causing damage and scarring. Antibodies to the adrenal cortex can be detected in the blood of some patients.

Secondary hypoadrenalism or ACTH deficiency

Secondary hypoadrenalism, or ACTH deficiency hypoadrenalism, is caused by diseases of the pituitary gland, which lead to adrenal failure as a secondary effect.

Other causes

Tuberculosis of the adrenal glands may also cause hypoadrenalism. This was a common cause of Addison's disease in Britain before the 20th century and remains a major cause in underdeveloped countries.

Tuberculosis destroys the whole gland, both the cortex and the medulla. There are usually signs of tuberculosis in other organs, particularly the lungs. Destruction of the adrenal glands by tuberculosis is irreversible once hormonal deficiencies are clinically detectable.

Rare causes

Many rare diseases may affect the adrenals. In general, at least 80 per cent of both adrenal glands have to be damaged in order for deficiencies to become clinically evident.

Rare conditions associated with primary hypoadrenalism

Adrenoleukodystrophy (a genetic disease in which the myelin sheath, or 'insulation', covering the nerve fibres within the brain is lost, along with degeneration of the adrenal gland).

Amyloidosis (a rare condition in which an abnormal substance called amyloid is laid down in various tissues, impairing their function).

Bilateral adrenalectomy (surgical removal of the adrenal glands).

Congenital adrenal hyperplasia (a common inherited condition in which an enzyme defect causes problems with the production of steroid hormones by the adrenal gland).

Drugs (eg ketoconazole, metyrapone, mitotane).

Familial glucocorticoid deficiency (ACTH receptor mutation).

Haemochromatosis.

Haemorrhage - usually in patients receiving anticoagulant drugs or in whom septicaemia ('blood poisoning') is present.

HIV-related adrenal inflammation.

Metastases (spread of cancer from another part of the body.

Sarcoidosis.

Rare conditions associated with secondary hypoadrenalism

This means adrenal deficiency from causes acting on the pituitary gland rather than directly on the adrenal glands.

The pituitary gland regulates adrenal cortisol production by responding to the amount of cortisol in the blood. However, the pituitary cannot distinguish between natural cortisol and synthetic steroid absorbed from medicines or steroid creams.

If someone takes such treatment the pituitary production of ACTH will drop and as a result the adrenal cortex will become relatively inactive. If the steroid treatment is stopped abruptly then the patient may suddenly become deficient in cortisol as the adrenal gland takes some time - weeks or months - to regain its full manufacturing ability again. This is the reason that patients on medium or long-term steroid treatment are advised not to stop taking their medicine suddenly.

Rarely, patients are affected by conditions that destroy the pituitary. Any cause of pituitary disease may cause ACTH deficiency.

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