Acute adrenocortical insufficiency (Addisonian crisis)

This is an emergency and hydrocortisone sodium succinate 100 mg should be given i.v. immediately it is suspected, or the patient may die.

• An i.v. infusion of sodium chloride solution (0.9%) is set up immediately and a second 100 mg of hydrocortisone is added to the first litre, which may be given over 2 h (several litres of fluid may be needed in the first 24 h).

• The patient should then receive hydrocortisone 50-100 mg i.v. or i.m. 6-hourly for 24 h; then 12-hourly, initiating oral use when appropriate; then a total of 40-60 mg a day orally in 2 or

3 doses.

Other treatment to restore electrolyte balance will depend on the circumstances. The cause of the crisis should be sought and treated; it is often an infection. When the dose of hydrocortisone falls below 40 mg a day, supplementary mineralo-corticoid (fludrocortisone) may be needed (see below).

The hyperkalemia of Addison's disease will respond to the above regimen and must not be treated with insulin because of the risk of severe hypoglycaemia.

Chronic primary adrenocortical insufficiency (Addison's disease)

Hydrocortisone orally is used (15^0 mg total daily) in the lowest dose that maintains wellbeing and body weight, with two-thirds of the total dose in the morning and one-third in the evening to mimic the natural diurnal rhythm of secretion.3 Plainly corticotropin is useless.

Some patients do well on hydrocortisone alone, with or without added salt, but most patients require a small amount of mineralocorticoid as well (fludrocortisone, 50-200 micrograms once a day, orally). If the dose of fludrocortisone should exceed 500 micrograms a day, an unlikely event, then its glucocorticoid effect must be taken into account.

The dosage of the hormones is determined in the individual by following general clinical progress and particularly by observing: weight, blood pressure, appearance of oedema, serum sodium and potassium concentrations and haematocrit. The dose of fludrocortisone can be adjusted against the plasma renin activity (routinely assayed in a number of chemical pathology laboratories by the radioimmunoassay of the amount of angiotensin I produced during a timed incubation of a plasma sample). Renin is secreted (by the juxtaglomerular apparatus of the kidney) in response to incomplete reversal of the sodium depletion in patients

3 But this can be associated with an unphysiologically low plasma concentration of hydrocortisone in the late afternoon (with loss of wellbeing). Such patients may be best managed on 3 equal doses per day. Air travellers on long flights across longitude east to west (> 12 h, i.e. longer day): take an extra dose near the end of the flight. For west to east flights (> 8 h, i.e. shorter day): the normal evening dose may be taken sooner and the usual dose taken on the 'new' morning. Night workers may adjust their dosage to their work pattern (Drug and Therapeutics Bulletin 1990 28: 71).

receiving inadequate replacement therapy. If any complicating disease arises, such as infection, a need for surgery or other stress, the hydrocortisone dosage should immediately be doubled, see above.

If there is vomiting, the replacement hormone must be given parenterally without delay.

There are no contraindications to replacement therapy. The risk lies in withholding rather than in giving it.

Some patients (particularly those with hypopituitarism), when first treated, cannot tolerate full doses of hydrocortisone because they become euphoric or otherwise mentally upset; 10 mg a day may be all they can take. The dose can usually soon be increased if it is done slowly. If diabetes is present the full dose is used and the diabetes controlled with insulin.

Chronic secondary adrenocortical insufficiency

This occurs in hypopituitarism. In theory the best treatment is corticotropin, but the disadvantages of frequent injection are such that hydrocortisone is preferred. Usually less hydrocortisone is needed than in primary insufficiency. Special sodium-retaining hormone is seldom required, for the pituitary has little control over aldosterone production which responds principally to plasma potassium concentration and to the renin-angiotensin system. Thyroxine and sex hormones are given when appropriate. The general conduct of therapy does not differ significantly from that in primary adrenal insufficiency.

Iatrogenic adrenocortical insufficiency: abrupt withdrawal

(See also Withdrawal of corticosteroid pharmacotherapy, below) This occurs in patients who have recently received prolonged pharmacotherapy with a corticosteroid which inhibits hypothalamic production of the corticotropin releasing hormone and so results in secondary adrenal failure. It is treated by reinstituting therapy or as for acute insufficiency, as appropriate. To avoid an acute crisis on stopping, steroid therapy must be withdrawn gradually to allow the hypothalamus, the pituitary and the adrenal to regain normal function. Also, when patients taking corticosteroids have an infection or surgical operation (major stress) they should be treated as for primary insufficiency.

After the use of large doses of hormone to suppress inflammation or allergy, sudden withdrawal may not only lead to an adrenal insufficiency crisis but to relapse of the disease, which has only been suppressed, not cured. Such relapse can be extremely severe, sometimes life-threatening.

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