Treatment of corticotropin deficiency

As corticotropin deficiency is potentially a life-threatening disease, its treatment takes precedence over that of all other anterior pituitary hormones. The goal of treatment in corticotropin deficiency is to restore the eucortisol state. This is achieved by administration of cortisol or one of its glucocorticoid analogs in a dose equivalent to daily normal cortisol production and in a way that mimics normal diurnic rhythm. The dose is increased during periods of acute stress to mimic augmented cortisol production physiologically occurring in such conditions.

Maintenance glucocorticoid therapy can be given as hydrocortisone 20 to 30 mg/day, cortisone acetate 25 to 37.5 mg/day, or prednisone 5 to 7.5 mg/day. Two-thirds should be given in the morning and the remaining third in the afternoon. High-potency long-acting glucocorticoids such as dexamethasone are not recommended for glucocorticoid replacement. Under conditions of acute medical or surgical illness, the dose should be increased to two to three times the usual maintenance dose, and injectable steroids (e.g. 100 mg hydrocortisone hemisuccinate intramuscularly) should be used whenever inadequate enteral absorption is suspected.

If corticotropin deficiency is partial, the patient may be able to secrete enough cortisol to take care of day-to-day needs, and will only need treatment in episodes of stress or illness. These are the patients who present with acute corticotropin deficiency in the critical care unit and for whom prompt recognition and treatment is vital.

A blood sample is drawn for serum cortisol and corticotropin before intravenous administration of a soluble glucocorticoid: hydrocortisone 100 mg followed by 50 to 100 mg every 6 h on the first day, 50 mg every 6 h on the second day, and 25 mg every 6 h on the third day, tapering to a maintenance dose by the fourth to fifth day.

To prevent acute corticotropin deficiency in the perioperative phase, 100 mg of hydrocortisone hemisuccinate is given intramuscularly or intravenously on call to the operating room, 50 mg is given in the recovery room, and 50 mg is given every 6 h for the first 24 h. If the patient's progress is satisfactory, the dose can be reduced to 25 mg every 6 h for 24 h and then gradually tapered to maintenance dose by the third to fifth day. However, if fever, hypotension, or any other complication occurs, the dose of hydrocortisone is increased to 200 to 400 mg/day in divided doses every 6 h followed by gradual tapering to maintenance dose. In prolonged critical conditions, the maintenance dose should be kept two to three times the basal need.

Special attention should be given to patients with concomitant diabetes insipidus, as lack of cortisol may prevent polyuria because cortisol is needed for free-water clearance. Glucocorticoid therapy may induce or aggravate diabetes insipidus in these patients. Another specific condition is the post-hypophysectomy phase of Cushing's disease, characterized by a high vulnerability to Addisionian-like crisis.

Drugs such as phenytoin, barbiturates, and rifampin (rifampicin) can accelerate glucocorticoid metabolism by induction of microsomal enzyme activity and can increase the glucocorticoid replacement dose requirements. If this increased requirement is not met, adrenal crisis may occur.

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