PITUITARY-ADRENAL FUNCTION IN PATIENTS GIVEN LONG-TERM ADRENAL STEROID THERAPY

ABSTRACT Pituitary-adrenal function was investigated in 23 patients with rheumatoid arthritis and in 19 patients with bronchial asthma following prolonged glucocorticoid therapy. The duration of continuous treatment varied from 2 months to 15 years and the total dose of steroids from 400 mg to 54 g of prednisolone or its equivalent. After treatment had been discontinued, pituitary ACTH-reserve was estimated by means of an oral metyrapone test and adrenal response to ACTH by means of an intravenous or intramuscular ACTH-test. The pituitary ACTH-response was evaluated by determining the increment in the excretion of 11-deoxy-17-hydroxycorticosteroids during the administration of the metyrapone blocking agent and adrenal response to ACTH by the excretion of 11-oxygenated corticosteroids. The reduction of the metyrapone and ACTH responses were found to be related to the duration of prednisolone treatment as well as to the daily and total administered dose, although a marked individual variation in several instances could be observed in the degree of suppression of endogenous ACTH or corticosteroid production. Deficient metyrapone and ACTH responses were more frequently encountered in bronchial asthma than in patients with rheumatoid arthritis who had received comparable doses of glucocorticoids during similar periods. No negative metyrapone tests, however, in either group of patients were obtained for 12 months or unless the total dose of steroids administered was at least 3.5 g of prednisolone or its equivalent. Most patients who showed reduced adrenocortical response to ACTH had received large total doses of corticosteroids and the lowest total dose on which a subnormal ACTH-response was observed was 6 g. The results demonstrate that both pituitary ACTH-reserve and adrenocortical response to ACTH can be reduced by long-term adrenal steroid therapy, although the loss of pituitary ACTH-response occurs earlier during the course of treatment.