Certain Endocrine and Metabolic Facets of the Steroid Withdrawal Syndrome

Abstract

Clinical features of Cushing''s syndrome developed in 22 male patients with pulmonary tuberculosis who received prednisone, 30 mg daily, and zinc corticotropin (ACTH), 40 U every other day, for 3 months in addition to antituberculous chemotherapy. The prednisone was tapered during an additional 3-week period and the zinc ACTH was continued throughout the tapering period for an additional 4 days. Following discontinuation of predni-sone-ACTH therapy, the patients developed features of the steroid withdrawal syndrome[long dash]anorexia, nausea, lethargy, arthralgia, weakness, desquamation and weight loss. The integrity of the hypothalamic-pituitary-adrenal system was evaluated in 13 patients while steroid withdrawal symptoms were present, and in randomly chosen controls with tuberculosis by measuring the response of plasma and urine steroids to the administration of methopyrapone (Su-4885) and to exogenous ACTH. The base line levels of plasma and urine steroids and response to ACTH were similar in the steroid-ACTH withdrawal and control groups. The steroid-ACTH withdrawal patients exhibited a definite but diminished response to methopyrapone compared to the controls. However, there was no correlation between the intensity or duration or steroid withdrawal symptoms and the response to methopyrapone. Furthermore, in 9 steroid-ACTH withdrawal patients serial measurements of urine and plasma steroids revealed normal levels while symptoms were present, and there was no correlation between the degree of symptomatology and the steroid level in the same patient or among different patients. In 5 patients the response to methopyrapone had returned to normal when they were retested 3 weeks to 6 months after the initial study. Six steroid withdrawal patients subsequently tolerated major pulmonary surgery without steroid coverage, and their levels of plasma 17-hydroxycorticoids pre- and postoperatively did not differ from those of controls undergoing similar surgery. Since the steroid withdrawal syndrome could not be ascribed to either hypoadrenocorticism or hypoadrenocorticotropism, the possibilities of hypervitaminosis A, hypercalcemia, pancreatitis and pseudo-tumor cerebri were considered and excluded. The etiology and pathogenesis of the steroid withdrawal syndrome in these patients and in other clinical and experimental situations remain obscure.