Sodium Elevates the Plasma Glucose Response to Glucose Ingestion in ManCushing's Disease: Transient Secondary Adrenal Insufficiency after Selective Removal of Pituitary Microadenomas; Evidence for a Pituitary Origin*

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Abstract
Of 12 patients with Cushing’s disease who had successful selective microadenoma resection documented by clinical remission and reversal of hypercortisolism, 11 developed postoperative hypoadrenalism with deficient adrenal responsiveness to exogenous ACTH. In addition, of 11 patients tested with hypoglycemia, all had subnormal cortisol responses, and 10 had deficient ACTH responses. Pituitary-adrenal function then gradually returned to normal; at last testing, normal cortisol responses to ACTH stimulation and insulin hypoglycemia were present in 8 of 12 and 6 of 11 patients, respectively, and 9 of 11 had normal plasma ACTH responses to hypoglycemia. Two patients with persistent hypoadrenalism had had prior incomplete bilateral adrenalectomies. The ACTH and glucocorticoid deficiency was not caused by the surgical procedure or hydrocortisone replacement, since it resolved despite replacement therapy; further, adrenal insufficiency did not occur in 10 acromegalic patients who received the same operation and identical glucocorticoid therapy. Other pituitary functions were not impaired postoperatively. The GH response to insulin-induced hypoglycemia, normal in only 2 of 7 patients tested preoperatively, improved after surgery so that 9 of 11 patients were normal. Baseline LH levels, suppressed preoperatively, increased significantly, and the response to gonadotropin-releasing hormone was normal in all patients. PRL and TSH responses to TRH were generally not different pre- and postoperatively. All patients were and remain clinically euthyroid. We conclude that: 1) the hypercortisolism caused by an ACTH-secreting pituitary microadenoma suppresses the normal pituitary secretion of ACTH and often that of GH and LH; 2) this suppression persists postoperatively, but gradually resolves in most patients; 3) a normal cortisol response to ACTH is a good indication that the pituitary-adrenal axis has recovered; 4) there was no evidence of a persisting hypothalamic defect after removal of ACTH-secreting microadenomas; and 5) pituitary microadenomas appear to be the primary cause of Cushing's disease in these patients. (J Clin Endocrinol Metab54: 413, 1982)

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