Adrenocorticotropin-Secreting Pituitary Adenomas Originate from the Anterior or the Intermediate Lobe in Cushing's Disease: Differences in the Regulation of Hormone Secretion

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Abstract
About 40‥ of patients with Cushing's disease respond to bromocriptine with a suppression of plasma ACTH and cortisol. In the present study, the reaction to bromocriptine in patients with Cushing's disease was correlated with pathological examination of the pituitary adenomas and the outcome of transsphenoidal operation. Fifteen consecutive patients with Cushing's disease were operated upon. In all patients, pituitary tumor tissue was removed. In nine tumors, no neural tissue was present in the adenomas (group I), but in the tissue removed from the other six patients, argyrophilic nerve fibers coursed freely through the adenoma tissue (group II). In two of these six patients, multiple adenomatous and/or hyperplastic cell nests containing nervous tissue were present, while a localization of tumor tissue in the intermediate lobe of the pituitary gland was evident in three of them. The two groups of patients showed the following differences: 1) normalization of the cortisol secretion rate was reached after operation in all patients of group I, except one, but in only one of the six patients of group II; 2) hyperprolactinemia was present in three of the six patients of group II, while all patients of group I had normal PRL levels; 3) the infusion of 5 mg dexamethasone over 5 h suppressed plasma cortisol by 71 ± 5‥ in the patients of group I and by only 43 ± 6‥ in group II (P < 0.01); and 4) ACTH and cortisol were significantly suppressed after bromocriptine administration in all three patients of group II, while there was no effect in four patients of group I. Thus, we hypothesize that Cushing's disease in man originates from two different locations. Most of the ACTH-secreting pituitary adenomas are located in the anterior part of the pituitary gland and can easily be removed during transsphenoidal operation. Part of the ACTH secreting pituitary adenomas are, however, intermediate lobe tumors containing nervous tissue. Multiple microadenomas and/or hyperplastic cell nests can be present in some of these patients, and transsphenoidal operation is less successful. This type of adenoma might be recognized by the demonstration of a suppression of plasma ACTH in response to bromocriptine and a lowered sensitivity to dexamethasone. (J Clin Endocrinol Metab54: 286, 1982)