0021-972X/82/5505-0947$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1982 by The Endocrine Society Vol. 55, No. 5 Printed in U.S.A. Concurrent Production of Adrenocorticotropin and Prolactin from Two Distinct Cell Lines in a Single Pituitary Adenoma: A Detailed Immunohistochemical Analysis STEPHEN H. SHERRY, ANDRfi T. GUAY, ARTHUR K. LEE, E. TESSA HEDLEY- WHYTE, MICHELINE FEDERMAN, STEPHEN R. FREIDBERG, AND PAUL D. WOOLF* Section of Endocrinology (S.H.S., A.T.G.) and the Department of Neurosurgery (S.R.F.), Lahey Clinic Medical Center, Burlington, Massachusetts 01805; the Department of Pathology, Tufts University and New England Medical Center Hospital (A.K.L.), Boston, Massachusetts 02111; the Department of Pathology, Harvard Medical School, New England Deaconess Hospital (E. T.H- W., M.F.), Boston, Massachusetts 02215; and the Endocrinology-Metabolism Unit, University of Rochester Medical Center (P.D.W.), Rochester, New York 14627 ABSTRACT. A pituitary tumor from a patient with severe Cushing's disease and marked hyperprolactinemia was exten- sively studied by immunohistochemical techniques. Tissues from two separate areas of the adenoma were found to contain similar cell proportions of PRL as well as ACTH and related peptides (/Mipotropin, ^-endorphin, and aMSH). The tumor was com- posed of approximately 70% immunoreactive PRL cells and 5% ACTH-containing cells. Double immunostaining revealed that PRL or ACTH and related peptides were found in two distinct populations of tumor cells. These results document for the first time inappropriate synthesis and secretion of an unusual com- bination of pituitary hormones from a mixed pituitary adenoma. (J Clin Endocrinol Metab 55: 947, 1982) I N THE past decade, the incidence of nonsecretory pituitary adenomas has fallen considerably because of the availability of specific RIAs for pituitary hormones, in vitro cell culture studies, and pathological analysis of tumors by immunohistochemistry and electron micros- copy (1, 2). Immunohistochemistry enables a specific demonstration of hormone-producing cells and offers a great advantage over conventional histochemistry, which has traditionally classified pituitary adenomas as baso- phil, acidophil, and chromophobe tumors. The combi- nation of immunohistochemical studies and ultrastruc- tural observations has permitted an accurate functional classification of pituitary adenomas. Hypersecretion of multiple hormones in an individual patient with a pituitary tumor has been recognized with increasing frequency. Although the existence of separate tumors in one patient has been reported (3), the majority of tumors have been single, with multiple hormone pro- Received February 16, 1982. Address requests for reprints to: Andr6 T. Guay, M.D., Section of Endocrinology, Lahey Clinic Medical Center, 41 Mall Road, Box 541, Burlington, Massashusetts 01805. * Supported in part by National Institute of Neurological and Com- municative Diseases and Stroke Grant NS-13734. duction demonstrated in vivo and in vitro (4). The com- monest combination is GH and PRL, which occurs in appreciable numbers of patients with acromegaly (5). The concurrent excessive secretion of either ACTH or PRL with other hormones is much less common, al- though simultaneous secretion of GH and ACTH has been reported (6), and simultaneous elevation of ACTH and PRL has been recognized clinically (7, 8). Because specific immunocytochemical correlations were not shown, the elevated levels of PRL might have been the result of pressure by the pituitary tumor on the pituitary stalk or median eminence, thereby removing the lacto- tropes from hypothalamic inhibition. Simultaneous hy- persecretion of PRL and TSH has been reported, and immunofluorescent studies showed that two separate cell types were present within the same tumor (9). Recently, four additional clinical cases of concurrent excessive se- cretion of PRL and ACTH have been reported (10, 11), but immunocytochemical analysis was not performed. In the patient reported here, Cushing's syndrome and markedly elevated PRL levels were present, and for the first time we were able to demonstrate by immunohis- tochemical evaluation that two distinct cell types were present in the adenoma. 947