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Endocrine, Biochemical, and Morphlogical Studies of a Pituitary Adenoma Secreting Growth Hormone, Thyrotropin (TSH), and -Subunit: Evidence for Secretion of TSH with Increased Bioactivity^*

Chair of Endocrinology, School of Medicine, and CNR Milan Italy
Center of Cytopharmacology Department of Pharmacology, University of Milan Milan Italy
Molecular, Cellular, and Nutritional Endocrinology Branch, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health Bethesda, Maryland 20205

Address all correspondence and requests for reprints to: Paolo Beck-Peccoz, M.D., Cattedra di Endocrinologia, Ospedale Policlinico, Pd. Sacco via F. Sforza 35, I-20122 Milan, Italy

A 40-yr-old man who had acromegaly and hyperthyroidism due to a GH/TSH-secreting pituitary adenoma is described. Serum free T₄ was 2.8 ng/dl, free T3 was 1.1 ng/dl, and TSH was 1.2–1.5 µU/ml; the latter was measured in an immunoradiometric assay with a sensitivity of 0.07µU/ml. Serum TSH was immunologically identical to standard TSH and did not decrease during a T₃ suppression test. Serum free asubunit and the molar -subunit to TSH ratio were high (6.1 ng/ml and 31.2, respectively). TRH administration induced significant increases in both GH (+129%) and -subunit (+156%) levels. Conversely, dopamine infusion resulted in a decrease in serum GH (–66%) and -subunit (–43%) levels, and subsequent administration of the dopamine antagonist sulpiride induced significant increases in both GH and a-subunit (+393 and +106%, respectively). Similarly, somatostatin infusion inhibited GH (–43%) and -subunit (–61%) secretion. Serum TSH levels were not affected by TRH, dopamine, or somatostatin. The biological to immunological activity ratio of serum TSH purified by immunoaffinity chromatography and measured in an adenylate cyclase assay was significantly increased compared to that in serum from hypothyroid or euthyroid subjects [biological to immunological activity ratio, 6.9 ± 0.2 (±SD) VS. 4.4 + 1.1; P < 0.001]. In gel chromatography, the apparent mol wt of thepatient's TSH was smaller than that of the controls. After adenomectomy, all of the altered parameters of pituitary function became normal. Double gold particle immunostaining of the adenomatous tissue showed that all of the cells contained secretory granules positive for GH and a-subunit, while very few cells were positive for TSHβ as well as GH and a-subunit. These data indicate that in this patient 1) serum TSH had an apparent mol wt smaller than that of normal TSH and an increased biological activity which, along with the autonomous TSH secretion, account for hyperthyroidism in the presence of low normal TSH levels; 2) -subunit originated from the same adenomatous cells that secreted GH but not TSH, thus explaining the in vivo observation that a-subunit responses to several agents were dissociated from TSH responses and parallel to GH responses; and 3) TSH and GH were colocalized in a minority of the neoplastic cells

^* This work was partially supported by grants from Ministero della Pubblica Istruzione (Rome, Italy) and Italian National Research Council (CNR), Special Project Oncology.

Received August 2, 1985.

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