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Thyrotropin-Secreting Pituitary Adenomas: Clinical and Biochemical Heterogeneity: Case Reports and Follow-up of Nine Patients

Neil Gesundheit, MD; Patricia A. Petrick, MD; Marina Nissim, MD; Per Anders Dahlberg, MD; John L. Doppman, MD; Charles H. Emerson, MD; Lewis E. Braverman, MD; Edward H. Oldfield, MD; and D. Weintraub Bruce, MD
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Grant Support: Supported in part by grants from the Swedish Medical Research Council (No. 7040), Henning and Johan Throne-Holst's Foundation, and Anders Otto Swärd's Foundation and grants DK-18919 and DK-27850 from NIDDK, NIH, Bethesda, Maryland.

Requests for Reprints: Bruce D. Weintraub, MD, Molecular, Cellular, and Nutritional Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 8D14, Bethesda, MD 20892.

Current Author Addresses: Dr. Gesundheit: Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080.

Dr. Petrick: 6246 Montrose Road, Rockville, MD 20852.

Dr. Nissim: Cattedra de Endocrinologia, Ospedale Policlinico, Pd. Sacco, via F. Sforza 35, Milan, Italy.

Dr. Dahlberg: Department of Internal Medicine, Karolinska Institute at Danderyds Hospital, Stockholm, Sweden.

Dr. Doppman: Department of Diagnostic Radiology, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.

Drs. Emerson and Braverman: Division of Endocrinology and Metabolism, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, MA 01655.

Dr. Oldfield: Surgical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.

Dr. Weintraub: Molecular, Cellular, and Nutritional Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

Ann Intern Med. 1989;111(10):827-835. doi:10.7326/0003-4819-111-10-827
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Study Objective: To evaluate the clinical and biochemical features of patients with TSH (thyroid-stimulating hormone, thyrotropin)-secreting pituitary tumors; to measure the biologic activity in vitro of circulating TSH from selected patients before and after pituitary surgery.

Design: Case series.

Setting: Patients in an endocrinology unit.

Patients: Nine patients with TSH-secreting pituitary tumors.

Measurements and Main Results: All patients had hyperthyroidism, elevated free thyroxine and triiodothyronine levels, and detected levels of TSH. The free alpha subunit, a tumor marker for neoplasms of gonadotropic or thyrotropic cell origin, was elevated in all nine patients. Seven of the nine patients had been treated with thionamides, radioactive iodine, or thyroidectomy for presumed primary hyperthyroidism. The delay from the initial treatment of hyperthyroidism to the correct diagnosis of a pituitary neoplasm was 6.2 ± 4.8 (mean ± SD) years. Two of the seven patients with macroadenomas died in the perioperative period (one at NIH, one at a referring hospital). Of the remaining five patients with macroadenomas, four have residual tumor and inappropriate TSH secretion, despite surgery and radiation therapy, at follow-up from 3.5 to 6 years. In contrast, the two patients with microadenomas are clinically cured 2.5 and 4 years after transsphenoidal adenomectomy. The biologic to immunologic (B/I) ratio of serum TSH, determined preoperatively in five patients with TSH-secreting tumors, was elevated compared with euthyroid subjects. In three patients the B/I ratio of serum TSH was also measured after pituitary surgery; in two the elevated B/I ratio returned to normal after successful pituitary adenomectomy, while in the third this ratio remained elevated after incomplete adenoma resection.

Conclusions: With the routine availability of ultrasensitive TSH assays and their increasing use to confirm thyrotoxicosis from all causes, we expect that TSH-secreting pituitary tumors will be diagnosed earlier, before inappropriate antithyroid therapy, permitting an improved outcome.





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