Response of a GH- and TSH-secreting pituitary adenoma to a somatostatin analogue (SMS 201-995): evidence that GH and TSH coexist in the same cell and secretory granules.
A 29-year-old male presented with acromegaly and hyperthyroidism and was found to be hypersecreting both GH and TSH. A somatostatin analogue, SMS 201-995, at doses of 50 and 100 micrograms s.c. 3 times a day produced an acute decrease in serum GH and TSH levels to less than 20% of basal concentrations. An increase in serum SMS 201-995 levels preceded the decline in serum GH and TSH levels. Partial resolution of signs and symptoms related to GH excess occurred and the patient developed normal serum thyroxine levels. These latter effects were maintained during the 3.5 months of SMS 201-995 therapy; however, pituitary adenoma size as judged by MRI was unchanged. Side effects of therapy were minimal and included transient abdominal pain, diarrhea and weight gain. Adenomatous pituitary tissue was surgically removed and placed in monolayer culture. It was observed that SMS 201-995 produced significant inhibition of GH and TSH release. Histology revealed a partly chromophobic, partly acidophilic adenoma containing GH and TSH. Electron microscopy showed a pituitary adenoma which appeared to consist of smaller cells resembling somatotrophs and larger cells exhibiting ultrastructural features of thyrotrophs. Immunoelectron microscopy localized the two biochemically distinct peptides in the same cell type, often in the same secretory granules. No morphologic abnormality, attributable to SMS 201-995 medication, was evident. Thus it can be concluded that pituitary adenomas can simultaneously secrete GH and TSH which produce acromegaly and hyperthyroidism. These bi-hormonal tumors may synthesize GH and TSH in the same cell type.(ABSTRACT TRUNCATED AT 250 WORDS)
Malarkey
W B
WB
Department of Internal Medicine, Ohio State University, Columbus.
Kovacs
K
K
O'Dorisio
T M
TM
D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D010903:Pituitary Gland, Anterior / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism*
D013972:Thyrotropin; D013006:Growth Hormone; D015282:Octreotide