Somatotroph Hyperplasia

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Abstract
A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95±9.4 ng/ml; mean±SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm3) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified.