Therapy for large prolactinomas remains controversial. Surgery is often unsuccessful in restoring endocrine function to normal. However, medical therapy with bromocriptine, a dopamine agonist, not only suppresses PRL levels, but may also lead to a reduction in tumor size. Previous reports have demonstrated radiographic evidence of tumor regression only after 3 or more months of bromocriptine therapy. We have now documented, for the first time, objective evidence of extremely rapid reduction in tumor size in two patients harboring large PRL-secreting pituitary tumors (mean pretreatment serum PRL levels, 2350 and 3900 ng/ml) who were prospectively treated with bromocriptine (7.5 mg/day) in preference to surgical intervention despite marked visual impairment in one of the patients. After 2 and 6 weeks of therapy, respectively, marked reduction in tumor size was demonstrated radiographically in both patients. Headache, visual acuity, and visual fields had improved after only 3 days. Although the mechanism of bromocriptine's antitumor activity is unclear, we believe that a large prospective trial to study the effects of bromocriptine therapy on the size of PRL-secreting macroadenomas is urgently needed to determine whether medical therapy should become the primary modality of treatment to reduce tumor size as well as restore endocrine function.

Medical therapy of prolactinomas with bromocriptine has been demonstrated to reduce serum PRL levels to normal and also to reduce the size of such tumors. This size reduction may occur very rapidly.It is widely recognized that PRL levels rise again after withdrawal of bromocriptine therapy. We now describe the effects of drug withdrawal and reinstitution on tumor size in two young men harboring large prolactinomas. Bromocriptine had been extremely successful in lowering serum PRL levels by more than 80%, as well as reducing tumor size. After 12 months of therapy bromocriptine was withdrawn. Within 48 h PRL levels had started to rise, reaching 2580 ng/ml at 13 days off therapy and 1040 ng/ml at 4 weeks off therapy in patients 1 and 2, respectively. At 13 days bitemporal hemianopsia recurred in patient 1, and this was associated with radiographic demonstration of expansion in the pituitary mass from a partially empty pituitary fossa to a large 12-mm suprasellar extension. The second patient remained asymptomatic, but his tumor also reexpanded after withdrawal of bromocriptine. Bromocriptine (2.5 mg, three times daily) was reinstituted in both cases and resulted in a rapid fall in serum PRL and reduction of tumor size in both patients; patient 1 had improvement in headaches at 24 h, vision at 3 days, and restoration of visual fields to normal at 6 months.Bromocriptine therapy is successful in reducing tumor size and lowering PRL levels with return of normal gonadal function. Patients with large prolactinomas treated with bromocriptine alone should be withdrawn from therapy very cautiously to avoid reexpansion of their tumor. (J Clin Endocrinol Metab 53: 480,1981)

A B S T R A CT 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 hormonereleasing 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

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