Presence of Human Prolactin-Producing Adenomas and Bromocriptine: A Histological, Immunocytochemical, Ultrastructural, and Morphometric Study*

Abstract

Bromocriptine inhibits PRL secretion and causes a size reduction of PRL-producing adenomas. To clarify its antitumor effect, PRL cell adenomas were studied by histology, immunocytochemistry, transmission electron microscopy, and light and electron microscopic morphometry. All patients had macroadenomas (diameter, >10 mm) and serum PRL levels from 420–9800 ng/ml. Patients 1 and 2 received no medication. Four patients were treated with bromocriptine (7.5 mg/day for 4–weeks); patients 3 and 4 continued therapy up until the operation, whereas patients 5 and 6 discontinued bromocriptine 7 and 14 days, respectively, before tumor removal. All four bromocriptine- treated patients demonstrated a reduction in serum PRL levels and tumor size on computed tomography. Patients 5 and 6 showed reexpansion of their tumors after drug withdrawal. By light microscopy, all six tumors represented chromophobe adenomas and were positive for PRL by the immunoperoxidase technique. The intensity of immunostaining and the number of immunostainable cells were markedly reduced in the two adenomas removed from bromocriptine-treated patients. The tumor cells of the untreated patients exhibited ultrastructural signs of active secretion, while those from bromocriptine-treated patients showed involution. Neither widespread cell necrosis, infarction, nor vascular injury was evident. Light and electron microscopic morphometry of the cells from bromocriptine-treated compared with that of cells from untreated patients showed a significant reduction in cytoplasmic, nuclear, and nucleolar areas. The percentage volume densities of the rough endoplasmic reticulum and Golgi complexes were decreased, whereas those of secretory granules were increased. The diameters of secretory granules, volume densities of mitochondria, lysosomes, and lipid droplets remained unchanged. In the tumors from patients 5 and 6, the changes in cell and cytoplasmic areas were intermediate between those from treated and untreated patients; however, 2- and 4- fold increases in nucleolar area were noted over those in cells from untreated and treated patients, respectively. The observed reversible decrease in the volume of PRL cell adenomas by bromocriptine treatment is explained, at least in part, by the reduction of cell volume and not by cell loss secondary to necrosis. (J Clin Endocrinol Metab55: 1178, 1982)