Electron Microscopic Study of Human Prolactin Producing Pituitary Adenoma

Abstract

An electron microscopic study of 15 cases of prolactin-producing pituitary adenomas removed by operations was performed. The cases consisted of 14 females and one male, and all of the female patients manifested galactorrhea. The resting serum level of prolactin ranged from 200 to 2, 650 ng/ml, which responded well to intravenous TRH, increasing to 7, 290 ng/ml. Out of 15 patients, nine harbored intrasellar microadenoma, and the others harbored large tumor masses showing suprasellar extension. The age distribution was from 20 to 70 years, with an average of 25.7 years for the microadenoma-group and an average of 42.7 years for the large tumor-group.
Electron microscopic observations of adenomas obtained from 11 patients who had not received bromocriptine revealed adenoma tissue composed of polyhedral adenoma cells. The large central nuclei had irregular outlines. Endoplasmic reticulum and Golgi apparatus were well developed. In two cases, the adenoma cells had abundant microvilli. In the cytoplasms, there were characteristic pleomorphic secretory granules measuring up to 450 my in the longest dimension, which were considered to be prolactin granules. There were also round secretory granules, measuring 100-300 my in diameter, intermingling with the pleomorphic secretory granules. These secretory granules were electrodense, and had a limiting membrane. Exocytosis of the secretory granules was frequently encountered. Cilia and junctional complexes were occasionally observed, but intraadenomatous calcification and intracytoplasmic accumulation of fine filaments were rarely seen. These findings suggested an increased cellular activity of the adenoma cells in hormone synthesis and release. No difference in the fine structures was noticed between the microadenomas and large tumors.
Bromocriptine was given preoperatively in three cases, and the serum prolactin levels were markedly reduced. In two cases, the secretory granules were increased in number and accumulated within the cytoplasm. Most of the granules were round in shape, measuring 100-400 mμ in diameter. These were fewer pleomorphic secretory granules, measuring up to 600 mμ in diameter. No exocytosis of the secretory granules was observed. In the other case, the secretory granules decreased in number and frequently were hardly observed. There were numerous multivesicular structures in the cytoplasm. These findings in bromocriptine-treated cases suggested that the drug acted to reduce the cellular activity in both hormone synthesis and release.
The remaining case clinically showed the galactorrhea-amenorrhea syndrome, but an electron microscopic study disclosed a fine structure similar to that of the non-functioning adenoma. The adenoma tissue was composed of polygonal adenoma cells, which contained a few round secretory granules measuring 100-200mμ in iameter. The granules were covered with a limiting membrane, leaving a clear halo between the membrane and the dense core. The ultrastructural findings in this particular case suggested an interference inproduction, release and transport of PIF by suprasellar extension of theadenoma.
Electron microscopy is an essential tool in establishing the final diagnosis of prolactin-producing adenomas of the pituitary.