Immunohistochemical and electron-microscopic studies of functional and non-functional pituitary adenomas including one TSH secreting tumor in a thyrotoxic patient

Twenty-nine pituitary adenomas were studied by histologic, electron-microscopic, and immunohistochemical techniques. By conventional histological stains, 19 cases were considered chromophobe, five cosinophilic, and five mixed chromophobe and eosinophilic adenomas. Immunohistochemistry, with specific antibodies against human GH, PRL, FSH_β, LH_β, and TSH_β showed, clearly, secreting and non-secreting groups of tumors: growth hormone-secreting adenomas (four cases), prolactin-secreting adenomas (eight cases), thyrotropin and/or gonadotropin-producing tumors (seven cases), and non-secreting adenomas (ten cases). Electron microscopy showed secretory granules of varying numbers, sizes, and shapes in all tumor cells in all 29 cases. The endoplasmic reticulum appeared markedly increased in 5/8 of the prolactin producing tumors; mitochondria also appeared markedly increased in 3/7 of the thyrotropin-gonadotropin group. These three cases could be considered "oncocytomas" by electron-microscopic criteria. Patients with prolactin-secreting adenomas had high serum prolactin and typical clinical symptoms associated with such tumors. One patient with large numbers of TSH-containing cells in her tumor and some cells with growth hormone and FSH had overt thyrotoxicosis. Although the remaining six tumors stained specifically for one hormone or another, no clinical correlation was possible. Conventional electron microscopy has some value in the generic identification of puritary tumor cells, but no value in the recognition of specific secretory products or specific cell types. Conventional histopathology is the least reliable method to correctly identify a specific type of pituitary adenoma, beyond the identification of the adenomatous changes. This study demonstrates the existence of gonadotropin- and/or thyrotropin-secreting pituitary adenomas, among so-called chromophobe adenomas, or "undifferentiated adenomas".