Prolactin and Growth Hormone in Patients with Pituitary Adenomas: A Correlative Study of Hormone in Tumor and Plasma by Immunoperoxidase Technique and Radioimmunoassay

Abstract
Excess secretion of growth hormone (hGH) and prolactin by some pituitary tumors has been associated with adenomas classified by tinctorial stains as acidophilic, mixed acidophilic-chromophobe, and chromophobe. In order to establish a functional classification of such tumors, immunoperoxidase stains specific for hGH and prolactin were applied to 21 surgically removed tumors from patients whose plasma levels of the two hormones had been determined preoperatively by radioimmunoassay. Five normal pituitary glands obtained at autopsy were also studied by immunoperoxidase technique. Eight patients had acromegaly and elevated plasma hGH; in 7 of these, hGH was located in the tumor cells by immunoperoxidase. Twelve patients had hyperprolactinemia; the immunoenzyme method identified prolactin in 10 of their tumors. Four patients with tumor prolactin were also acromegalic with demonstrable tumor hGH. Tumor hGH was found in 1 patient with normal plasma hGH, and tumor prolactin in 1 patient with normal plasma prolactin. All the tumors were classified as chromophobe adenomas by nonimmunological stains except for 3 from acromegalic patients, which were mixed acidophilicchromophobe. No purely acidophilic tumor was found. The results demonstrate a high degree of correlation between the elevation of these hormones in plasma and their presence in tumor cells by the immunological methods used. Since the nonimmunological staining methods showed acidophilia in only a few of the hypersecreting tumors, the immunoperoxidase technique is far more sensitive, as well as specific, than tinctorial methods for classification of hormone-secreting tumors. The large amount of hormones demonstrated in the adenoma cells and their relative absence from adjacent “normal” pituitary suggests that the tumor cells are the source of the hypersecretory state. This study also demonstrates a high incidence of prolactin hypersecretion, often clinically inapparent, by pituitary tumors. In the normal pituitaries the study reveals a larger number of cells containing immunoreactive prolactin (31%) than previously found by tinctorial methods, and provides evidence that hGH and prolactin may be produced in the same cell as well as in separate cells.