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A Growth Hormone-Releasing Hormone-Producing Pancreatic Islet Cell Tumor Metastasized to the Pituitary Is Associated with Pituitary Somatotroph Hyperplasia and Acromegaly

Department of Neurosurgery, Nippon Medical School (N.S., A.T.), 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, Japan; Department of Pathology, Tokai University School of Medicine (N.S., R.Y.O.), Boseidai, Isehara-city Kanagawa 259-11, Japan; Department of Neurosurgery, Yokohama Shin Midori Hospital (S.G.), Kanagawa, Japan; Department of Internal Medicine, Miyazaki Medical College (H.K.), Miyazaki, Japan; Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation (L.J., R.V.L.), Rochester Minnesota 55905; Department of Pathology, St. Michael’s Hospital (K.K.), Toronto, Ontario, M5B 1W8 Canada

Address all correspondence and requests for reprints to: Naoko Sanno, Department of Neurosurgery, Nippon Medical School, 1-1-5, Sendagi Bunkyo-ku, Tokyo 113, Japan.

The functional and morphological changes in the pituitary gland caused by a GHRH-producing pancreatic islet cell tumor that metastasized to the pituitary and caused somatotroph hyperplasia are described. A 52- yr-old woman presented with loss of visual acuity, diabetes insipidus, and acromegaly caused by a GHRH-producing endocrine carcinoma metastasized to the pituitary. The serum GHRH, GH, and insulin-like growth factor I levels of the patient were elevated. Immunohistochemical and in situ hybridization study revealed GHRH immunoreactivity and GHRH messenger RNA (mRNA) in the metastatic tumor cells. The anterior pituitary showed hyperplasia of somatotroph cells with intact acinar structure that did not contain an adenoma, determined by light microscopy using silver impregnation. Electron microscopy revealed hyperplastic characteristics of densely granulated somatotrophs. In situ hybridization documented strong signals for GH mRNA and pituitary-specific transcriptional factor Pit-1 mRNA in the hyperplastic somatotrophs. A weak signal for GHRH receptor mRNA was detected in these somatotrophs. However, using in situ RT-PCR, GHRH receptor mRNA was more conclusively observed in most of the somatotrophs. The excessive production of GHRH by metastatic tumor may have resulted in somatotroph hyperplasia by the synergistic effects of Pit-1 and GHRH receptor. It can be concluded that the pathogenesis of pituitary adenoma formation is primarily mediated by other factors than hypothalamic hormone.

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