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ECTOPIC HORMONE AND RECEPTOR SYNDROMES
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Some of the most challenging endocrine problems occur in patients with malignancies of diverse cell types, because both endocrine and nonendocrine tumors secrete polypeptide hormones. As it became recognized that a polypeptide hormone could be produced by tumor cells derived from a tissue that normally did not secrete the hormone, the notion of ectopic hormone production developed. Most tumors associated with ectopic hormone syndromes are derived from cells that are normally capable of producing peptide hormones. Initially, it was thought that ectopic hormone production by tumor cells was a rare event. Interestingly, both the frequency and the original conception of this syndrome have been redefined over the last few decades. It has come to be appreciated—through the use of biochemical and molecular biologic techniques—that the synthesis of peptide hormones and the transcription of their genes by tumor cells are in fact quite common occurrences. Tumor cells may differ from normal cells in their ability or inability to process precursor molecules, which may account for the presence or absence of hormone excess states and for the profile of peptide hormone forms and fragments present in the circulation and in tumor cell extracts. However, tumor production of hormone fragments or precursors is much more common than the clinical syndromes of hormone excess.
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The classic criteria used to confirm that a tumor is the source of a hormone excess state include the following: (1) evidence of an endocrinopathy in a patient with a tumor; (2) remission of the endocrinopathy after tumor resection; (3) detection of an arteriovenous gradient across the tumor; and (4) confirmation of protein and messenger RNA encoding the hormone produced by tumor tissue.
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In addition to classic hormone excess states resulting from the ectopic or inappropriate secretion of a hormone by an endocrine or nonendocrine tumor, endocrinopathies can result from the ectopic expression of a hormone’s receptor. This is well illustrated, for example, by the occurrence of Cushing syndrome in pregnancy or in relation to meals, due to the ectopic expression of luteinizing hormone (LH) or gastric inhibitory polypeptide (GIP) receptors in adrenal tissue, respectively. Several other ...