SAT-343 Immunohistochemical Expression of Luteinizing Hormone/Human Chorionic Gonadotropin Receptor (LH/hCG Receptor) in Adrenal Adenomas of Postmenopausal Women

Abstract

Background: Increasingly, patients are found to have incidentally found adrenal adenomas on imaging performed for other purposes. Further biochemical work-up results in a diagnosis of mild hypercortisolism in as many as 30% of these patients. The incidence of adrenal adenomas and Cushing’s is higher in women than men with peak incidence ages 50-70. Elevated expression of gonadal markers such as LH/hCG receptor and the gonadal transcription factor GATA-4 has been well described in post-gonadectomy induced adrenal cortical neoplasia in neutered ferrets and certain mouse strains. The majority of these neoplasms of the adrenal cortex, which share a common embryologic progenitor with the gonads in the urogenital ridge, produce sex steroids and appear to differentiate towards a “gonadal” molecular profile. Isolated case reports have demonstrated LH/hCG receptor expression in adrenal secretory tumors in postmenopausal women and pregnant females. Taken together, there is strong evidence that a subset of adrenal tumors is driven by LH in postmenopausal women. Hypothesis: We hypothesized that adrenal adenomas producing secretory syndromes in postmenopausal women express LH/hCG receptor. Methods: 24 archival adrenal tissues from women >50 years of age with hypersecretory syndromes (primary aldosteronism and Cushing’s) were obtained with IRB approval. The samples were immunostained for expression of the LH/hCG receptor (monoclonal unconjugated LHR Antibody (LHCGR/1417), Novus Biologicals, CO) utilizing the Streptavidin–Biotin staining method. The slides were reviewed in a blinded fashion, and cytoplasmic, membrane, and nuclear expression of the markers were graded as no immunoreactivity, or 1+, 2+, or 3+ staining. Results: All 24 adenomas had demonstrated expression of LH/hCG receptor in both normal and adenomatous tissue. The staining in adenomas was heterogeneous, with clusters of densely stained LH/hCG receptor positive cells found selectively in areas of the adenomas. In addition, these clusters were found in normal adjacent adrenal tissue primarily in the subcapsular, zona glomerulosa region, an area where the putative adrenal cortical stem cells are found. Conclusion: LH/hCG receptor was found to be expressed in normal adrenocortical and adenomatous tissue in postmenopausal women, a population that has elevated serum LH levels. These findings may have clinical implications and provide a rationale for the treatment of secretory adrenal adenomas with GnRH agonists or antagonists in postmenopausal women.