MON-474 - An Evaluation of LH/Hcg Receptors in Adrenal Adenomas and Aldosterone Producing Micronodules in Adrenalectomy Samples from Postmenopausal Women

Introduction: Benign adrenal tumors are more common in women than in men. LH/hCG receptors (LH/hCG-R) are present in the normal adrenal gland, mainly in the zona reticularis (ZR) where adrenal androgen production occurs under the regulation of 17α-hydroxylase/17, 20 lyase and its cofactor cytochrome B5 (CYB5). Several clinical examples exist of elevated LH stimulating adrenal cortical tumorigenesis in postmenopausal women. Somatic mutations in the WNT/β-Catenin pathway have been identified as potential drivers of LH/hCG-R expression in these tumors, including in aldosterone producing adenomas (APAs). In the normal adrenal gland, aldosterone producing micronodules (APMs) are known to share somatic mutations with APAs. We studied the immunohistochemical expression of LH/hCG-R in adrenal adenomas and APMs in the adjacent normal adrenal gland of postmenopausal women.

Methods: Archival specimens from adrenal adenomas derived from 12 postmenopausal women were examined. Clinical data for each sample was obtained in a blinded fashion. Our cohort included 2 patients with Cushing’s Syndrome, 2 with APAs, 3 with mild autonomous cortisol secretion (MACS) plus some biochemical evidence of primary aldosteronism (PA), and 5 with incomplete hormonal evaluation. All samples had adjacent normal adrenal tissue. Staining was performed for 11β-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), LH/hCG-R, WNT/β-Catenin, and CYB5 expression in adenomas and adjacent normal gland.

Results: 10/12 adenomas expressed LH/hCG-R (2/2 Cushing’s, 2/2 APAs, 2/3 MACS plus PA, and 4/5 with incomplete data). 10/12 adenomas expressed CYB5 (1/2 Cushing’s, 1/2 APAs, 3/3 MACS plus PA, and 5/5 with incomplete data). 10/12 samples contained APMs in the normal adjacent adrenal gland. 9/10 APMs were positive for LH/hCG-R, 7 of which were positive for CYB5.

Conclusions: LH/hCG-R is expressed in all types of adrenal adenomas in postmenopausal women as well as APMs. In addition, CYB5 is frequently expressed in adenomas and APMs that also demonstrate LH/hCG-R positivity. High LH levels in postmenopausal women may promote tumorigenesis and APMs.

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