Category: Adrenal Disorders

Monitor: 28

28 - Expression of luteinizing hormone/human chorionic gonadotropin receptor in adrenal adenomas of post-menopausal women

Thursday, Apr 25
1:30 PM – 2:00 PM

Objective : Increasingly, patients have been noted to have incidentally found adrenal adenomas on imaging performed for other purposes. The incidence of adrenal adenomas is higher in women than men with peak incidence at ages 50-70. Elevated expression of gonadal markers such as luteinizing hormone/human chorionic gonadotropin receptor (LH/hCG-R) 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. In addition, several case reports have demonstrated LH/hCG-R expression in adrenal secretory tumors in postmenopausal and pregnant females. Given the strong evidence that adrenal tumor development is driven by LH in other species, we hypothesized that the LH/hCG-R is expressed in adrenal adenomas derived from post-menopausal women.  We retrospectively studied the immunohistochemical expression of LH/hCG-R in archival adrenal cortical adenoma specimens derived from post-menopausal women.

Methods : Adrenal tissues from 23 women >50 years of age were examined.  Clinical data was obtained in a blinded fashion and hormonal data was available in 9/23 cases.  Of the 9 cases where secretory status was known, 6/9 were secreting cortisol whereas 3/9 adenomas were secreting aldosterone.  All 23 specimens were immunostained for LH/hCG-R utilizing the Streptavidin–Biotin staining method. The slides were reviewed by a pathologist 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 : Expression of LH/hCG-R was demonstrated in both normal and adenomatous tissue in all 23 specimens.  The staining in adenomas was heterogeneous, with clusters of densely stained (3+) LH/hCG-R positive cells in all specimens. There were no demonstrable differences in the intensity or homogeneity of staining in cortisol-secreting vs. aldosterone-secreting adenomas There were less densely stained clusters (1-2+) in normal adjacent adrenal cortical tissue in all three zones but most prominent in the subcapsular, zona glomerulosa region, an area where the putative adrenal cortical stem cells are found.  

Discussion : Adrenal adenomas derived from 23 postmenopausal women exhibited heterogeneous but strong immunohistochemical expression of LH/hCG-R.  Adjacent normal adrenal cortical tissue also expressed some LH/hCG-R protein in all specimens.

Conclusion : LH/hCG-R is expressed in adrenal adenomatous tissue in postmenopausal women. Therapies aimed at LH/hCG-R (GnRH agonists and antagonists) may be beneficial in this population to reduce tumor size and hypersecretion.


Effie Tsomos

Mount Sinai Hospital
Great Neck, New York

Dr. Effie Tsomos is a first year endocrine fellow in the Division of Endocrinology, Diabetes, and bone diseases at the Icahn School of Medicine in New York, NY. She has publications and presentations at national meetings in the area of diabetes, thyroid, and adrenal diseases. She will be doing scholarly work in adrenal diseases during the second year of her fellowship.

Alice C Levine

Professor of Medicine (Endocrinology)
Icahn School of Medicine at Mount Sinai
New York, New York

Alice C. Levine M.D., Professor of Medicine in the Division of Endocrinology, Diabetes and Bone Diseases at the Icahn School of Medicine at Mount Sinai, received her M.D. degree from Columbia University College of Physicians and Surgeons and completed her residency in internal medicine at the New York University-Manhattan V.A. Medical Center. She did her Fellowship in Endocrinology at the Mount Sinai School of Medicine during which time, she began her academic career which focuses on hormonal neoplasia. They were the first to report on the successful treatment of benign prostatic hyperplasia (BPH) with hormonal (GnRH agonist) therapy. These clinical studies led to more basic translational studies focusing on the interactive effects of steroid hormones and growth factors on benign and malignant prostate growth, carried out in collaboration with Alexander Kirschenbaum, M.D., Clinical Associate Professor of Urology. Together they direct a laboratory effort that has been continuously funded for over 25 years and has produced highly cited and landmark studies on the roles of 5 alpha-reductase and cyclooxygenase-2 in normal prostate development and prostate cancer. More recently their focus has turned to the understanding of factors involved in prostate cancer bone metastases and the development of new therapies for advanced, bone-metastatic disease.
Dr. Levine serves as Co-Founder and Co-Director of the Mount Sinai Adrenal Center. Since its inception in 2010, the center has garnered national recognition and has become one of the leading programs for adrenal referrals on the east coast. Dr. Levine has published extensively on the management of adrenal diseases including primary aldosteronism, pheochromocytoma, adrenal hypercortisolism and adrenal cortical carcinoma.
Dr. Levine also is a highly regarded teacher and has been the Course Director for the 2nd Year Endocrine Pathophysiology Course at the Mount Sinai School of Medicine, as well as the Director of Endocrine Grand Rounds and Endocrine Fellows Research. She has mentored generations of undergraduate, graduate, and postgraduate trainees in her laboratory and in the clinic, and is often cited by them as being a strong influence on their subsequent career choices. In 2011 she received the Mount Sinai Institute of Medicine’s Excellence in Teaching Award.
Dr. Levine also maintains a busy clinical practice at the Mount Sinai Faculty Practice in which her main focus is diseases of the Adrenal, Pituitary and Reproductive Glands with an emphasis on hormonal neoplasia. She is consistently listed on Best Doctors List both in the NYC Metropolitan Area and Nationally.

Regina Belokovskaya

Endocrinology fellow
Icahn School of Medicine at Mount Sinai, New York

Dr. Regina Belokovskaya is Endocrinology fellow at Icahn School of Medicine at Mount Sinai.

Dushyanthy Arumugam

Visiting Scientist
Icahn School of Medicine at Mount Sinai, New York

Dr. Arumugam is a visiting scientist in the division of endocrinology at the Icahn School of Medicine at Mount Sinai.

Alexander Kirschenbaum

Clinical Associate Professor of Urology
Icahn School of Medicine at Mount Sinai, New York

Dr. Kirschenbaum is a clinical associate professor of urology at the Icahn School of Medicine at Mount Sinai.

Kenneth Haines

Professor of Pathology
Icahn School of Medicine at Mount Sinai

Dr. Kenneth Haines is a Professor of Pathology at Icahn School of Medicine at Mount Sinai.