MON-354 Undiagnosed Addison's Disease as a Cause of Infertility

Abstract

Background: There are multiple potential mechanisms for infertility in AD (Addison’s disease) including suppression of HPG axis, LFOR (low functional ovarian reserve) secondary to AH (adrenal hypoandrogenism) or concomitant autoimmune POF (premature ovarian failure), as well as suppressive effect from high 17-OHP (17α-hydroxyprogesterone). Nonetheless, there is scarce literature concerning this complication of AD. Clinical Case: A 28 year old female with a normal BMI and a history of hypothyroidism, suspected PCOS, and spontaneous abortion presented to RE (Reproductive Endocrinology) for a 2 year history of primary infertility. She had menarche at age 12, with regular menses for 6 years until OCP was initiated. At age 24 she spontaneously conceived, but unfortunately miscarried. She subsequently developed oligomenorrhea, reporting menses every 3-4 months in the absence of hirsutism or acne. Initial evaluation demonstrated negative β-hCG, normal TSH 1.27 mcIU/ml (0.27-4.2), high anti-TPO antibodies 1040 IU/ml (<34), progesterone 12.79 ng/ml (0.06-0.89 follicular, 1.83-23.9 luteal), AMH 13.5 ng/ml (1.03-11.1), and 17-OHP 272 ng/dl (<80 follicular, <285 luteal), and low DHEA-S 20.6 mcg/dl (98.8-340) and free testosterone 1.6 pg/ml (0.16.4). AFC (antral follicle count) was 50, and semen analysis and HSG were unrevealing. Elevated 17-OHP was thought to represent luteal phase, but repeat in early follicular phase remained elevated, prompting referral to Endocrinology. Co-syntropin stimulation test was performed with pre-ACTH 17-OHP persistently elevated (546 ng/dl), with minimal increase 1 hour post-ACTH (598 ng/dl). Cortisol failed to stimulate increasing only from 11 to 14 mcg/dl post-ACTH. Further evaluation revealed elevated ACTH (324 pg/ml), and positive anti-adrenal antibodies. Following diagnosis of AD, HC (hydrocortisone) 10 mg in the morning and 2.5 mg in the afternoon was initiated with improvement in menstrual regularity to 34 day cycles. RE recommended initiation of letrozole for ovulation induction, and intrauterine insemination. However, given improvement in cycles with HC, Endocrinology recommended delaying fertility treatments temporarily. Four months after HC initiation, pregnancy was confirmed, and she subsequently delivered a healthy baby girl. Conclusion: This case emphasizes the importance of a thorough endocrinologic evaluation in patients with infertility, particularly those with other autoimmune endocrinopathies. The etiology of infertility in AD is likely multifactorial, and there is minimal supportive literature to date. While some authors have proposed LFOR secondary to adrenal hypoandrogenism or POF as an underlying etiology, this unique case describes a patient with high AMH and AFC, who had successful conception and pregnancy following initiation of HC replacement.