SUN-026 Unusual Presentation of Aromatase Excess Syndrome

Abstract

Introduction: Aromatase excess syndrome is a rare disorder with gynecomastia being the main symptoms. Its prevalence is unknown with approximately twenty cases reported. We describe an unusual case of Aromatase excess syndrome. It was diagnosed incidentally at a much older age than expected while evaluating for hypersomnia. Case presentation: A 28 year old male with no significant past medical history, presented with complaint of hypersomnolence, developed during puberty. He had multiple evaluations with no apparent etiology; sleep study and all his other laboratory tests were normal including testosterone levels, normal IGF-1 and cortisol. When patient was evaluated in the Endocrine clinic, he was found to have bilateral gynecomastia, which he had for many years. His estradiol was 150 pg/ml (Normal <50 pg/ml). Repeat was 137 pg/ml with normal DHEA-S Subsequent concomitant estradiol of 204 pg/ml with an estrone of 35.7 pg/ml (9–36). Total testosterone was normal at 588 ng/dl. Evaluation for a tumor with abdominal CT, testicular ultrasound, and HCG was negative. As his symptoms of fatigue and hypersomnolence were not improving and his estradiol to testosterone ratio was >10, he was started on an aromatase inhibitor and his ratio dropped from 1:40 to 1:24, as his estradiol went down to 75 pg/ml. Discussion: Gynecomastia is the benign proliferation of breast tissue due to imbalance between estrogen and testosterone. It could be caused by medications or medical illnesses. Occasionally its presence can harbor a serious endocrine issue especially if presenting in the prepubertal period. Thus, evaluation is often necessary. Among the pathological causes is the Aromatase excess syndrome. In this syndrome there are three types of cryptogenic genomic rearrangements identified. Those rearrangement affect the aromatase gene CYP19 and results in gain of function of the aromatase enzyme. Patients will have high estradiol and estrone level, lower FSH and LH levels that will normalize after treatment with aromatase inhibitor. Their testosterone levels could be low or normal. For the clinical diagnosis, there are four criteria; bilateralgynecomastia, pre or peripubertal onset, exclusion of other causes of gynecomastia and having a genetic trait. The first three criteria are indispensable for diagnosis while fourth one is not obligatory, but rather pathognomonic. An elevated estradiol to testosterone ratio above 1:10 is a supportive finding, as well as having a low FSH with low to normal LH. Genetic identification of the CYP19 A1 mutation remains the definitive method of diagnosis. Our patient met the first three criteria and also had estradiol to testosterone ratio is > 1:10. Genetic confirmation is challenging. Consequently, whole genome sequencing may be required. Though unusual, this case highlights the importance of looking deep in the differential when evaluating gynecomastia.