Elevated Adrenal Steroids, Advanced Bone Ages, and Skewed Adult Heights in Trans Male Adolescents: Indications for Comprehensive Evaluation

Purpose: Several studies demonstrate endogenous androgen excess in adult trans male patients, but data are lacking in adolescents. Identifying hyperandrogenism in growing children is relevant, as it can be the first sign of serious adrenal conditions and can be associated with advanced skeletal maturity and premature growth cessation. We sought to identify the percentage of adolescent trans male patients who, prior to gender affirming treatment, had biochemical hyperandrogenism relative to reference ranges and to a comparison group. Methods: We conducted a retrospective chart review of patients seen between 2013 and 2020 at an academic pediatric center with a multidisciplinary gender team. Participants included 177 trans male patients and 166 cisgender female patients who underwent endocrine evaluation and 11 trans males and 15 cisgender females who completed adrenocorticotropic hormone (ACTH) stimulation tests for hyperandrogenism. We analyzed differences in androgen levels, bone ages, and adult heights. Results: Eighty-eight of 172 (51.2%) trans males tested exhibited elevations of one or more androgens compared to 24/158 (15.2%) cisgender females ( p < 0.0001). Trans males were more likely than cisgender females to have elevated dehydroepiandrostenedione (DHEA) ( p = 0.0056) and dehydroepiandrostenedione sulfate ( p = 0.0005) levels compared to age-adjusted reference ranges. Trans males displayed significantly higher DHEA responses to ACTH ( p = 0.019), more advanced bone ages ( p = 0.00014), and lower median adult height ( p = 0.001) compared to cisgender females. Conclusions: A higher percentage of trans male patients had elevated levels of adrenal steroids, more advanced bone ages, and lower median adult heights compared to cisgender females.