Testosterone

Abstract

Central precocious puberty following accidental exposure: case report A 4-month old boy developed central precocious puberty (CPP) following accidental exposure to testosterone. The boy was born at full term via caesarean section and had an uncomplicated postnatal course. At four months of age, his parents noticed enlargement of his penis. At eight-month well-child check, his paediatrician also noted sparse pubic hair and a rapid increase in length and weight. He did not have axillary hair or acne and his testes had not enlarged. Review of systems was negative for neurologic symptoms recurrent emesis or changes in behaviour. There was no family history of precocious puberty. At 10 months of age, he was referred for an initial endocrinology consultation. The examination revealed a large penis (stretched length 8cm and circumference 3cm), Tanner stage II pubic hair, and 2mL testes bilaterally. Bone age was 13–15 months. Scrotal ultrasound examination demonstrated normal prepubertal testes and no evidence of an adrenal or hepatic mass. At 12 months of age, an adrenocorticotropic hormone stimulation test was performed which did not show evidence of a disorder of adrenal steroid biosynthesis. Laboratory investigation revealed elevated levels of both baseline and stimulated plasma total testosterone to 243 ng/dL and 396 ng/dL, respectively. At 14 months of age, a leuprolide stimulation test showed peak serum luteinizing hormone (LH) of 1.41 mIU/mL and peak plasma total testosterone of 21 ng/dL. A presumptive diagnosis of familial gonadotropin-independent male-limited sexual precocity was considered. He was prescribed bicalutamide and anastrozole. However, before starting the treatment, his parents sought for a second opinion. He was admitted to a Endocrinology clinic. At the time of the second opinion consultation at 16 months of age, his weight and length had exceeded the 99th percentile for age, with evidence of prior acceleration and an estimated growth velocity of 1.61 cm/month. Examination showed stretched penile length of 7.5cm and mid-shaft diameter of 2cm. The scrotum was thin and pendulous and there were a few pubic hair at the base of the penis. His testes were 2mL bilaterally. Ultrasound of the testes was found to be normal. Laboratory investigation revealed plasma total testosterone < 10 ng/dL, serum LH < 0.1 mIU/mL and beta-human chorionic gonadotropin < 0.1 mIU/mL. Due to inconsistent findings obtained at present compared to available history, sequencing of the LHCGR gene was performed, which did not reveal any pathogenic variants. Due to negative evaluation, mother was asked for more brief history. She denied parental use of androgen-containing products. However, she reported that the maternal grandfather, who provided direct care to the boy in the first year of life, used transdermal testosterone gel daily for treatment of hypogonadism for himself. During that period, the boy was exposed to testosterone [dosage not stated]. As the grandfather stopped caring for him after his first birthday, the boy had no further progression of secondary sex characteristics. Also, his plasma testosterone levels showed a decrease. On follow-up at 17 months of age, his examination was unchanged. He was diagnosed with CPP due to accidental exposure to testosterone through his grandfather. He was discharged from Endocrinology Clinic after further counseling on CPP.