ESPE Abstracts

Introduction: In a large series, approximately 65% of boys with delayed puberty have constitutional delay in growth and puberty (CDGP). We report an adolescent male who presented with delayed puberty and managed as presumed CDGP. Unexpected pubertal progression while receiving treatment made us question the diagnosis of CDGP.

Case-report: A 15-year-old African adolescent male presented with delayed growth and puberty. He reported development of minimal pubic hair, no deepening of voice and no growth spurt. There was no associated history of headache, visual disturbances, anosmia or synkinesis. He had left proximal radioulnar synostosis and was Haemoglobin-C carrier. He attended mainstream school without additional help. His father also had delayed onset of puberty. On examination, his height and weight were between 9th-25th centile (midparental height 50th centile). Clinical examination showed no dysmorphic features or gynecomastia, prepubertal testes (2ml) with genitalia stage 1 and pubic hair stage 2. Investigations showed normal renal, liver and bone profile, and negative coeliac screen. Endocrine investigations showed normal thyroid function, insulin-like growth factor-1, and serum prolactin. Basal serum gonadotropins (LH <0.8IU/L, FSH 2.6IU/L) were pre-pubertal with low serum testosterone (0.3nmol/l). Bone age was delayed (12.6 years TWII). Probable diagnosis of CDGP was considered and treatment started with monthly testosterone injections. COVID-19 restrictions prevented regular pubertal assessment. No significant increase in testes volumes by 16.67 years (4ml testes after 18months of testosterone injections) resulted in MRI pituitary and olfactory bulbs, which was normal. Continued absence of increase in testes volume by 17.42years led to further investigations after interruption of testosterone injections (LHRH stimulation test and molecular genetic testing for hypogonadotrophic hypogonadism). An exaggerated LH/FSH response on LHRH stimulation test (LH 5.1 – 72 - 66U/L; FSH 8.9 - 17.9 - 22U/L) and early afternoon serum testosterone (7.4nmol/L) off testosterone injections in the presence of small testes made us consider the diagnosis of Klinefelter syndrome (KS). Subsequent comparative genomic hybridisation (CGH) array identified two copies of X chromosome and one copy of Y-chromosome in approximately 35% of cells, confirming mosaic KS.

Conclusion: Klinefelter syndrome is a profoundly underdiagnosed condition. Approximately 25% of adult males with KS are ever diagnosed. Mosaic KS is even rarer contributing to 15 - 20% of KS patients and requires a high index of suspicion. Regular assessment of testicular volumes until mid-late pubertal testicular volumes are achieved is vital in the management of adolescent boys with presumed CDGP.