Endocrine Abstracts

Activation of the hypothalamo-pituitary-gonadal axis, from the third trimester of pregnancy to the first post-natal months in males, results in serum concentrations of gonadotrophins and testosterone approaching adult levels. This phase, known as male mini-puberty, represents a key window of opportunity to identify congenital GnRH deficiency in early childhood.

We present a case to illustrate the diagnostic efficiency of screening for mini-puberty in a male neonate born to a mother with congenital hypogonadotrophic hypogonadism (CHH). She conceived with her second cycle of IVF, having failed to fall pregnant with natural-cycle ovulation induction and on her 1^st IVF cycle. She had an unremarkable pregnancy and delivered at term via an elective caesarean section. Prior to conception research-based genotyping failed to identify any known CHH-associated mutation. She did not exhibit any non-reproductive phenotypes, such as anosmia, clefting, or hearing impairment. She was concerned about the risk of her son having inherited CHH. At birth there was no strong indication for absent male mini-puberty; namely he had normal genitalia and bilateral descended testes, but we nevertheless proceeded to serum assay of gonadotrophins and testosterone at 2 months. These were unequivocally normal: testosterone 8.9 nmol/l, LH 3.0 IU/l and FSH 2.3 IU/l.

In male neonates with suspected CHH a single serum sample (between 4 and 8 weeks of life) can detect early GnRH deficiency far more rapidly and with much greater accuracy than any number of dynamic tests performed in adolescence. Hormonal profiling during mini-puberty has been demonstrated to offer better diagnostic specificity than genetic studies in predicting the adult phenotype, with the exception of ANOS1 mutation. Early diagnosis of CHH through hormonal profiling to detect absent mini-puberty in high-risk cases would allow for a more coordinated monitoring and therapeutic intervention schedule for timely pubertal progression, thus maximising later fertility potential, physical and psychosexual well-being.