Diagnosis of Male Central Hypogonadism During Childhood

GRINSPON, ROMINA P; CASTRO, SEBASTIÁN; BRUNELLO, FRANCO G; SANSÓ, GABRIELA; ROPELATO, MARÍA GABRIELA; REY, RODOLFO A

Journal of the Endocrine Society

Oxford

Año: 2021 vol. 5

The diagnosis of male central (or hypogonadotropic) hypogonadism, typically basedon low luteinizing hormone (LH) and testosterone levels, is challenging during childhoodsince both hormones are physiologically low from the sixth month until the onsetof puberty. Conversely, follicle-stimulating hormone (FSH) and anti-Müllerian hormone(AMH), which show higher circulating levels during infancy and childhood, are not usedas biomarkers for the condition. We report the case of a 7-year-old boy with a history ofbilateral cryptorchidism who showed repeatedly low FSH and AMH serum levels duringprepuberty. Unfortunately, the diagnosis could not be ascertained until he presentedwith delayed puberty at the age of 14 years. A gonadotropin-releasing hormone (GnRH)test showed impaired LH and FSH response. By then, his growth and bone mineralizationwere partially impaired. Gene panel sequencing identified a variant in exon 15 ofFGFR1, affecting the tyrosine kinase domain of the receptor, involved in GnRH neuronmigration and olfactory bulb morphogenesis. Testosterone replacement was started,which resulted in the development of secondary sexual characteristics and partial improvementof bone mineral density. This case illustrates the difficulty in making the diagnosisof central hypogonadism in boys during childhood based on classical criteria, andhow serum FSH and AMH assessment may be helpful if it is suspected before the age of puberty, and confirm it using next-generation sequencing. The possibility of making anearly diagnosis of central hypogonadism may be useful for a timely start of hormone replacementtherapy, and to avoid delays that could affect growth and bone health as wellas psychosocial adjustment.