Endocrine Abstracts

A gentleman in his 20s, was referred to the endocrinology clinic due to delayed puberty with absent secondary sexual characteristics and low total testosterone level 1.7 nmol/l (8.64-29), and free testosterone 38 pmol/l (198-619). He had no past medical history or drug history. He reported no anosmia and no family history of delayed puberty. However, he had an 11 year-old brother who remained pre-pubertal. On further questioning, he had no secondary sexual characteristics such as hair growth, deepening of the voice or increase in size of testicles. Initial investigations showed LH 1.1 iu/l (1.7 – 8.6), FSH 1.9 iu/l (1.5-12.4), SHBG 21 nmol/l (16.5 – 55.9), TSH 1.02 mu/l (0.27 – 4.2), free T4 15.8 pmol/l (11.1-22), prolactin 158 miu/l (86-324) and IGF-1 17.0 nmol/l (17.7-43). MRI of pituitary with contrast showed no pituitary adenoma and normal posterior pituitary with no ectopic tissue. DEXA scan revealed osteopenia in the spine with normal bone density elsewhere. He underwent genetic testing which showed two heterozygous mis-sense mutations in the Gonadotropin-releasing hormone receptor (GNRHR) gene at Chr4:g.67740661g>A and Chr4:g.67754019T>G. Genetic testing was recommended for his parents to determine their carrier status and confirm genetic diagnosis of their child. He was initiated on Testogel, calcium and Vitamin D3 replacement. His latest testosterone was 12.9 mmol/l with improved secondary sexual characteristics. He remained under endocrinology follow up. Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic type of hypogonadism, characterised by absence or delayed pubertal development and infertility, resulting from inadequate production, secretion or action of GnRH. GNRHR mutations account for approximately 3.5%-16% of sporadic cases of normosmic IHH. Diagnosis can be challenging, particularly in early adolescence, as clinical presentation often mimics constitutional delay of growth and puberty. Early awareness by clinicians is crucial.

References: 1 https://ec.bioscientifica.com/view/journals/ec/6/6/360.xml