Reversibility of congenital hypogonadotropic hypogonadism: lessons from a rare disease

Congenital hypogonadotropic hypogonadism (CHH) is caused by abnormal gonadotropin secretion or action. Although rare, CHH is approximately twice as common in men than in women. 1 Young J Xu C Papadakis GE et al. Clinical management of congenital hypogonadotropic hypogonadism. Endocr Rev. 2019; 40: 669-710 Crossref PubMed Scopus (218) Google Scholar , 2 Boehm U Bouloux PM Dattani MT et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism–pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015; 11: 547-564 Crossref PubMed Scopus (606) Google Scholar Around 50% of patients with CHH have anosmia (Kallmann syndrome). 1 Young J Xu C Papadakis GE et al. Clinical management of congenital hypogonadotropic hypogonadism. Endocr Rev. 2019; 40: 669-710 Crossref PubMed Scopus (218) Google Scholar , 2 Boehm U Bouloux PM Dattani MT et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism–pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015; 11: 547-564 Crossref PubMed Scopus (606) Google Scholar CHH is generally first suspected by the absence of puberty at the typical age. Boys and girls of pubertal age with CHH are treated with testosterone or oestrogen to induce secondary sexual characteristics. Men and women with CHH require pulsatile subcutaneous GnRH therapy or subcutaneous injections of luteinising hormone (LH) and follicle-stimulating hormone (FSH) for gametogenesis and fertility. Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centresApplying LCMM to a large cohort of male patients with CHH reversal uncovered two distinct classes of reversal. Genetic investigation combined with careful clinical phenotyping could help surveillance of reversal after withdrawing treatment, representing the first tailored management approach for male patients with this rare endocrine disorder. Full-Text PDF