Congenital hypogonadotropic hypogonadism/Kallmann syndrome is associated with statural gain in both men and women: a monocentric study

Abstract

Context Congenital hypogonadotropic hypogonadism/Kallmann syndrome (CHH/KS) is a rare condition characterized by gonadotropin deficiency and pubertal failure. Adult height (AH) in patients with CHH/KS has not been well studied. Objective To assess AH in a large cohort of patients with CHH/KS. Patients A total of 219 patients (165 males, 54 females). Parents and siblings were included. Methods AH was assessed in patients and family members. AH was compared to the general French population, mid parental target height (TH) and between patients and same-sex siblings. Delta height (∆H) was considered as the difference between AH and parental TH. ∆H was compared between patients and siblings, normosmic CHH and KS (CHH with anosmia/hyposmia), and according to underlying genetic defect. We examined the correlations between ∆H and age at diagnosis and therapeutically induced individual statural gain. Results Mean AH in men and women with CHH/KS was greater than that in the French general population. Patients of both sexes had AH > TH. Males with CHH/KS were significantly, albeit moderately, taller than their brothers. ∆H was higher in CHH/KS compared to unaffected siblings (+6.2 ± 7.2 cm vs +3.4 ± 5.2 cm, P < 0.0001). ∆H was positively correlated with age at diagnosis. Neither olfactory function (normosmic CHH vs KS) nor specific genetic cause impacted ∆H. Individual growth during replacement therapy inversely correlated with the age at initiation of hormonal treatment (P < 0.0001). Conclusions CHH/KS is associated with higher AH compared to the general population and mid-parental TH. Greater height in CHH/KS than siblings indicates that those differences are in part independent of an intergenerational effect.