Endocrine Abstracts

Introduction: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder. It can be sporadic or familiar and is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome - KS) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism ‐ IHH). A growing number of genes are involved in its etiology, suggesting the heterogeneity and complexity of this condition.

Cases Reports: Six cases of CHH are presented - 3 KS and 3 IHH cases. All KS patients were male and the diagnosis was suspected by pubertal delay (sparse hairbody and small testicles/penis for age) when they aged 13 years (one patient) and 18 years old (two patients). Smell was tested by ORL: two of them had anosmia and one had hyposmia. One patient also had bilateral deafness, congenital cardiomyopathy, cognitive impairment and thyroid papillary carcinoma. Its CT revealed vermis hypoplasia and an enlarged sixth ventricle. Olfactory bulbs were absent in the two other patient’s MRI. Two of 3 IHH cases represented a familiar form (being sister and brother), while the other case occurred as a sporadic condition in a male patient (detected at 28 years old because of ginecomastia with no other symptoms). The female patient with familiar IHH was diagnosed at 18 years because of primary amenorrhea (karyotye 46,XX) and her brother was diagnosed at 22 years old because of pubertal delay. Both patients had positive genetic test and shared the same mutation. Genetic test (KAL1, FGF1 and GnRHR genes) was negative in other 3 patients and still is in progress for one KS patient.

Conclusion: Although the cases presented share the main manifestations of CHH, each one has specific characteristics demonstrating the heterogeneity of this condition. They also highlight how diagnosis can be challenging and sometimes delayed to adult age, because distinction from constitutional delay of puberty may be difficult.