Endocrine Abstracts

Idiopathic congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive disorder that is primarily caused by a gonadotrophin-realising hormone (GnRH) deficiency. When CHH is associated with hyposmia or anosmia is designated by Kallmann Syndrome (KS). This syndrome is a genetic disorder with significant genetic heterogeneity that may present as a sporadic or familial case, following autosomal dominant, autosomal recessive, or X – linked recessive modes of inheritance. This work aim is to review all KS cases followed in the Endocrinology service. A total of 11 cases were evaluated, 10 men and 1 woman. Patients were mainly diagnosed in late adolescence, between 17 and 18 years old, when sought a doctor for delayed puberty. All cases presented hypogonadotropic hypogonadism and hyposmia or anosmia with MRI olfactory bulb atrophy criteria. No other changes in the neuroendocrine axis were found. The patients were followed between 2 and 33 years (mean time 12 years). All had gonadal steroid hormones treatment (testosterone or estrogens) and had a good secondary development of the sexual characteristics, Tanner stage IV/V. Three patients had fertility therapy with gonadotropin and until now only the girl had clinical improvements. Four cases made a genetic study: two mutations in KAL1 gene, one in FGFR1, and one in PROK2 were found. The two patients with KAL1 mutation presented cryptorchidism and one the two also had unilateral renal agenesis. The patient with FGFR1 mutation also had an history of cryptorchidism. The one with recessive mutation for PROK2 only presented anosmia and hypogonadotropic hypogonadism.

Conclusion: The presence of a delayed pubertal development is suspicious of CHH/KS occurrence. In our study, patients with KS presented good clinical results with the use of gonadal steroid hormones attaining stages IV/V of Tanner. Women appear to have better fertility responses to therapy than men, although this findings demand further investigation.