Congenital Hypogonadotropic Hypogonadism (Isolated GnRH Deficiency)

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder caused by the absence of GnRH secretion from the hypothalamus or defective GnRH action in the pituitary. CHH patients present with absent or incomplete sexual maturation and infertility, with low serum sex steroids in the context of low/normal gonadotropins. CHH can occur either with normal sense of smell or with lack of sense of smell (i.e., anosmia). The co-occurrence of CHH and anosmia is termed as Kallmann syndrome (KS). Mutations in more than 25 genes are identified in CHH patients, either alone or in combination. Hormonal therapy can induce secondary sexual characteristics, increase bone mass, and restore fertility. In this chapter, we will discuss the pathogenesis, clinical manifestation, diagnosis, and treatment of CHH.