Congenital hypogonadotropic hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is a condition characterized by pubertal delay or absence and infertility due to an impaired production, secretion or action of gonadotropin-releasing hormone (GnRH). This condition is caused by a deficiency in the hypothalamus or the pituitary gland, which are responsible for the production of sex hormones.

Etiology

CHH is a genetic disorder that can be inherited in an autosomal recessive, autosomal dominant, or X-linked recessive manner. Several genes have been associated with CHH, including KAL1, FGFR1, PROKR2, PROK2, CHD7, HS6ST1, SEMA3A, and GNRHR. Mutations in these genes can disrupt the development and function of the hypothalamus or pituitary gland, leading to the symptoms of CHH.

Clinical Presentation

Patients with CHH typically present with delayed puberty, which is defined as the absence of secondary sexual characteristics by age 13 in girls and age 14 in boys. Other symptoms may include a decreased sense of smell (anosmia), which is a characteristic feature of Kallmann syndrome, a subtype of CHH. In addition, patients may have a small penis (micropenis) or undescended testes (cryptorchidism).

Diagnosis

The diagnosis of CHH is based on clinical findings, hormonal testing, and genetic testing. Hormonal testing typically shows low levels of gonadotropins (LH and FSH) and sex steroids (testosterone in males and estradiol in females). Genetic testing can confirm the diagnosis and help identify the specific gene mutation.

Treatment

Treatment of CHH aims to induce puberty, maintain secondary sexual characteristics, and achieve fertility. This is typically achieved through hormone replacement therapy, which includes the administration of sex steroids and gonadotropins.

Prognosis

With appropriate treatment, the prognosis for individuals with CHH is generally good. Most individuals are able to achieve normal sexual development and fertility. However, lifelong hormone replacement therapy is usually required.