Isolated hypogonadotropic hypogonadism

Isolated Hypogonadotropic Hypogonadism (IHH) is a condition characterized by a deficiency in the production of gonadotropin-releasing hormone (GnRH), leading to insufficient production of sex hormones by the gonads. This results in delayed or absent puberty and, in some cases, infertility. IHH is considered "isolated" because it occurs without other pituitary or hypothalamic abnormalities.

Causes

IHH can be caused by a variety of genetic mutations affecting the production, secretion, or action of GnRH. It can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner, depending on the specific genetic mutation. Common genes involved include KAL1, FGFR1, PROKR2, GNRHR, and KISS1R.

Symptoms

The primary symptom of IHH is delayed puberty. Males may present with a lack of secondary sexual characteristics, such as facial hair, voice deepening, and increased muscle mass. Females may present with a lack of menstruation (amenorrhea) and secondary sexual characteristics, such as breast development. Both sexes may exhibit a reduced sense of smell (anosmia), especially in cases related to Kallmann syndrome, a variant of IHH.

Diagnosis

Diagnosis of IHH involves a combination of clinical evaluation, laboratory testing, and sometimes genetic testing. Key tests include measurements of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are typically low or inappropriately normal given the low levels of sex hormones. Magnetic resonance imaging (MRI) of the brain may be performed to rule out other causes of hypogonadotropic hypogonadism.

Treatment

Treatment of IHH focuses on hormone replacement therapy to induce and maintain secondary sexual characteristics and, in some cases, to achieve fertility. For males, testosterone replacement therapy is the mainstay. For females, estrogen and progesterone therapy is used to induce menstruation and secondary sexual characteristics. In cases where fertility is desired, gonadotropins or GnRH pump therapy can be used to stimulate the gonads directly.

Prognosis

With appropriate hormone therapy, individuals with IHH can lead normal lives, achieving puberty, developing secondary sexual characteristics, and potentially achieving fertility. Long-term management may be required to maintain sexual function, bone health, and fertility.

Epidemiology

IHH is a rare condition, though its exact prevalence is unknown. It affects both males and females, with a slight male predominance reported in some studies.

See also

• Kallmann syndrome
• Hypogonadism
• Gonadotropin-releasing hormone
• Puberty