Gonadotropin-releasing hormone insensitivity

A condition characterized by the body's inability to respond to gonadotropin-releasing hormone

Gonadotropin-releasing hormone insensitivity (GnRH insensitivity) is a rare endocrine disorder characterized by the body's inability to respond to gonadotropin-releasing hormone (GnRH). This condition leads to a deficiency in the production of gonadotropins, which are crucial for the normal functioning of the reproductive system.

Pathophysiology

GnRH is a decapeptide hormone produced by the hypothalamus. It plays a critical role in the regulation of the pituitary gland, stimulating the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are essential for gonadal function, including the production of sperm in males and the regulation of the menstrual cycle in females.

In individuals with GnRH insensitivity, there is a disruption in the signaling pathway of GnRH, leading to inadequate stimulation of the pituitary gland. This results in low levels of LH and FSH, causing hypogonadism and affecting puberty and fertility.

Causes

GnRH insensitivity can be caused by mutations in the GnRH receptor gene, which impair the receptor's ability to bind to GnRH or transduce the signal. These mutations can be inherited in an autosomal recessive manner, meaning that both copies of the gene must be affected for the condition to manifest.

Clinical Presentation

The clinical presentation of GnRH insensitivity varies depending on the severity of the receptor defect. Common features include:

• Delayed or absent puberty
• Infertility
• Low levels of sex steroids such as testosterone in males and estrogen in females
• Underdeveloped secondary sexual characteristics

Diagnosis

Diagnosis of GnRH insensitivity involves a combination of clinical evaluation, hormonal assays, and genetic testing. Low levels of LH and FSH in the presence of low sex steroids suggest a central cause of hypogonadism. Genetic testing can confirm mutations in the GnRH receptor gene.

Treatment

Management of GnRH insensitivity focuses on hormone replacement therapy to induce and maintain secondary sexual characteristics and support fertility. In males, testosterone replacement therapy is commonly used, while females may receive estrogen and progesterone therapy. Assisted reproductive technologies may be necessary for individuals seeking to achieve fertility.

Prognosis

With appropriate treatment, individuals with GnRH insensitivity can lead normal lives, although fertility may remain a challenge. Early diagnosis and intervention are crucial for optimal outcomes.

Related pages

• Hypogonadotropic hypogonadism
• Endocrinology
• Reproductive endocrinology