Isolated hypogonadotropic hypogonadism

Isolated hypogonadotropic hypogonadism (IHH), also called idiopathic or congenital hypogonadotropic hypogonadism (CHH), as well as isolated or congenital gonadotropin-releasing hormone deficiency (IGD), is a condition that results in a small subset of cases of hypogonadotropic hypogonadism (HH) due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH) where the function and anatomy of the anterior pituitary is otherwise normal and secondary causes of HH are not present. It presents as hypogonadism (e.g., reduced or absent puberty (Ref.1), low libido, infertility, etc.) due to an impaired release of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and a resultant lack of sex steroid and peptides production by the gonads (Ref. 2 and Ref 3). In addition, anosmia (loss of the sense of smell) occurs in instances of IHH that are the result of Kallmann syndrome, which is responsible for approximately 50% of all cases of the condition. Other causes of IHH include GnRH insensitivity, which is the second most common cause of IHH and is thought to be responsible for up to 20% of cases, and a minority (less than 5-10%) due to inactivating mutations in a variety of other genes which positively regulate GnRH secretion such as CHD7, KISS1R, and TACR3. The causes of approximately 25% of all cases of IHH are still unknown.

1- Young J. Approach to the male patient with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2012 Mar;97(3):707-18. doi: 10.1210/jc.2011-1664. PMID: 22392951

2- Giton F, Trabado S, Maione L, Sarfati J, Le Bouc Y, Brailly-Tabard S, Fiet J, Young J. Sex steroids, precursors, and metabolite deficiencies in men with isolated hypogonadotropic hypogonadism and panhypopituitarism: a GCMS-based comparative study. J Clin Endocrinol Metab. 2015 Feb;100(2):E292-6. doi: 10.1210/jc.2014-2658. Epub 2014 Nov 13. PMID: 25393641

3- Trabado S, Maione L, Bry-Gauillard H, Affres H, Salenave S, Sarfati J, Bouvattier C, Delemer B, Chanson P, Le Bouc Y, Brailly-Tabard S, Young J. Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients. J Clin Endocrinol Metab. 2014 Feb;99(2):E268-75. doi: 10.1210/jc.2013-2288. Epub 2013 Nov 15. PMID: 24243640

See also

• Hypogonadism
• Hypogonadotropic hypogonadism
• Hypergonadotropic hypogonadism
• Delayed puberty and infertility
• Hypothalamus, pituitary gland, and HPG axis
• Gonads (testicles and ovaries)
• GnRH and gonadotropins (FSH and LH)
• Sex hormones (androgens and estrogens)
• Kallmann syndrome and GnRH insensitivity
• Fertile eunuch syndrome