Isolated hypogonadotropic hypogonadism

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Isolated hypogonadotropic hypogonadism
SynonymsNormosmic idiopathic 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 which 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.

Presentation[edit]

Congenital hypogonadotropic hypogonadism presents as hypogonadism, e.g., reduced or absent puberty,[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.[2][3]

In Kallmann syndrome, a variable non-reproductive phenotype occurs with anosmia (loss of the sense of smell) including sensorineural deafness, coloboma, bimanual synkinesis, craniofacial abnormalities, and/or renal agenesis.[4]

Causes[edit]

IHH is divided into two syndromes: IHH with olfactory alterations or anosmia, Kallmann syndrome and IHH with normal smell (normosmic IHH).[4]

Kallmann syndrome is responsible for approximately 50% of all cases of the condition. It is associated with mutations in KAL1, FGFR1/FGF8, FGF17, IL17RD, PROKR2, NELF, CHD7(which positively regulates GnRH secretion), HS6ST1, FLRT3, SPRY4, DUSP6, SEMA3A, and WDR11 (gene), genes which are related to defects in neuronal migration.[4]

Gene defects associated with IHH and normal smell include PROKR2, FGFR1, FGF8, CHD7, DUSP6, and WDR11, as in KS, but in addition also mutations in KISS1R, TACR3, GNRH1/GNRHR, LEP/LEPR, HESX1, FSHB, and LHB.[4] GnRH insensitivity is the second most common cause of IHH, responsible for up to 20% of cases.[citation needed]

A minority of less than 5-10% is due to inactivating mutations in genes which positively regulate GnRH secretion such as ,CHD7, KISS1R, and TACR3.[citation needed]

The causes of about 25% of all IHH cases are still unknown.[5][dead link]

Genetics[edit]

See Genetics of GnRH deficiency conditions

Diagnosis[edit]


Treatment[edit]

See also[edit]

References[edit]

  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, et al . 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, et al. 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
  4. ^ a b c d Hernan Valdes-Socin, Matilde Rubio Almanza, Mariana Tomé Fernández-Ladreda, et al. Reproduction, smell, and neurodevelopmental disorders: genetic defects in different hypogonadotropic hypogonadal syndromes. Frontiers in Endocrinology 2014, 5: 109. review
  5. ^ "Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency Overview - GeneReviews™ - NCBI Bookshelf".

External links[edit]

Classification
External resources