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Abnormality of the Leydig cells

MedGen UID:
869277
Concept ID:
C4023703
Anatomical Abnormality
HPO: HP:0010789

Conditions with this feature

Isolated lutropin deficiency
MedGen UID:
82881
Concept ID:
C0271582
Disease or Syndrome
Male patients with hypogonadotropic hypogonadism due to isolated luteinizing hormone (LH) deficiency have normal sexual differentiation but fail to develop spontaneous puberty. Absence of LH alters Leydig cell proliferation and maturation and impairs the onset of normal spermatogenesis, which requires high levels of intratesticular testosterone. Infertility and very low levels of spermatogenesis generally persist in affected men despite long-term exposure to gonadotropin therapy. Female patients exhibit normal pubertal development and menarche, followed by oligomenorrhea and anovulatory secondary amenorrhea (summary by Basciani et al., 2012). Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a general phenotypic description and discussion of genetic heterogeneity of hypogonadotropic hypogonadism, see 147950. Reviews Arnhold et al. (2009) noted that the clinical manifestations of female patients with hypogonadotropic hypogonadism due to mutations in LHB are very similar to those of women with hypergonadotropic hypogonadism due to inactivating mutations of the LH receptor (see 238320): all have female external genitalia, spontaneous development of normal pubic hair and breasts at puberty, and normal to late menarche followed by oligoamenorrhea and infertility. Pelvic ultrasound shows a small or normal uterus and normal or enlarged ovaries with cysts. However, women with LHB mutations can be treated with luteinizing hormone or chorionic gonadotropin (CG; 118860) replacement therapy; women with LH receptor mutations are resistant to LH, and no treatment is effective in recovering their fertility.

Professional guidelines

PubMed

Rojewska P, Meczekalski B, Bala G, Luisi S, Podfigurna A
Gynecol Endocrinol 2022 Jul;38(7):537-542. Epub 2022 Jun 1 doi: 10.1080/09513590.2022.2083104. PMID: 35647677
Martin LJ
Mol Reprod Dev 2016 Jun;83(6):470-87. Epub 2016 Apr 26 doi: 10.1002/mrd.22648. PMID: 27079813
Hughes IA, Williams DM, Batch JA, Patterson MN
Horm Res 1992;38 Suppl 2:77-81. doi: 10.1159/000182604. PMID: 1292987

Recent clinical studies

Etiology

La Vignera S, Vita R
Int J Immunopathol Pharmacol 2018 Jan-Dec;32:2058738418775241. doi: 10.1177/2058738418775241. PMID: 29737216Free PMC Article
Hurtado-Gonzalez P, Mitchell RT
Curr Opin Endocrinol Diabetes Obes 2017 Jun;24(3):225-232. doi: 10.1097/MED.0000000000000338. PMID: 28277341Free PMC Article
Agoulnik AI, Huang Z, Ferguson L
Methods Mol Biol 2012;825:127-47. doi: 10.1007/978-1-61779-436-0_11. PMID: 22144242
Hutson JM, Balic A, Nation T, Southwell B
Semin Pediatr Surg 2010 Aug;19(3):215-24. doi: 10.1053/j.sempedsurg.2010.04.001. PMID: 20610195
Clayton RN
Baillieres Clin Endocrinol Metab 1996 Jan;10(1):1-8. doi: 10.1016/s0950-351x(96)80250-3. PMID: 8734448

Diagnosis

Dong S, Chen C, Zhang J, Gao Y, Zeng X, Zhang X
Front Endocrinol (Lausanne) 2022;13:1012119. Epub 2022 Oct 13 doi: 10.3389/fendo.2022.1012119. PMID: 36313743Free PMC Article
Planinić A, Marić T, Bojanac AK, Ježek D
Andrology 2022 Sep;10(6):1107-1120. Epub 2022 Jun 15 doi: 10.1111/andr.13201. PMID: 35661438
Aldahhan RA, Stanton PG
Mol Cell Endocrinol 2021 May 1;527:111216. Epub 2021 Feb 24 doi: 10.1016/j.mce.2021.111216. PMID: 33639219
La Vignera S, Vita R
Int J Immunopathol Pharmacol 2018 Jan-Dec;32:2058738418775241. doi: 10.1177/2058738418775241. PMID: 29737216Free PMC Article
Rey RA, Gottlieb S, Pasqualini T, Bastida MG, Grinspon RP, Campo SM, Bergadá I
Acta Paediatr 2011 Jun;100(6):830-8. Epub 2011 Feb 3 doi: 10.1111/j.1651-2227.2010.02137.x. PMID: 21214886

Therapy

Esposito M, Salerno M, Calvano G, Agliozzo R, Ficarra V, Sessa F, Favilla V, Cimino S, Pomara C
Panminerva Med 2023 Mar;65(1):43-50. Epub 2022 Feb 11 doi: 10.23736/S0031-0808.22.04677-8. PMID: 35146992
Drobnis EZ, Nangia AK
Adv Exp Med Biol 2017;1034:39-57. doi: 10.1007/978-3-319-69535-8_6. PMID: 29256126
Hurtado-Gonzalez P, Mitchell RT
Curr Opin Endocrinol Diabetes Obes 2017 Jun;24(3):225-232. doi: 10.1097/MED.0000000000000338. PMID: 28277341Free PMC Article
Ulloa-Aguirre A, Lira-Albarrán S
Prog Mol Biol Transl Sci 2016;143:121-174. Epub 2016 Sep 13 doi: 10.1016/bs.pmbts.2016.08.003. PMID: 27697201
Lombardo F, Sgrò P, Salacone P, Gilio B, Gandini L, Dondero F, Jannini EA, Lenzi A
J Endocrinol Invest 2005;28(3 Suppl):51-5. PMID: 16042361

Prognosis

Miyado M, Fukami M, Ogata T
Sex Dev 2022;16(2-3):126-137. Epub 2021 Oct 25 doi: 10.1159/000519298. PMID: 34695834
Freire AV, Grinspon RP, Rey RA
Sex Dev 2018;12(1-3):30-40. Epub 2017 Aug 30 doi: 10.1159/000479572. PMID: 28850950
Fuller PJ, Leung D, Chu S
Clin Genet 2017 Feb;91(2):285-291. doi: 10.1111/cge.12917. PMID: 27813081
Hutson JM, Balic A, Nation T, Southwell B
Semin Pediatr Surg 2010 Aug;19(3):215-24. doi: 10.1053/j.sempedsurg.2010.04.001. PMID: 20610195
Clayton RN
Baillieres Clin Endocrinol Metab 1996 Jan;10(1):1-8. doi: 10.1016/s0950-351x(96)80250-3. PMID: 8734448

Clinical prediction guides

Planinić A, Marić T, Bojanac AK, Ježek D
Andrology 2022 Sep;10(6):1107-1120. Epub 2022 Jun 15 doi: 10.1111/andr.13201. PMID: 35661438
Miyado M, Fukami M, Ogata T
Sex Dev 2022;16(2-3):126-137. Epub 2021 Oct 25 doi: 10.1159/000519298. PMID: 34695834
Docampo MJ, Hadziselimovic F
Sex Dev 2015;9(5):269-78. Epub 2015 Dec 8 doi: 10.1159/000442059. PMID: 26642196
Hutson JM, Balic A, Nation T, Southwell B
Semin Pediatr Surg 2010 Aug;19(3):215-24. doi: 10.1053/j.sempedsurg.2010.04.001. PMID: 20610195
Clayton RN
Baillieres Clin Endocrinol Metab 1996 Jan;10(1):1-8. doi: 10.1016/s0950-351x(96)80250-3. PMID: 8734448

Recent systematic reviews

Bradshaw AW, Deebel NA, Xu MC, Kogan S, Atala A, Sadri-Ardekani H
Andrology 2023 Mar;11(3):435-443. Epub 2022 Oct 27 doi: 10.1111/andr.13327. PMID: 36252136
Esposito M, Salerno M, Calvano G, Agliozzo R, Ficarra V, Sessa F, Favilla V, Cimino S, Pomara C
Panminerva Med 2023 Mar;65(1):43-50. Epub 2022 Feb 11 doi: 10.23736/S0031-0808.22.04677-8. PMID: 35146992
Vandekerckhove P, Lilford R, Vail A, Hughes E
Cochrane Database Syst Rev 2007 Jul 18;(4):CD000151. doi: 10.1002/14651858.CD000151. PMID: 17636604
Vandekerckhove P, Lilford R, Vail A, Hughes E
Cochrane Database Syst Rev 2000;(2):CD000151. doi: 10.1002/14651858.CD000151. PMID: 10796497

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