Hypogonadism pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 69: Line 69:
|
|
|-
|-
| rowspan="4" |Idiopathic hypogonadotrophic hypogonadism (IHH) (Normal smelling sensation - normosmia)
| rowspan="5" |Idiopathic hypogonadotrophic hypogonadism (IHH) (Normal smelling sensation - normosmia)
|KISS1R
|KISS1R
|
|
* Gain of function mutations
|
|
|
|
* KISS1R is important for GnRH secretion and puberty process.<ref name="pmid18272894">{{cite journal| author=Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S et al.| title=A GPR54-activating mutation in a patient with central precocious puberty. | journal=N Engl J Med | year= 2008 | volume= 358 | issue= 7 | pages= 709-15 | pmid=18272894 | doi=10.1056/NEJMoa073443 | pmc=2859966 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18272894  }}</ref>
|-
|-
|KISS
|KISS1
|
|
* Autosomal recessive
* Loss of functions mutations
|
|
|
|
|-
|GNRHR
|
* Loss of function mutations
|
|
* Patients with hypogonadism due to GNRHR mutations usually do not respond properly to the exogenous GnRH.
* On big doses of GnRH, ovulation may be initiated in some patients.
|-
|-
|GNRH1
|GNRH1
|
|
* Autosomal recessive
|
|
|
|
* GNRH1 is responsible of pre-pro GnRH encoding.<ref name="pmid19535795">{{cite journal| author=Bouligand J, Ghervan C, Tello JA, Brailly-Tabard S, Salenave S, Chanson P et al.| title=Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 26 | pages= 2742-8 | pmid=19535795 | doi=10.1056/NEJMoa0900136 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19535795  }}</ref>
|-
|-
|TAC3
|TAC3
|
|
* Autosomal recessive
|
|
* Microcephallus
* Cryptorchidism
|
|
* Mutation in the pituitary - hypothalamic pathway signaling.<ref name="pmid20332248">{{cite journal| author=Gianetti E, Tusset C, Noel SD, Au MG, Dwyer AA, Hughes VA et al.| title=TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 6 | pages= 2857-67 | pmid=20332248 | doi=10.1210/jc.2009-2320 | pmc=2902066 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20332248  }}</ref>
|-
|-
| rowspan="5" |Mixed anosmic and nosmic IHH  
| rowspan="5" |Mixed anosmic and nosmic IHH  

Revision as of 20:19, 20 July 2017

Hypogonadism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Hypogonadism from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Hypogonadism pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Hypogonadism pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Hypogonadism pathophysiology

CDC on Hypogonadism pathophysiology

Hypogonadism pathophysiology in the news

Blogs on Hypogonadism pathophysiology

Directions to Hospitals Treating Hypogonadism

Risk calculators and risk factors for Hypogonadism pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Overview

Pathophysiology

Pathogenesis

Hypogonadism in males

  • The hypogonadism pathogenesis in males depends mainly on the testosterone deficiency. Testosterone secretion occurs as the following:
    • Testosterone is secreted in response to stimulation signals from the brain cortex to the hypothalamus. The hypothalamus by its role secrets the gonadotropin releasing hormones (GnRH).
    • GnRH stimulates the pituitary gland which by its role secretes the gonadal hormones the Follicle Stimulating Hormone (FSH) and the Luteinizing Hormone (LH).
    • In males, LH stimulates the leydig cells in the testes which produce testosterone by converting the cholesterol to testosterone.
    • Production of testosterone from the testes gives negative feed back to the pituitary. This feedback inhibit the production of FSH and LH from the pituitary.
  • Testosterone deficiency can occur when different acquired or congenital disease affect the organs responsible for its secretion. So, pathogenesis of the hypogonadism in males depends on the underlying cause.[1]
  • GnRH deficiency has a main role in hypogonadism pathogenesis in males as it leads to decrease of the gonadal hormone and deficiency of testosterone eventually.[2]
  • It has been proved that GnRH deficiency is associated with most cases of idiopathic hypogonadotrophic hypogonadism in males.

Genetic

  • Gentic mutations have a big role in development of the hypogonadism especially congenital hypogonadotropic hypogonadism. There are more than 25 genes participate in the pathogenesis of hypogonadism.[3]
  • In this table number of genes with the associated diseases causing hypogonadism are enlisted:
Associated disease Genes Mutation Associated features with the gene Comments
Kalman syndrome (With loss of smelling sense - Anosmia) ANOS 1[4]
  • X - linked recessive
  • Gene deletion or point mutations
  • Anosmia
  • Renal agenesis
 GnRH deficiency results from impairment of migration of the hormonal neurons to the hypothalamus in the embryological development.[5]
SOX 10
  • Autosomal dominant
  • Deafness[6]
  • Iris pigmentation
SEMA3A
  • Loss of function mutations
  • SEMA3A gene's funciton is to encode the semaphorin 3A.
  • Semaphorin 3A is important for the GnRH neurons migration.
  • Defect in SEMA3A gene will end up with GnRH deficiency.[7]
IL17RD
  • Autosomal dominant
  • Deafness
FEZF1
  • Autosomal recessive
  • Loss of function mutations
Idiopathic hypogonadotrophic hypogonadism (IHH) (Normal smelling sensation - normosmia) KISS1R
  • Gain of function mutations
  • KISS1R is important for GnRH secretion and puberty process.[8]
KISS1
  • Autosomal recessive
  • Loss of functions mutations
GNRHR
  • Loss of function mutations
  • Patients with hypogonadism due to GNRHR mutations usually do not respond properly to the exogenous GnRH.
  • On big doses of GnRH, ovulation may be initiated in some patients.
GNRH1
  • Autosomal recessive
  • GNRH1 is responsible of pre-pro GnRH encoding.[9]
TAC3
  • Autosomal recessive
  • Microcephallus
  • Cryptorchidism
  • Mutation in the pituitary - hypothalamic pathway signaling.[10]
Mixed anosmic and nosmic IHH FGFR1
FGF8
PROK2

PROKR2

CHD7
NSMF

References

  1. ↑ Kumar P, Kumar N, Thakur DS, Patidar A (2010). "Male hypogonadism: Symptoms and treatment". J Adv Pharm Technol Res. 1 (3): 297–301. doi:10.4103/0110-5558.72420. PMC 3255409. PMID 22247861.
  2. ↑ Spratt DI, Carr DB, Merriam GR, Scully RE, Rao PN, Crowley WF (1987). "The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations". J Clin Endocrinol Metab. 64 (2): 283–91. doi:10.1210/jcem-64-2-283. PMID 3098771.
  3. ↑ Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L; et al. (2015). "Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment". Nat Rev Endocrinol. 11 (9): 547–64. doi:10.1038/nrendo.2015.112. PMID 26194704.
  4. ↑ Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R; et al. (1991). "A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules". Nature. 353 (6344): 529–36. doi:10.1038/353529a0. PMID 1922361.
  5. ↑ Schwanzel-Fukuda M, Bick D, Pfaff DW (1989). "Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome". Brain Res Mol Brain Res. 6 (4): 311–26. PMID 2687610.
  6. ↑ Pingault V, Bodereau V, Baral V, Marcos S, Watanabe Y, Chaoui A; et al. (2013). "Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness". Am J Hum Genet. 92 (5): 707–24. doi:10.1016/j.ajhg.2013.03.024. PMC 3644631. PMID 23643381.
  7. ↑ Cariboni A, Davidson K, Rakic S, Maggi R, Parnavelas JG, Ruhrberg C (2011). "Defective gonadotropin-releasing hormone neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for the aetiology of hypogonadotropic hypogonadism". Hum Mol Genet. 20 (2): 336–44. doi:10.1093/hmg/ddq468. PMID 21059704.
  8. ↑ Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S; et al. (2008). "A GPR54-activating mutation in a patient with central precocious puberty". N Engl J Med. 358 (7): 709–15. doi:10.1056/NEJMoa073443. PMC 2859966. PMID 18272894.
  9. ↑ Bouligand J, Ghervan C, Tello JA, Brailly-Tabard S, Salenave S, Chanson P; et al. (2009). "Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation". N Engl J Med. 360 (26): 2742–8. doi:10.1056/NEJMoa0900136. PMID 19535795.
  10. ↑ Gianetti E, Tusset C, Noel SD, Au MG, Dwyer AA, Hughes VA; et al. (2010). "TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood". J Clin Endocrinol Metab. 95 (6): 2857–67. doi:10.1210/jc.2009-2320. PMC 2902066. PMID 20332248.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Hypogonadism_pathophysiology&oldid=1328023"