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hypogonadotropic hypogonadism; gonadotropin deficiency
Hypogonadotropic hypogonadism plus pituitary or hypothalamic anatomic lesions & anosmia is known as Kallmann syndrome.
Etiology:
- congenital disorders
- Kallmann syndrome
- Prader-Willi syndrome
- obstructive sleep apnea
- chronic opioid use
- anorexia nervosa [6]
- idiopathic
Pathology:
1) selective failure of the neuroendocrine components of the reproductive system in the absence of an anatomic or functional cause
2) deficiency of pituitary secretion of gonadotropins FSH & LH resulting from failure to release sufficient gonadotropin-releasing hormone
Genetics:
- associated with defects in GNRHR, KISS1R, NELF, FGFR1, CHD7, FGF8
Clinical manifestations:
1) oligomenorrhea or amenorrhea
2) retardation of growth & sexual development
3) absence of pubertal development by age 18 years in males
4) microphallus &/or cryptorchidism in males
5) wide clinical spectrum
Laboratory:
1) prepubertal sex steroids (serum testosterone, serum estrogen)
2) serum FSH, serum LH
- low or inappropriately normal serum gonadotropin
3) serum prolactin to rule out prolactinoma
4) urine drug screen for opioids
5) karyotyping if suspected congenital disorder
* a history of normal menses rules out hypogonadotropic hypogonadism & further workup not required [5]
Special laboratory:
- sleep study (polysomnography) if obese &/or suspected obstructive sleep apena
Radiology:
- MRI neuroimaging of pituitary & sella turcica
- suspected prolactinoma or other pituitary neoplasm
Management:
- if associated with weight loss ascribed to change in diet with low BMI, diagnose anorexia nervosa & refer for nutritional & psychiatric consultation [6]
General
secondary hypogonadism
Database Correlations
OMIM correlations
References
- UniProt :accession P30968
- OMIM :accession 146110
- Miraoui H, Dwyer AA, Sykiotis GP et al
Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are
identified in individuals with congenital hypogonadotropic
hypogonadism.
Am J Hum Genet. 2013 May 2;92(5):725-43
PMID: 23643382
- Attal P, Chanson P.
Endocrine aspects of obstructive sleep apnea.
J Clin Endocrinol Metab. 2010 Feb;95(2):483-95. Review.
PMID: 20061419
- Medical Knowledge Self Assessment Program (MKSAP) 18,
American College of Physicians, Philadelphia 2018
- NEJM Knowledge+ Endocrinology