Jump to content

Late onset congenital adrenal hyperplasia

This is a good article. Click here for more information.
From Wikipedia, the free encyclopedia
(Redirected from LOCAH)

Late onset congenital adrenal hyperplasia
Other namesNonclassic onset congenital adrenal hyperplasia
Frequency0.1%–2%

Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia (NCCAH or NCAH), is a milder form of congenital adrenal hyperplasia (CAH),[1] a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.[1][2][3][4]

The causes of LOCAH are the same as of classic CAH, and in the majority of the cases are the mutations in the CYP21A2 gene resulting in corresponding activity changes in the associated P450c21 (21-hydroxylase) enzyme which ultimately leads to excessive androgen production. Other causes, albeit less frequent, are mutations in genes affecting other enzymes involved in steroid metabolism, like 11β-hydroxylase or 3β-hydroxysteroid dehydrogenase.[3] It has a prevalence between 0.1% and 2% depending on population,[2] and is one of the most common autosomal recessive genetic diseases in humans.[5][6][7] The pathophysiology is complex and not all individuals are symptomatic.[2]

Presentation

[edit]

Patients with LOCAH usually present with signs of hyperandrogenism, rather than of glucocorticoid deficiency, a condition characterized by inadequate cortisol production.[8][9] Cortisol synthesis impairment is mild but clinically silent (asymptomatic).[10][11] LOCAH patients usually have the same baseline but lower peak cortisol levels comparing to healthy controls.[12][13] Flatter diurnal cortisol slopes contribute to stress-related dysregulation of central and peripheral circadian mechanisms with negative health outcomes.[14][15][16]

Due to hyperandrogenism, females may present with symptoms like hirsutism, oligomenorrhea, acne, infertility,[17][18] and androgenetic alopecia.[19][20][21]

Males are generally asymptomatic,[22][8] but may present with acne,[23][24][25] early balding,[26][27][28] chronic prostatitis and/or chronic pelvic pain syndrome.[29][30][31] Rare presentation of testicular adrenal rest tumors[32][18][26] which do not affect fertility and do not require regular ultrasound examinations of the scrotum[1] is also possible.

While symptoms are usually diagnosed after puberty, children may present with premature adrenarche.[8]

The degree of hormonal disorder in patients with LOCAH is relatively mild. However, alterations in the hypothalamic–pituitary–adrenal axis (HPA axis) are present even in this mild form of the disease and might contribute to psychiatric vulnerability.[11]

Molecular genetics

[edit]

LOCAH is most commonly attributed to mutations in the CYP21A2 gene, which encodes the 21-hydroxylase enzyme. Cases of LOCAH due to deficiencies in other enzymes that are known causes of CAH (3β-hydroxysteroid dehydrogenase, steroid 11β-hydroxylase, etc.) are rare and have no established prevalence estimates.[33]

Several severe mutations have been associated with LOCAH: the deletion of the CYP21A2 gene, small gene conversions, the p. I172N (rs6475, c.518T>A, CYP21A2*11) mutation, the c.293-13A/C>G (rs6467, CYP21A2*9) mutation, and the p.Gln318Stop (p.Q318X, rs7755898, c.952C>T, CYP21A2*17) mutation.[34] Besides that, LOCAH due to 21-hydroxylase deficiency can be caused by duplications of CYP21A1P pseudogene and C4B gene. Due to the high degree of homology between the CYP21A2 gene and the CYP21A1P pseudogene, and the complexity of the locus, research on the sequencing level can be difficult.[35] A 2021 study showed that mild genotypes associated with LOCAH have a low concordance rate with those phenotypes, probably due to the complex characteristics of 21-hydroxylase genotyping and the limitation of using massive parallel sequencing alone without combining with other comprehensive methods.[36]

The following three mutations to the CYP21A2 gene have been found to result in a moderate reduction in enzyme activity associated with that allele (20–60% residual activity),[34] and are associated with LOCAH:[37]

  • p.V281L (rs6471, c.844G>C, CYP21A2*15);
  • p.P453S (rs6445, c.1360C>T, CYP21A2*19);
  • p.P30L (rs9378251, c.92C>T, CYP21A2*8).

A point mutation in exon 7 of CYP21A2, (p.V281L), is commonly found in LOCAH-associated alleles.[37][35][34] Carriers for this mutation retain 20%–50% of 21-hydroxylase activity,[38][22] but are at higher risk of symptoms of androgen excess than carriers of the severe mutations,[39] and had higher adrenocorticotropic hormone (ACTH) stimulated 17α-hydroxyprogesterone,[40] suggesting that the mutant protein V281L enzyme co-expressed with the wild-type (healthy) enzyme resulted in an apparent dominant negative effect on the enzymatic activity.[41]

The particularly mild clinical symptoms of LOCAH such as hyperandrogenism, hirsutism and acne or infertility overlap with other diseases such as polycystic ovary syndrome. Biochemical parameters like 17α-hydroxyprogesterone may not be elevated in very mild cases of LOCAH, and may vary between labs that makes interpretation difficult. It may not be possible to perform ACTH stimulation tests in all institutions, depending on the availability of the injectable adrenocorticotropic hormone medication. This is why a comprehensive CYP21A2 genotyping (rather than variant-specific assays alone) is a good way to exclude/confirm 21-hydroxylase deficiency and heterozygosity (carrier) status.[42] Genetic testing can be used to exclude false positive diagnosis based on biochemical parameters alone, even with ACTH stimulation, since elevated 17-OHP levels may be also caused by ovarian or adrenal tumors, rather than by the variants in the CYP21A2 gene.[43]

Diagnosis

[edit]

Originally characterized in 1957 by French biochemist Jacques Decourt,[44] LOCAH differs from classic CAH in that it does not cause atypical neonatal genital morphology, is not life-threatening and presents after birth. Unlike classic CAH, LOCAH generally cannot be reliably detected with neonatal screening.[45] Many individuals (both male and female) present no symptoms during childhood and adolescence and only become aware of the possibility of LOCAH due to the diagnosis of another family member. It is thought that 90% of women with LOCAH never receive a diagnosis.[11] In young females, premature pubarche is generally the first symptom to present.[20] The earliest known diagnosis was in a 6 month old female who developed pubic hair.[46] Additional symptoms include acne, menstrual irregularities and hirsutism in females as well as alopecia in males. LOCAH is often misdiagnosed as polycystic ovarian disease (PCOS).[47]

LOCAH is often diagnosed in the context of infertility assessment in women. During the follicular phase of the menstrual cycle, progesterone accumulates along with 17α-hydroxyprogesterone which can thin the endometrium and change cervical mucus in a manner similar to the effect of progestogen contraceptives, interferes with the normal menstrual cycle, which can lead to oligomenorrhea or amenorrhea[11] and impairs sperm penetration.[48] Abnormal endometrial development leads to decreased uterine receptivity, which also contributes to infertility.[49] Once attempting to conceive, most women with LOCAH will become pregnant within a year with or without treatment, but women with LOCAH have an increased risk of miscarriage.[11]

The diagnostic procedure varies according to the specific enzyme deficiency causing LOCAH and the precise serum androgen levels required for diagnosis are the subject to variance from different measurement methods, refinement in specific cases and are under active research. Some protocols are based on measuring 17α-hydroxyprogesterone levels, with or without ACTH stimulation test.[45][50]

21-Hydroxylase deficiency

[edit]

Screening

[edit]
Main article: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency

The condition of 21-hydroxylase deficiency is screened by measuring serum levels of 17α-hydroxyprogesterone (17-OHP) in the morning and between day 3 and 5 of the menstrual cycle (for females) to reduce the possibility of false positive results.[11] 17-OHP is used as a marker of the 21-hydroxylase enzyme activity since the 1980s.[51] The cutoff basal 17-OHP value is matter of debate.[22] Most commonly, the value of 2.0 ng/mL[2][52] is used, but a value of 1.7 ng/mL provides better selectivity.[22][45] Most research on the biochemical diagnosis of LOCAH relied on direct immunoassays, such as radioimmunoassays or time-resolved fluorescence assay to measure 17-OHP, therefore, cross-reactivity and reliability problems of these methods might have caused differences in the 17-OHP cutoff values recommended, so the use of liquid chromatography–mass spectrometry aims to improve the accuracy of 17-OHP measurement and increase diagnostic quality of LOCAH.[22] Randomly timed measurements of 17-OHP have not been shown to be useful for screening since they are often normal and are known to be very high in the luteal phase of the female menstrual cycle. After basal levels have been measured, confirmation is done by administering ACTH, and comparing 17-OHP pre and post test. 17-OHP levels over 10 ng/mL at the 60th minute post stimulation is considered diagnostic for LOCAH.[45]

Androgen backdoor pathway

[edit]
Main article: Androgen backdoor pathway

In 21-hydroxylase deficiency, especially in mild cases (LOCAH), the androgen "backdoor" pathway[17] may be the reason of androgen excess.[53] This backdoor pathway is not always considered in the clinical evaluation of patients with hyperandrogenism conditions such as LOCAH and may be a source of diagnostic pitfalls and confusion.[54] One case study demonstrated the importance of considering serum 5α-dihydrotestosterone (DHT) levels and the androgen backdoor pathway in a LOCAH diagnosis that would have not been apparent from testosterone levels alone.[54]

11β-Hydroxylase deficiency

[edit]
Main article: Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

The activity of 11β-hydroxylase can be determined by observing the basal 11-deoxycortisol level. A level over 10 ng/mL, indicates followup with ACTH stimulation test. The 60th minute post-stimulation 11-deoxycortisol levels higher than 18 ng/mL are diagnostic of LOCAH.[45]

3β-Hydroxysteroid dehydrogenase deficiency

[edit]
Main article: Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency

The activity of 3β-hydroxysteroid dehydrogenase can be determined by observing the basal 17α-hydroxypregnenolone level. A level above 30 ng/mL and 17α-hydroxypregnenolone/cortisol ratio above 10 SD are diagnostic of LOCAH.[45][3]

Management

[edit]

Management and treatment of LOCAH is case specific[1] and the application of glucocorticoid treatment is not standard as it is in classic CAH.[1] LOCAH is not a life-threatening medical condition and the risks of treatment given prenatally or to asymptomatic children outweigh potential benefits.[55][56][57] In appropriate cases, glucocorticoids (usually hydrocortisone in children) are administered to suppress secretion of corticotropin releasing hormone (CRH) produced by hypothalamus and of adrenocorticotropic hormone (ACTH) produced by pituitary gland. This suppression will reduce concentration in blood of sex steroids produced by adrenal glands.[1] Some of the main considerations in treatment include the watchful waiting of symptom severity as well as adverse responses to glucocorticoids administered as drugs, seen in patient bone mineral density, height and weight.[1] For women, an oral contraceptive pill and androgen blockers such as spironolactone or cyproterone acetate are alternatives to glucocorticoids for managing symptoms of androgen excess.[1] There is still debate whether miscarriage rates in women with LOCAH are influenced by hydrocortisone treatment.[1]

Prevalence

[edit]

According to haplotype association studies, the prevalence of LOCAH in the US Ashkenazi Jew and Caucasian populations is estimated to be 1:500 to 1:1000, but in people with a high rate of marriage between relatives, the prevalence rate is as high as 1:50 to 1:100. A 2017 CYP21A2 genotype analysis predicted that the total frequency of LOCAH in the general population of the United States is about 1:200 (95% confidence level, from 1:100 to 1:280).[2][37]

According to a 2017 meta-analysis, the prevalence of LOCAH among women with signs and symptoms of androgen excess is 4.2% globally, and between 1% and 10% depending on the ethnicity of the population being studied.[22]

Anne Fausto-Sterling, an American sexologist, in a 2000 book "Sexing the Body" came up with an estimate that people with intersex conditions account for 1.7% of the general population.[58] This estimate is cited by a number of prominent intersex advocacy organizations.[59][60][61][62] Of these intersex individuals, according to Fausto-Sterling, 88% have LOCAH.[58] Leonard Sax, an American psychologist and a family physician, criticized these figures in a review published in 2002 in The Journal of Sex Research, stating that from the clinician's perspective, LOCAH is not an intersex condition.[63] Including LOCAH in intersex prevalence estimates has been cited as an example of misleading statistical practice.[64]

See also

[edit]

References

[edit]
  1. ^ a b c d e f g h i Adriaansen BP, Schröder MA, Span PN, Sweep FC, van Herwaarden AE, Claahsen-van der Grinten HL (2022). "Challenges in treatment of patients with non-classic congenital adrenal hyperplasia". Front Endocrinol (Lausanne). 13: 1064024. doi:10.3389/fendo.2022.1064024. PMC 9791115. PMID 36578966.
  2. ^ a b c d e Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. (November 2018). "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 103 (11): 4043–4088. doi:10.1210/jc.2018-01865. PMC 6456929. PMID 30272171.
  3. ^ a b c Hattori N, Ishihara T, Moridera K, Hino M, Ikekubo K, Kurahachi H (February 1993). "A case of late-onset congenital adrenal hyperplasia due to partial 3 beta-hydroxysteroid dehydrogenase deficiency". Endocrine Journal. 40 (1): 107–9. doi:10.1507/endocrj.40.107. PMID 7951484. Archived from the original on 2020-10-19. Retrieved 2020-10-04.
  4. ^ "OMIM Entry - # 202010 - ADRENAL HYPERPLASIA, CONGENITAL, DUE TO STEROID 11-BETA-HYDROXYLASE DEFICIENCY". www.omim.org. Archived from the original on 2021-03-21. Retrieved 2020-10-04.
  5. ^ Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI (July 1985). "High frequency of nonclassical steroid 21-hydroxylase deficiency". American Journal of Human Genetics. 37 (4): 650–67. PMC 1684620. PMID 9556656.
  6. ^ Krone N, Arlt W (April 2009). "Genetics of congenital adrenal hyperplasia". Best Practice & Research. Clinical Endocrinology & Metabolism. 23 (2): 181–92. doi:10.1016/j.beem.2008.10.014. PMC 5576025. PMID 19500762.
  7. ^ Turcu AF, Nanba AT, Chomic R, Upadhyay SK, Giordano TJ, Shields JJ, et al. (May 2016). "Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency". European Journal of Endocrinology. 174 (5): 601–9. doi:10.1530/EJE-15-1181. PMC 4874183. PMID 26865584.
  8. ^ a b c Witchel SF, Azziz R (2010). "Nonclassic congenital adrenal hyperplasia". International Journal of Pediatric Endocrinology. 2010: 625105. doi:10.1155/2010/625105. PMC 2910408. PMID 20671993.
  9. ^ Dineen R, Martin-Grace J, Thompson CJ, Sherlock M (June 2020). "The management of glucocorticoid deficiency: Current and future perspectives". Clinica Chimica Acta; International Journal of Clinical Chemistry. 505: 148–159. doi:10.1016/j.cca.2020.03.006. PMID 32145273. S2CID 212629520.
  10. ^ Koren I, Weintrob N, Kebesch R, Majdoub H, Stein N, Naor S, et al. (September 2023). "Genotype-Specific Cortisol Reserve in a Cohort of Subjects with Non-Classic Congenital Adrenal Hyperplasia (NCCAH)". J Clin Endocrinol Metab. 109 (3): 852–857. doi:10.1210/clinem/dgad546. PMID 37715965.
  11. ^ a b c d e f Merke DP, Auchus RJ (September 2020). "Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency". The New England Journal of Medicine. 383 (13): 1248–1261. doi:10.1056/NEJMra1909786. PMID 32966723. S2CID 221884108.
  12. ^ Karachaliou FH, Kafetzi M, Dracopoulou M, Vlachopapadopoulou E, Leka S, Fotinou A, et al. (December 2016). "Cortisol response to adrenocorticotropin testing in non-classical congenital adrenal hyperplasia (NCCAH)". Journal of Pediatric Endocrinology & Metabolism. 29 (12): 1365–1371. doi:10.1515/jpem-2016-0216. PMID 27849625. S2CID 43390012.
  13. ^ Chung S, Son GH, Kim K (May 2011). "Circadian rhythm of adrenal glucocorticoid: its regulation and clinical implications". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1812 (5): 581–91. doi:10.1016/j.bbadis.2011.02.003. PMID 21320597.
  14. ^ Dickmeis T (January 2009). "Glucocorticoids and the circadian clock". The Journal of Endocrinology. 200 (1): 3–22. doi:10.1677/JOE-08-0415. PMID 18971218.
  15. ^ Koch CE, Leinweber B, Drengberg BC, Blaum C, Oster H (February 2017). "Interaction between circadian rhythms and stress". Neurobiology of Stress. 6: 57–67. doi:10.1016/j.ynstr.2016.09.001. PMC 5314421. PMID 28229109.
  16. ^ Nicolaides NC, Charmandari E, Kino T, Chrousos GP (2017). "Stress-Related and Circadian Secretion and Target Tissue Actions of Glucocorticoids: Impact on Health". Frontiers in Endocrinology. 8: 70. doi:10.3389/fendo.2017.00070. PMC 5408025. PMID 28503165.
  17. ^ a b Masiutin M, Yadav M (2023). "Alternative androgen pathways". WikiJournal of Medicine. 10: X. doi:10.15347/WJM/2023.003. S2CID 257943362.
  18. ^ a b Miller WL, Auchus RJ (April 2019). "The "backdoor pathway" of androgen synthesis in human male sexual development". PLOS Biology. 17 (4): e3000198. doi:10.1371/journal.pbio.3000198. PMC 6464227. PMID 30943210. S2CID 92999312.
  19. ^ Pignatelli D (2013). "Non-classic adrenal hyperplasia due to the deficiency of 21-hydroxylase and its relation to polycystic ovarian syndrome". Frontiers of Hormone Research. 40: 158–70. doi:10.1159/000342179. ISBN 978-3-318-02238-4. PMID 24002412.
  20. ^ a b Livadas S, Bothou C (2019). "Management of the Female With Non-classical Congenital Adrenal Hyperplasia (NCCAH): A Patient-Oriented Approach". Frontiers in Endocrinology. 10: 366. doi:10.3389/fendo.2019.00366. PMC 6563652. PMID 31244776. S2CID 174798615.
  21. ^ Powell D, Inoue T, Bahtiyar G, Fenteany G, Sacerdote A (2017). "Treatment of Nonclassic 11-Hydroxylase Deficiency with Ashwagandha Root". Case Reports in Endocrinology. 2017: 1869560. doi:10.1155/2017/1869560. PMC 5496100. PMID 28713602.
  22. ^ a b c d e f Carmina E, Dewailly D, Escobar-Morreale HF, Kelestimur F, Moran C, Oberfield S, et al. (September 2017). "Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women". Human Reproduction Update. 23 (5): 580–599. doi:10.1093/humupd/dmx014. PMID 28582566.
  23. ^ Degitz K, Placzek M, Arnold B, Schmidt H, Plewig G (June 2003). "Congenital adrenal hyperplasia and acne in male patients". The British Journal of Dermatology. 148 (6): 1263–6. doi:10.1046/j.1365-2133.2003.05369.x. PMID 12828760. S2CID 42921625.
  24. ^ Sharquie KE, Noaimi AA, Saleh BO, Anbar ZN (December 2009). "The frequency of 21-alpha hydroxylase enzyme deficiency and related sex hormones in Iraqi healthy male subjects versus patients with acne vulgaris". Saudi Medical Journal. 30 (12): 1547–50. PMID 19936418.
  25. ^ Falhammar H, Nordenström A (September 2015). "Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome". Endocrine. 50 (1): 32–50. doi:10.1007/s12020-015-0656-0. PMID 26082286. S2CID 23469344.
  26. ^ a b New MI (November 2006). "Extensive clinical experience: nonclassical 21-hydroxylase deficiency". The Journal of Clinical Endocrinology and Metabolism. 91 (11): 4205–14. doi:10.1210/jc.2006-1645. PMID 16912124. Loss of scalp hair in females and males is embarrassing, requiring treatment with 5α-reductase inhibitors
  27. ^ Bernal González C, Fernández Salas C, Martínez S, Ezquieta Zubicaray B (October 2006). "[Premature androgenetic alopecia in adult male with nonclassic 21-OH deficiency. A novel nonsense CYP21A2 mutation (Y336X) in 2 affected siblings]". Medicina Clinica (in European Spanish). 127 (16): 617–21. doi:10.1016/s0025-7753(06)72688-4. PMID 17145028.
  28. ^ Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, et al. (April 2019). Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment. MDText.com. PMID 25905311. Archived from the original on 2020-11-14. Retrieved 2020-10-15.
  29. ^ Dimitrakov J, Joffe HV, Soldin SJ, Bolus R, Buffington CA, Nickel JC (February 2008). "Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome". Urology. 71 (2): 261–6. doi:10.1016/j.urology.2007.09.025. PMC 2390769. PMID 18308097.
  30. ^ Masiutin MG, Yadav MK (2022). "Letter to the editor regarding the article "Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome"". Urology. 169: 273. doi:10.1016/j.urology.2022.07.051. ISSN 0090-4295. PMID 35987379. S2CID 251657694. Archived from the original on 2023-06-30. Retrieved 2022-10-14.
  31. ^ Dimitrakoff J, Nickel JC (2022). "AUTHOR REPLY". Urology. 169: 273–274. doi:10.1016/j.urology.2022.07.049. ISSN 0090-4295. PMID 35985522. S2CID 251658492.
  32. ^ Corcioni B, Renzulli M, Marasco G, Baronio F, Gambineri A, Ricciardi D, et al. (February 2021). "Prevalence and ultrasound patterns of testicular adrenal rest tumors in adults with congenital adrenal hyperplasia". Translational Andrology and Urology. 10 (2): 562–573. doi:10.21037/tau-20-998. PMC 7947447. PMID 33718059.
  33. ^ Speiser PW (March 2009). "Nonclassic adrenal hyperplasia". Reviews in Endocrine & Metabolic Disorders. 10 (1): 77–82. doi:10.1007/s11154-008-9097-x. PMID 18690539. S2CID 30469525.
  34. ^ a b c Dörr HG, Schulze N, Bettendorf M, Binder G, Bonfig W, Denzer C, et al. (July 2020). "Genotype-phenotype correlations in children and adolescents with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Molecular and Cellular Pediatrics. 7 (1): 8. doi:10.1186/s40348-020-00100-w. PMC 7347723. PMID 32647925.
  35. ^ a b Espinosa Reyes TM, Collazo Mesa T, Lantigua Cruz PA, Agramonte Machado A, Domínguez Alonso E, Falhammar H (November 2020). "Molecular diagnosis of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency". BMC Endocrine Disorders. 20 (1): 165. doi:10.1186/s12902-020-00643-z. PMC 7653887. PMID 33168061.
  36. ^ Karaoğlan M, Nacarkahya G, Aytaç EH, Keskin M (March 2021). "Challenges of CYP21A2 genotyping in children with 21-hydroxylase deficiency: determination of genotype-phenotype correlation using next generation sequencing in Southeastern Anatolia". Journal of Endocrinological Investigation. 44 (11): 2395–2405. doi:10.1007/s40618-021-01546-z. PMID 33677812. S2CID 232133292.
  37. ^ a b c Hannah-Shmouni F, Morissette R, Sinaii N, Elman M, Prezant TR, Chen W, et al. (November 2017). "Revisiting the prevalence of nonclassic congenital adrenal hyperplasia in US Ashkenazi Jews and Caucasians". Genetics in Medicine. 19 (11): 1276–1279. doi:10.1038/gim.2017.46. PMC 5675788. PMID 28541281.
  38. ^ Tusie-Luna MT, Traktman P, White PC (December 1990). "Determination of functional effects of mutations in the steroid 21-hydroxylase gene (CYP21) using recombinant vaccinia virus". The Journal of Biological Chemistry. 265 (34): 20916–22. doi:10.1016/S0021-9258(17)45304-X. PMID 2249999.
  39. ^ Neocleous V, Shammas C, Phedonos AP, Karaoli E, Kyriakou A, Toumba M, et al. (September 2012). "Genetic defects in the cyp21a2 gene in heterozygous girls with premature adrenarche and adolescent females with hyperandrogenemia". Georgian Medical News (210): 40–7. PMID 23045419.
  40. ^ Admoni O, Israel S, Lavi I, Gur M, Tenenbaum-Rakover Y (June 2006). "Hyperandrogenism in carriers of CYP21 mutations: the role of genotype". Clinical Endocrinology. 64 (6): 645–51. doi:10.1111/j.1365-2265.2006.02521.x. PMID 16712666. S2CID 37571628.
  41. ^ Félix-López X, Riba L, Ordóñez-Sánchez ML, Ramírez-Jiménez S, Ventura-Gallegos JL, Zentella-Dehesa A, et al. (September 2003). "Steroid 21-hydroxylase (P450c21) naturally occurring mutants I172N, V281L and I236n/V237E/M239K exert a dominant negative effect on enzymatic activity when co-expressed with the wild-type protein". J Pediatr Endocrinol Metab. 16 (7): 1017–24. doi:10.1515/jpem.2003.16.7.1017. PMID 14513879. S2CID 40680772.
  42. ^ Baumgartner-Parzer S, Witsch-Baumgartner M, Hoeppner W (October 2020). "EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency". European Journal of Human Genetics. 28 (10): 1341–1367. doi:10.1038/s41431-020-0653-5. PMC 7609334. PMID 32616876. S2CID 220295067.
  43. ^ Tsai WH, Wong CH, Dai SH, Tsai CH, Zeng YH (2020). "Adrenal Tumor Mimicking Non-Classic Congenital Adrenal Hyperplasia". Frontiers in Endocrinology. 11: 526287. doi:10.3389/fendo.2020.526287. PMC 7551200. PMID 33117272. S2CID 221979120.
  44. ^ Decourt J, Jayle MF, Baulieu E (May 1957). "[Clinically late virilism with excretion of pregnanetriol and insufficiency of cortisol production]" [Clinically late virilism with excretion of pregnanetriol and insufficiency of cortisol production]. Annales d'Endocrinologie (in French). 18 (3): 416–22. PMID 13470408.
  45. ^ a b c d e f Kurtoğlu S, Hatipoğlu N (March 2017). "Non-Classical Congenital Adrenal Hyperplasia in Childhood". Journal of Clinical Research in Pediatric Endocrinology. 9 (1): 1–7. doi:10.4274/jcrpe.3378. PMC 5363159. PMID 27354284.
  46. ^ Kohn B, Levine LS, Pollack MS, Pang S, Lorenzen F, Levy D, et al. (November 1982). "Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia". The Journal of Clinical Endocrinology and Metabolism. 55 (5): 817–27. doi:10.1210/jcem-55-5-817. PMID 6288753.
  47. ^ Chrousos GP, Loriaux DL, Mann DL, Cutler GB (February 1982). "Late-onset 21-hydroxylase deficiency mimicking idiopathic hirsutism or polycystic ovarian disease". Annals of Internal Medicine. 96 (2): 143–8. doi:10.7326/0003-4819-96-2-143. PMID 6977282.
  48. ^ Turcu AF, Auchus RJ (June 2015). "Adrenal steroidogenesis and congenital adrenal hyperplasia". Endocrinology and Metabolism Clinics of North America. 44 (2): 275–96. doi:10.1016/j.ecl.2015.02.002. PMC 4506691. PMID 26038201.
  49. ^ Pignatelli D, Pereira SS, Pasquali R (2019). "Androgens in Congenital Adrenal Hyperplasia". Frontiers of Hormone Research. 53: 65–76. doi:10.1159/000494903. ISBN 978-3-318-06470-4. PMID 31499506. S2CID 202412336.
  50. ^ Polat S, Arslan YK (March 2022). "17-Hydroxyprogesterone Response to Standard Dose Synacthen Stimulation Test in CYP21A2 Heterozygous Carriers and Non-carriers in Symptomatic and Asymptomatic Groups: Meta-analyses". J Clin Res Pediatr Endocrinol. 14 (1): 56–68. doi:10.4274/jcrpe.galenos.2021.2021.0184. PMC 8900072. PMID 34743977.
  51. ^ Azziz R, Zacur HA (September 1989). "21-Hydroxylase deficiency in female hyperandrogenism: screening and diagnosis". The Journal of Clinical Endocrinology and Metabolism. 69 (3): 577–84. doi:10.1210/jcem-69-3-577. PMID 2547827.
  52. ^ "Клинические рекомендации Российской ассоциации эндокринологов по диагностике и лечебно-профилактическим мероприятиям при врожденной дисфункции коры надпочечников у пациентов во взрослом возрасте". Consilium Medicum. 2016. doi:10.26442/2075-1753_2016.4.8-19 (inactive 2024-11-02).{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  53. ^ White PC (June 2018). "Update on diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Current Opinion in Endocrinology, Diabetes and Obesity. 25 (3): 178–184. doi:10.1097/MED.0000000000000402. PMID 29718004. S2CID 26072848.
  54. ^ a b Sumińska M, Bogusz-Górna K, Wegner D, Fichna M (June 2020). "Non-Classic Disorder of Adrenal Steroidogenesis and Clinical Dilemmas in 21-Hydroxylase Deficiency Combined with Backdoor Androgen Pathway. Mini-Review and Case Report". International Journal of Molecular Sciences. 21 (13): 4622. doi:10.3390/ijms21134622. PMC 7369945. PMID 32610579.
  55. ^ Miller WL, Witchel SF (May 2013). "Prenatal treatment of congenital adrenal hyperplasia: risks outweigh benefits". American Journal of Obstetrics and Gynecology. 208 (5): 354–9. doi:10.1016/j.ajog.2012.10.885. PMID 23123167.
  56. ^ Clayton PE, Miller WL, Oberfield SE, Ritzén EM, Sippell WG, Speiser PW (2002). "Consensus statement on 21-hydroxylase deficiency from the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society". Hormone Research. 58 (4): 188–95. doi:10.1159/000065490. PMID 12324718. S2CID 41346214.
  57. ^ Joint LWPES/ESPE CAH Working Group (September 2002). "Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology". The Journal of Clinical Endocrinology and Metabolism. 87 (9): 4048–53. doi:10.1210/jc.2002-020611. PMID 12213842.
  58. ^ a b Fausto-Sterling A (30 November 2000). Sexing the body : gender politics and the construction of sexuality. New York: Basic Books. ISBN 978-0-465-07713-7.
  59. ^ "Intersex babies are perfect just as they are!". UN Free & Equal. Archived from the original on 2016-11-12. Retrieved 2020-10-12. up to 1.7 percent of babies are born with sex characteristics that don't fit typical definitions of male and female. That makes being intersex almost as common as being a redhead!
  60. ^ "Its Intersex Awareness Day - here are 5 myths we need to shatter". www.amnesty.org. 26 October 2018. Archived from the original on 18 October 2020. Retrieved 12 October 2020. According to experts, around 1.7% of the population is born with intersex traits - comparable to the number of people born with red hair.
  61. ^ "What is Intersex? Frequently Asked Questions". interACT: Advocates for Intersex Youth. Archived from the original on 2024-01-06. Retrieved 2021-02-02. About 1.7% of people are born intersex. (Compare that to a ~0.3% chance of having identical twins!) 1 in 2,000 babies (0.05% of humans) are born with genital differences that a doctor might suggest changing with unnecessary surgery.
  62. ^ "Intersex population figures". Intersex Human Rights Australia. 28 September 2013. Archived from the original on 17 July 2018. Retrieved 30 October 2020. Given that intersex people only come to the attention of data collectors through chance or an apparent medical reason, the actual numbers of people with intersex variations are likely to be as much as 1.7%. Despite the limitations of the data, 1.7% seems more justifiable as an upper limit figure than alternatives, to date.
  63. ^ Sax L (August 2002). "How common is intersex? a response to Anne Fausto-Sterling". Journal of Sex Research. 39 (3): 174–8. doi:10.1080/00224490209552139. PMID 12476264. S2CID 33795209. Archived from the original on 2021-02-28. Retrieved 2020-10-11. Reviewing the list of conditions which Fausto-Sterling considers to be intersex, we find that this one condition–late-onset congenital adrenal hyperplasia (LOCAH)–accounts for 88% of all those patients whom Fausto-Sterling classifies as intersex (1.5/1.7 = 88%). From a clinician's perspective, however, LOCAH is not an intersex condition. The genitalia of these babies are normal at birth, and consonant with their chromosomes: XY males have normal male genitalia, and XX females have normal female genitalia.
  64. ^ Best J (14 September 2013). Stat-spotting: a field guide to identifying dubious data (1st, Updated and expand ed.). Berkeley: University of California Press. pp. 12–13. ISBN 978-0-520-27998-8.
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Late_onset_congenital_adrenal_hyperplasia&oldid=1254921940"