21-hydroxylase deficiency medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
Medical therapy for classic type of 21-hydroxylase deficiency includes maternal administration of [[dexamethasone]] for [[genetically]] | Medical therapy for classic type of 21-hydroxylase deficiency includes maternal administration of [[dexamethasone]] for [[genetically]] diagnosed intranatal patients. [[Hydrocortisone]] and [[fludrocortisone]] is given in children and [[Adult|adults]]. Treatment for non-classic type of 21 hydroxylase deficiency in children includes [[hydrocortisone]] up to [[puberty]] and in women in reproductive age, [[oral contraceptive pills]] are given for regulation of [[menstrual cycle]]. Men with non-classic type of 21 hydroxylase deficiency are [[asymptomatic]] and do not need any treatment. | ||
==Medical Therapy for classic type of 21 hydroxylase deficiency== | ==Medical Therapy for classic type of 21 hydroxylase deficiency== | ||
Medical therapy for 21-hydroxylase deficiency in [[prenatal]] period, [[neonates]], children and [[Adult|adults]], is as below:<ref name="pmid15964450">{{cite journal |vauthors=Merke DP, Bornstein SR |title=Congenital adrenal hyperplasia |journal=Lancet |volume=365 |issue=9477 |pages=2125–36 |year=2005 |pmid=15964450 |doi=10.1016/S0140-6736(05)66736-0 |url=}}</ref><ref name="pmid12213842">{{cite journal |vauthors= |title=Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=9 |pages=4048–53 |year=2002 |pmid=12213842 |doi=10.1210/jc.2002-020611 |url=}}</ref><ref name="pmid11344938">{{cite journal |vauthors=Speiser PW |title=Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=31–59, vi |year=2001 |pmid=11344938 |doi= |url=}}</ref><ref name="pmid20823466">{{cite journal| author=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP et al.| title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4133-60 | pmid=20823466 | doi=10.1210/jc.2009-2631 | pmc=2936060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823466 }}</ref><ref name="pmid2 22237438">{{cite journal| author=Bose KS, Sarma RH| title=Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution. | journal=Biochem Biophys Res Commun | year= 1975 | volume= 66 | issue= 4 | pages= 1173-9 | pmid=2 22237438 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2 }}</ref> | Medical therapy for 21-hydroxylase deficiency in [[prenatal]] period, [[neonates]], children and [[Adult|adults]], is as below:<ref name="pmid15964450">{{cite journal |vauthors=Merke DP, Bornstein SR |title=Congenital adrenal hyperplasia |journal=Lancet |volume=365 |issue=9477 |pages=2125–36 |year=2005 |pmid=15964450 |doi=10.1016/S0140-6736(05)66736-0 |url=}}</ref><ref name="pmid12213842">{{cite journal |vauthors= |title=Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=9 |pages=4048–53 |year=2002 |pmid=12213842 |doi=10.1210/jc.2002-020611 |url=}}</ref><ref name="pmid11344938">{{cite journal |vauthors=Speiser PW |title=Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=31–59, vi |year=2001 |pmid=11344938 |doi= |url=}}</ref><ref name="pmid20823466">{{cite journal| author=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP et al.| title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4133-60 | pmid=20823466 | doi=10.1210/jc.2009-2631 | pmc=2936060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823466 }}</ref><ref name="pmid2 22237438">{{cite journal| author=Bose KS, Sarma RH| title=Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution. | journal=Biochem Biophys Res Commun | year= 1975 | volume= 66 | issue= 4 | pages= 1173-9 | pmid=2 22237438 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2 }}</ref> | ||
=== | === 1. Prenatal treatment=== | ||
In the [[prenatal]] period [[virilization]] of female [[fetus]] begins early; therefore, early | In the [[prenatal]] period [[virilization]] of female [[fetus]] begins early; therefore, early treatment is required as follows: | ||
* If classic [[CYP21A2]] [[gene]] [[mutations]] exist in parents, [[maternal]] administration of [[dexamethasone]] should be prescribed | * If classic [[CYP21A2]] [[gene]] [[mutations]] exist in parents, [[maternal]] administration of [[dexamethasone]] should be prescribed. | ||
** Preferred regimen: [[Dexamethasone]] 20 micrograms/kg | ** Preferred regimen: [[Dexamethasone]] 20 micrograms/kg q24h in 2 or 3 fractioned doses [[Orally ingested|orally]]. | ||
** [[Dexamethasone]] crosses the [[placenta]] into the [[fetal circulation]] and prevents [[ambiguous genitalia]] in female [[fetus]] | *** [[Dexamethasone]] crosses the [[placenta]] into the [[fetal circulation]] and prevents [[ambiguous genitalia]] in female [[fetus]]. | ||
** This treatment should be started before 9 weeks of [[pregnancy]] age; if treatment cannot be started by 9 weeks, it should not be given at all | *** This treatment should be started before 9 weeks of [[pregnancy]] age; if treatment cannot be started by 9 weeks, it should not be given at all. | ||
** If [[Cell-free system|cell-free]] [[fetal]] [[DNA testing]] reveals the gender to be male, treatment should be discontinued | *** If [[Cell-free system|cell-free]] [[fetal]] [[DNA testing]] reveals the gender to be male, treatment should be discontinued. | ||
** Approximately 85% of managed cases appear quite normal after [[delivery]] | *** Approximately 85% of managed cases appear quite normal after [[delivery]]. | ||
** [[Side effects]] of [[prenatal]] [[dexamethasone]] are:<ref name="pmid208234662">{{cite journal| author=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP et al.| title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4133-60 | pmid=20823466 | doi=10.1210/jc.2009-2631 | pmc=2936060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823466 }}</ref><ref name="pmid9814461">{{cite journal| author=Lajic S, Wedell A, Bui TH, Ritzén EM, Holst M| title=Long-term somatic follow-up of prenatally treated children with congenital adrenal hyperplasia. | journal=J Clin Endocrinol Metab | year= 1998 | volume= 83 | issue= 11 | pages= 3872-80 | pmid=9814461 | doi=10.1210/jcem.83.11.5233 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9814461 }}</ref><ref name="pmid18060943">{{cite journal| author=Carmichael SL, Shaw GM, Ma C, Werler MM, Rasmussen SA, Lammer EJ et al.| title=Maternal corticosteroid use and orofacial clefts. | journal=Am J Obstet Gynecol | year= 2007 | volume= 197 | issue= 6 | pages= 585.e1-7; discussion 683-4, e1-7 | pmid=18060943 | doi=10.1016/j.ajog.2007.05.046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18060943 }}</ref><ref name="pmid27482827">{{cite journal| author=Wallensteen L, Zimmermann M, Thomsen Sandberg M, Gezelius A, Nordenström A, Hirvikoski T et al.| title=Sex-Dimorphic Effects of Prenatal Treatment With Dexamethasone. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 10 | pages= 3838-3846 | pmid=27482827 | doi=10.1210/jc.2016-1543 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27482827 }}</ref><ref name="pmid24278432">{{cite journal| author=Khalife N, Glover V, Taanila A, Ebeling H, Järvelin MR, Rodriguez A| title=Prenatal glucocorticoid treatment and later mental health in children and adolescents. | journal=PLoS One | year= 2013 | volume= 8 | issue= 11 | pages= e81394 | pmid=24278432 | doi=10.1371/journal.pone.0081394 | pmc=3838350 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24278432 }}</ref> | *** [[Side effects]] of [[prenatal]] [[dexamethasone]] are:<ref name="pmid208234662">{{cite journal| author=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP et al.| title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4133-60 | pmid=20823466 | doi=10.1210/jc.2009-2631 | pmc=2936060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823466 }}</ref><ref name="pmid9814461">{{cite journal| author=Lajic S, Wedell A, Bui TH, Ritzén EM, Holst M| title=Long-term somatic follow-up of prenatally treated children with congenital adrenal hyperplasia. | journal=J Clin Endocrinol Metab | year= 1998 | volume= 83 | issue= 11 | pages= 3872-80 | pmid=9814461 | doi=10.1210/jcem.83.11.5233 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9814461 }}</ref><ref name="pmid18060943">{{cite journal| author=Carmichael SL, Shaw GM, Ma C, Werler MM, Rasmussen SA, Lammer EJ et al.| title=Maternal corticosteroid use and orofacial clefts. | journal=Am J Obstet Gynecol | year= 2007 | volume= 197 | issue= 6 | pages= 585.e1-7; discussion 683-4, e1-7 | pmid=18060943 | doi=10.1016/j.ajog.2007.05.046 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18060943 }}</ref><ref name="pmid27482827">{{cite journal| author=Wallensteen L, Zimmermann M, Thomsen Sandberg M, Gezelius A, Nordenström A, Hirvikoski T et al.| title=Sex-Dimorphic Effects of Prenatal Treatment With Dexamethasone. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 10 | pages= 3838-3846 | pmid=27482827 | doi=10.1210/jc.2016-1543 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27482827 }}</ref><ref name="pmid24278432">{{cite journal| author=Khalife N, Glover V, Taanila A, Ebeling H, Järvelin MR, Rodriguez A| title=Prenatal glucocorticoid treatment and later mental health in children and adolescents. | journal=PLoS One | year= 2013 | volume= 8 | issue= 11 | pages= e81394 | pmid=24278432 | doi=10.1371/journal.pone.0081394 | pmc=3838350 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24278432 }}</ref> | ||
*** [[Postnatal]] [[failure to thrive]] | **** [[Postnatal]] [[failure to thrive]] | ||
*** [[Psychomotor retardation|Psychomotor]] [[developmental delay]] | **** [[Psychomotor retardation|Psychomotor]] [[developmental delay]] | ||
***Increased risk of [[cleft lip and palate]] | ****Increased risk of [[cleft lip and palate]] | ||
***Increased risk for [[Psychiatric disorders|psychiatric disturbances]] and [[ADHD]] | ****Increased risk for [[Psychiatric disorders|psychiatric disturbances]] and [[ADHD]] | ||
=== | === 2. Neonatal treatment === | ||
Medical therapy for 21-hydroxylase deficiency in the | '''2.1 Medical therapy for 21-hydroxylase deficiency in the neonates is as follows:'''<ref name="pmid20823466">{{cite journal| author=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP et al.| title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4133-60 | pmid=20823466 | doi=10.1210/jc.2009-2631 | pmc=2936060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823466 }}</ref> | ||
* Preferred regimen: [[Hydrocortisone]] 20 to 30 mg/m<sup>2</sup> | * Preferred regimen: [[Hydrocortisone]] 20 to 30 mg/m<sup>2</sup> q24h divided in three doses [[Orally ingested|PO]] '''<u>AND</u>''' [[Fludrocortisone]] 100 mcg q12h [[Orally ingested|PO]] '''<u>AND</u>''' [[sodium chloride]] one gram or 4 mEq/kg q24h divided in several doses [[Orally ingested|PO.]] | ||
** The minimization of [[steroid]] doses should be considered to avoid [[steroid]] [[complications]] in [[infants]] | ** The minimization of [[steroid]] doses should be considered to avoid [[steroid]] [[complications]] in [[infants|infants.]] | ||
** Growth suppression and shorter height in adulthood are the [[complications]] of using high dose [[steroids]] which occurs in [[neonates]] | ** Growth suppression and shorter height in adulthood are the [[complications]] of using high dose [[steroids]] which occurs in [[neonates]]. | ||
'''2.2 Ambiguous genitalia:''' | |||
* [[Ambiguous genitalia]] should be managed immediately. | |||
* [[Infants]] with [[ambiguous genitalia]] and non palpable [[gonads]] should be considered to have [[congenital adrenal hyperplasia]] and [[empirical treatment]] should be start early after obtaining [[blood]] sample for [[17-hydroxyprogesterone]]. | |||
* Initial [[empiric therapy]] should contains doses of [[glucocorticoid]] and [[mineralocorticoid]] and [[sodium chloride]] supplementation. | |||
** Preferred regimen: [[Hydrocortisone]] is 20 to 30 mg/m<sup>2</sup> q24h divided in three doses [[Orally ingested|PO]] '''<u>AND</u>''' [[Fludrocortisone]] 100 mcg q12h [[Orally ingested|PO]] '''<u>AND</u>''' [[sodium chloride]] one gram or 4 mEq/kg q24h divided in several doses [[Route of administration|PO]]. | |||
'''2.3 Adrenal crisis:''' | |||
* Preferred regimen: [[Normal saline]] 0.9 percent, 20 mL/kg [[intravenous]] [[Bolus (medicine)|bolus]] '''<u>AND</u>''' [[dextrose]] 10 percent 2 to 4 mL/kg [[intravenous]] [[Bolus (medicine)|bolus]] (if there is significant [[hypoglycemia]]) '''<u>AND</u>''' [[hydrocortisone]] 50 to 100 mg/m<sup>2</sup> [[intravenous]] [[Bolus (medicine)|bolus]], '''<u>THEN</u>''' continue [[hydrocortisone]] alone 50 to 100 mg/m<sup>2</sup> [[Intravenous therapy|IV]] per day divided into four times per 24 hours. | |||
** The [[blood]] sample should be obtained for [[steroid hormone]] levels before giving [[hydrocortisone]]. | |||
** [[Hyperkalemia]] should be corrected on the base of its level and [[complications]]. | |||
=== | ===3. Management in children=== | ||
* [[ | * Preferred regimen: [[Hydrocortisone]] ([[cortisol]]) in a dose of 10 to 15 mg/m<sup>2</sup> [[body surface area]]/day [[Orally ingested|PO]] '''<u>AND</u>''' [[fludrocortisone]] in a dose of 50 to 200 mcg per day (0.05 to 0.20 mg/day) [[Orally ingested|PO]]. | ||
** [[Mineralocorticoid]] replacement should be started in all 21-hydroxylase deficient patients, and often may be tapered after six months of age. | |||
'''3.1 Response to therapy can be monitored by checking the following parameters:''' | |||
* Serum [[17-hydroxyprogesterone]] | |||
* [[Androstenedione]] | |||
* [[Plasma renin activity]] or direct [[renin]] | |||
* Height measurements | |||
==== | ===4. Management in adults=== | ||
'''21 hydroxylase deficiency should be managed as follows:'''<ref name="pmid20823466">{{cite journal| author=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP et al.| title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4133-60 | pmid=20823466 | doi=10.1210/jc.2009-2631 | pmc=2936060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823466 }}</ref><ref name="pmid2843311">{{cite journal| author=Horrocks PM, London DR| title=Effects of long term dexamethasone treatment in adult patients with congenital adrenal hyperplasia. | journal=Clin Endocrinol (Oxf) | year= 1987 | volume= 27 | issue= 6 | pages= 635-42 | pmid=2843311 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2843311 }}</ref><ref name="pmid27623069">{{cite journal| author=Stewart PM, Biller BM, Marelli C, Gunnarsson C, Ryan MP, Johannsson G| title=Exploring Inpatient Hospitalizations and Morbidity in Patients With Adrenal Insufficiency. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 12 | pages= 4843-4850 | pmid=27623069 | doi=10.1210/jc.2016-2221 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27623069 }}</ref><ref name="pmid3060026">{{cite journal| author=Hughes IA| title=Management of congenital adrenal hyperplasia. | journal=Arch Dis Child | year= 1988 | volume= 63 | issue= 11 | pages= 1399-404 | pmid=3060026 | doi= | pmc=1779155 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3060026 }}</ref><ref name="pmid11344938">{{cite journal |vauthors=Speiser PW |title=Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=31–59, vi |year=2001 |pmid=11344938 |doi= |url=}}</ref><ref name="pmid9829228">{{cite journal |vauthors=Lopes LA, Dubuis JM, Vallotton MB, Sizonenko PC |title=Should we monitor more closely the dosage of 9 alpha-fluorohydrocortisone in salt-losing congenital adrenal hyperplasia? |journal=J. Pediatr. Endocrinol. Metab. |volume=11 |issue=6 |pages=733–7 |year=1998 |pmid=9829228 |doi= |url=}}</ref><ref name="pmid7015786">{{cite journal |vauthors=Jansen M, Wit JM, van den Brande JL |title=Reinstitution of mineralocorticoid therapy in congenital adrenal hyperplasia. Effects on control and growth |journal=Acta Paediatr Scand |volume=70 |issue=2 |pages=229–33 |year=1981 |pmid=7015786 |doi= |url=}}</ref> | |||
'''4.1 Treatment goals''' | |||
* Provide proper dosing of [[glucocorticoid]] and [[mineralocorticoid]]. | |||
* Decrease secretion of [[cosyntropin]]; therefore decrease [[adrenal]] overstimulation and [[androgen]] production. | |||
'''4.2 Glucocorticoids and mineralocorticoid replacement''' | |||
* Preferred regimen: [[Hydrocortisone]] 15-30 mg q24h divided into three doses [[Orally ingested|PO]] '''<u>AND</u>''' [[Fludrocortisone Acetate|9-alpha-fludrocortisone acetate]] 0.1 to 0.2 mg q24h [[Orally ingested|PO]]. | |||
* Alternative regimen (1): [[Dexamethasone]] 0.75 mg q24h [[Orally ingested|PO]] '''<u>AND</u>''' [[Fludrocortisone Acetate|9-alpha-fludrocortisone acetate]] 0.1 to 0.2 mg q24h [[Route of administration|PO]]. | |||
* Alternative regimen (2): [[Prednisone]] 5mg q24h [[Orally ingested|PO]] '''<u>AND</u>''' [[Fludrocortisone Acetate|9-alpha-fludrocortisone acetate]] 0.1 to 0.2 mg q24h [[Orally ingested|PO]]. | |||
'''4.3 Considerations''' | |||
*[[Glucocorticoids]] reduce the excess production of [[adrenal]] [[androgens]] and reduce the excessive secretion of both [[corticotropin-releasing hormone]] and [[ACTH]]. | |||
* Stress dosing: In patients with 21-hydroxylase deficiency and serious [[illness]], [[glucocorticoids]] stress dosing is necessary. | |||
* [[Dexamethasone]] is very potent and long-acting [[glucocorticoid]] that effectively suppresses [[ACTH]] secretion but almost always causes the development of [[cushingoid appearance]] with chronic use. | |||
* The proper dose of [[Fludrocortisone Acetate|fludrocortisone acetate]] should be used to restore normal [[serum]] [[potassium]] concentrations and [[plasma renin activity]]. | |||
'''4.4 Therapy consideration in women''' | |||
* Provide proper dosing of [[glucocorticoid]] and [[mineralocorticoid]] | * Lowering blood [[androgen]] levels with [[glucocorticoids]], can helps women to control annoying [[Cosmetics|cosmetic]] [[symptoms]] such as [[acne]] and [[hirsutism]]. | ||
* Decrease secretion of [[cosyntropin]]; therefore decrease [[adrenal]] overstimulation and [[androgen]] production | * In 21-hydroxylase deficient patients [[oral contraceptive pills]] in combination with [[glucocorticoids]] can be used to regulate the [[menstrual cycle]] and induction of [[ovulation]]. | ||
* Preferred regimen: [[Hydrocortisone]] 15-30 mg | |||
* Alternative regimen (1): [[Dexamethasone]] 0.75 mg | |||
* Alternative regimen (2): [[Prednisone]] 5mg | |||
*[[Glucocorticoids]] reduce the excess production of [[adrenal]] [[androgens]] and reduce the excessive secretion of both [[corticotropin-releasing hormone]] and [[ACTH]] | |||
* Stress dosing: In patients with 21-hydroxylase deficiency and serious [[illness]], [[glucocorticoids]] stress dosing is necessary | |||
* [[Dexamethasone]] is very potent and long-acting [[glucocorticoid]] that effectively suppresses [[ACTH]] secretion but almost always causes the development of [[cushingoid appearance]] with chronic use | |||
* The proper dose of [[Fludrocortisone Acetate|fludrocortisone acetate]] should be used to restore normal [[serum]] [[potassium]] concentrations and [[plasma renin activity]] | |||
* Lowering blood [[androgen]] levels with [[glucocorticoids]], can helps women to control annoying [[Cosmetics|cosmetic]] [[symptoms]] such as [[acne]] and [[hirsutism]] | |||
* In 21-hydroxylase deficient patients [[oral contraceptive pills]] in combination with [[glucocorticoids]] can be used to regulate the [[menstrual cycle]] and induction of [[ovulation]] | |||
== Medical Therapy for non-classic type of 21 hydroxylase deficiency == | == Medical Therapy for non-classic type of 21 hydroxylase deficiency == | ||
Medical therapy for non-classic type of 21 hydroxylase deficiency is as following:<ref name="pmid2137832">{{cite journal |vauthors=Spritzer P, Billaud L, Thalabard JC, Birman P, Mowszowicz I, Raux-Demay MC, Clair F, Kuttenn F, Mauvais-Jarvis P |title=Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia |journal=J. Clin. Endocrinol. Metab. |volume=70 |issue=3 |pages=642–6 |year=1990 |pmid=2137832 |doi=10.1210/jcem-70-3-642 |url=}}</ref><ref name="pmid20823466">{{cite journal |vauthors=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC |title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline |journal=J. Clin. Endocrinol. Metab. |volume=95 |issue=9 |pages=4133–60 |year=2010 |pmid=20823466 |pmc=2936060 |doi=10.1210/jc.2009-2631 |url=}}</ref><ref name="pmid2142968">{{cite journal |vauthors=Frank-Raue K, Junga G, Raue F, Vecsei P, Ziegler R |title=[Therapy of hirsutism in females with adrenal enzyme defects of steroid hormone biosynthesis: comparison of dexamethasone with cyproterone acetate] |language=German |journal=Klin. Wochenschr. |volume=68 |issue=12 |pages=597–601 |year=1990 |pmid=2142968 |doi= |url=}}</ref><ref name="pmid24622419">{{cite journal |vauthors=Merke DP, Poppas DP |title=Management of adolescents with congenital adrenal hyperplasia |journal=Lancet Diabetes Endocrinol |volume=1 |issue=4 |pages=341–52 |year=2013 |pmid=24622419 |pmc=4163910 |doi=10.1016/S2213-8587(13)70138-4 |url=}}</ref> | Medical therapy for non-classic type of 21 hydroxylase deficiency is as following:<ref name="pmid2137832">{{cite journal |vauthors=Spritzer P, Billaud L, Thalabard JC, Birman P, Mowszowicz I, Raux-Demay MC, Clair F, Kuttenn F, Mauvais-Jarvis P |title=Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia |journal=J. Clin. Endocrinol. Metab. |volume=70 |issue=3 |pages=642–6 |year=1990 |pmid=2137832 |doi=10.1210/jcem-70-3-642 |url=}}</ref><ref name="pmid20823466">{{cite journal |vauthors=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC |title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline |journal=J. Clin. Endocrinol. Metab. |volume=95 |issue=9 |pages=4133–60 |year=2010 |pmid=20823466 |pmc=2936060 |doi=10.1210/jc.2009-2631 |url=}}</ref><ref name="pmid2142968">{{cite journal |vauthors=Frank-Raue K, Junga G, Raue F, Vecsei P, Ziegler R |title=[Therapy of hirsutism in females with adrenal enzyme defects of steroid hormone biosynthesis: comparison of dexamethasone with cyproterone acetate] |language=German |journal=Klin. Wochenschr. |volume=68 |issue=12 |pages=597–601 |year=1990 |pmid=2142968 |doi= |url=}}</ref><ref name="pmid24622419">{{cite journal |vauthors=Merke DP, Poppas DP |title=Management of adolescents with congenital adrenal hyperplasia |journal=Lancet Diabetes Endocrinol |volume=1 |issue=4 |pages=341–52 |year=2013 |pmid=24622419 |pmc=4163910 |doi=10.1016/S2213-8587(13)70138-4 |url=}}</ref> | ||
=== Children === | === 1. Children === | ||
* Preferred regimen: [[Hydrocortisone]] 10 to 15 mg/m<sup>2</sup> divided into three doses | * Preferred regimen: [[Hydrocortisone]] 10 to 15 mg/m<sup>2</sup> divided into three doses q24h. | ||
** Treatment should be continued until [[puberty]]. | ** Treatment should be continued until [[puberty]]. | ||
**In [[symptomatic]] girls after [[puberty]], other treatment options such as [[oral contraceptive pills]] may be used in order to avoid [[glucocorticoids]]. | |||
=== 2. Adults === | |||
* Female patients may need [[oral contraceptive pills]] for regulation of [[menstrual cycle]]; [[oral contraceptive pills]] are preferred other than [[glucocorticoids]] in this condition. | |||
=== Adults === | |||
* Female patients may need [[oral contraceptive pills]] | |||
* Female patients with [[infertility]] and [[Anovulatory cycle|anovulatory cycles]] who desire [[Conceive a child|conceive]], [[glucocorticoids]] with above dosage are the initial choice for [[ovulation]] induction. | * Female patients with [[infertility]] and [[Anovulatory cycle|anovulatory cycles]] who desire [[Conceive a child|conceive]], [[glucocorticoids]] with above dosage are the initial choice for [[ovulation]] induction. | ||
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==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
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[[Category:Disease]] | |||
[[Category:Pediatrics]] | |||
[[Category:Endocrinology]] | |||
[[Category:Genetic disorders]] | |||
[[Category:Intersexuality]] | |||
[[Category:Medicine]] | |||
[[Category: Up-To-Date]] | |||
Latest revision as of 15:32, 24 July 2020
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21-hydroxylase deficiency Microchapters |
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Differentiating 21-Hydroxylase Deficiency from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
Medical therapy for classic type of 21-hydroxylase deficiency includes maternal administration of dexamethasone for genetically diagnosed intranatal patients. Hydrocortisone and fludrocortisone is given in children and adults. Treatment for non-classic type of 21 hydroxylase deficiency in children includes hydrocortisone up to puberty and in women in reproductive age, oral contraceptive pills are given for regulation of menstrual cycle. Men with non-classic type of 21 hydroxylase deficiency are asymptomatic and do not need any treatment.
Medical Therapy for classic type of 21 hydroxylase deficiency
Medical therapy for 21-hydroxylase deficiency in prenatal period, neonates, children and adults, is as below:[1][2][3][4][5]
1. Prenatal treatment
In the prenatal period virilization of female fetus begins early; therefore, early treatment is required as follows:
- If classic CYP21A2 gene mutations exist in parents, maternal administration of dexamethasone should be prescribed.
- Preferred regimen: Dexamethasone 20 micrograms/kg q24h in 2 or 3 fractioned doses orally.
- Dexamethasone crosses the placenta into the fetal circulation and prevents ambiguous genitalia in female fetus.
- This treatment should be started before 9 weeks of pregnancy age; if treatment cannot be started by 9 weeks, it should not be given at all.
- If cell-free fetal DNA testing reveals the gender to be male, treatment should be discontinued.
- Approximately 85% of managed cases appear quite normal after delivery.
- Side effects of prenatal dexamethasone are:[6][7][8][9][10]
- Postnatal failure to thrive
- Psychomotor developmental delay
- Increased risk of cleft lip and palate
- Increased risk for psychiatric disturbances and ADHD
- Preferred regimen: Dexamethasone 20 micrograms/kg q24h in 2 or 3 fractioned doses orally.
2. Neonatal treatment
2.1 Medical therapy for 21-hydroxylase deficiency in the neonates is as follows:[4]
- Preferred regimen: Hydrocortisone 20 to 30 mg/m2 q24h divided in three doses PO AND Fludrocortisone 100 mcg q12h PO AND sodium chloride one gram or 4 mEq/kg q24h divided in several doses PO.
- The minimization of steroid doses should be considered to avoid steroid complications in infants.
- Growth suppression and shorter height in adulthood are the complications of using high dose steroids which occurs in neonates.
2.2 Ambiguous genitalia:
- Ambiguous genitalia should be managed immediately.
- Infants with ambiguous genitalia and non palpable gonads should be considered to have congenital adrenal hyperplasia and empirical treatment should be start early after obtaining blood sample for 17-hydroxyprogesterone.
- Initial empiric therapy should contains doses of glucocorticoid and mineralocorticoid and sodium chloride supplementation.
- Preferred regimen: Hydrocortisone is 20 to 30 mg/m2 q24h divided in three doses PO AND Fludrocortisone 100 mcg q12h PO AND sodium chloride one gram or 4 mEq/kg q24h divided in several doses PO.
2.3 Adrenal crisis:
- Preferred regimen: Normal saline 0.9 percent, 20 mL/kg intravenous bolus AND dextrose 10 percent 2 to 4 mL/kg intravenous bolus (if there is significant hypoglycemia) AND hydrocortisone 50 to 100 mg/m2 intravenous bolus, THEN continue hydrocortisone alone 50 to 100 mg/m2 IV per day divided into four times per 24 hours.
- The blood sample should be obtained for steroid hormone levels before giving hydrocortisone.
- Hyperkalemia should be corrected on the base of its level and complications.
3. Management in children
- Preferred regimen: Hydrocortisone (cortisol) in a dose of 10 to 15 mg/m2 body surface area/day PO AND fludrocortisone in a dose of 50 to 200 mcg per day (0.05 to 0.20 mg/day) PO.
- Mineralocorticoid replacement should be started in all 21-hydroxylase deficient patients, and often may be tapered after six months of age.
3.1 Response to therapy can be monitored by checking the following parameters:
- Serum 17-hydroxyprogesterone
- Androstenedione
- Plasma renin activity or direct renin
- Height measurements
4. Management in adults
21 hydroxylase deficiency should be managed as follows:[4][11][12][13][3][14][15]
4.1 Treatment goals
- Provide proper dosing of glucocorticoid and mineralocorticoid.
- Decrease secretion of cosyntropin; therefore decrease adrenal overstimulation and androgen production.
4.2 Glucocorticoids and mineralocorticoid replacement
- Preferred regimen: Hydrocortisone 15-30 mg q24h divided into three doses PO AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg q24h PO.
- Alternative regimen (1): Dexamethasone 0.75 mg q24h PO AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg q24h PO.
- Alternative regimen (2): Prednisone 5mg q24h PO AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg q24h PO.
4.3 Considerations
- Glucocorticoids reduce the excess production of adrenal androgens and reduce the excessive secretion of both corticotropin-releasing hormone and ACTH.
- Stress dosing: In patients with 21-hydroxylase deficiency and serious illness, glucocorticoids stress dosing is necessary.
- Dexamethasone is very potent and long-acting glucocorticoid that effectively suppresses ACTH secretion but almost always causes the development of cushingoid appearance with chronic use.
- The proper dose of fludrocortisone acetate should be used to restore normal serum potassium concentrations and plasma renin activity.
4.4 Therapy consideration in women
- Lowering blood androgen levels with glucocorticoids, can helps women to control annoying cosmetic symptoms such as acne and hirsutism.
- In 21-hydroxylase deficient patients oral contraceptive pills in combination with glucocorticoids can be used to regulate the menstrual cycle and induction of ovulation.
Medical Therapy for non-classic type of 21 hydroxylase deficiency
Medical therapy for non-classic type of 21 hydroxylase deficiency is as following:[16][4][17][18]
1. Children
- Preferred regimen: Hydrocortisone 10 to 15 mg/m2 divided into three doses q24h.
- Treatment should be continued until puberty.
- In symptomatic girls after puberty, other treatment options such as oral contraceptive pills may be used in order to avoid glucocorticoids.
2. Adults
- Female patients may need oral contraceptive pills for regulation of menstrual cycle; oral contraceptive pills are preferred other than glucocorticoids in this condition.
- Female patients with infertility and anovulatory cycles who desire conceive, glucocorticoids with above dosage are the initial choice for ovulation induction.
- Male patient with non-classic 21-hydroxylase deficiency are asymptomatic and they do not need treatment.
References
- ↑ Merke DP, Bornstein SR (2005). "Congenital adrenal hyperplasia". Lancet. 365 (9477): 2125–36. doi:10.1016/S0140-6736(05)66736-0. PMID 15964450.
- ↑ "Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology". J. Clin. Endocrinol. Metab. 87 (9): 4048–53. 2002. doi:10.1210/jc.2002-020611. PMID 12213842.
- ↑ 3.0 3.1 Speiser PW (2001). "Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency". Endocrinol. Metab. Clin. North Am. 30 (1): 31–59, vi. PMID 11344938.
- ↑ 4.0 4.1 4.2 4.3 Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP; et al. (2010). "Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 95 (9): 4133–60. doi:10.1210/jc.2009-2631. PMC 2936060. PMID 20823466.
- ↑ Bose KS, Sarma RH (1975). "Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution". Biochem Biophys Res Commun. 66 (4): 1173–9. PMID 22237438 2 22237438 Check
|pmid=value (help). - ↑ Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP; et al. (2010). "Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 95 (9): 4133–60. doi:10.1210/jc.2009-2631. PMC 2936060. PMID 20823466.
- ↑ Lajic S, Wedell A, Bui TH, Ritzén EM, Holst M (1998). "Long-term somatic follow-up of prenatally treated children with congenital adrenal hyperplasia". J Clin Endocrinol Metab. 83 (11): 3872–80. doi:10.1210/jcem.83.11.5233. PMID 9814461.
- ↑ Carmichael SL, Shaw GM, Ma C, Werler MM, Rasmussen SA, Lammer EJ; et al. (2007). "Maternal corticosteroid use and orofacial clefts". Am J Obstet Gynecol. 197 (6): 585.e1–7, discussion 683-4, e1–7. doi:10.1016/j.ajog.2007.05.046. PMID 18060943.
- ↑ Wallensteen L, Zimmermann M, Thomsen Sandberg M, Gezelius A, Nordenström A, Hirvikoski T; et al. (2016). "Sex-Dimorphic Effects of Prenatal Treatment With Dexamethasone". J Clin Endocrinol Metab. 101 (10): 3838–3846. doi:10.1210/jc.2016-1543. PMID 27482827.
- ↑ Khalife N, Glover V, Taanila A, Ebeling H, Järvelin MR, Rodriguez A (2013). "Prenatal glucocorticoid treatment and later mental health in children and adolescents". PLoS One. 8 (11): e81394. doi:10.1371/journal.pone.0081394. PMC 3838350. PMID 24278432.
- ↑ Horrocks PM, London DR (1987). "Effects of long term dexamethasone treatment in adult patients with congenital adrenal hyperplasia". Clin Endocrinol (Oxf). 27 (6): 635–42. PMID 2843311.
- ↑ Stewart PM, Biller BM, Marelli C, Gunnarsson C, Ryan MP, Johannsson G (2016). "Exploring Inpatient Hospitalizations and Morbidity in Patients With Adrenal Insufficiency". J Clin Endocrinol Metab. 101 (12): 4843–4850. doi:10.1210/jc.2016-2221. PMID 27623069.
- ↑ Hughes IA (1988). "Management of congenital adrenal hyperplasia". Arch Dis Child. 63 (11): 1399–404. PMC 1779155. PMID 3060026.
- ↑ Lopes LA, Dubuis JM, Vallotton MB, Sizonenko PC (1998). "Should we monitor more closely the dosage of 9 alpha-fluorohydrocortisone in salt-losing congenital adrenal hyperplasia?". J. Pediatr. Endocrinol. Metab. 11 (6): 733–7. PMID 9829228.
- ↑ Jansen M, Wit JM, van den Brande JL (1981). "Reinstitution of mineralocorticoid therapy in congenital adrenal hyperplasia. Effects on control and growth". Acta Paediatr Scand. 70 (2): 229–33. PMID 7015786.
- ↑ Spritzer P, Billaud L, Thalabard JC, Birman P, Mowszowicz I, Raux-Demay MC, Clair F, Kuttenn F, Mauvais-Jarvis P (1990). "Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia". J. Clin. Endocrinol. Metab. 70 (3): 642–6. doi:10.1210/jcem-70-3-642. PMID 2137832.
- ↑ Frank-Raue K, Junga G, Raue F, Vecsei P, Ziegler R (1990). "[Therapy of hirsutism in females with adrenal enzyme defects of steroid hormone biosynthesis: comparison of dexamethasone with cyproterone acetate]". Klin. Wochenschr. (in German). 68 (12): 597–601. PMID 2142968.
- ↑ Merke DP, Poppas DP (2013). "Management of adolescents with congenital adrenal hyperplasia". Lancet Diabetes Endocrinol. 1 (4): 341–52. doi:10.1016/S2213-8587(13)70138-4. PMC 4163910. PMID 24622419.