21-hydroxylase deficiency medical therapy: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
Medical therapy for classic type of 21-hydroxylase deficiency includes maternal administration of [[dexamethasone]] for [[genetically]] recognized patients. [[Hydrocortisone]] and [[fludrocortisone]] is given in children and [[Adult|adults]]. Treatment for non-classic type of 21 hydroxylase deficiency in children includes [[hydrocortisone]] until [[puberty]] and in women [[oral contraceptive pills]] for regulating [[menstrual cycle]]. Men with non-classic type of 21 hydroxylase deficiency are asymptomatic and they do not need treatment. | Medical therapy for classic type of 21-hydroxylase deficiency includes maternal administration of [[dexamethasone]] for [[genetically]] recognized patients. [[Hydrocortisone]] and [[fludrocortisone]] is given in children and [[Adult|adults]]. Treatment for non-classic type of 21 hydroxylase deficiency in children includes [[hydrocortisone]] until [[puberty]] and in women [[oral contraceptive pills]] are given for regulating [[menstrual cycle]]. Men with non-classic type of 21 hydroxylase deficiency are [[asymptomatic]] and they do not need treatment. | ||
==Medical Therapy for classic type of 21 hydroxylase deficiency== | ==Medical Therapy for classic type of 21 hydroxylase deficiency== | ||
=== Neonatal management === | === Neonatal management === | ||
Medical therapy | 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> | ||
==== Prenatal treatment==== | ==== Prenatal treatment==== | ||
In the [[prenatal]] period [[virilization]] of female [[fetus]] begins early; therefore, early [[diagnosis]] and treatment are required as | In the [[prenatal]] period [[virilization]] of female [[fetus]] begins early; therefore, early [[diagnosis]] and treatment are required as follows: | ||
* If classic [[CYP21A2]] [[gene]] mutations exist in parents, maternal administration of [[dexamethasone]] should be | * If classic [[CYP21A2]] [[gene]] [[mutations]] exist in parents, [[maternal]] administration of [[dexamethasone]] should be prescribed.. | ||
** Preferred regimen: [[Dexamethasone]] 20 micrograms/kg/day in 2 or 3 fractioned doses orally. | ** Preferred regimen: [[Dexamethasone]] 20 micrograms/kg/day 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 | ** 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 in cell-free fetal [[DNA testing]] male fetus detected, treatment should be discontinued. | ** If in [[Cell-free system|cell-free]] [[fetal]] [[DNA testing]] male [[fetus]] is detected, 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]] | ||
| Line 25: | Line 25: | ||
==== Neonatal treatment ==== | ==== Neonatal treatment ==== | ||
21 hydroxylase deficiency | 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]] | * Preferred regimen: [[Hydrocortisone]] 20 to 30 mg/m<sup>2</sup>/day divided in three doses PO '''<u>AND</u>''' [[Fludrocortisone]] 100 mcg twice daily PO '''<u>AND</u>''' [[sodium chloride]] one gram or 4 mEq/kg/day 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]]. | ||
** 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]]. | ||
==== '''Ambiguous genitalia''' ==== | ==== '''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]]. | * [[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. | * 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>/day divided in three doses PO '''<u>AND</u>''' [[Fludrocortisone]] 100 mcg twice daily PO '''<u>AND</u>''' [[sodium chloride]] one gram or 4 mEq/kg/day divided in several doses PO. | ** Preferred regimen: [[Hydrocortisone]] is 20 to 30 mg/m<sup>2</sup>/day divided in three doses PO '''<u>AND</u>''' [[Fludrocortisone]] 100 mcg twice daily PO '''<u>AND</u>''' [[sodium chloride]] one gram or 4 mEq/kg/day divided in several doses PO. | ||
| Line 37: | Line 38: | ||
==== Adrenal crisis ==== | ==== 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> IV per day divided | * 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]]. | * 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]]. | * [[Hyperkalemia]] should be corrected on the base of its level and [[complications]]. | ||
===Children management=== | ===Children management=== | ||
* Preferred regimen: [[Hydrocortisone]] ([[cortisol]]) in a dose of 10 to 15 mg/m2 [[body surface area]]/day orally '''<u>AND</u>''' [[fludrocortisone]] in a dose of 50 to 200 mcg per day (0.05 to 0.20 mg/day) orally. | * Preferred regimen: [[Hydrocortisone]] ([[cortisol]]) in a dose of 10 to 15 mg/m2 [[body surface area]]/day orally '''<u>AND</u>''' [[fludrocortisone]] in a dose of 50 to 200 mcg per day (0.05 to 0.20 mg/day) [[Orally ingested|orally]]. | ||
** [[Mineralocorticoid]] replacement should be started in all 21 hydroxylase deficient | ** [[Mineralocorticoid]] replacement should be started in all 21-hydroxylase deficient patients, and often may be tapered after six months of age. | ||
===== Response to therapy can be monitored by below items: ===== | ===== Response to therapy can be monitored by below items: ===== | ||
| Line 57: | Line 58: | ||
* Decrease secretion of [[cosyntropin]]; therefore decrease [[adrenal]] overstimulation and [[androgen]] production. | * Decrease secretion of [[cosyntropin]]; therefore decrease [[adrenal]] overstimulation and [[androgen]] production. | ||
====='''Glucocorticoids and mineralocorticoid replacement:''' ===== | ====='''Glucocorticoids and mineralocorticoid replacement:''' ===== | ||
* Preferred regimen: [[Hydrocortisone]] 15-30 mg | * Preferred regimen: [[Hydrocortisone]] 15-30 mg per day divided into three doses [[Orally ingested|orally]] '''<u>AND</u>''' [[Fludrocortisone Acetate|9-alpha-fludrocortisone acetate]] 0.1 to 0.2 mg/day [[Orally ingested|PO]] | ||
* Alternative regimen (1): [[Dexamethasone]] 0.75 mg | * Alternative regimen (1): [[Dexamethasone]] 0.75 mg per day [[Orally ingested|orally]] '''<u>AND</u>''' [[Fludrocortisone Acetate|9-alpha-fludrocortisone acetate]] 0.1 to 0.2 mg/day [[Route of administration|PO]] | ||
* Alternative regimen (2): [[Prednisone]] 5mg | * Alternative regimen (2): [[Prednisone]] 5mg pe day [[Orally ingested|orally]] '''<u>AND</u>''' [[Fludrocortisone Acetate|9-alpha-fludrocortisone acetate]] 0.1 to 0.2 mg per day [[Orally ingested|PO]] | ||
===== Considerations: ===== | ===== Considerations: ===== | ||
*[[Glucocorticoids]] reduce the excess production of [[adrenal]] [[androgens]] and reduce the excessive secretion of both [[corticotropin-releasing hormone]] and [[ACTH]] | *[[Glucocorticoids]] reduce the excess production of [[adrenal]] [[androgens]] and reduce the excessive secretion of both [[corticotropin-releasing hormone]] and [[ACTH]] | ||
* Stress dosing: | * Stress dosing: In patients with 21-hydroxylase deficiency and serious [[illness]], [[glucocorticoids]] stress dosing is necessary | ||
* [[Dexamethasone]] is very potent and long-acting [[glucocorticoid]] effectively suppresses [[ACTH]] secretion but almost always causes the development of [[cushingoid appearance]] with chronic use | * [[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]] | * The proper dose of [[Fludrocortisone Acetate|fludrocortisone acetate]] should be used to restore normal [[serum]] [[potassium]] concentrations and [[plasma renin activity]] | ||
=====Therapy consideration in women===== | =====Therapy consideration in women===== | ||
* Lowering blood [[androgen]] levels with [[glucocorticoids]], can helps women to control annoying [[Cosmetics|cosmetic]] symptoms such as [[acne]] and [[hirsutism]]. | * Lowering blood [[androgen]] levels with [[glucocorticoids]], can helps women to control annoying [[Cosmetics|cosmetic]] symptoms such as [[acne]] and [[hirsutism]]. | ||
Revision as of 15:11, 5 September 2017
|
21-hydroxylase deficiency Microchapters |
|
Differentiating 21-Hydroxylase Deficiency from other Diseases |
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
21-hydroxylase deficiency medical therapy On the Web |
|
American Roentgen Ray Society Images of 21-hydroxylase deficiency medical therapy |
|
Risk calculators and risk factors for 21-hydroxylase deficiency medical therapy |
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 recognized patients. Hydrocortisone and fludrocortisone is given in children and adults. Treatment for non-classic type of 21 hydroxylase deficiency in children includes hydrocortisone until puberty and in women oral contraceptive pills are given for regulating menstrual cycle. Men with non-classic type of 21 hydroxylase deficiency are asymptomatic and they do not need treatment.
Medical Therapy for classic type of 21 hydroxylase deficiency
Neonatal management
Medical therapy for 21-hydroxylase deficiency in prenatal period, neonates, children and adults, is as below:[1][2][3][4][5]
Prenatal treatment
In the prenatal period virilization of female fetus begins early; therefore, early diagnosis and treatment are required as follows:
- If classic CYP21A2 gene mutations exist in parents, maternal administration of dexamethasone should be prescribed..
- Preferred regimen: Dexamethasone 20 micrograms/kg/day 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 in cell-free fetal DNA testing male fetus is detected, 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
Neonatal treatment
Medical therapy for 21-hydroxylase deficiency in the neonates is as follows:[4]
- Preferred regimen: Hydrocortisone 20 to 30 mg/m2/day divided in three doses PO AND Fludrocortisone 100 mcg twice daily PO AND sodium chloride one gram or 4 mEq/kg/day 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.
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/day divided in three doses PO AND Fludrocortisone 100 mcg twice daily PO AND sodium chloride one gram or 4 mEq/kg/day divided in several doses PO.
- Reconstructive surgery can be done in patients.[2][4]
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.
Children management
- Preferred regimen: Hydrocortisone (cortisol) in a dose of 10 to 15 mg/m2 body surface area/day orally AND fludrocortisone in a dose of 50 to 200 mcg per day (0.05 to 0.20 mg/day) orally.
- Mineralocorticoid replacement should be started in all 21-hydroxylase deficient patients, and often may be tapered after six months of age.
Response to therapy can be monitored by below items:
- Serum 17-hydroxyprogesterone
- Androstenedione
- Plasma renin activity or direct renin
- Height measurements
Adults management
21 hydroxylase deficiency should be managed as follows:[4][11][12][13][3][14][15]
Treatment goals
- Provide proper dosing of glucocorticoid and mineralocorticoid.
- Decrease secretion of cosyntropin; therefore decrease adrenal overstimulation and androgen production.
Glucocorticoids and mineralocorticoid replacement:
- Preferred regimen: Hydrocortisone 15-30 mg per day divided into three doses orally AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg/day PO
- Alternative regimen (1): Dexamethasone 0.75 mg per day orally AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg/day PO
- Alternative regimen (2): Prednisone 5mg pe day orally AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg per day PO
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
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]
Children
- Preferred regimen: Hydrocortisone 10 to 15 mg/m2 divided into three doses per day.
- Treatment should be continued until puberty.
- In symptomatic girls after puberty, other treatment options such as oral contraceptive pills can be used in order to avoid glucocorticoids.
Adults
- Female patients may need oral contraceptive pills in order to regulate 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.
- ↑ 2.0 2.1 "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 4.4 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.