Congenital adrenal hyperplasia medical therapy: Difference between revisions
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{{Congenital adrenal hyperplasia}} | {{Congenital adrenal hyperplasia}} | ||
{{CMG}} | {{CMG}} <ref name="pmid2318944">{{cite journal| author=Migeon CJ| title=Comments about the need for prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=J Clin Endocrinol Metab | year= 1990 | volume= 70 | issue= 4 | pages= 836-7 | pmid=2318944 | doi=10.1210/jcem-70-4-836 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2318944 }}</ref>'''Associate Editor-In-Chief:''' {{CZ}} | ||
==Overview== | ==Overview== | ||
| Line 12: | Line 12: | ||
* Virilization of female fetuses begins early so early diagnosis and treatment are required. | * Virilization of female fetuses begins early so early diagnosis and treatment are required. | ||
* Maternal administration of dexamethasone which crosses the placenta into the fetal circulation. | * Maternal administration of dexamethasone which crosses the placenta into the fetal circulation. | ||
* If treatment cannot be started by 9 weeks, it should not be given at all. | * If treatment cannot be started by 9 weeks, it should not be given at all. | ||
* Treatment should be discontinued if male fetus which can be determined by cell-free fetal DNA | * Treatment should be discontinued if male fetus which can be determined by cell-free fetal DNA.<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> | ||
* 85% of managed cases appear quite normal after delivery. | * 85% of managed cases appear quite normal after delivery.<ref name="pmid12213842">{{cite journal| author=Joint LWPES/ESPE CAH Working Group.| 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 | year= 2002 | volume= 87 | issue= 9 | pages= 4048-53 | pmid=12213842 | doi=10.1210/jc.2002-020611 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12213842 }}</ref> | ||
* Side effects of prenatal | * Side effects of prenatal dexamethasone: | ||
* Postnatal failure to thrive | * Postnatal failure to thrive.<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> | ||
* Psychomotor developmental delay. | * Psychomotor developmental delay.<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> | ||
* No effect on IQ | * No effect on IQ.<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> | ||
* Increased risk of cleft lip and palate | * Increased risk of cleft lip and palate.<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> | ||
* Increased risk for psychiatric disturbances and ADHD. | * Increased risk for psychiatric disturbances and ADHD.<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> | ||
==== Neonatal treatment ==== | ==== Neonatal treatment ==== | ||
* Hydrocortisone is 20 to 30 mg/m<sup>2</sup>/ | * Hydrocortisone is 20 to 30 mg/m<sup>2</sup>/day. | ||
* Fludrocortisone 100 mcg one gram or 4 mEq/kg/day of sodium chloride | * Fludrocortisone 100 mcg one gram or 4 mEq/kg/day of sodium chloride. | ||
* Growth suppression | * Growth suppression occurs in neonates treated with high doses of hydrocortisone. | ||
==== '''Ambiguous genitalia''' ==== | ==== '''Ambiguous genitalia''' ==== | ||
* | * The initial evaluation is pelvic ultrasonography to evaluate internal genitalia, karyotype for sex chromosome (SRY probe) material, measurement of 17-hydroxyprogesterone and serum electrolytes. Until results release, glucocorticoid, mineralocorticoid and sodium chloride should be initiated | ||
* Girls with classic CAH typically undergo reconstructive surgery, usually clitoroplasty and vaginoplasty | * Girls with classic CAH typically undergo reconstructive surgery, usually clitoroplasty and vaginoplasty. | ||
==== Adrenal crisis ==== | ==== Adrenal crisis ==== | ||
| Line 45: | Line 45: | ||
* '''daily doses:''' hydrocortisone, a short-acting glucocorticoid, is the treatment of choice. | * '''daily doses:''' hydrocortisone, a short-acting glucocorticoid, is the treatment of choice. | ||
* Dexamethasone a very potent and long-acting glucocorticoid | * Dexamethasone a very potent and long-acting glucocorticoid effectively suppresses ACTH secretion but almost always causes the development of Cushingoid features with chronic use.<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> | ||
* Combination therapy, with typical doses of hydrocortisone to replace the cortisol deficiency during the day and a very small dose of a long-acting glucocorticoid | * Combination therapy, with typical doses of hydrocortisone to replace the cortisol deficiency during the day and a very small dose of a long-acting glucocorticoid. We suggest this approach when standard hydrocortisone regimens are ineffective. | ||
* '''Stress dosing''': patients with classic 21OHD should be provided stress dosing 12 | * '''Stress dosing''': patients with classic 21OHD should be provided stress dosing.<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> | ||
'''Mineralocorticoid replacement''' | '''Mineralocorticoid replacement''' | ||
* Fludrocortisone acetate, in a dose sufficient to restore normal serum potassium concentrations and plasma renin activity. | * Fludrocortisone acetate, in a dose sufficient to restore normal serum potassium concentrations and plasma renin activity.<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> | ||
* The usual adult dose of fludrocortisone is 0.1 to 0.2 mg/day. | * The usual adult dose of fludrocortisone is 0.1 to 0.2 mg/day.<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> | ||
* Patients who are undertreated and in chronic poor control develop testicular adrenal rest tumors. | * Patients who are undertreated and in chronic poor control develop testicular adrenal rest tumors. | ||
===== '''Infertility in men''' ===== | ===== '''Infertility in men''' ===== | ||
*Sperm production is often impaired in untreated men due to defected spermatogenesis and | *Sperm production is often impaired in untreated men due to defected spermatogenesis and Leydig cells suppression.<ref name="pmid19258407">{{cite journal| author=Reisch N, Flade L, Scherr M, Rottenkolber M, Pedrosa Gil F, Bidlingmaier M et al.| title=High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. | journal=J Clin Endocrinol Metab | year= 2009 | volume= 94 | issue= 5 | pages= 1665-70 | pmid=19258407 | doi=10.1210/jc.2008-1414 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19258407 }}</ref> | ||
*Most of patients have severe oligospermia. Moreover, Most of | *Most of the patients have severe oligospermia. Moreover, Most of the untreated patients have testicular tumors that need surgical removal. | ||
*An elevated FSH is a sensitive indicator for patients fertility condition but semen analysis is the specific test. | *An elevated FSH is a sensitive indicator for patients fertility condition but semen analysis is the specific test.<ref name="pmid17090637">{{cite journal| author=Claahsen-van der Grinten HL, Otten BJ, Takahashi S, Meuleman EJ, Hulsbergen-van de Kaa C, Sweep FC et al.| title=Testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia: evaluation of pituitary-gonadal function before and after successful testis-sparing surgery in eight patients. | journal=J Clin Endocrinol Metab | year= 2007 | volume= 92 | issue= 2 | pages= 612-5 | pmid=17090637 | doi=10.1210/jc.2006-1311 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17090637 }}</ref> | ||
===== '''Infertility in women''' ===== | ===== '''Infertility in women''' ===== | ||
* Lowering blood androgen levels helps women to control annoying | * Lowering blood androgen levels helps women to control annoying cosmetic symptoms such as acne and hirsutism. | ||
* Similar to polycystic ovary syndrome, CAH patients need oral contraceptive pills to regulate menstrual cycle and induction of ovulation | * Similar to polycystic ovary syndrome, CAH patients need oral contraceptive pills to regulate the menstrual cycle and induction of ovulation.<ref name="pmid19250265">{{cite journal| author=Casteràs A, De Silva P, Rumsby G, Conway GS| title=Reassessing fecundity in women with classical congenital adrenal hyperplasia (CAH): normal pregnancy rate but reduced fertility rate. | journal=Clin Endocrinol (Oxf) | year= 2009 | volume= 70 | issue= 6 | pages= 833-7 | pmid=19250265 | doi=10.1111/j.1365-2265.2009.03563.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19250265 }}</ref> | ||
* hydrocortisone | * Women need pregnancy should consult a surgeon to repair previous genital malformations. | ||
* Glucocorticoids doses need to | * hydrocortisone doesn’t pass placenta so, it can be used safely during pregnancy. | ||
* Glucocorticoids doses need to increase at end of pregnancy with careful monitoring. | |||
===11-Hydroxylase=== | ===11-Hydroxylase=== | ||
Revision as of 15:01, 21 July 2017
|
Congenital adrenal hyperplasia main page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] [1]Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Overview
Medical Therapy
Neonatal management
Prenatal diagnosis
- Virilization of female fetuses begins early so early diagnosis and treatment are required.
- Maternal administration of dexamethasone which crosses the placenta into the fetal circulation.
- If treatment cannot be started by 9 weeks, it should not be given at all.
- Treatment should be discontinued if male fetus which can be determined by cell-free fetal DNA.[2]
- 85% of managed cases appear quite normal after delivery.[3]
- Side effects of prenatal dexamethasone:
- Postnatal failure to thrive.[4]
- Psychomotor developmental delay.[5]
- No effect on IQ.[6]
- Increased risk of cleft lip and palate.[7]
- Increased risk for psychiatric disturbances and ADHD.[8]
Neonatal treatment
- Hydrocortisone is 20 to 30 mg/m2/day.
- Fludrocortisone 100 mcg one gram or 4 mEq/kg/day of sodium chloride.
- Growth suppression occurs in neonates treated with high doses of hydrocortisone.
Ambiguous genitalia
- The initial evaluation is pelvic ultrasonography to evaluate internal genitalia, karyotype for sex chromosome (SRY probe) material, measurement of 17-hydroxyprogesterone and serum electrolytes. Until results release, glucocorticoid, mineralocorticoid and sodium chloride should be initiated
- Girls with classic CAH typically undergo reconstructive surgery, usually clitoroplasty and vaginoplasty.
Adrenal crisis
- 20 mL/kg of normal saline should be administered.
- An intravenous bolus of 2 to 4 mL/kg of 10 percent dextrose should be considered if there is significant hypoglycemia.
- Hyperkalemia should be corrected with the administration of glucose and insulin if necessary.
Adults management
21-Hydroxylase
Glucocorticoids
- Glucocorticoids reduce the excess production of adrenal androgens and reduce the excessive secretion of both corticotropin-releasing hormone and ACTH.
- daily doses: hydrocortisone, a short-acting glucocorticoid, is the treatment of choice.
- Dexamethasone a very potent and long-acting glucocorticoid effectively suppresses ACTH secretion but almost always causes the development of Cushingoid features with chronic use.[9]
- Combination therapy, with typical doses of hydrocortisone to replace the cortisol deficiency during the day and a very small dose of a long-acting glucocorticoid. We suggest this approach when standard hydrocortisone regimens are ineffective.
- Stress dosing: patients with classic 21OHD should be provided stress dosing.[10]
Mineralocorticoid replacement
- Fludrocortisone acetate, in a dose sufficient to restore normal serum potassium concentrations and plasma renin activity.[11]
- The usual adult dose of fludrocortisone is 0.1 to 0.2 mg/day.[12]
- Patients who are undertreated and in chronic poor control develop testicular adrenal rest tumors.
Infertility in men
- Sperm production is often impaired in untreated men due to defected spermatogenesis and Leydig cells suppression.[13]
- Most of the patients have severe oligospermia. Moreover, Most of the untreated patients have testicular tumors that need surgical removal.
- An elevated FSH is a sensitive indicator for patients fertility condition but semen analysis is the specific test.[14]
Infertility in women
- Lowering blood androgen levels helps women to control annoying cosmetic symptoms such as acne and hirsutism.
- Similar to polycystic ovary syndrome, CAH patients need oral contraceptive pills to regulate the menstrual cycle and induction of ovulation.[15]
- Women need pregnancy should consult a surgeon to repair previous genital malformations.
- hydrocortisone doesn’t pass placenta so, it can be used safely during pregnancy.
- Glucocorticoids doses need to increase at end of pregnancy with careful monitoring.
11-Hydroxylase
Treatment is similar to 21-hydroxylase deficiency with glucocorticoid replacement. Clinical assessment of virilization, growth velocity, hair growth, menstrual function and blood pressure are necessary. Despite adequate glucocorticoid replacement, medication may be required to control blood pressure. Spironolactone is a good choice as well as calcium blockers.
References
- ↑ Migeon CJ (1990). "Comments about the need for prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency". J Clin Endocrinol Metab. 70 (4): 836–7. doi:10.1210/jcem-70-4-836. PMID 2318944.
- ↑ 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). - ↑ Joint LWPES/ESPE CAH Working Group. (2002). "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. doi:10.1210/jc.2002-020611. PMID 12213842.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Hughes IA (1988). "Management of congenital adrenal hyperplasia". Arch Dis Child. 63 (11): 1399–404. PMC 1779155. PMID 3060026.
- ↑ Reisch N, Flade L, Scherr M, Rottenkolber M, Pedrosa Gil F, Bidlingmaier M; et al. (2009). "High prevalence of reduced fecundity in men with congenital adrenal hyperplasia". J Clin Endocrinol Metab. 94 (5): 1665–70. doi:10.1210/jc.2008-1414. PMID 19258407.
- ↑ Claahsen-van der Grinten HL, Otten BJ, Takahashi S, Meuleman EJ, Hulsbergen-van de Kaa C, Sweep FC; et al. (2007). "Testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia: evaluation of pituitary-gonadal function before and after successful testis-sparing surgery in eight patients". J Clin Endocrinol Metab. 92 (2): 612–5. doi:10.1210/jc.2006-1311. PMID 17090637.
- ↑ Casteràs A, De Silva P, Rumsby G, Conway GS (2009). "Reassessing fecundity in women with classical congenital adrenal hyperplasia (CAH): normal pregnancy rate but reduced fertility rate". Clin Endocrinol (Oxf). 70 (6): 833–7. doi:10.1111/j.1365-2265.2009.03563.x. PMID 19250265.