21-hydroxylase deficiency medical therapy: Difference between revisions
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{{21-hydroxylase deficiency}} | {{21-hydroxylase deficiency}} | ||
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==Overview== | ==Overview== | ||
Revision as of 17:00, 29 August 2017
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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 recognized patients, and hydrocortisone and fludrocortisone 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 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 in 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 following:
- If classic CYP21A2 gene mutations exist in parents, maternal administration of dexamethasone should be applied. Dexamethasone crosses the placenta into the fetal circulation and prevents ambiguous genitalia in female fetus.
- This treatment should be started before nine 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
- 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
21 hydroxylase deficiency therapy medications in the neonates are as following:[4]
- Hydrocortisone is 20 to 30 mg/m2/day divided in three doses.
- Fludrocortisone 100 mcg twice daily.
- One gram or 4 mEq/kg/day of sodium chloride divided in several doses.
- One first time high doses of hydrocortisone, 50 mg/m2/day, can be used in order to suppress adrenal hormones.
- 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
- Reconstructive surgery can be done in patients.[2][4]
Adrenal crisis
- Normal saline 0.9 percent, 20 mL/kg should be administered.
- An intravenous bolus of 2 to 4 mL/kg of 10 percent dextrose should be considered if there is significant hypoglycemia.
- Initial dose of hydrocortisone of 50 to 100 mg/m2 should be administered as an intravenous bolus bolus, then 50 to 100 mg/m2 IV per day divided four times a day.
- 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
- Hydrocortisone (cortisol) in a dose of 10 to 15 mg/m2 body surface area/day orally.
- 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 patient, 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
- Glucocorticoids reduce the excess production of adrenal androgens and reduce the excessive secretion of both corticotropin-releasing hormone and ACTH.
- Preferred Regimen
- Hydrocortisone 15-30 mg/d divided into three doses orally.
- Alternative Regimen:
- Dexamethasone 0.75 mg/d orally.
- Dexamethasone is very potent and long-acting glucocorticoid effectively suppresses ACTH secretion but almost always causes the development of cushingoid appearance with chronic use.
- Prednisone 5mg/d orally.
- Dexamethasone 0.75 mg/d orally.
- Stress dosing: in patients with 21 hydroxylase deficiency and serious illness glucocorticoids stress dosing is necessary.
Mineralocorticoid replacement
- 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg/day.
- 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
- 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 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.