21-hydroxylase deficiency medical therapy: Difference between revisions
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=== Children === | === Children === | ||
* Preferred regimen: [[Hydrocortisone]] 10 to 15 mg/m<sup>2</sup> divided into three doses per day. | * Preferred regimen: [[Hydrocortisone]] 10 to 15 mg/m<sup>2</sup> 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]]. | ** In symptomatic girls after [[puberty]], other treatment options such as [[oral contraceptive pills]] can be used in order to avoid [[glucocorticoids]]. | ||
Revision as of 16:28, 5 September 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. 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
Management in neonates
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 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
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
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
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
Response to therapy can be monitored by checking the following parameters:
- Serum 17-hydroxyprogesterone
- Androstenedione
- Plasma renin activity or direct renin
- Height measurements
Management in adults
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 PO AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg per day PO
- Alternative regimen (1): Dexamethasone 0.75 mg per day PO AND 9-alpha-fludrocortisone acetate 0.1 to 0.2 mg per day PO
- Alternative regimen (2): Prednisone 5mg per day PO 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.
- ↑ "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.