21-hydroxylase deficiency medical therapy
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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], Mohammed Abdelwahed M.D[3]
Overview
Medical Therapy
Neonatal management
Prenatal diagnosis
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. 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.[1]
- 85% of managed cases appear quite normal after delivery.[2]
- Side effects of prenatal dexamethasone are:[3][4][5][6][7]
- Postnatal failure to thrive
- Psychomotor developmental delay
- Increased risk of cleft lip and palate
- Increased risk for psychiatric disturbances and ADHD
Neonatal treatment
- 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 d occurs in neonates treated with high doses of hydrocortisone.
Ambiguous genitalia
- Ambiguous genitalia should be managed immediately. Infants with ambiguous genitalia and nonpalpable 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.
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 IV 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
- Mineralocorticoid replacement should be started in all children 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
- Treatment goals are:
- Provide proper dosing of glucocorticoid and mineralocorticoid, decrease secretion of cosintropin.
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
- Alternative Regimen:
- Dexamethasone a very potent and long-acting glucocorticoid effectively suppresses ACTH secretion but almost always causes the development of Cushingoid features with chronic use.[8]
- 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.[9]
Mineralocorticoid replacement
- Fludrocortisone acetate, in a dose sufficient to restore normal serum potassium concentrations and plasma renin activity.[10]
- The usual adult dose of fludrocortisone is 0.1 to 0.2 mg/day.[11]
- 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.[12]
- 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.[13]
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.[14]
- 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.
References
- ↑ 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.
- ↑ 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.
- ↑ 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.