Abstract
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by the deficiency of one of the enzymes involved in cortisol synthesis. More than 95% of the cases occur as a result of defects in the gene encoding 21-hydroxylase (CYP21A2). 21-hydroxylase deficiency has been divided into classical and non-classical forms. In the treatment of classical CAH, it is necessary to replace both glucocorticoid (GC) and mineralocorticoid hormones to prevent salt wasting crisis and reduce excessive corticotropin. In addition to biochemical measurements to evaluate the adequacy of GC and mineralocorticoid treatment; growth rate, body weight, blood pressure and physical examination should be evaluated regularly. There is insufficient data regarding the use of continuous slow-release or modified-release hydrocortisone (HC) preparations and continuous subcutaneous HC infusion, additional/alternative treatment approaches, and cell-based therapies and gene editing technology in children with CAH. GC therapy is recommended in children with inappropriately early onset and rapidly progressing pubarche or accelerated bone age progression, and in adolescents with non-classical CAH (NCCAH) who have overt virilization. In patients with NCCAH, stress doses of HC is recommended for major surgery, trauma, or childbirth but only if the patient has a suboptimal cortisol response to the adrenocorticotropic hormone test. Here, members of the ‘Adrenal Working Group’ of ‘The Turkish Society for Pediatric Endocrinology and Diabetes’ present an evidence-based review with good practice points and recommendations for optimize treatment, and follow-up of children with CAH due to 21-hydroxylase deficiency in the light of the most recent evidence.
Keywords: Congenital adrenal hyperplasia, children, adolescent, 21-hydroxylase deficiency, non-classic congenital adrenal hyperplasia, glucocorticoid replacement treatment
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References
Jha S, Turcu AF. Nonclassic congenital adrenal hyperplasia: what do endocrinologists need to know? Endocrinol Metab Clin North Am. 2021;50:151-165. Epub 2021 Jan 9
Claahsen-van der Grinten HL, Speiser PW, Ahmed SF, Arlt W, Auchus RJ, Falhammar H, Flück CE, Guasti L, Huebner A, Kortmann BBM, Krone N, Merke DP, Miller WL, Nordenström A, Reisch N, Sandberg DE, Stikkelbroeck NMML, Touraine P, Utari A, Wudy SA, White PC. Congenital adrenal hyperplasia-current insights in pathophysiology, diagnostics, and management. Endocr Rev. 2022;43:91-159.
Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, Meyer-Bahlburg HFL, Miller WL, Murad MH, Oberfield SE, White PC. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103:4043-4088.
Kamrath C, Wettstaedt L, Hartmann MF, Wudy SA. Height velocity defined metabolic control in children with congenital adrenal hyperplasia using urinary steroid GC-MS analysis. J Clin Endocrinol Metab. 2019;104:4214-4224.
Merke DP, Bornstein SR, Avila NA, Chrousos GP. NIH conference. Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med. 2002;136:320-334.
Weitzman ED, Fukushima D, Nogeire C, Roffwarg H, Gallagher TF, Hellman L. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab. 1971;33:14-22.
Michaud K, Matheson K, Kelly O, Anisman H. Impact of stressors in a natural context on release of cortisol in healthy adult humans: a meta-analysis. Stress. 2008;11:177-197.
Bryan SM, Honour JW, Hindmarsh PC. Management of altered hydrocortisone pharmacokinetics in a boy with congenital adrenal hyperplasia using a continuous subcutaneous hydrocortisone infusion. J Clin Endocrinol Metab. 2009;94:3477-3480. Epub 2009 Jun 30
Merza Z, Rostami-Hodjegan A, Memmott A, Doane A, Ibbotson V, Newell-Price J, Tucker GT, Ross RJ. Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 2006;65:45-50.
El-Maouche D, Arlt W, Merke DP. Congenital adrenal hyperplasia. Lancet. 2017;390:2194-2210. Epub 2017 May 30. Erratum in: Lancet. 2017;390:2142.
Lajic S, Nordenström A, Ritzén EM, Wedell A. Prenatal treatment of congenital adrenal hyperplasia. Eur J Endocrinol. 2004;151(Suppl 3):U63-69.
Nordenström A, Marcus C, Axelson M, Wedell A, Ritzén EM. Failure of cortisone acetate treatment in congenital adrenal hyperplasia because of defective 11beta-hydroxysteroid dehydrogenase reductase activity. J Clin Endocrinol Metab. 1999;84:1210-1213.
Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 200;365:2125-2136.
Neumann U, Burau D, Spielmann S, Whitaker MJ, Ross RJ, Kloft C, Blankenstein O. Quality of compounded hydrocortisone capsules used in the treatment of children. Eur J Endocrinol. 2017;177:239-242. Epub 2017 May 16
Barillas JE, Eichner D, Van Wagoner R, Speiser PW. Iatrogenic Cushing syndrome in a child with congenital adrenal hyperplasia: erroneous compounding of hydrocortisone. J Clin Endocrinol Metab. 2018;103:7-11.
Merke DP, Cho D, Calis KA, Keil MF, Chrousos GP. Hydrocortisone suspension and hydrocortisone tablets are not bioequivalent in the treatment of children with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2001;86:441-445.
Porter J, Withe M, Ross RJ. Immediate-release granule formulation of hydrocortisone, Alkindi®, for treatment of paediatric adrenal insufficiency (Infacort development programme). Expert Rev Endocrinol Metab. 2018;13:119-124. Epub 2018 Mar 26
Neumann U, Whitaker MJ, Wiegand S, Krude H, Porter J, Davies M, Digweed D, Voet B, Ross RJ, Blankenstein O. Absorption and tolerability of taste-masked hydrocortisone granules in neonates, infants and children under 6 years of age with adrenal insufficiency. Clin Endocrinol (Oxf). 2018;88:21-29. Epub 2017 Sep 7
Bonfig W, Bechtold S, Schmidt H, Knorr D, Schwarz HP. Reduced final height outcome in congenital adrenal hyperplasia under prednisone treatment: deceleration of growth velocity during puberty. J Clin Endocrinol Metab. 2007;92:1635-1639. Epub 2007 Feb 13
Miller WL. The adrenal cortex and its disorders. In: Brook CGD, Clayton P, Brown R (eds). Clinical Pediatric Endocrinology (5th ed.) Oxford: Blackwell Science, 2001;283-327.
German A, Suraiya S, Tenenbaum-Rakover Y, Koren I, Pillar G, Hochberg Z. Control of childhood congenital adrenal hyperplasia and sleep activity and quality with morning or evening glucocorticoid therapy. J Clin Endocrinol Metab. 2008;93:4707-4710. Epub 2008 Sep 9
Ng SM, Stepien KM, Krishan A. Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia. Cochrane Database Syst Rev. 2020;3:CD012517.
Auchus RJ, Witchel SF, Leight KR, Aisenberg J, Azziz R, Bachega TA, Baker LA, Baratz AB, Baskin LS, Berenbaum SA, Breault DT, Cerame BI, Conway GS, Eugster EA, Fracassa S, Gearhart JP, Geffner ME, Harris KB, Hurwitz RS, Katz AL, Kalro BN, Lee PA, Alger Lin G, Loechner KJ, Marshall I, Merke DP, Migeon CJ, Miller WL, Nenadovich TL, Oberfield SE, Pass KA, Poppas DP, Lloyd-Puryear MA, Quigley CA, Riepe FG, Rink RC, Rivkees SA, Sandberg DE, Schaeffer TL, Schlussel RN, Schneck FX, Seely EW, Snyder D, Speiser PW, Therrell BL, Vanryzin C, Vogiatzi MG, Wajnrajch MP, White PC, Zuckerman AE. Guidelines for the development of comprehensive care centers for congenital adrenal hyperplasia: guidance from the CARES Foundation initiative. Int J Pediatr Endocrinol. 2010;2010:275213. Epub 2011 Jan 10
Pijnenburg-Kleizen KJ, Thomas CMG, Otten BJ, Roeleveld N, Claahsen-van der Grinten HL. Long-term follow-up of children with classic congenital adrenal hyperplasia: suggestions for age dependent treatment in childhood and puberty. J Pediatr Endocrinol Metab. 2019;32:1055-1063.
Nimkarn S, Lin-Su K, Berglind N, Wilson RC, New MI. Aldosterone-to-renin ratio as a marker for disease severity in 21-hydroxylase deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2007;92:137-142. Epub 2006 Oct 10
Mullis PE, Hindmarsh PC, Brook CG. Sodium chloride supplement at diagnosis and during infancy in children with salt-losing 21-hydroxylase deficiency. Eur J Pediatr. 1990;150:22-25.
Bonfig W, Roehl F, Riedl S, Brämswig J, Richter-Unruh A, Fricke-Otto S, Hübner A, Bettendorf M, Schönau E, Dörr H, Holl RW, Mohnike K. Sodium chloride supplementation is not routinely performed in the majority of German and Austrian infants with classic salt-wasting congenital adrenal hyperplasia and has no effect on linear growth and hydrocortisone or fludrocortisone dose. Horm Res Paediatr. 2018;89:7-12. Epub 2017 Oct 26
Charmandari E, Chrousos GP, Merke DP. Adrenocorticotropin hypersecretion and pituitary microadenoma following bilateral adrenalectomy in a patient with classic 21-hydroxylase deficiency. J Pediatr Endocrinol Metab. 2005;18:97-101.
Rivkees SA, Crawford JD. Dexamethasone treatment of virilizing congenital adrenal hyperplasia: the ability to achieve normal growth. Pediatrics. 2000;106:767-773.
Charmandari E, Hindmarsh PC, Johnston A, Brook CG. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: alterations in cortisol pharmacokinetics at puberty. J Clin Endocrinol Metab. 2001;86:2701-2708.
Bachelot A. Transition of care from childhood to adulthood: congenital adrenal hyperplasia. Endocr Dev. 2018;33:17-33. Epub 2018 Jun 8
Jiang X, Xu C, Lei F, Liao M, Wang W, Xu N, Zhang Y, Xie W. MiR-30a targets IL-1α and regulates islet functions as an inflammation buffer and response factor. Sci Rep. 2017;7:5270.
Arlt W, Willis DS, Wild SH, Krone N, Doherty EJ, Hahner S, Han TS, Carroll PV, Conway GS, Rees DA, Stimson RH, Walker BR, Connell JM, Ross RJ; United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE). Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab. 2010;95:5110-5121. Epub 2010 Aug 18
Hughes IA. Congenital adrenal hyperplasia: transitional care. Growth Horm IGF Res. 2004;14(Suppl):60-66.
Pofi R, Prete A, Thornton-Jones V, Bryce J, Ali SR, Faisal Ahmed S, Balsamo A, Baronio F, Cannuccia A, Guven A, Guran T, Darendeliler F, Higham C, Bonfig W, de Vries L, Bachega TASS, Miranda MC, Mendonca BB, Iotova V, Korbonits M, Krone NP, Krone R, Lenzi A, Arlt W, Ross RJ, Isidori AM, Tomlinson JW. Plasma renin measurements are unrelated to mineralocorticoid replacement dose in patients with primary adrenal insufficiency. J Clin Endocrinol Metab. 2020;105:314-326.
Turcu AF, Rege J, Chomic R, Liu J, Nishimoto HK, Else T, Moraitis AG, Palapattu GS, Rainey WE, Auchus RJ. Profiles of 21-carbon steroids in 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2015;100:2283-2290. Epub 2015 Apr 7
Turcu AF, Rege J, Auchus RJ, Rainey WE. 11-Oxygenated androgens in health and disease. Nat Rev Endocrinol. 2020;16:284-296. Epub 2020 Mar 16
Kamrath C, Hartmann MF, Boettcher C, Zimmer KP, Wudy SA. Diagnosis of 21-hydroxylase deficiency by urinary metabolite ratios using gas chromatography-mass spectrometry analysis: Reference values for neonates and infants. J Steroid Biochem Mol Biol. 2016;156:10-16. Epub 2015 Oct 19
Kamrath C, Hartmann MF, Pons-Kühnemann J, Wudy SA. Urinary GC-MS steroid metabotyping in treated children with congenital adrenal hyperplasia. Metabolism. 2020;112:154354. Epub 2020 Sep 9
Wieacker I, Peter M, Borucki K, Empting S, Roehl FW, Mohnike K. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples. J Pediatr Endocrinol Metab. 2015;28:867-871.
Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engström BE, Olsson T, Ragnarsson O, Ryberg M, Wahlberg J, Biller BM, Monson JP, Stewart PM, Lennernäs H, Skrtic S. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab. 2012;97:473-481. Epub 2011 Nov 23
Isidori AM, Venneri MA, Graziadio C, Simeoli C, Fiore D, Hasenmajer V, Sbardella E, Gianfrilli D, Pozza C, Pasqualetti P, Morrone S, Santoni A, Naro F, Colao A, Pivonello R, Lenzi A. Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2018;6:173-185. Epub 2017 Dec 8
Auchus RJ. Management considerations for the adult with congenital adrenal hyperplasia. Mol Cell Endocrinol. 2015;408:190-197. Epub 2015 Jan 30
Plat L, Leproult R, L’Hermite-Baleriaux M, Fery F, Mockel J, Polonsky KS, Van Cauter E. Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning. J Clin Endocrinol Metab. 1999;84:3082-3092.
Debono M, Ghobadi C, Rostami-Hodjegan A, Huatan H, Campbell MJ, Newell-Price J, Darzy K, Merke DP, Arlt W, Ross RJ. Modified-release hydrocortisone to provide circadian cortisol profiles. J Clin Endocrinol Metab. 2009;94:1548-1554. Epub 2009 Feb 17
Whitaker M, Debono M, Huatan H, Merke D, Arlt W, Ross RJ. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure. Clin Endocrinol (Oxf). 2014;80:554-561. Epub 2013 Sep 20
Merke DP, Mallappa A, Arlt W, de la Perriere AB, Hirschberg AL, Juul A, Newell-Price JD, Perry CG, Prete A, Rees A, Reisch N, Stikkelbroeck M, Touraine PA, Maltby K, Treasure P, Porter J, Ross RJM. OR25-02 A Phase 3 study of a modified-release hydrocortisone in the treatment of congenital adrenal hyperplasia. J Endocr Soc. 2020;4(Suppl 1):OR25-02.
Oksnes M, Björnsdottir S, Isaksson M, Methlie P, Carlsen S, Nilsen RM, Broman JE, Triebner K, Kämpe O, Hulting AL, Bensing S, Husebye ES, Løvås K. Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of addison’s disease: a randomized clinical trial. J Clin Endocrinol Metab. 2014;99:1665-1674. Epub 2014 Feb 11
Webb EA, Krone N. Current and novel approaches to children and young people with congenital adrenal hyperplasia and adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015;29:449-468. Epub 2015 Apr 22
Merke DP, Keil MF, Jones JV, Fields J, Hill S, Cutler GB Jr. Flutamide, testolactone, and reduced hydrocortisone dose maintain normal growth velocity and bone maturation despite elevated androgen levels in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2000;85:1114-1120.
Hawton K, Walton-Betancourth S, Rumsby G, Raine J, Dattani M. Growth hormone with aromatase inhibitor may improve height in CYP11B1 congenital adrenal hyperplasia. Pediatrics. 2017;139:e20160730.
Goedegebuure WJ, Hokken-Koelega ACS. Aromatase inhibitor as treatment for severely advanced bone age in congenital adrenal hyperplasia: a case report. Horm Res Paediatr. 2019;92:209-213. Epub 2019 Aug 7
Auchus RJ, Sharifi N. Sex hormones and prostate cancer. Annu Rev Med. 2020;71:33-45. Epub 2019 Oct 15
Wright C, O’Day P, Alyamani M, Sharifi N, Auchus RJ. Abiraterone acetate treatment lowers 11-oxygenated androgens. Eur J Endocrinol. 2020;182:413-421.
Güran T. Latest insights on the etiology and management of primary adrenal insufficiency in children. J Clin Res Pediatr Endocrinol. 2017;9(Suppl 2):9-22. Epub 2017 Dec 27
Auchus RJ, Buschur EO, Chang AY, Hammer GD, Ramm C, Madrigal D, Wang G, Gonzalez M, Xu XS, Smit JW, Jiao J, Yu MK. Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2014;99:2763-2770. Epub 2014 Apr 29
Turcu AF, Spencer-Segal JL, Farber RH, Luo R, Grigoriadis DE, Ramm CA, Madrigal D, Muth T, O’Brien CF, Auchus RJ. Single-dose study of a corticotropin-releasing factor receptor-1 antagonist in women with 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2016;101:1174-1180. Epub 2016 Jan 11
Gehrand AL, Phillips J, Malott K, Raff H. A Long-acting neutralizing monoclonal ACTH antibody blocks corticosterone and adrenal gene responses in neonatal rats. Endocrinology. 2019;160:1719-1730.
Sanders K, Mol JA, Kooistra HS, Galac S. Melanocortin 2 receptor antagonists in canine pituitary-dependent hypercortisolism: in vitro studies. Vet Res Commun. 2018;42:283-288. Epub 2018 Sep 5
Turcu AF, Auchus RJ. Novel treatment strategies in congenital adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes. 2016;23:225-232.
Van Wyk JJ, Gunther DF, Ritzén EM, Wedell A, Cutler GB Jr, Migeon CJ, New MI. The use of adrenalectomy as a treatment for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1996;81:3180-3190.
MacKay D, Nordenström A, Falhammar H. Bilateral adrenalectomy in congenital adrenal hyperplasia: a systematic review and meta- analysis. J Clin Endocrinol Metab. 2018;103:1767-1778.
Burman P, Falhammar H, Waldenström E, Sundin A, Bitzén U. 11C-metomidate PET/CT detected multiple ectopic adrenal rest tumors in a woman with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2021;106:675-679.
Bry-Gauillard H, Cartes A, Young J. Mitotane for 21-hydroxylase deficiency in an infertile man. N Engl J Med. 2014;371:2042-2044.
Muthusamy K, Elamin MB, Smushkin G, Murad MH, Lampropulos JF, Elamin KB, Abu Elnour NO, Gallegos-Orozco JF, Fatourechi MM, Agrwal N, Lane MA, Albuquerque FN, Erwin PJ, Montori VM. Clinical review: adult height in patients with congenital adrenal hyperplasia: a systematic review and metaanalysis. J Clin Endocrinol Metab. 2010;95:4161-4172.
New MI, Gertner JM, Speiser PW, Del Balzo P. Growth and final height in classical and nonclassical 21-hydroxylase deficiency. J Endocrinol Invest. 1989;12(8 Suppl 3):91-95.
Quintos JB, Vogiatzi MG, Harbison MD, New MI. Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2001;86:1511-1517.
Lin-Su K, Harbison MD, Lekarev O, Vogiatzi MG, New MI. Final adult height in children with congenital adrenal hyperplasia treated with growth hormone. J Clin Endocrinol Metab. 2011;96:1710-1717. Epub 2011 Mar 30
Ruiz-Babot G, Balyura M, Hadjidemetriou I, Ajodha SJ, Taylor DR, Ghataore L, Taylor NF, Schubert U, Ziegler CG, Storr HL, Druce MR, Gevers EF, Drake WM, Srirangalingam U, Conway GS, King PJ, Metherell LA, Bornstein SR, Guasti L. Modeling congenital adrenal hyperplasia and testing interventions for adrenal insufficiency using donor-specific reprogrammed cells. Cell Rep. 2018;22:1236-1249.
Naiki Y, Miyado M, Horikawa R, Katsumata N, Onodera M, Pang S, Ogata T, Fukami M. Extra-adrenal induction of Cyp21a1 ameliorates systemic steroid metabolism in a mouse model of congenital adrenal hyperplasia. Endocr J. 2016;63:897-904. Epub 2016 Jul 14
Perdomini M, Dos Santos C, Goumeaux C, Blouin V, Bougnères P. An AAVrh10-CAG-CYP21-HA vector allows persistent correction of 21-hydroxylase deficiency in a Cyp21-/- mouse model. Gene Ther. 2017;24:275-281. Epub 2017 Feb 6
Auchus RJ. The classic and nonclassic concenital adrenal hyperplasias. Endocr Pract. 2015;21:383-389. Epub 2014 Dec 22
Reichman DE, White PC, New MI, Rosenwaks Z. Fertility in patients with congenital adrenal hyperplasia. Fertil Steril. 2014;101:301-309. Epub 2013 Dec 17
Nordenström A, Falhammar H. Management of endocrine disease: diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency. Eur J Endocrinol. 2019;180:127-145.
Weintrob N, Dickerman Z, Sprecher E, Galatzer A, Pertzelan A. Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height. Eur J Endocrinol. 1997;136:188-195.
Eyal O, Tenenbaum-Rakover Y, Shalitin S, Israel S, Weintrob N. Adult height of subjects with nonclassical 21-hydroxylase deficiency. Acta Paediatr. 2013;102:419-423. Epub 2013 Jan 28
Falhammar H, Nordenstrom A. Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome. Endocrine. 2015;50:32-50. Epub 2015 Jun 17
Trapp CM, Oberfield SE. Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): an update. Steroids. 2012;77:342-346. Epub 2011 Dec 13
Bidet M, Bellanné-Chantelot C, Galand-Portier MB, Tardy V, Billaud L, Laborde K, Coussieu C, Morel Y, Vaury C, Golmard JL, Claustre A, Mornet E, Chakhtoura Z, Mowszowicz I, Bachelot A, Touraine P, Kuttenn F. Clinical and molecular characterization of a cohort of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and 330 family members. J Clin Endocrinol Metab. 2009;94:1570-1578. Epub 2009 Feb 10
Martin KA, Anderson RR, Chang RJ, Ehrmann DA, Lobo RA, Murad MH, Pugeat MM, Rosenfield RL. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103:1233-1257.
Spritzer P, Billaud L, Thalabard JC, Birman P, Mowszowicz I, Raux-Demay MC, Clair F, Kuttenn F, Mauvais-Jarvis P. Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia. J Clin Endocrinol Metab. 1990;70:642-646.
Matthews D, Cheetham T. What is the best approach to the teenage patient presenting with nonclassical congenital adrenal hyperplasia: should we always treat with glucocorticoids? Clin Endocrinol (Oxf). 2013;78:338-341.
Corvol P, Michaud A, Menard J, Freifeld M, Mahoudeau J. Antiandrogenic effect of spirolactones: mechanism of action. Endocrinology. 1975;97:52-58.
Swiglo BA, Cosma M, Flynn DN, Kurtz DM, Labella ML, Mullan RJ, Erwin PJ, Montori VM. Clinical review: antiandrogens for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials. J Clin Endocrinol Metab. 2008;93:1153-1160. Epub 2008 Feb 5
Birnbaum MD, Rose LI. The partial adrenocortical hydroxylase deficiency syndrome in infertile women. Fertil Steril. 1979;32:536-541.
Lo JC, Grumbach MM. Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia. Endocrinol Metab Clin North Am. 2001;30:207-229.
Falhammar H, Nyström HF, Ekström U, Granberg S, Wedell A, Thorén M. Fertility, sexuality and testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia. Eur J Endocrinol. 2012;166:441-449. Epub 2011 Dec 9
Nandagopal R, Sinaii N, Avila NA, Van Ryzin C, Chen W, Finkielstain GP, Mehta SP, McDonnell NB, Merke DP. Phenotypic profiling of parents with cryptic nonclassic congenital adrenal hyperplasia: findings in 145 unrelated families. Eur J Endocrinol. 2011;164:977-984. Epub 2011 Mar 28
Stoupa A, González-Briceño L, Pinto G, Samara-Boustani D, Thalassinos C, Flechtner I, Beltrand J, Bidet M, Simon A, Piketty M, Laborde K, Morel Y, Bellanné-Chantelot C, Touraine P, Polak M. Inadequate cortisol response to the tetracosactide (Synacthen®) test in non-classic congenital adrenal hyperplasia: an exception to the rule? Horm Res Paediatr. 2015;83:262-267. Epub 2015 Feb 7
Odabaşı Güneş S, Peltek Kendirci HN, Ünal E, Buluş AD, Dündar İ, Şıklar Z. Clinical, biochemical and molecular characteristics of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Res Pediatr Endocrinol. 2025;17(Suppl 1):3-11.
