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Student Authors

A review of congenital adrenal hyperplasia with emphasis on life-long management

Kathryn Lewis
University of California Riverside
School of Medicine - Class of 2020

Congenital adrenal hyperplasias (CAH) constitute a spectrum of autosomal recessive disorders that involve defective biosynthesis of adrenal cortex derived hormones, including androgens, cortisol, and aldosterone. Deficiency of 21 hydroxylase is the most common congenital adrenal hyperplasia, constituting approximately 95% of cases worldwide(1). Rarer forms include 11-Beta hydroxylase, 17-Alpha hydroxylase, and 3-Beta hydroxysteroid deficiencies.

21 hydroxylase deficiency can be separated into classical and non-classical forms, both involving mutations of the CYP21A gene. In the United States, most cases of classical CAH (CCAH) are diagnosed in infancy through newborn 17 hydroxyprogestrone screening. Presentation typically includes hypotension, electrolyte imbalance (hyperkalemia, hyponatremia), and failure-to-thrive. Male CCAH patients are likely to experience central precocious puberty (CPP), while female patients are born with virilization. Non-classical CAH (NCCAH) may not be diagnosed until childhood or puberty and is considered to be milder, with elevated androgen levels alone(1). Presentation may include childhood accelerated skeletal maturation, early thelarche and pubarche, cliteromegaly, advanced phallic growth, and hirsutism(1).

Following diagnosis of CAH, treatment involves life-long medical and psychosocial management for the patient and their changing needs with age. NCCAH typically does not require treatment unless there is desire for fertility and pregnancy. CCAH, however, requires lifelong management with exogenous corticosteroids. The 2010 Endrocrine Society Consensus Statement on CAH recommends hydroxycortisone with mineralocorticoid supplementation during infancy and childhood. Dexamethasone and prednisolone, though sometimes used, are not recommended during this time due to resorptive effects on bone(1).

In fact, suboptimal stature is a common complication of CAH due to precocious puberty, early epiphyseal plate closure, late diagnosis, and the potency of corticosteroids prescribed. Cordeiro et al found that better height outcomes were associated with lower doses of corticosteroids. However, children with predicted height more than 2 SD below their mid-parental target height may undergo supplemental therapy(2). Gonadothropinreleasing hormone (GnRH) analogs for central precocious puberty (CPP)-related height deficits, growth hormone (GH) and luteinizing hormone releasing hormone analog (LHRHa), or GH alone have been shown in clinical trials to improve final adult height in CAH patients(3,4).

As patients with CAH transition to adulthood, management with corticosteroids continues but additional health concerns shift into focus. Counseling regarding obesity, bone loss, and infertility are necessary and may require additional treatments or considerations(5). Patients with CAH are often subfertile. Elevated progestin levels and anovulation are common causes in women, while oligospermia and testicular adrenal rest tumors cause subfertility in men(6). Early compliance with medications has been shown to improve fertility in both men and women with CAH. For women, suppression of progestin levels also improve fertility(7).

Treating the biochemical complications of CAH is only one aspect of management. Johannsen et al performed a case control study on 70 women with disorders of sexual development (DSD), finding that women with CAH had higher rates of anxiety and suicide attempts(8). Additional studies have reported that patients with CAH have poorer quality of life. Patients were less sexually active, exhibited less self-confidence, and had more negative views of their own social acceptance(7). Currently, there are no guidelines that specify the psychosocial management of CAH(9). However, it is evident that ongoing mental health care is essential for the patient’s wellbeing and journey in managing social and sexual relationships.

Citations:

1. Speiser PW, Azziz R, Baskin LS, et al. A Summary of the Endocrine Society Clinical Practice Guidelines on Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency. International Journal of Pediatric Endocrinology. 2010;2010:494173. doi:10.1155/2010/494173.

2. Cordeiro, GiovanaVignoli, Silva, Ivani Novato, et al. Final height in congenital adrenal hyperplasia: the dilemma of hypercortisolism versus hyperandrogenism. ArquivosBrasileiros de Endocrinologia&Metabologia, 2010;57(2), 126-131. https://dx.doi.org/10.1590/S0004-27302013000200005

3. Guven Ayla, CebeciNurcan, HanciliSuna. Gonadotropin releasing hormone analog treatment in children with congenital adrenal hyperplasia complicated by central precocious puberty. HORMONES. 2015;14(2):265-271. DOI: 10.14310/horm.2002.1555

4. Lin-Su, K, Harbison MD, Lekarev O et al. Final adult height in children with congenital adrenal hyperplasia treated with growth hormone. J Clinical Endocrinology and Metabolism. 2011;96(6):1710-7. doi: 10.1210/jc.2010-269

5. Auchus RJ. Management considerations for the adult with congenital adrenal hyperplasia. Molecular and Cellular Endocrinology. 2015;408:190-197. https://doi.org/10.1016/j.mce.2015.01.039

6. Witchel SF. Management of CAH during pregnancy: optimizing outcomes. CurrOpinEndocrinol Diabetes Obes. 2012;19(6):489-96. doi: 10.1097/MED.0b013e32835a1a2e.

7. Kamoun M, Feki MM, Sfar MH, Abid M. Congenital adrenal hyperplasia: Treatment and outcomes. Indian Journal of Endocrinology and Metabolism. 2013;17(Suppl1):S14-S17. doi:10.4103/2230-8210.119491.

8. Quality of life in 70 women with disorders of sex development.Johannsen TH, Ripa CP, Mortensen EL, Main KM. Eur J Endocrinol. 2006 Dec; 155(6):877-85.

9. Choi J-H, Yoo H-W. Management issues of congenital adrenal hyperplasia during the transition from pediatric to adult care. Korean Journal of Pediatrics. 2017;60(2):31-37. doi:10.3345/kjp.2017.60.2.31.