Clinical Manifestations and Treatment Challenges in Infants and Children With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Abstract

The most common form of congenital adrenal hyperplasia (CAH) is secondary to 21-hydroxylase deficiency (21OHD). This review will summarize the clinical manifestations, recommended treatments, monitoring, clinical challenges and management strategy, and treatment challenges in special situations for infants and children with classic CAH due to 21OHD. Specifically, we review newborn screening and the initial diagnosis, glucocorticoid and mineralocorticoid treatment, and recommended monitoring, including anthropometric and laboratory measures. Children with CAH may have premature adrenarche, precocious puberty, and early growth plate closure and have an increased risk of hypertension and overweight/obesity. Many 46,XX individuals will also have genital differences, which may include clitoromegaly and/or a urogenital sinus. We review psychosocial and surgical considerations, including suggestions on how to talk with children, family, and caregivers about bodily difference. These suggestions may be used by families and/or providers caring for individuals with CAH.

Keywords: 17-hydroxyprogesterone; 21-hydroxylase deficiency; congenital adrenal hyperplasia; fludrocortisone; hydrocortisone.

Figure 1.

Suggested diagnostic algorithm for CAH in the neonatal period. *Note that these suggestions include fewer labs than current guidelines recommend (1). Many neonates, particularly premature babies, cannot have a complete adrenocortical profile drawn as suggested by guidelines (1) due to blood volume limitations. For premature infants or small for gestational age infants with abnormal newborn screens and/or those with repeated minimally elevated 17-OHP values, we suggest periodic 17-OHP draws until normal or until the value meets criteria for additional workup based on the algorithm. These are suggested labs when blood draw volume limits a complete adrenocortical profile and will evaluate for the most common causes of CAH, 21-hydroxylase deficiency and 11β-hydroxysteroid dehydrogenase deficiency. ‡A negative newborn screen or normal 17-OHP does not rule out CAH due to other enzymatic defects; if there are signs/symptoms of adrenal insufficiency, additional evaluation should be performed. Note that not all regions have a second newborn screen. This figure was adapted from the following publications (5, 7). Abbreviations: 17-OHP, 17-hydroxyprogesterone; CAH, congenital adrenal hyperplasia; K, potassium; Na, sodium; NBS, newborn screen; NCCAH, non-classical congenital adrenal hyperplasia.

Figure 2.

Urogenital sinus. Lower urogenital anatomy of mild (A) and severe (B) CAH. In mild CAH, the vagina and urethra meet close to the skin (low confluence). In severe CAH, the confluence of the vagina and bladder is close to the bladder neck. Reproduced with permission from The 2018 Endocrine Society Guidelines (1). Abbreviation: CAH, congenital adrenal hyperplasia.

Figure 3.

The balance between under- and overtreatment with glucocorticoids during childhood. Abbreviation: CAH, congenital adrenal hyperplasia.

Figure 4.

Infancy handout. Guide for parents on talking to friends, family, and other caregivers about their infant with CAH.

Figure 5.

Childhood handout. Guide for parents on supporting their child with CAH.