Congenital Adrenal Hyperplasia (CAH) is a disease of multiple hormonal imbalances. Mutations in CYP21A2 (the gene encoding 21-hydroxylase, a cytochrome P-450 enzyme) result in lack of 21-hydroxylase, which is required for the production of cortisol and aldosterone in the adrenal cortex. A deficiency of this enzyme has cascading effects. Reduced cortisol leads to overproduction of pituitary corticotropin, which stimulates the accumulation of cortisol precursors and their subsequent diversion through the steroid pathways that produce adrenal androgens. Today, the classic form is the most common cause of atypical genitalia in 46,XX newborns and of primary adrenal insufficiency during childhood.
Diagnosis of Congenital Adrenal Hyperplasia
|Approach||Infancy||Childhood||Adolescence and Adulthood|
|Symptoms and signs at presentation||Positive newborn screen, atypical genitalia (46,XX), poor feeding, weight loss, dehydration with low sodium, high potassium||Increased growth velocity, precocious pubarche†, early-onset adult apocrine odor||Hirsutism, oligomenorrhea, subfertility|
|Hormonal findings||Increased 17-OHP* and androstenedione, decreased cortisol (in classic CAH)
Corticotropin (cosyntropin) stimulation: 17-OHP >1000 ng/dl (30 nmol/liter), usually >5000 ng/dl (150 nmol/liter) in classic CAH
Rule out other rare disorders of steroidogenesis‡
|Same as for infancy||Corticotropin (cosyntropin) stimulation: 17-OHP >1000 ng/dl (30 nmol/liter)
In nonclassic CAH, cortisol normal or near normal
|Additional considerations||Pelvic ultrasonography to determine presence or absence of uterus in cases of atypical genitalia
Measurement of electrolytes to evaluate sodium and potassium homeostasis
Stimulation test may be delayed in sick infants
|Radiographic assessment of bone age (left hand) to assess for skeletal maturation
Distinguish classic from nonclassic CAH on the basis of cortisol values and disease severity
|Early-morning, follicular-phase 17-OHP <200 ng/dl (6 nmol/liter) often rules out nonclassic CAH
Genotyping and genetic counseling before pregnancy
*17-OHP denotes 17-hydroxyprogesterone.
† Precocious pubarche is defined as the presence of pubic hair before 8 years of age in girls and 9 years of age in boys.
‡ Measure 17-OHP, cortisol, 11-deoxycortisol, 17-hydroxypregnenolone, dehydroepiandrosterone, and androstenedione.
- Merke DP, Auchus RJ. Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. N Engl J Med. 2020 Sep 24;383(13):1248-1261. [Medline]
- 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 Nov 1;103(11):4043-4088. [Medline]
Created Jun 11, 2021.