Symptoms of Congenital Adrenal Hyperplasia (CAH)
Clinical Presentation in Newborns
The most critical presentation of CAH in newborns is ambiguous genitalia in 46,XX infants (virilization with clitoromegaly and presence of uterus) and life-threatening salt-wasting crisis within the first weeks of life in both sexes. 1, 2
Classic Salt-Wasting Form (Most Severe)
- Adrenal crisis symptoms develop within the first 1-4 weeks of life, presenting with severe hyponatremia, hyperkalemia, shock, vomiting, dehydration, and potential death if untreated 1, 2
- Ambiguous genitalia in 46,XX newborns characterized by clitoromegaly and urogenital sinus, representing the most common cause of genital ambiguity in genetic females 1, 3
- Normal-appearing external genitalia in 46,XY newborns, making diagnosis more challenging and emphasizing the critical importance of recognizing salt-wasting symptoms 2, 3
Simple Virilizing Form (Less Severe)
- Virilization in 46,XX infants without salt-wasting crisis 2, 4
- Elevated 17-hydroxyprogesterone detected on newborn screening in the United States 2
Clinical Presentation in Children
Childhood Manifestations
- Premature adrenarche with early appearance of pubic and axillary hair 2, 3
- Accelerated linear growth with advanced bone age leading to early growth plate closure 2, 3
- Progressive virilization in inadequately treated patients 3
- Precocious puberty can occur 3
- Compromised final adult height due to advanced bone age, early peak height velocity, and increased glucocorticoid sensitivity during puberty 5
Late-Onset (Non-Classic) CAH Symptoms
- Hirsutism (excessive body hair) 2
- Irregular menses in adolescent females 2
- Signs of androgen excess from childhood through adulthood 4
Clinical Presentation in Adolescents and Adults
Female-Specific Manifestations
- Menstrual irregularities due to adrenal progestagens and androgens disrupting ovarian activity 6, 5
- Reduced fertility with pregnancy rates depending on severity (salt-wasting < simple virilizing < non-classic) 6, 5
- Hyperandrogenism symptoms including hirsutism and acne 6
- Psychosexual complications related to atypical genitalia and/or previous surgical treatment 6, 3
Male-Specific Manifestations
- Testicular adrenal rest tumors originating from aberrant adrenal tissue, representing the main cause of subfertility in males 5
- Subfertility problems with origins in childhood years 5
Long-Term Comorbidities
- Cardiometabolic complications including hypertension, obesity, and diabetes risk 2, 6, 3
- Decreased bone mineral density requiring continuous monitoring 6
- Impaired cognitive function in some patients 2
- Overweight/obesity with increased prevalence 3
Critical Diagnostic Considerations
Any newborn with bilateral nonpalpable gonads and ambiguous genitalia requires immediate evaluation for CAH as a life-threatening emergency. 1 The presence of a uterus with clitoromegaly in a 46,XX individual is pathognomonic for CAH, with 21-hydroxylase deficiency accounting for approximately 72.7% of such cases 1. Failure to diagnose can result in Addisonian crisis with shock and death 1.
Treatment Overview
Hormonal Replacement
- Hydrocortisone for glucocorticoid replacement in growing children 2, 3
- Increased stress doses for acute illness, trauma, and procedures 2, 3
- Mineralocorticoid and salt replacement in salt-wasting forms 2, 3
Surgical Considerations
- Feminizing genitoplasty should be performed within the first 2 months of life when female gender is assigned, ensuring external genitalia appearance is consistent with sex of rearing 7
- Early gender assignment and removal of androgen source (hydrocortisone administration) prevents further brain masculinization after birth 7
- Circumcision should be avoided until complete workup is finished, even if phallus appears normal 1
Critical Treatment Pitfall
Infants diagnosed and treated beyond 4-6 months of age should not undergo sex reversal to female gender due to prenatal and postnatal androgen imprinting of the brain. 7 Early diagnosis and expert management are critical given potential long-term adverse health outcomes from prolonged hypercortisolism and treatment-related morbidity 7.