Testosterone Levels in Congenital Adrenal Hyperplasia
Testosterone levels in untreated CAH are markedly elevated—often many-fold above normal for age and sex—with values ranging from 20 ng/dL to over 150 ng/dL in children, and can exceed 400 ng/dL in severely affected individuals. 1, 2
Baseline Testosterone Elevations
- Untreated patients with CAH due to 21-hydroxylase deficiency demonstrate testosterone levels that are manyfold increased compared to age-matched controls 2
- In a cohort of treated girls with CAH, mean testosterone was 150.21 ± 155.44 ng/dL, with a wide range reflecting variable disease control 3
- Blood testosterone values above 20 ng/dL distinguish inadequately suppressed patients from well-controlled cases in prepubertal children 1
- In untreated prepubertal females with CAH, testosterone can range from 3-151 ng/100 mL (30-1510 ng/dL), with the majority of elevation derived from peripheral conversion of androstenedione 4
Source of Elevated Testosterone
- Approximately 76% of plasma testosterone in prepubertal females with CAH originates from peripheral conversion of adrenal-secreted androstenedione, rather than direct testicular or adrenal testosterone production 2
- In prepubertal males with CAH, 36% of plasma testosterone derives from androstenedione conversion 2
- The conversion ratio of androstenedione to testosterone remains similar to normal adults, but the massively elevated androstenedione substrate (mean 4.15 ± 5.32 ng/mL) drives excessive testosterone production 3, 2
Response to Treatment
- Glucocorticoid therapy causes marked suppression of testosterone levels, with adequately treated patients achieving near-normal values 1, 2
- Despite proper hydrocortisone supplementation (10-19 mg/m²), excessive hyperandrogenism remains a frequent clinical problem, with testosterone levels correlating positively with the degree of prenatal androgenization 3
- After ACTH stimulation, testosterone levels increase dramatically in parallel with 17-hydroxyprogesterone and androstenedione, confirming adrenal origin 4
Clinical Monitoring Considerations
- Serial testosterone measurement provides superior assistance in evaluating disease control compared to 24-hour urine collections for 17-ketosteroids, particularly when accurate urine collections cannot be obtained in children 1
- The correlation between 17-hydroxyprogesterone and testosterone is strong (r = 0.761, P < 0.001), making either marker useful for monitoring 4
- In prepubertal children with moderately elevated 17-OHP (10-70 ng/mL), testosterone may remain within normal range (mean 16.0 ng/100 mL) despite inadequate overall control, creating a potential monitoring pitfall 4
Virilization Context
- The 11β-hydroxylase deficiency subtype of CAH presents with hypertension, hypokalemia, and virilization with elevated androgens 5, 6
- In 46,XX patients with CAH, detectable PSA levels (>0.01 ng/mL in 25% of cases over 5 years old) correlate with elevated testosterone and androstenedione, serving as a marker of virilization severity 7