Androgen Testing for 11-Beta-Hydroxylase Deficiency
For suspected 11-beta-hydroxylase deficiency, measure testosterone, androstenedione, DHEA-S, and 17-OH-progesterone as initial androgens, with 11-deoxycortisol being the definitive diagnostic marker that distinguishes this from 21-hydroxylase deficiency. 1, 2, 3
Primary Diagnostic Androgens
The essential androgen panel for 11-beta-hydroxylase deficiency includes:
- Testosterone - typically elevated in affected patients 1, 4
- Androstenedione (Δ4-A) - markedly elevated and a key marker 1, 2, 5, 4
- DHEA-sulfate (DHEA-S) - elevated in most cases 1
- 17-OH-progesterone - modestly elevated (but less dramatically than in 21-hydroxylase deficiency) 1, 3
Critical Distinguishing Steroid
11-deoxycortisol (compound S) is the pathognomonic marker - it will be grossly elevated in 11-beta-hydroxylase deficiency while remaining normal in 21-hydroxylase deficiency 1, 2, 3, 5. This is the single most important test to differentiate between these two forms of congenital adrenal hyperplasia 3, 5.
Additional Useful Markers
- 21-deoxycortisol - remains normal in 11-beta-hydroxylase deficiency but is elevated in 21-hydroxylase deficiency, providing another distinguishing feature 3, 5
- Cortisol - typically low, which helps confirm adrenal enzyme deficiency 2, 5
Clinical Context and Pitfalls
The most common diagnostic error is misdiagnosing 11-beta-hydroxylase deficiency as 21-hydroxylase deficiency because both conditions present with elevated 17-OH-progesterone 1, 3. However, in 11-beta-hydroxylase deficiency, the 17-OH-progesterone rise is modest (e.g., from 92 to 133 nmol/L after ACTH stimulation), whereas in 21-hydroxylase deficiency it rises dramatically 1.
Studies suggest that approximately 1% of patients initially diagnosed with 21-hydroxylase deficiency actually have 11-beta-hydroxylase deficiency, indicating this condition is underdiagnosed 3. The key to avoiding this pitfall is measuring 11-deoxycortisol in all suspected cases of congenital adrenal hyperplasia 3, 5.
Practical Testing Approach
For newborn screening or initial workup:
- Start with 17-OH-progesterone (will be elevated but not as dramatically as 21-hydroxylase deficiency) 2, 5
- If positive, proceed immediately to second-tier testing with LC-MS/MS measuring 11-deoxycortisol, cortisol, androstenedione, and 21-deoxycortisol 2, 5
- The pattern of markedly elevated 11-deoxycortisol with low cortisol and elevated androstenedione confirms the diagnosis 2, 5
Hypertension in a virilized infant strongly suggests 11-beta-hydroxylase deficiency rather than 21-hydroxylase deficiency, as the accumulated 11-deoxycorticosterone has mineralocorticoid activity 4.