What are the elevated levels of 17 hydroxyprogesterone, androstenedione, and Dehydroepiandrosterone sulfate (DHEAS) in this patient?

Elevated Levels of 17-Hydroxyprogesterone, Androstenedione, and DHEAS

For diagnostic purposes, elevated levels of 17-hydroxyprogesterone (17-OHP) >200 ng/dl, androstenedione above the upper limit of normal, and DHEAS >100 μg/dl are considered elevated and clinically significant in this patient. 1

Reference Ranges and Clinical Significance

17-Hydroxyprogesterone

• Normal range: <50 nmol/L (generally <200 ng/dl) 1
• Possible autonomous secretion: 51-138 nmol/L
• Evidence of hypersecretion: >138 nmol/L
• Clinical significance: Primary marker for 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) 2

Androstenedione

• Normal range: Varies by laboratory, but generally:
  • Adult females: 0.7-3.1 ng/mL
  • Adult males: 0.5-2.6 ng/mL
• Elevated level: Any value above the upper limit of normal
• Clinical significance: Elevated in PCOS, non-classical CAH, and adrenocortical tumors 1

DHEAS (Dehydroepiandrosterone sulfate)

• Normal range: Varies by age and sex
• Elevated level: >100 μg/dl indicates poor control in treated CAH 3
• Highly elevated level: >3800 ng/ml in women 20-29 years or >2700 ng/ml in women 30-39 years warrants adrenal imaging to rule out adrenal tumor 4

Clinical Implications of Elevated Levels

Diagnostic Value

• 17-OHP: Primary marker for diagnosing 21-hydroxylase deficiency in CAH; levels >200 ng/dl in well-controlled patients suggest inadequate treatment 3
• Androstenedione: Shows good correlation with 17-OHP levels (r = 0.647) and can be used as a complementary marker 5
• DHEAS: Less sensitive but more specific marker; elevated levels (>100 μg/dl) strongly indicate poor control in treated CAH 6

Monitoring Treatment

• Morning levels of all three hormones are typically higher than afternoon or evening levels 5
• DHEAS responds more slowly to treatment changes but is more specific for determining control status 3, 6
• 17-OHP levels <200 ng/dl indicate good control in treated patients 3

Differential Diagnosis Based on Hormone Patterns

1. Congenital Adrenal Hyperplasia:

   • Markedly elevated 17-OHP (often >1000 ng/dl)
   • Moderately elevated androstenedione
   • Variable DHEAS levels 2, 5

2. Adrenocortical Tumor:

   • Elevated DHEAS (often >3800 ng/ml in younger women)
   • Elevated androstenedione
   • Variable 17-OHP levels 1, 7

3. Polycystic Ovary Syndrome:

   • Mildly elevated androstenedione
   • Mildly elevated DHEAS
   • Normal to slightly elevated 17-OHP 1, 4

Key Considerations for Interpretation

• Timing of sample collection affects levels (morning samples typically higher)
• Age and sex influence normal ranges, particularly for DHEAS
• Medications (especially glucocorticoids) can suppress levels
• Assay methods affect results - LC-MS/MS provides more accurate measurements than immunoassays 1

Pitfalls to Avoid

• Relying solely on one hormone measurement for diagnosis
• Failing to consider diurnal variation in hormone levels
• Not accounting for assay-specific reference ranges
• Overlooking the possibility of 11β-hydroxylase deficiency, which can present similarly to 21-hydroxylase deficiency but requires different management 2

In summary, when evaluating this patient, values of 17-OHP >200 ng/dl, androstenedione above the upper limit of normal, and DHEAS >100 μg/dl should be considered elevated and warrant further investigation based on the clinical context.