Management of Elevated DHEAS with Normal CBC
The next step is to perform a comprehensive hormone panel including free and total testosterone, LH, FSH, SHBG, and free androgen index, while simultaneously conducting a focused clinical assessment for signs of hyperandrogenism to differentiate between the major causes: non-classical congenital adrenal hyperplasia, PCOS, and androgen-secreting tumors. 1
Initial Hormone Panel
The diagnostic workup should include the following tests 1:
- Free and total testosterone - essential for characterizing the androgen excess pattern
- LH and FSH - to evaluate for PCOS (elevated LH:FSH ratio suggests PCOS)
- SHBG and free androgen index - provides more accurate assessment of bioavailable androgens
- Consider insulin and glucose - for metabolic assessment, particularly if PCOS is suspected 1
Critical Clinical Assessment
Signs of Hyperandrogenism to Evaluate
In prepubertal children, look for 1:
- Early-onset body odor
- Premature axillary or pubic hair
- Accelerated growth velocity
- Advanced bone age
- Genital maturation
In postpubertal females, assess for 1:
- Androgenetic alopecia
- Clitoromegaly
- Hirsutism (modified Ferriman-Gallwey score)
- Seborrheic acne
Differential Diagnosis Based on DHEAS Level
Extremely Elevated DHEAS (>600 μg/dL or 16.3 μmol/L)
If DHEAS exceeds age-specific thresholds (>3800 ng/mL for ages 20-29, >2700 ng/mL for ages 30-39), non-classical congenital adrenal hyperplasia must be ruled out first 1. However, the positive predictive value of extremely elevated DHEAS for adrenal tumors is low 2.
- DHEAS >600 μg/dL (16.3 μmol/L) suggests possible androgen-secreting adrenal cortical adenoma 3
- Adrenal imaging (CT) is indicated when DHEAS is markedly elevated and testosterone is twice the upper limit of normal 3
- The specificity of DHEAS >16.3 μmol/L for neoplasm is 98%, but sensitivity cannot be reliably calculated due to rarity 2
Moderately Elevated DHEAS with Normal or Mildly Elevated Testosterone
If testosterone is normal or mildly elevated with elevated DHEAS, the most likely diagnosis is PCOS 1, 3:
- PCOS involves accelerated pulsatile GnRH secretion, insulin resistance, and metabolic dysregulation 1
- Address insulin resistance, metabolic factors, and ovulatory dysfunction 1
- SHBG is typically reduced in overweight patients, metabolic syndrome, or family history of diabetes 3
Elevated Testosterone (>2× Upper Limit Normal) with Elevated DHEAS
If testosterone exceeds twice the upper limit of normal 3:
- Perform DHEAS assay to determine source
- If DHEAS is normal despite elevated testosterone, consider ovarian hyperthecosis (associated with insulin resistance) or androgen-secreting ovarian tumor 3
- Transvaginal sonography is indicated for suspected ovarian source 2
Important Clinical Pitfalls
Avoid Unnecessary Imaging
The positive predictive value of elevated testosterone (>8.7 nmol/L or 250 ng/dL) for neoplasm is only 9%, despite 98% specificity 2. Clinical evaluation alone is often sufficient screening - imaging should be reserved for:
- Rapidly progressive virilization
- Testosterone >8.7 nmol/L (250 ng/dL) with concerning clinical features
- DHEAS >600 μg/dL with elevated testosterone 3, 2
Consider Rare Causes
In cases where common etiologies are excluded 4, 5:
- Isolated functional adrenal DHEAS hypersecretion (rare, confirmed by dexamethasone suppression) 5
- Transporter protein defects (extremely rare, associated with very high DHEAS without tumor) 4
- Medication effects: tamoxifen, raloxifene, or Op'DDD can elevate SHBG and alter testosterone interpretation 3
Algorithmic Approach Summary
- Obtain hormone panel (testosterone, LH, FSH, SHBG, free androgen index) 1
- Assess for clinical hyperandrogenism using age-appropriate criteria 1
- If testosterone >2× ULN: Check DHEAS level and consider imaging based on source 3
- If DHEAS extremely elevated (>600 μg/dL): Rule out non-classical CAH first, then consider adrenal imaging only with concerning features 1, 3
- If pattern suggests PCOS: Address metabolic factors and insulin resistance 1