What is elevated DHEA-s (Dehydroepiandrosterone sulfate) called?

Elevated DHEA-S: Terminology and Clinical Significance

Elevated DHEA-S (dehydroepiandrosterone sulfate) is called hyperandrogenism or adrenal androgen excess when it occurs in the context of androgen excess disorders. 1, 2

Clinical Context and Terminology

Elevated DHEA-S does not have a single universally accepted term, as the nomenclature depends on the clinical context:

In Polycystic Ovary Syndrome (PCOS)

• When DHEA-S is elevated in women with PCOS, it is referred to as adrenal hyperandrogenism or adrenal androgen excess 1, 3, 4
• This occurs in approximately 33-40% of women with PCOS, though prevalence varies by phenotype 1, 3, 4
• DHEA-S elevation in PCOS represents one component of the broader biochemical hyperandrogenism that characterizes the syndrome 1

In Adrenal Pathology

• Markedly elevated DHEA-S (>600 mg/dL or age-adjusted thresholds) suggests androgen-secreting adrenal cortical adenoma or adrenocortical carcinoma (ACC) 1, 5
• Age-specific thresholds for concern include: >3800 ng/mL in women aged 20-29 years and >2700 ng/mL in women aged 30-39 years 1

In Congenital Adrenal Hyperplasia

• Elevated DHEA-S in the context of non-classical congenital adrenal hyperplasia (NCAH) is part of the adrenal hyperandrogenism pattern 1, 3
• NCAH is characterized by predominant adrenal androgen secretion, with 70-80% of patients showing androgen excess from multiple sources 3

Diagnostic Approach to Elevated DHEA-S

Initial Assessment

• Evaluate for clinical signs of androgen excess: hirsutism, acne, male-pattern baldness, menstrual irregularities, and virilization signs (clitoromegaly, voice deepening, increased muscle mass) 2
• Assess for features of other endocrine disorders including truncal obesity, hypertension, and glucose intolerance 2

Degree of Elevation Matters

• Moderate elevations are most commonly associated with PCOS (affecting 4-6% of women) or NCAH 1, 2
• Marked elevations (>600 mg/dL or twice the upper limit of normal) warrant imaging to exclude adrenal tumors 1, 5

Imaging and Further Testing

• Obtain adrenal CT or MRI to exclude adrenal tumor when DHEA-S is markedly elevated 2
• Perform pelvic ultrasound in women to evaluate for ovarian pathology 2
• Clinical diagnosis based on menstrual irregularity, hirsutism, acne, and obesity is often sufficient for moderate elevations with PCOS features 2

Diagnostic Accuracy Considerations

• DHEA-S has moderate diagnostic accuracy for PCOS with pooled sensitivity and specificity around 70-75% 1, 2
• DHEA-S is considered a second-line diagnostic marker for PCOS, with total testosterone and free testosterone being first-line tests 1
• The 2023 International PCOS Guidelines recommend considering A4 and DHEA-S only when first-line androgen tests are negative but clinical suspicion remains high, due to poorer specificity 1

Common Pitfalls

• Age-related variation: DHEA-S levels peak at approximately age 25 years and decline progressively thereafter, decreasing by 95% by age 85 6
• Low positive predictive value: Despite high specificity (98%), the positive predictive value of elevated DHEA-S for androgen-secreting neoplasms is only around 9% due to the rarity of these tumors 7
• Multiple sources: In hyperandrogenic disorders, androgen secretion from more than one source is common—occurring in 70-80% of NCAH patients, 35% of PCOS patients, and 50% of idiopathic hyperandrogenism patients 3