What to do if Dehydroepiandrosterone sulfate (DHEA-S) levels are abnormal?

Management of Abnormal DHEA-S Levels

The approach to abnormal DHEA-S depends critically on whether levels are elevated or low, with elevated levels requiring systematic evaluation for androgen excess and potential neoplasms, while low levels primarily occur in primary adrenal insufficiency requiring replacement therapy. 1

Elevated DHEA-S Levels

Initial Clinical Assessment

• Assess for signs of androgen excess including hirsutism, acne, male-pattern baldness, menstrual irregularities, and signs of virilization (clitoromegaly, voice deepening, increased muscle mass). 1
• Evaluate for features of other endocrine disorders such as truncal obesity, hypertension, and glucose intolerance. 1

Determining the Degree of Elevation

The magnitude of DHEA-S elevation guides the diagnostic approach:

• DHEA-S >600 mg/dL (>16.3 µmol/L) raises concern for androgen-secreting adrenal cortical adenoma and warrants imaging. 2
• Very high DHEA-S levels (>6000 ng/mL) historically suggested adrenal tumors, though specificity is only 98% with a low positive predictive value of approximately 9%. 3
• Moderate elevations are most commonly associated with PCOS (affecting 4-6% of women) or non-classical congenital adrenal hyperplasia. 1

Diagnostic Workup

For markedly elevated DHEA-S or rapid symptom progression:

• Obtain adrenal CT or MRI to exclude adrenal tumor. 1
• Perform pelvic ultrasound in women to evaluate for ovarian pathology. 1
• Consider total testosterone measurement; if testosterone is twice the upper limit of normal, this further supports the need for imaging. 2

For moderate elevations with PCOS features:

• Clinical diagnosis based on menstrual irregularity, hirsutism, acne, and obesity is often sufficient. 1
• DHEA-S has moderate diagnostic accuracy for PCOS with pooled sensitivity and specificity around 70-75%. 4

Management Based on Etiology

For PCOS-related elevation:

• Weight loss is first-line for overweight or obese patients. 1
• Hormonal contraceptives regulate menstrual cycles and reduce androgen effects. 1
• Metformin or other insulin-sensitizing agents if insulin resistance is present. 1
• Anti-androgen therapy (spironolactone) for persistent hirsutism or acne. 1

For adrenal or ovarian tumors:

• Surgical resection is indicated. 2, 3

Monitoring

• Repeat DHEA-S measurements every 3-6 months until normalized or stable. 1
• Monitor clinical symptoms of androgen excess and assess treatment response. 1
• Long-term follow-up for persistent elevations to detect evolving pathology. 1

Low DHEA-S Levels

Primary Context: Adrenal Insufficiency

Low DHEA-S is a characteristic finding in primary adrenal insufficiency (PAI), along with low cortisol, elevated ACTH, and low aldosterone. 4

DHEA Replacement Therapy

DHEA replacement should be considered specifically in women with PAI who have persistent symptoms despite optimized glucocorticoid and mineralocorticoid replacement:

• Offer a 6-month trial of oral DHEA (10-50 mg, typically 25 mg daily) to women with persistent lack of libido and/or low energy levels. 4
• Dose guided by morning serum DHEA-S, androstenedione, and testosterone levels, which should be maintained in the normal range measured prior to DHEA ingestion. 4
• Continue therapy only if clinically effective after the 6-month trial. 4
• Use with caution as long-term effects are not fully established, with only limited objective evidence of clinical benefit from large studies. 4

Additional Considerations for Low DHEA-S

• In elderly patients, DHEA supplementation may improve physical and psychological well-being, muscle strength, bone density, and immune function, though evidence remains mixed. 5
• Low DHEA-S can accompany adrenal suppression from exogenous corticosteroid use and could potentially screen for steroid side effects. 5

Special Populations

Premature Adrenarche

• Regular monitoring without specific treatment is recommended, with follow-up every 6-12 months to monitor growth velocity, bone age, and pubertal development. 6
• Evaluate further if signs of true central puberty develop. 6

Pregnancy in PAI

• DHEA-S monitoring is less critical than adjusting glucocorticoid and mineralocorticoid doses during pregnancy. 4