When is Dehydroepiandrosterone (DHEA) typically checked in patients?

When DHEA is Checked in Clinical Practice

DHEA (dehydroepiandrosterone) and DHEA-S (DHEA sulfate) are checked primarily to evaluate adrenal androgen excess in women with signs of virilization or hirsutism, to diagnose polycystic ovary syndrome (PCOS), to assess for adrenocortical carcinoma when adrenal masses are present, and to monitor adrenal androgen deficiency in patients with adrenal insufficiency. 1, 2, 3

Primary Indications for DHEA/DHEA-S Testing

Suspected Androgen Excess and Virilization

• DHEA-S should be measured when clinical signs of virilization are present, including deepening voice, increased muscle mass, rapid progression of androgenic symptoms, hirsutism, androgenetic alopecia, acne, male-pattern baldness, menstrual irregularities, or clitoromegaly in women. 1, 2
• In children, testing is indicated for early-onset body odor, premature axillary or pubic hair, accelerated growth velocity, advanced bone age, and genital maturation. 2
• DHEA-S represents the most reliable measure of adrenal androgen production and is the preferred marker for adrenal-origin androgen excess. 3

Evaluation of Adrenal Incidentalomas

• All patients with suspected adrenocortical carcinoma (ACC) should have DHEA-S testing, as ACC is responsible for more than half of androgen hypersecretion cases. 1, 3
• When ACC is suspected or virilization is present, an extended androgen panel should include DHEA-S, testosterone, 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol. 1, 3
• Higher DHEA-S levels suggest greater disease burden, particularly in adrenocortical carcinoma. 3

Diagnosis of Polycystic Ovary Syndrome (PCOS)

• DHEA-S has a pooled sensitivity of 0.75 and specificity of 0.57 for diagnosing PCOS, with an area under the curve (AUC) of 0.77 when using appropriate diagnostic thresholds. 1
• DHEA-S should be included in the initial hormone panel along with free and total testosterone, LH, FSH, sex hormone binding globulin, and free androgen index when evaluating suspected PCOS. 1, 2
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays provide superior diagnostic accuracy compared to direct immunoassays for DHEA-S measurement. 1

Assessment of Adrenal Insufficiency

• In primary adrenal insufficiency, patients become deficient in all adrenal androgen secretion, particularly affecting female patients who lack gonadal androgen production. 3
• DHEA-S, androstenedione, and testosterone levels should be measured in the morning prior to DHEA ingestion to assess for deficiency. 3
• Testing guides DHEA replacement therapy (10-50 mg, typically 25 mg daily) in female patients with persistent lack of libido or low energy despite optimized glucocorticoid and mineralocorticoid replacement. 3

Erectile Dysfunction and Cardiovascular Risk Assessment

• Testosterone levels should be measured in all men with organic erectile dysfunction, especially those for whom PDE5 inhibitor therapy failed, though DHEA-S is not routinely part of this initial evaluation. 1
• This recommendation differs from some guidelines but is based on evidence linking low testosterone to both erectile dysfunction and cardiovascular disease. 1

Diagnostic Workup Algorithm

Initial Evaluation

• Measure DHEA-S when any of the following are present: signs of virilization, rapid progression of androgenic symptoms, suspected PCOS, adrenal mass on imaging, or suspected adrenal insufficiency. 1, 2, 3
• Obtain morning blood samples for optimal accuracy, as DHEA-S levels can vary throughout the day. 3

Interpretation of Results

• Very high DHEA-S levels (>700 μg/dL) warrant immediate adrenal imaging with CT or MRI to evaluate for adrenocortical carcinoma. 1, 2
• Moderately elevated DHEA-S in reproductive-age women suggests PCOS, particularly when accompanied by menstrual irregularities and clinical hyperandrogenism. 1, 2
• Low or undetectable DHEA-S in the context of fatigue and other symptoms of adrenal insufficiency confirms adrenal androgen deficiency. 3

Follow-Up Testing

• Repeat DHEA-S measurements every 3-6 months until normalized or stable when initial elevation is detected. 2
• Monitor clinical symptoms of androgen excess and assess for treatment response in patients receiving therapy. 2
• Long-term follow-up for persistent elevations is essential to detect evolving pathology, particularly when initial workup was negative for tumors. 2

Common Pitfalls to Avoid

• Do not rely on direct immunoassays alone for DHEA-S measurement in critical diagnostic situations; LC-MS/MS provides superior accuracy and should be used when available, particularly for PCOS diagnosis. 1
• Do not assume normal DHEA-S excludes adrenal pathology; some adrenal adenomas and early ACC may not significantly elevate DHEA-S initially. 1
• Do not check DHEA-S in isolation; always obtain a comprehensive androgen panel including testosterone, androstenedione, and 17-OH progesterone for complete evaluation of androgen excess. 1, 2, 3
• In women with suspected PCOS, ensure potassium repletion and medication review before testing, as these factors can affect results. 1