What is the workup for elevated Dehydroepiandrosterone sulfate (DHEA-S) levels?

From the Guidelines

The workup for elevated DHEA-S levels should begin with a thorough clinical evaluation, confirmation of the elevation with repeat testing, and a focused history and physical examination to identify signs/symptoms of adrenal hormone excess, as recommended by the most recent guidelines 1. The initial step is to rule out laboratory error by repeating the DHEA-S measurement. Next, obtain a complete history focusing on symptoms of androgen excess such as hirsutism, acne, or menstrual irregularities in women, and assess for medication use that could affect levels, particularly exogenous DHEA supplements. The initial laboratory evaluation should include morning cortisol, ACTH, 17-hydroxyprogesterone, androstenedione, testosterone, and sex hormone-binding globulin, as well as DHEA-S, to characterize glucocorticoid excess and sex steroids and steroid precursors excess 1. Imaging studies are essential, with adrenal CT scan (with contrast) being the primary modality to evaluate for adrenal tumors or hyperplasia, and non-contrast CT as first-line imaging to distinguish benign lesions from those which require further radiologic investigation 1. For women of reproductive age, a pelvic ultrasound may be indicated to assess for polycystic ovary syndrome. If an adrenal tumor is identified, surgical consultation is appropriate, and adrenalectomy should be considered for patients with unilateral cortisol-secreting adrenal masses and clinically apparent Cushing's syndrome, or for patients with unilateral aldosterone-secreting adrenal masses and pheochromocytomas 1. The significance of elevated DHEA-S lies in its role as an adrenal androgen precursor, with markedly elevated levels potentially indicating adrenal tumors (benign or malignant), while moderate elevations may suggest conditions like PCOS or non-classical congenital adrenal hyperplasia. Key points to consider in the workup include:

• Repeating the DHEA-S measurement to confirm the elevation
• Obtaining a complete history and physical examination to identify signs/symptoms of adrenal hormone excess
• Initial laboratory evaluation including morning cortisol, ACTH, 17-hydroxyprogesterone, androstenedione, testosterone, and sex hormone-binding globulin
• Imaging studies with adrenal CT scan (with contrast) as the primary modality
• Consideration of surgical consultation if an adrenal tumor is identified
• Adrenalectomy for patients with unilateral cortisol-secreting adrenal masses and clinically apparent Cushing's syndrome, or for patients with unilateral aldosterone-secreting adrenal masses and pheochromocytomas.

From the Research

Workup for Elevated DHEA-S Levels

The workup for elevated Dehydroepiandrosterone sulfate (DHEA-S) levels involves several steps to determine the underlying cause of the elevation. Some key points to consider include:

• Elevated DHEA-S levels can be associated with adrenal androgen-secreting neoplasms, but the sensitivity and positive predictive value of DHEA-S for diagnosing these neoplasms are low 2
• DHEA-S levels can also be elevated in women with polycystic ovary syndrome (PCOS) and other forms of hyperandrogenism 3
• An ACTH stimulation test can be used to evaluate adrenal steroidogenesis and help differentiate between various causes of elevated DHEA-S levels 4
• Measurements of other androgens, such as testosterone and androstenedione, may also be helpful in diagnosing hyperandrogenism 5

Diagnostic Tests

Some diagnostic tests that may be used in the workup for elevated DHEA-S levels include:

• Serum DHEA-S measurement
• ACTH stimulation test
• Measurement of other androgens, such as testosterone and androstenedione
• Imaging studies, such as adrenal computed tomography (CT) scan, to evaluate for adrenal tumors

Interpretation of Test Results

The interpretation of test results is crucial in determining the underlying cause of elevated DHEA-S levels. Some key points to consider include:

• Elevated DHEA-S levels in combination with other signs of hyperandrogenism, such as hirsutism and acne, may suggest a diagnosis of PCOS or other forms of hyperandrogenism 5
• An abnormal response to an ACTH stimulation test may suggest a defect in adrenal steroidogenesis, such as congenital adrenal hyperplasia 4
• Imaging studies may be used to evaluate for adrenal tumors or other abnormalities that may be causing elevated DHEA-S levels 2