Elevated DHEA Sulfate Levels: Causes and Diagnostic Approach

Primary Causes

• Non-classical congenital adrenal hyperplasia should be ruled out in patients with elevated DHEAS, particularly when levels exceed age-specific thresholds (>3800 ng/ml for ages 20-29, >2700 ng/ml for ages 30-39) 1, 2
• The pathogenesis of polycystic ovary syndrome (PCOS) involves acceleration of pulsatile gonadotropin-releasing hormone secretion, insulin resistance, and downstream metabolic dysregulation 1

Diagnostic Approach

Initial Evaluation

• Assess for clinical signs of hyperandrogenism: hirsutism, acne, menstrual irregularities, androgenetic alopecia, infertility 3, 4
• In prepubertal children, look for early-onset body odor, axillary or pubic hair, accelerated growth, advanced bone age, and genital maturation 4
• In postpubertal females, evaluate for infrequent menses, hirsutism, androgenetic alopecia, infertility, polycystic ovaries, clitoromegaly, and truncal obesity 4

Laboratory Testing

• A typical hormone-screening panel should include free and total testosterone, DHEAS, androstenedione, luteinizing hormone, and follicle-stimulating hormone 4
• Consider additional testing for growth hormone, insulin-like growth factor, lipid levels, insulin, sex hormone binding globulin, free androgen index, prolactin, estrogen, and progesterone in selected cases 4
• Rule out non-classical congenital adrenal hyperplasia with appropriate testing 1, 5

Imaging Studies

• Pelvic ultrasound may be indicated to evaluate for polycystic ovaries in females 1, 4

Clinical Implications

• Identifying the underlying cause of elevated DHEAS is important for appropriate management and treatment of associated conditions 1, 5
• The American Academy of Dermatology recommends assessing for clinical signs of hyperandrogenism in patients with elevated DHEAS levels 3, 4

Differential Diagnoses for Elevated DHEA/DHEAS

Initial Clinical Assessment and Diagnostic Approach

• The National Comprehensive Cancer Network recommends initial hormone panel should include androstenedione, LH, and FSH for evaluating elevated DHEA/DHEAS 6
• The American College of Internal Medicine suggests adrenal CT scan when 21-hydroxylase antibodies negative for diagnosing adrenal tumors 7, 8
• The Endocrine Society recommends 2-day dexamethasone suppression test to distinguish functional from neoplastic causes of hyperandrogenism 6

Diagnostic Criteria for Specific Conditions

• The American College of Internal Medicine states that adrenoleukodystrophy in males can cause very high DHEAS without tumor, and recommends measuring very long-chain fatty acids in serum 7, 8
• The National Comprehensive Cancer Network recommends evaluating patients with DHEAS >16.3 μmol/L (6000 ng/ml) for androgen-secreting adrenal carcinomas, which may present with hirsutism, voice deepening, oligomenorrhea/amenorrhea in women 6

Laboratory Evaluation and Imaging Studies

• The American College of Internal Medicine suggests that initial hormone panel should include free and total testosterone, DHEAS, androstenedione, LH, and FSH for evaluating elevated DHEA/DHEAS 6
• The National Comprehensive Cancer Network recommends additional testing, including 17-hydroxyprogesterone, sex hormone binding globulin, prolactin, estrogen, progesterone, insulin, lipid levels, and IGF-1, in selected cases 6
• The American College of Internal Medicine recommends adrenal CT scan when 21-hydroxylase antibodies negative, and transvaginal ultrasound for polycystic ovaries in females 7, 8