What are the causes and management of elevated Dehydroepiandrosterone (DHEA) levels in a 50-year-old female patient?

Causes of Elevated DHEA in a 50-Year-Old Female

The most critical cause to rule out in a 50-year-old woman with elevated DHEA is an androgen-secreting adrenal tumor, which requires urgent imaging with adrenal CT to assess for malignancy, particularly if accompanied by virilization symptoms such as hirsutism, deepening voice, or menstrual changes. 1

Primary Pathological Causes

Adrenal Tumors (Most Important)

• Androgen-secreting adrenocortical tumors present in approximately 60% of cases with evidence of adrenal steroid hormone excess, with or without virilization 1
• In women, these tumors induce hirsutism, deepening of the voice, and oligo/amenorrhea 1
• Adrenocortical carcinomas show peak incidence in the fourth to fifth decades of life with a female-to-male ratio of 1.5:1 1
• Malignancy should be suspected if the tumor is larger than 4-5 cm, has irregular margins, is lipid-poor, does not wash out on contrast-enhanced CT, or secretes more than one hormone 1, 2
• Notably, pure testosterone-secreting adrenal adenomas can occur with normal DHEAS and androstenedione levels, making source identification challenging 3

Polycystic Ovary Syndrome (PCOS)

• PCOS involves acceleration of pulsatile gonadotropin-releasing hormone secretion and insulin resistance 4
• Clinical manifestations include infrequent menses, hirsutism, androgenetic alopecia, infertility, polycystic ovaries, and truncal obesity 4

Non-Classical Congenital Adrenal Hyperplasia

• Should be ruled out when DHEAS levels exceed age-specific thresholds (>2700 ng/ml for ages 30-39, >3800 ng/ml for ages 20-29) 4
• This represents an enzymatic defect in adrenal steroidogenesis 4

Diagnostic Algorithm

Step 1: Clinical Assessment

• Evaluate for hyperandrogenism signs: hirsutism (upper lip, armpit), acne, menstrual irregularities, androgenetic alopecia, clitoromegaly 4, 3
• Assess for Cushing syndrome features: weight gain, proximal muscle weakness, hypertension, psychiatric disturbances, centripetal obesity, purple striae, buffalo hump 1

Step 2: Laboratory Evaluation

• Obtain comprehensive hormone panel: free and total testosterone, DHEAS, androstenedione, LH, FSH 4
• Measure morning ACTH and cortisol to distinguish adrenal from pituitary sources 1
• Check electrolytes (sodium, potassium) to assess for concurrent aldosterone excess 1
• Consider 17-hydroxyprogesterone to evaluate for non-classical CAH 4

Step 3: Imaging Studies

• Adrenal CT scan is mandatory to evaluate for adrenal masses when DHEA elevation is confirmed 3
• Pelvic ultrasound to assess for polycystic ovaries in appropriate clinical context 4
• PET-CT may help distinguish benign from malignant lesions and exclude ectopic tumors 3

Management Approach

Surgical Management (First-Line for Tumors)

• Laparoscopic adrenalectomy is recommended for benign adrenal tumors when feasible 2
• Open adrenalectomy is preferred for suspected malignant tumors >4-5 cm with irregular margins or heterogeneous appearance 2
• Post-surgical testosterone levels should normalize, with resolution of clinical symptoms 3

Medical Management

• Ketoconazole (400-1200 mg/day) can inhibit adrenal steroidogenesis and reduce DHEA production for functional excess 2
• Requires regular monitoring of DHEA/DHEAS levels and liver function tests 2
• Monitor for signs of adrenal insufficiency with high-dose steroid suppression 2

Critical Pitfalls to Avoid

• Do not assume ovarian origin based solely on elevated testosterone with normal DHEAS and androstenedione—adrenal tumors can present this way 3
• Always image both adrenals and ovaries in postmenopausal women with virilization, even when androgen precursors appear normal 3
• Do not delay imaging in the presence of rapidly progressive virilization symptoms, as this suggests malignancy 1
• In this age group (50 years), physiologic DHEA decline is expected, making any elevation pathological and requiring investigation 5, 6