What additional tests and evaluations are recommended for elevated Dehydroepiandrosterone (DHEA) and cortisol levels?

Workup for Elevated DHEA and Cortisol

When both DHEA and cortisol are elevated, you must immediately evaluate for adrenocortical carcinoma (ACC) and complete a comprehensive hormonal and imaging workup to exclude malignancy and assess for other hormone excess syndromes.

Essential Additional Testing

Hormonal Evaluation

Complete the glucocorticoid excess workup with the following tests (minimum 3 of 4) 1:

• Dexamethasone suppression test (1 mg at 23:00 h) - cortisol >138 nmol/L indicates autonomous hypersecretion 1
• 24-hour urinary free cortisol 1
• Basal ACTH (plasma) - to distinguish ACTH-independent from ACTH-dependent causes 1
• Midnight salivary cortisol - if dexamethasone suppression test shows 51-138 nmol/L 1

Expand the steroid precursor panel beyond DHEA to assess for ACC 1:

• 17-OH-progesterone (serum) 1
• Androstenedione (serum) 1
• Testosterone (serum) 1
• 17-beta-estradiol (in men and postmenopausal women) 1
• 24-hour urine steroid metabolite examination 1

The combination of elevated DHEA and cortisol is particularly concerning for ACC, as this malignancy frequently produces multiple steroids simultaneously 1.

Mineralocorticoid Assessment

Screen for mineralocorticoid excess if hypertension or hypokalemia is present 1:

• Serum potassium 1
• Aldosterone/renin ratio - a ratio >20 ng/dL per ng/mL/hr has >90% sensitivity and specificity for hyperaldosteronism 1

Malignancy should be suspected if the tumor secretes more than one hormone 1.

Catecholamine Evaluation

Exclude pheochromocytoma with 1:

• Plasma free metanephrines (normetanephrine, metanephrine, and methoxytyramine) 1
• Alternatively: 24-hour urine fractionated metanephrines 1

This is critical because pheochromocytoma can coexist with adrenal cortical tumors, and missing this diagnosis can be life-threatening during surgery 1.

Imaging Studies

Obtain CT or MRI of abdomen immediately 1:

• CT is first-line - less expensive and equally effective 1
• Measure Hounsfield units on unenhanced CT - benign adenomas typically show <10 HU 1
• Assess for rapid washout on 15-minute delayed contrast-enhanced CT 1

Features suggesting malignancy include 1:

• Size >5 cm 1
• Irregular morphology 1
• Lipid-poor appearance 1
• Hounsfield units >10 1
• Poor contrast washout 1
• Local invasion or irregular margins 1

Complete staging workup if ACC is suspected 1:

• CT thorax - to evaluate for metastases 1
• Bone scintigraphy - when skeletal metastases are suspected 1
• FDG-PET - optional but helpful for staging 1

Critical Clinical Context

The simultaneous elevation of both DHEA and cortisol is particularly worrisome because 1:

• ACC is responsible for more than half of androgen hypersecretion cases 1
• ACC frequently produces multiple steroids, creating a pattern of "immature, early-stage steroidogenesis" 1
• The incidence of ACC in adrenal incidentalomas is approximately 2% 1

Important caveat: While DHEA can have an "anticortisol effect" in some contexts 2, 3, elevated levels of both hormones together do not indicate a protective mechanism but rather suggest autonomous adrenal steroid production 4, 5.

Immediate Next Steps

Refer to endocrinology and surgical oncology for multidisciplinary evaluation if imaging shows 1:

• Any mass with concerning features for malignancy
• Evidence of hormone hypersecretion
• Tumor growth on follow-up imaging

The preoperative hormone pattern serves as a "fingerprint" for tumor surveillance during follow-up 1.