Elevated DHEA/DHEAS Levels: Diagnosis and Evaluation

Primary Pathological Causes

The American College of Endocrinology recommends evaluating patients with DHEAS >16.3 μmol/L (6000 ng/ml) urgently for adrenal carcinomas using adrenal CT imaging 1, 2
Androgen-secreting adrenocortical carcinomas present in approximately 60% of cases with adrenal steroid hormone excess and virilization symptoms including hirsutism, voice deepening, and oligomenorrhea/amenorrhea in women 3, 2
Malignancy should be suspected when tumors are >4-5 cm, have irregular margins, are lipid-poor, fail to wash out on contrast-enhanced CT, or secrete multiple hormones 2
Peak incidence of androgen-secreting adrenocortical carcinomas occurs in the fourth to fifth decades with a female-to-male ratio of 1.5:1 3

The Endocrine Society recommends an initial hormone panel that must include free and total testosterone, DHEAS, androstenedione, LH, and FSH 1, 4
Measure morning ACTH and cortisol to distinguish adrenal from pituitary sources 2
Check 17-hydroxyprogesterone to screen for non-classical congenital adrenal hyperplasia 1
Obtain adrenal CT scan when 21-hydroxylase antibodies are negative or when DHEAS >6000 ng/ml to evaluate for adrenal tumors 1, 2
Perform transvaginal ultrasound to assess for polycystic ovaries in females with suspected PCOS 1

Do not delay imaging when rapidly progressive virilization symptoms are present, as this strongly suggests malignancy 2
Non-classical congenital adrenal hyperplasia must be ruled out first, particularly when DHEAS exceeds age-specific thresholds: >3800 ng/ml for ages 20-29 or >2700 ng/ml for ages 30-39 1, 4
Adrenoleukodystrophy in males can cause very high DHEAS without tumor; measure very long-chain fatty acids in serum when suspected 1