Treatment of Elevated DHEA-S Levels
Surgical removal via adrenalectomy is the primary treatment for elevated DHEA-S caused by adrenal neoplasms, while medical management with adrenostatic agents like ketoconazole can be considered for functional DHEA excess. 1
Initial Diagnostic Workup
The first priority is determining the underlying cause of elevated DHEA-S:
Evaluate for adrenocortical carcinoma (ACC) or androgen-secreting tumors, particularly when DHEA-S elevation is accompanied by clinical virilization (rapid onset of male-pattern hair growth, voice deepening, clitoromegaly, or temporal balding). 2
Obtain imaging studies to identify adrenal masses—ultrasound initially, followed by CT or MRI if a mass is suspected. 1
Measure serum androgens including total and free testosterone, as 82% of hyperandrogenic women will have either elevated DHEA-S or elevated unbound testosterone. 3
Consider dexamethasone suppression testing (0.5 mg nightly) to assess whether DHEA-S production is suppressible, which helps distinguish functional excess from autonomous tumor production. 3
Surgical Management (First-Line for Neoplasms)
Laparoscopic adrenalectomy is recommended for benign-appearing adrenal tumors causing androgen excess when the mass is ≤4-5 cm with regular margins and homogeneous appearance. 1
Open adrenalectomy is preferred for suspected malignant tumors indicated by size >4-5 cm, irregular margins, or heterogeneous appearance on imaging. 1
Unilateral adrenalectomy should be performed using minimally-invasive techniques when feasible for adrenal masses causing androgen excess. 2
Medical Management (For Functional Excess)
When surgical intervention is not indicated or appropriate:
Ketoconazole at doses of 400-1200 mg/day can inhibit adrenal steroidogenesis and reduce DHEA production in cases of functional DHEA excess. 1
Monitor liver function tests regularly in patients receiving ketoconazole due to hepatotoxicity risk. 1
Assess for signs of adrenal insufficiency with high-dose steroid suppression therapy, as excessive suppression can lead to cortisol deficiency. 1
Follow DHEA/DHEAS levels serially to assess treatment efficacy and adjust dosing accordingly. 1
Important Clinical Caveats
The positive predictive value of markedly elevated testosterone (>250 ng/dL or 8.7 nmol/L) for detecting neoplasms is only 9%, meaning most elevations are not tumor-related, though the negative predictive value is 100%. 4
DHEA-S levels >6000 ng/mL (16.3 μmol/L) warrant aggressive investigation for adrenocortical tumors, though false positives occur. 4
Rare genetic variants in steroid sulfatase (STS) or transporter proteins (BCRP) can cause very high DHEA-S without tumor presence, though this is exceptionally uncommon. 5
In postmenopausal women with rapid virilization and very high DHEA-S, ovarian hilar cell tumors should be considered alongside adrenal sources. 4