High DHEA Sulphate: Clinical Implications and Management
Elevated DHEA sulphate (DHEAS) requires systematic evaluation to distinguish physiological variation from pathological androgen excess, with the primary focus on identifying adrenal tumors, virilization syndromes, and conditions requiring endocrine intervention.
Initial Assessment and Diagnostic Approach
Evaluate for clinical signs of hyperandrogenism and virilization as the critical first step. Patients presenting with hirsutism, oligomenorrhea, androgenic alopecia, infertility, clitoromegaly, or truncal obesity warrant comprehensive endocrine testing 1. These clinical features distinguish pathological androgen excess from benign elevations.
Key Laboratory Evaluation
When DHEAS is elevated, obtain a complete androgen panel including 1, 2:
- Total and free testosterone
- Androstenedione
- 17-hydroxyprogesterone (to evaluate for nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency)
- Luteinizing hormone and follicle-stimulating hormone
DHEAS represents the most reliable measure of adrenal androgen production and should be measured in the morning for accurate assessment 2.
Threshold for Adrenal Imaging
Markedly elevated DHEAS levels (typically >700 mcg/dL, though specific thresholds vary by laboratory) warrant adrenal imaging to exclude adrenocortical carcinoma 2, 3. An extended panel for suspected adrenocortical carcinoma should include 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 2. Higher androgen levels suggest greater disease burden, particularly in adrenocortical carcinoma where androgen hypersecretion occurs in more than half of cases 2.
Context-Specific Considerations
Patients on Hormone Therapy
In patients receiving exogenous testosterone or estradiol, elevated DHEA is generally expected and not pathologic unless accompanied by virilization signs 3. Estradiol administration can modulate steroidogenic enzyme expression, potentially enhancing conversion pathways that generate DHEA 3.
No intervention is required if DHEA elevation is proportional to testosterone dosing and the patient lacks virilization symptoms 3. However, adjust testosterone pellet dosing if DHEA or testosterone levels are excessively elevated 3.
Acne Patients
Routine endocrinologic testing is not indicated for most patients with acne 1. However, patients with acne plus clinical signs of hyperandrogenism (hirsutism, oligomenorrhea, androgenic alopecia) should undergo testing for serum total and/or free testosterone, DHEAS, luteinizing hormone, and follicle-stimulating hormone 1.
Polycystic ovarian syndrome is a common cause of hyperandrogenism in this population, characterized by ovulatory dysfunction or polycystic ovaries on ultrasonography 1. Patients with abnormal endocrine testing or persistent concern for underlying endocrine disorder should be evaluated by an endocrinologist 1.
Hyperprolactinemia Connection
Elevated prolactin levels can directly increase plasma DHEA and DHEAS levels 4. This increase has been observed in both women and men with prolactinomas or those on chronic psychotropic drug treatment, suggesting prolactin has a direct effect on the adrenal cortex 4. Consider measuring prolactin levels when DHEAS is elevated without clear explanation.
Red Flags Requiring Urgent Evaluation
Immediate further workup is indicated for 2, 3:
- Clinical signs of virilization (clitoromegaly, voice deepening, male-pattern baldness)
- DHEAS levels markedly above normal range (typically >700 mcg/dL)
- Rapid onset of symptoms
- Irregular menses or breakthrough bleeding in women on hormone therapy
Management Based on Etiology
Adrenal Tumors
If adrenal imaging reveals a mass, surgical consultation is required. Adrenocortical carcinoma requires aggressive management given its association with androgen hypersecretion in more than half of cases 2.
Functional Hyperandrogenism
For patients with polycystic ovarian syndrome or other functional causes 1:
- Combined oral contraceptives are first-line for women
- Spironolactone for persistent hyperandrogenism
- Topical retinoids for associated acne
Physiological Elevation
In the absence of virilization or pathological findings, mildly elevated DHEAS in healthy adults does not require intervention 5, 6. DHEA/DHEAS levels naturally decline with age, and supplementation studies have shown mixed results regarding clinical benefits 5, 7, 6.
Common Pitfalls to Avoid
- Do not order routine DHEAS testing without clinical indication - it should be reserved for patients with signs of hyperandrogenism 1
- Do not ignore markedly elevated levels - failure to image the adrenals when DHEAS is significantly elevated can delay diagnosis of adrenocortical carcinoma 2
- Do not assume all elevations in hormone therapy patients are benign - virilization signs always warrant dose adjustment or further evaluation 3
- Ensure morning sampling - DHEAS should be measured in the morning for accurate assessment 2