What is Dehydroepiandrosterone (DHEA) and how to manage elevated levels?

Understanding DHEA and Management of Elevated Levels

DHEA (dehydroepiandrosterone) is a steroid hormone produced primarily by the adrenal glands that serves as a precursor to sex hormones, and elevated levels should be investigated for underlying causes with management focused on treating the root condition rather than the DHEA level itself.

What is DHEA?

• DHEA (dehydroepiandrosterone) is the most abundant circulating steroid hormone in humans, primarily secreted by the zona reticularis of the adrenal cortex 1
• It functions as an important prohormone that can be converted into androgens and estrogens in peripheral target tissues through a process called "intracrinology" 2
• DHEA exists in two forms: free DHEA and DHEAS (DHEA sulfate), with DHEAS being the sulfated storage form that circulates at higher concentrations 3
• DHEA secretion follows a characteristic age-related pattern, peaking in early adulthood and then declining at approximately 2% per year, reaching only 10-20% of young adult levels by age 70-80 1, 4

Physiological Roles of DHEA

• DHEA serves as an indirect precursor to testosterone and estrogen, with all enzymes required for this transformation expressed in target tissues 2
• In women, especially after menopause, DHEA is a significant source for local production of sex hormones that affect bone formation, adiposity, muscle, insulin metabolism, skin health, and libido 2, 4
• In men, DHEA contributes approximately 50% of androgens in certain tissues such as the prostate 2
• DHEA has immunomodulatory effects, influencing the number of monocytes, T cells, and natural killer cells 3

Causes of Elevated DHEA Levels

• Adrenal hyperplasia or tumors (benign or malignant) 5
• Adrenal carcinoma (should be suspected particularly when associated with virilization) 5
• Polycystic ovary syndrome (PCOS)
• Congenital adrenal hyperplasia
• Cushing's syndrome (may be associated with elevated adrenal androgens) 5

Evaluation of Elevated DHEA

• Comprehensive hormonal assessment including:
  • DHEAS levels (the sulfated form, which is more stable for measurement) 5
  • Other androgens: testosterone, androstenedione 5
  • In cases of suspected adrenocortical carcinoma: 17β-estradiol, 17-OH progesterone, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 5
• Imaging studies:
  • CT or MRI of adrenal glands to evaluate for adrenal masses 5
  • For suspected malignancy: chest, abdomen, and pelvis imaging to evaluate for metastases 5

Management of Elevated DHEA

1. Identify and treat the underlying cause:

   • For adrenal tumors secreting excess androgens, surgical removal is typically recommended 5
   • For adrenocortical carcinoma, surgical resection is the primary treatment 5

2. For functional adrenal lesions with androgen excess:

   • Unilateral adrenalectomy (preferably laparoscopic when feasible) for unilateral adenomas 5
   • Medical management may be considered for bilateral disease or non-surgical candidates 5

3. Monitoring:

   • Regular follow-up with repeat hormonal assessments to evaluate treatment efficacy
   • For patients with adrenal tumors, follow-up imaging according to guidelines for adrenal incidentalomas 5

Special Considerations

• Differential diagnosis: Elevated DHEA should be distinguished from other causes of hyperandrogenism, such as Cushing's syndrome, which may present with similar clinical features 5
• Malignancy risk: Adrenal carcinoma should be strongly suspected in cases of rapidly progressive virilization or when imaging shows irregular margins, heterogeneity, or size >4-5 cm 5
• Gender-specific effects: The clinical manifestations of elevated DHEA may differ between men and women, with women more likely to exhibit signs of androgen excess (hirsutism, acne, menstrual irregularities) 6

Pitfalls to Avoid

• Do not treat the elevated DHEA level in isolation without identifying the underlying cause
• Avoid attributing non-specific symptoms solely to DHEA elevation without comprehensive evaluation
• Be cautious about supplemental DHEA use in patients with already elevated levels, as this could exacerbate hormonal imbalances 3
• Remember that DHEA can have both androgenic and estrogenic effects depending on the hormonal milieu, which may complicate clinical presentation 6