What is the best course of action for a patient with elevated Dehydroepiandrosterone sulfate (DHEA-S) levels, a history of Hashimoto's thyroiditis and hypothyroidism, and a previous hysterectomy?

Elevated DHEA-S in a Young Woman with Hashimoto's Thyroiditis and Prior Hysterectomy

The elevated DHEA-S level of 332 µg/dL requires investigation for androgen excess disorders, particularly polycystic ovary syndrome (PCOS), non-classic congenital adrenal hyperplasia, or androgen-secreting tumors, rather than treatment with DHEA supplementation. This patient's clinical context does not indicate DHEA deficiency requiring replacement therapy.

Understanding the Clinical Context

The provided evidence focuses primarily on DHEA deficiency and replacement therapy in primary adrenal insufficiency (PAI), not elevated DHEA-S levels 1. This distinction is critical:

• DHEA replacement is indicated only for women with PAI who have severe androgen deficiency, typically manifesting as persistent lack of libido and/or low energy despite optimized glucocorticoid and mineralocorticoid replacement 1
• The target for DHEA therapy is to maintain DHEAS levels in the normal range, not to address elevated levels 1
• Your patient has elevated DHEA-S, which represents the opposite clinical scenario

Hashimoto's Thyroiditis and DHEA-S Relationship

Interestingly, research demonstrates an inverse relationship between DHEA-S levels and thyroid autoimmunity:

• Women with Hashimoto's thyroiditis and premature ovarian failure show lower DHEA-S levels compared to those without thyroid autoimmunity (1.2 µg/ml vs. 1.9 µg/ml) 2
• DHEA-S correlates inversely with both thyroglobulin antibodies (r = -0.426) and thyroperoxidase autoantibodies (r = -0.362) 2
• This suggests that elevated DHEA-S in your patient is unlikely to be related to her Hashimoto's thyroiditis and points toward an alternative androgen excess disorder 2

Recommended Diagnostic Workup

Evaluate for causes of androgen excess systematically:

• Measure total and free testosterone, androstenedione, and 17-hydroxyprogesterone to characterize the androgen excess pattern and assess for non-classic congenital adrenal hyperplasia
• Obtain early morning cortisol and ACTH to evaluate for adrenal tumors or Cushing syndrome, particularly if the patient has clinical features of hypercortisolism 1
• Perform pelvic ultrasound to assess for ovarian pathology, though note she has had a hysterectomy (clarify if ovaries were preserved)
• Consider adrenal imaging (CT or MRI) if DHEA-S remains significantly elevated or if other adrenal hormones are abnormal, as adrenal tumors can produce excess androgens 1

Management Approach

Do not initiate DHEA supplementation in this patient, as:

• She has elevated, not deficient, DHEA-S levels
• DHEA supplementation is only indicated for women with PAI and documented androgen deficiency with specific symptoms 1
• Adding exogenous DHEA would worsen her androgen excess state

Ensure optimal thyroid hormone replacement:

• Verify TSH and free T4 levels are within target range for her age 3, 4
• Inadequately treated hypothyroidism can affect multiple endocrine axes 3
• Standard levothyroxine dosing aims for TSH within the reference range 4

Important Clinical Pitfall

A critical historical observation: hyperparathyroidism can be unmasked by treatment of hypothyroidism in patients with Hashimoto's thyroiditis 5. While not directly related to DHEA-S elevation, this underscores the importance of:

• Checking calcium, phosphorus, and PTH levels in patients with Hashimoto's thyroiditis, particularly when initiating or adjusting thyroid hormone replacement 5
• Monitoring for development of other endocrine abnormalities in this population 5

Post-Hysterectomy Considerations

The patient's hysterectomy status is relevant because:

• If ovaries were removed, she lacks ovarian androgen production, making adrenal sources more likely for the elevated DHEA-S
• If ovaries were preserved, both ovarian and adrenal sources must be considered
• Clarify the surgical details (total hysterectomy with bilateral salpingo-oophorectomy vs. hysterectomy with ovarian preservation) to guide the differential diagnosis