Is an estrogen level of hyperestrogenism a concern in a patient post left adrenalectomy, on progesterone and Dehydroepiandrosterone (DHEA)?

Elevated Estrogen After Adrenalectomy on DHEA and Progesterone

Yes, an estrogen level of 862 pg/mL is highly concerning and requires immediate evaluation and intervention. This level is approximately 25-30 times the upper limit of normal for postmenopausal women and raises serious concerns about thrombotic risk, endometrial hyperplasia, and potential malignancy 1, 2.

Immediate Clinical Concerns

Thrombotic Risk

• Estrogen levels this elevated significantly increase risk for venous thromboembolism and potentially arterial thrombosis 1
• This risk is amplified if additional factors are present: antiphospholipid antibodies, obesity, immobility, or prolonged sitting 1
• Monitor immediately for leg swelling, chest pain, shortness of breath, or neurologic symptoms 1

Endometrial Safety

• Unopposed estrogen at this level dramatically increases endometrial hyperplasia risk 3
• While progesterone provides some endometrial protection, the FDA label shows that even with progesterone 200 mg daily, 6% of women developed hyperplasia over 3 years with normal estrogen levels 3
• At estrogen levels of 862 pg/mL, progesterone may be insufficient to prevent endometrial pathology 1

Source Identification

DHEA Aromatization

• DHEA supplementation increases circulating androgens that can be aromatized to estrogens 1
• This is the most likely source given the medication regimen 1
• After adrenalectomy, the remaining adrenal gland typically produces reduced but measurable DHEA-S levels 4, 5

Exclude Malignancy

• Estrogen-secreting adrenocortical carcinomas, though rare, present with extremely elevated estrogen levels (818 pg/mL in one case report) and postmenopausal bleeding 2
• These tumors are almost pathognomonic of malignancy when feminization occurs with an adrenal mass 2
• The remaining adrenal gland requires imaging evaluation if not recently performed 2

Required Laboratory Workup

Measure the following to determine estrogen source and assess conversion:

• Estradiol AND estrone separately (not just total estrogen) to identify which is elevated 1
• Total and free testosterone to assess androgenic conversion from DHEA 1
• DHEA-S levels to confirm DHEA supplementation is the source 1
• FSH and LH to assess any residual ovarian function (though unlikely post-adrenalectomy) 1

Immediate Management Steps

Discontinue DHEA

• Stop DHEA supplementation immediately given the excessive estrogen elevation 1
• DHEA should be avoided when aromatization to estrogen poses risks 1

Imaging Evaluation

• Obtain transvaginal ultrasound to assess endometrial thickness 1
• If endometrial stripe >4-5 mm, endometrial biopsy is indicated 6
• Consider imaging of the remaining adrenal gland if not recently performed to exclude estrogen-secreting tumor 2

Recheck Hormone Levels

• Recheck estrogen levels 4-6 weeks after discontinuing DHEA 1
• If levels remain elevated despite stopping DHEA, this suggests an alternative source requiring further investigation 2, 4

Ongoing Monitoring Protocol

• Perform transvaginal ultrasound every 6-12 months while on any regimen containing DHEA (if restarted at lower dose) 1
• Monitor for thrombotic symptoms at each visit 1
• If DHEA is restarted, use the lowest effective dose and monitor estrogen levels closely 1

Common Pitfalls to Avoid

• Do not assume progesterone provides adequate endometrial protection at these estrogen levels - the FDA data showing 6% hyperplasia risk was with physiologic estrogen levels, not supraphysiologic 3
• Do not restart DHEA without confirming estrogen normalization - aromatization varies significantly between individuals 1, 7
• Do not ignore the possibility of an estrogen-secreting tumor - while rare, these present with exactly this clinical picture in post-adrenalectomy patients 2
• Do not delay imaging evaluation - endometrial pathology can develop rapidly with estrogen levels this elevated 6, 3