What are the management and treatment options for a patient with a history of unilateral adrenalectomy (removal of one adrenal gland) due to hyperfunctioning, presenting with elevated estrogen levels and potential hormonal imbalances?

Management of Post-Unilateral Adrenalectomy Patient with Elevated Estrogen

After unilateral adrenalectomy for a hyperfunctioning adrenal gland, the remaining adrenal gland typically compensates adequately, but you must immediately screen for adrenal insufficiency and assess whether the elevated estrogen represents residual disease, contralateral pathology, or a new hormonal syndrome requiring intervention. 1

Immediate Assessment for Adrenal Insufficiency

The contralateral adrenal gland may have been suppressed by the hyperfunctioning gland and requires time to recover hypothalamus-pituitary-adrenal (HPA) axis function. 2

Critical screening tests include:

• Morning (8 AM) cortisol and ACTH levels to assess for secondary adrenal insufficiency 2
• Serum electrolytes (sodium, potassium) to detect hyponatremia or hyperkalemia suggesting mineralocorticoid deficiency 2
• Standard-dose ACTH stimulation test if morning cortisol is indeterminate (between 3-15 μg/dL) 2

If adrenal insufficiency is confirmed:

• Initiate hydrocortisone 15-20 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon) 2, 1
• Add fludrocortisone 50-200 μg daily if mineralocorticoid deficiency is present 1
• Provide immediate education on stress dosing (double or triple dose during illness), emergency injectable hydrocortisone, and medical alert identification 2, 3
• Arrange endocrinology consultation for ongoing management 2

Critical pitfall: ACTH stimulation testing can give false-negative results early after adrenalectomy because adrenal reserve declines slowly after pituitary stimulation is lost—when clinically uncertain, opt for replacement therapy and retest at 3 months. 2

Evaluation of Elevated Estrogen Levels

The elevated estrogen requires investigation to determine if this represents a new functional tumor, contralateral adrenal pathology, or residual disease. 2

Diagnostic workup should include:

• Non-contrast CT of the remaining adrenal gland to assess for new mass or hyperplasia (Hounsfield units <10 suggest benign adenoma, >10 requires further imaging) 2
• If CT shows indeterminate lesion, proceed to washout CT or chemical-shift MRI as second-line imaging 2
• Measure serum DHEA-S, testosterone, and androstenedione to characterize androgen excess pattern 2
• Review pathology from the original adrenalectomy to confirm the diagnosis and rule out adrenocortical carcinoma 2

If imaging reveals a new functional mass on the contralateral side:

• Laparoscopic adrenalectomy is indicated for unilateral functional tumors when feasible 2, 1
• However, bilateral adrenalectomy creates permanent adrenal insufficiency requiring lifelong glucocorticoid and mineralocorticoid replacement 4

Management Based on Findings

If Contralateral Adrenal Shows New Adenoma

• Offer laparoscopic adrenalectomy for hormone-secreting tumors regardless of size 2, 5
• Before bilateral adrenalectomy, ensure patient understands permanent need for hormone replacement and risk of adrenal crisis 4
• Postoperatively, immediate stress-dose hydrocortisone (100 mg IV every 6-8 hours) until stable, then transition to maintenance therapy 2, 1

If Bilateral Adrenal Hyperplasia is Discovered

• Medical management is preferred over bilateral adrenalectomy 1, 4
• For aldosterone excess: spironolactone or eplerenone 1, 4
• For cortisol excess: ketoconazole 400-1200 mg/day or mitotane 2, 1
• Consider adrenal vein sampling to determine if unilateral function predominates, which could allow unilateral adrenalectomy 1, 4

If No Structural Abnormality Found

• The elevated estrogen may represent compensatory changes in the remaining gland 6
• Monitor with repeat imaging at 6-12 months if the gland appears normal but is ≥4 cm 2
• Annual biochemical screening for development of new hormone excess 2, 1

Long-Term Monitoring Protocol

All patients post-unilateral adrenalectomy require:

• Annual clinical assessment including blood pressure, weight, and symptoms of hormone excess or deficiency 1
• Serum electrolytes and morning cortisol annually 1
• Repeat imaging at 6-12 months if initial post-operative imaging shows any abnormality 2
• Bone mineral density every 3-5 years if on glucocorticoid replacement 1
• Screening for autoimmune thyroid disease annually 1

Emergency preparedness is non-negotiable:

• All patients must carry steroid emergency card and wear medical alert identification 2, 1, 3
• Prescribe emergency injectable hydrocortisone (100 mg IM) with clear instructions for use 2, 3
• Educate on signs of impending adrenal crisis (severe weakness, vomiting, hypotension, confusion) requiring immediate emergency department presentation 3

The incidence of adrenal crisis is 8 per 100 patient-years in patients with adrenal insufficiency, making prevention through education the cornerstone of management. 3