What laboratory tests are recommended for a patient after adrenolectomy (adrenal gland removal), particularly those with a history of pheochromocytoma or Cushing's syndrome?

Laboratory Testing After Adrenalectomy

The specific laboratory tests required after adrenalectomy depend critically on the underlying pathology—patients with pheochromocytoma require biochemical testing at 14 days post-surgery and lifelong surveillance, while those with Cushing's syndrome need immediate postoperative cortisol measurement to confirm remission, followed by annual late-night salivary cortisol (LNSC) testing after HPA axis recovery.

Immediate Postoperative Testing (Within 24-48 Hours)

For Cushing's Syndrome/Disease

• Measure serum cortisol on postoperative day 1 (POD1) as the defining criterion for remission—low or undetectable cortisol in the immediate postoperative period confirms successful resection, though it does not guarantee against future recurrence 1
• A POD1 cortisol ≥10 μg/dL indicates sufficient adrenal reserve and no patient with this level develops adrenal insufficiency symptoms 2
• Patients with POD1 cortisol <10 μg/dL warrant clinical monitoring for symptoms of adrenal insufficiency, though 90% of asymptomatic patients resolve spontaneously within one week 2
• Consider ACTH stimulation testing selectively for patients with low POD1 cortisol who are asymptomatic, as 75% demonstrate adequate cortisol response and can avoid unnecessary steroid replacement 2

For Mild Autonomous Cortisol Secretion (MACS)

• Early postoperative cortisol assessment is essential even in patients with preoperative dexamethasone suppression test (DST) values of 1.8-5 mcg/dL, as these patients have higher postoperative cortisol levels (mean 8.0 vs 5.0 mcg/dL) and require shorter duration of glucocorticoid replacement compared to those with DST >5 mcg/dL 3
• Patients with MACS are less likely to require discharge on glucocorticoid replacement (59% vs 89%) and have decreased treatment duration (4.4 vs 10.7 months) 3

Early Postoperative Testing (14 Days Post-Surgery)

For Pheochromocytoma/Paraganglioma

• Repeat biochemical testing approximately 14 days following surgery to check for residual disease using plasma or urinary metanephrine, normetanephrine, chromogranin A, and methoxythyramine 1
• This early testing is critical as it establishes the baseline for long-term surveillance and identifies incomplete resection requiring additional intervention 4

Long-Term Surveillance Testing

For Pheochromocytoma/Paraganglioma (Highest Priority)

• Perform biochemical testing every 3-4 months for the first 2-3 years, then every 6 months thereafter with lifelong surveillance 1
• Measure plasma or urinary metanephrine, normetanephrine, chromogranin A, and methoxythyramine at each interval 1
• Lifelong surveillance is especially critical for patients with extra-adrenal primary disease, tumor size >5 cm, or SDHB mutations due to higher malignancy risk 1, 4
• In cases of proven malignant disease, SDHB mutation, or extra-adrenal primary disease, imaging should be repeated at least every 6 months during the first year and yearly afterward, irrespective of negative biochemical tests 1

For Cushing's Disease (After HPA Axis Recovery)

• Begin annual LNSC testing after HPA axis recovery, as this is the most sensitive test for detecting recurrence and typically becomes abnormal before DST and urinary free cortisol (UFC) 1
• Lifelong monitoring for recurrence is required, as published recurrence rates vary between 5-35%, with half appearing within the first 5 years and half after 10 years or more 1
• Consider which specific tests were abnormal at initial diagnosis when designing the surveillance protocol, as individual patterns may vary 1
• If only slight biochemical abnormalities are detected without clinical features of hypercortisolism, close monitoring with repeat testing rather than immediate treatment intervention is appropriate 1

For Adrenocortical Carcinoma (ACC)

• Follow-up every 3 months for 2 years with monitoring of initially elevated steroids, then continue surveillance for at least 10 years due to risk of late recurrence 4

Critical Pitfalls to Avoid

• Do not initiate glucocorticoid replacement based solely on POD1 cortisol levels—management based on clinical symptoms or selective ACTH stimulation testing spares more patients from unnecessary steroids (100% vs 8% vs 25% initiation rates for cortisol-based, symptom-based, and ACTH stimulation test-based approaches, respectively) 2
• Be aware that chronic primary adrenal insufficiency can develop after unilateral adrenalectomy, especially when patients experience severe postoperative adrenal stress involving cardiopulmonary disturbance or systemic infection 5
• Never assume that normal early postoperative cortisol guarantees against late recurrence in Cushing's disease—some patients with very low postoperative cortisol levels indicating remission may still experience recurrence years later 1
• For pheochromocytoma patients, do not rely solely on biochemical testing in high-risk cases (SDHB mutation, extra-adrenal disease, large tumors)—these patients require both biochemical and imaging surveillance regardless of normal hormone levels 1