What is the most urgent next step in management for a patient with significant weight loss and PET‑CT findings of a bulky, metabolically active left adrenal gland, an enlarged metabolically active left supraclavicular lymph node, and a partially occlusive, metabolically active main portal vein?

Immediate Biopsy of the Left Supraclavicular Lymph Node After Excluding Pheochromocytoma

The most urgent next step is to measure plasma-free or urinary-fractionated metanephrines to rule out pheochromocytoma before proceeding with tissue diagnosis via biopsy of the accessible left supraclavicular lymph node. 1

Critical First Action: Rule Out Pheochromocytoma

Before any invasive procedure, you must systematically exclude pheochromocytoma because these tumors can trigger life-threatening hypertensive crises during biopsy or any intervention 1. This takes absolute priority over tissue diagnosis:

• Measure plasma-free or urinary-fractionated metanephrines immediately 1
• Consider plasma methoxytyramine if available, as elevated levels suggest malignancy risk 1
• This testing is mandatory even though the adrenal mass shows metabolic activity on PET-CT, as pheochromocytomas and metastases can have overlapping imaging characteristics 2

Second Priority: Obtain Tissue Diagnosis

Once pheochromocytoma is excluded, biopsy the left supraclavicular lymph node - this is your most accessible target for definitive diagnosis:

• The supraclavicular node is enlarged and metabolically active, making it an ideal biopsy target
• Direct adrenal biopsy is contraindicated due to risk of tumor spillage, poor diagnostic accuracy for benign versus malignant differentiation, and potential hypertensive crisis 1
• The exception for adrenal biopsy would be if you had a known extra-adrenal primary malignancy and needed to confirm adrenal metastasis, but you don't have a primary diagnosis yet 1

Concurrent Evaluation: Assess Adrenal Function

While arranging biopsy, evaluate for adrenal insufficiency given the bulky bilateral involvement:

• Check morning cortisol and ACTH
• Consider ACTH stimulation test if baseline cortisol is borderline
• Bilateral adrenal metastases can cause primary adrenal insufficiency, which impacts both immediate management and quality of life 3
• This is particularly important given the patient's significant weight loss, which could reflect adrenal insufficiency 3

Additional Hormonal Work-Up

If pheochromocytoma is excluded and imaging suggests possible adrenocortical carcinoma, obtain extensive steroid hormone assessment 1:

• Glucocorticoids, mineralocorticoids, sex steroids, and precursor steroids
• These can serve as tumor markers for follow-up
• Massive steroid excess impacts short-term survival and quality of life, requiring specific treatment 1

Clinical Context and Differential

The constellation of findings—metabolically active adrenal mass, supraclavicular adenopathy, portal vein thrombus with metabolic activity, and significant weight loss—strongly suggests metastatic disease rather than primary adrenal malignancy. The metabolically active portal vein thrombus is particularly concerning for tumor thrombus rather than bland thrombus. However, you need tissue diagnosis to guide treatment.

Common pitfall to avoid: Do not proceed directly to adrenal biopsy without excluding pheochromocytoma first. The overlapping imaging features between pheochromocytoma and metastases on FDG PET-CT make biochemical exclusion mandatory 2.