dromlakhani Conduct diagnostic workup for non-catecholamine-producing pheochromocytoma and paraganglioma
STEP 1 — Gather Information
Collect clinical history (head/neck symptoms, family history of PPGL), prior imaging (CT/MRI) showing a lesion, and biochemical results (fractionated metanephrines and catecholamines). If catecholamines are within normal limits and imaging reveals a PPGL-suggestive mass, proceed to Step 2.
STEP 2 — Rule In / Rule Out
Confirm non-catecholamine-producing PPGL by verifying fractionated metanephrines and catecholamines are less than three times the upper limit of normal (or within reference range). If normal, rule in suspicion for non-catecholamine-producing PPGL; if elevated, follow standard catecholamine-producing PPGL workup (outside this skill). Action: If normal, advance to Step 3; otherwise, manage as catecholamine-producing PPGL.
STEP 3 — Classify or Stratify
Determine tumor location: head/neck (carotid body, jugular bulb, vagal) versus other (adrenal, abdominal, thoracic). If head/neck lesion is identified, flag for SDHD germline testing; if non-head/neck, proceed without genetic testing. Action: Based on location, proceed to Step 4 with appropriate testing plan.
STEP 4 — Decide
Order mandatory diagnostic imaging: contrast-enhanced MRI of the primary site, contrast-enhanced CT of chest/abdomen/pelvis, and somatostatin receptor nuclear imaging (e.g., 68Ga-DOTATATE PET/CT). For head/neck lesions, additionally arrange SDHD germline genetic testing. If imaging confirms PPGL, initiate multidisciplinary discussion for treatment planning.
Clinical Guardrails / Mimics / Pitfalls
Do not rely solely on 123I-MIBG scintigraphy due to high false‑negative rates in non‑catecholamine PPGL and SDHD‑related tumors. Do not omit somatostatin receptor imaging when MIBG is negative. Do not forget to screen for hereditary SDHD in multifocal or familial head/neck lesions. Avoid repeating plasma‑free metanephrine testing more than once under Japanese insurance restrictions for differential diagnosis.
Concrete Clinical Example
A 48‑year‑old woman presents with a palpable left neck mass. Ultrasound shows a 1.8 cm carotid body tumor. Fractionated metanephrines and plasma catecholamines are normal. She proceeds to MRI neck (flow void), CT chest/abdomen/pelvis (negative), and 68Ga‑DOTATATE PET/CT (uptake in the carotid body). SDHD testing reveals a pathogenic variant. She is counseled on surveillance and possible surgical resection.
Source: Japan Endocrine Society Clinical Practice Guideline for the Diagnosis and Management of Pheochromocytoma and Paraganglioma 2025, Japan Endocrine Society, 2025, doi:10.1507/endocrj.EJ25-0165