dromlakhani PPGL Genetic Testing Indication and Patient Education
STEP 1 — Gather Information
Confirm PPGL diagnosis via biochemical (elevated fractionated metanephrines/catecholamines) and imaging; obtain detailed family history of PPGL, related syndromes (VHL, RET, SDHx, NF1), and personal history of multifocal/bilateral tumors, early onset, or metastatic disease.
STEP 2 — Rule In / Rule Out
Is the patient diagnosed with PPGL? If yes, proceed to offer genetic testing; if no, do not indicate PPGL-specific genetic testing (consider other indications).
STEP 3 — Classify or Stratify
All PPGL patients are candidates for genetic testing regardless of family history; however, prioritize counseling for those with SDHB-negative immunostaining, metastatic disease, young age (<45 years), bilateral/multifocal tumors, or known familial history.
STEP 4 — Decide
Offer germline genetic testing (multigene panel) after pre-test counseling; discuss hereditary PPGL prevalence (20-40%), implications for prognosis, family screening, and potential surveillance; obtain informed consent and refer to genetic counseling.
Clinical Guardrails / Mimics / Pitfalls
Do not order testing without genetic counseling; avoid interpreting variants of unknown significance as pathogenic; do not rely solely on family history to decide testing (hereditary PPGL can occur de novo); do not forget that testing is not covered by Japanese health insurance except for medullary thyroid carcinoma; do not neglect to inform patients about possible psychological and insurance implications.
Concrete Clinical Example
A 38-year-old woman with newly diagnosed left adrenal pheochromocytoma (elevated plasma metanephrine) and no family history is counseled about the 20-40% chance of hereditary PPGL, offered germline SDHB/VHL/RET/SDHD testing, and advised that a positive result would guide surveillance for metastases and familial screening.
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