Something came up in my timeline this week and I really enjoyed reading it.  I have many alerts set for various subjects including Pheochromocytomas and Paragangliomas.  Often an old published article is republished making it to my alert system and it got pushed up the timeline. It did seem like it was up to date but I eventually spotted it was from 2006! I appreciated some of the content because it had confirmed many parts of my knowledge about these interesting tumours. Two things stood out in this 2006 document:  Firstly, the mention of how many of these tumours are found on autopsies, this document quoted 50% which is an astonishing figure. I had previously written about these autopsy findings (including Eisenhower) in this article along with a few mentions of  other types of NET.  Another really important factor is the dangers of operating or even carrying out biopsies and other interventional techniques on these catecholamine secreting tumours.  But one thing stood out and I smiled when I read it – it was a blogger’s dream to be given a post title like this one.  The authors used the word ‘treacherous’ to describe their nature, cementing that description with the quote “There is no more deceptive and treacherous disease than this neuroendocrine tumor”.  The quote was specific to Pheochromocytoma but knowing what I know about Paraganglioma, you can certainly apply it to both.  You can read this excellent article in the list below but note while it’s a good article, it’s now 19 years old, so tests, treatment and imaging may be different.  




One of the other key points made by this author, who was writing for a ‘renal’ focussed publication (the adrenals sit on top of the kidney), was that first line renal clinicians must “think” of pheochromoctyomas when looking at issues in this area.  I guess you could ,make that statement for many types of NET.  But I was struck by the term “Think of it”.  I’ve written a ‘spotlight’ post on Pheo/Para – it’s a simple document compared to this one but worth reading still – click here.

However, this gift of this headline prompted me to write something in more detail – so here’s an up-to-date, expert-authored clinical summary of pheochromocytoma and paraganglioma (PPGL) which pulls together the most important recent guidance, classifications, genetics, diagnosis, imaging, management and follow-up points. I’ve cited the key expert sources for the load-bearing statements so you can jump to the original papers quickly. As I am really busy, I compiled this intro using AI but at least you have the references as certification.  I also added my friends in The PheoPara Alliance as they have a great website for information and experts on their board to advise them (some of whom are authors in the references below). 

Quick summary

Pheochromocytomas (adrenal) and paragangliomas (extra-adrenal) are rare chromaffin-cell neuroendocrine tumours with a high heritable fraction (~30–40%) and well-defined molecular clusters (pseudohypoxia, kinase-signalling, WNT). Clinical presentation is variable (sustained or paroxysmal hypertension, headaches, sweating, palpitations, anxiety, or incidentalomas). Plasma free metanephrines are the most sensitive biochemical screen. Cross-sectional imaging (CT/MRI) localizes most tumours; functional nuclear imaging (68Ga-DOTATATE, 18F-FDOPA, 123/124/131I-MIBG or 18F-FDG depending on genotype) is essential for staging and theranostic planning. Preoperative alpha-blockade and volume repletion remain standard before resection. Metastatic disease may be treated with 131I-MIBG, peptide-receptor radionuclide therapy (177Lu-DOTATATE), chemotherapy (CVD) or targeted/tyrosine kinase agents depending on biology and uptake. Lifelong follow-up is recommended because recurrence and new tumours can occur many years later. ese-hormones.org+4PMC+4PubMed+4

Key points (expanded)

1) Definitions & epidemiology

• Pheochromocytomas arise in adrenal medulla; paragangliomas arise from extra-adrenal paraganglia (sympathetic or parasympathetic). Most adrenal tumours are catecholamine-secreting. PMC+1

• PPGLs are rare but among the most heritable tumours in medicine — commonly quoted hereditary rate is ~30–40% in modern series (higher in paediatric cases). PMC+1

2) Genetics & molecular classification (clinically critical)

• Modern classification groups PPGLs into three molecular clusters:

  1. Pseudohypoxia (SDHx, VHL, EPAS1/HIF2A) — often extra-adrenal, high metastatic risk especially SDHB.

  2. Kinase-signalling (RET, NF1, TMEM127, MAX) — often adrenal.

  3. WNT-signalling (rarer).

• Genetic testing is recommended for essentially all patients with PPGL because of high actionable yield and impact on surveillance and imaging choices. PMC+1

3) Clinical presentation

• Symptoms range from asymptomatic/incidental adrenal mass to classic catecholamine excess (sustained or paroxysmal hypertension, headaches, diaphoresis, tachycardia, pallor, panic-like attacks). Pediatric PPGLs more often hereditary and multifocal. ScienceDirect+1

4) Biochemistry (screening & diagnosis)

• First-line test: plasma free metanephrines (or 24-hour urine fractionated metanephrines if plasma sampling is difficult). Proper patient preparation (avoid interfering drugs, supine rest when indicated) improves accuracy. Clonidine test has niche uses for equivocal cases. PMC+1

5) Imaging strategy

• Anatomic imaging: CT (adrenal protocol) or MRI (preferred for head/neck paragangliomas, children, pregnancy).

• Functional imaging (genotype-directed):

  • 68Ga-DOTATATE PET/CT (somatostatin receptor imaging) is excellent for many PPGLs and for selecting PRRT.

  • 18F-FDG PET/CT often used for SDHB-related and aggressive/metastatic disease.

  • 18F-DOPA and MIBG (123/131I) retain roles depending on context and availability.

• Choice of radiotracer should be informed by genotype and clinical question (localization vs whole-body staging vs theranostic planning). Oxford Academic+1

6) Pathology & classification updates

• The 2022 WHO classification clarifies diagnostic categories and emphasizes integration of morphology with molecular/genetic data. The approach to calling a PPGL “malignant” has shifted—risk stratification and genetics are emphasized over purely histologic criteria. PubMed+1

7) Treatment — localized disease

• Preoperative: alpha-adrenergic blockade (phenoxybenzamine or selective alpha-1 blockers) and adequate volume expansion remain standard to reduce perioperative hemodynamic complications. Beta-blockers added only after alpha blockade when needed for tachyarrhythmia. Oxford Academic

• Surgery: minimally invasive adrenalectomy for most pheochromocytomas; open approach for large/invasive tumours or many paragangliomas. Cortical-sparing (partial) adrenalectomy can be considered in hereditary bilateral disease to preserve adrenal function (selected patients). Oxford Academic

8) Treatment — metastatic or unresectable disease

• Options depend on tumor biology and imaging uptake:

  • 131I-MIBG therapy for MIBG-avid disease.

  • Peptide receptor radionuclide therapy (PRRT, e.g., 177Lu-DOTATATE) for somatostatin-receptor positive tumours.

  • Systemic chemotherapy (CVD: cyclophosphamide, vincristine, dacarbazine) can be used for progressive disease.

  • Targeted therapies / TKIs (e.g., sunitinib) are used in selected cases/clinical trials. Choice is individualized; referral to specialized centres is recommended. Nature+1

9) Prognosis & risk factors for metastasis

• SDHB mutations and extra-adrenal location are associated with higher metastatic risk. Long interval recurrences can occur; 5-year survival for localized disease is generally favourable but declines with metastatic spread. PMC+1

10) Follow-up and surveillance

• Lifelong follow-up after resection is recommended because late recurrence/new tumours are possible; follow-up frequency and tests should be stratified by genetics, initial tumour behaviour and completeness of resection. ESE and recent guidelines give specific schedules for biochemical testing and imaging. ese-hormones.org+1

11) Special populations & practical notes

• Children: higher hereditary rate and metastatic risk — urgent genetic testing and family screening. Nature

• Pregnancy: multidisciplinary management; alpha blockade and timing of surgery require specialist input. Oxford Academic

Most useful recent expert sources (start here)

1. WHO 2022 classification and follow-up primers (Mete et al.) — updates on pathological classification and integration with genetics. PubMed+1

2. Endocrine Society guideline (Lenders et al., 2014) — classic, still central for perioperative care and many management principles. Oxford Academic(for imaging, reference 4 is more up to date)

3. European Society of Endocrinology (ESE) Clinical Practice Guideline (long-term follow-up) — guidance on surveillance after resection. ese-hormones.org+1

4. Imaging review (Timmers et al., 2024, Endocrine Reviews) — up-to-date, genotype-directed imaging and theranostic planning. Oxford Academic+1

5. International consensus / expert statements (2023–2024) on genetic-risk stratification and management (including SDHB consensus). PubMed+1

6. Themed Collection:  A special 2024 Impact Factor Collection – Advances and future directions in pheochromocytoma and paraganglioma – Society for Endocrinology 

7. No useful expert sources would be complete without The PheoPara Alliance. Click here
   
   

   
   
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   I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

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