Pheochromocytoma & Thyroid Cancer | Dr. Liu Jianmin (Endocrinology) | CMCS Shanghai

About Dr. Liu Jianmin

Dr. Liu Jianmin is a senior endocrinologist and Professor of Medicine at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — one of China's foremost academic centres for endocrinology, metabolic disease, and adrenal disorders. He is a nationally recognised leader in the diagnosis and management of complex adrenal diseases, including pheochromocytoma, paraganglioma, Cushing's syndrome, and primary aldosteronism, with particular expertise in hereditary endocrine tumour syndromes and precision molecular medicine. Dr. Liu's practice is defined by the philosophy that complex metabolic presentations — particularly those involving multiple simultaneous endocrine abnormalities in young patients — demand a genetic-first, imaging-guided, multidisciplinary approach before any therapeutic intervention. His centre is a national reference site for 68Ga-DOTATATE PET/CT somatostatin receptor imaging for occult paraganglioma localisation, whole-exome sequencing (WES) for hereditary endocrine tumour syndromes, and perioperative catecholamine crisis management. Dr. Liu has published extensively in Journal of Clinical Endocrinology and Metabolism, Endocrine-Related Cancer, and Hypertension, and serves on the expert committees of the Chinese Society of Endocrinology and the Chinese Society of Adrenal Diseases.

Case Overview

Ms. Claire Beaumont, a 32-year-old French financial analyst based in Shanghai, presented with a three-year history of paroxysmal hypertension (peak 220/120 mmHg), palpitations, diaphoresis, and pallor — each episode lasting 10–20 minutes and resolving spontaneously. Over the preceding six months, episode frequency had increased to three to four per day, accompanied by 10 kg weight loss, tremor, and anxiety. External workup had identified new-onset diabetes (fasting glucose 9.8 mmol/L) and apparent hyperthyroidism (elevated FT3/FT4, suppressed TSH) — leading to a working diagnosis of Graves' disease with secondary diabetes. Dr. Liu Jianmin recognised the constellation of paroxysmal hypertension, hypermetabolism, and new-onset diabetes in a young woman as a classic catecholamine excess syndrome, not primary hyperthyroidism. Biochemical confirmation: 24-hour urinary vanillylmandelic acid (VMA) elevated three-fold above normal; plasma free normetanephrine (NMN) elevated five-fold. Adrenal CT was negative — indicating extra-adrenal disease. 68Ga-DOTATATE PET/CT — Ruijin Hospital's signature molecular imaging modality for occult paraganglioma — identified a 2.5 x 2.0 cm high-uptake retroperitoneal nodule adjacent to the aorta (SUVmax 25.6) and a high-uptake nodule at the right thyroid lower pole. Whole-exome sequencing confirmed an SDHB germline mutation — explaining the extra-adrenal location, the synchronous thyroid lesion, and the elevated malignant potential of the tumour. Following two weeks of alpha-adrenergic blockade with phenoxybenzamine (titrated to 40 mg twice daily), single-stage laparoscopic retroperitoneal paraganglioma resection with right thyroid lobectomy and central lymph node dissection was performed. Intraoperative pathology confirmed paraganglioma (SDHB immunohistochemistry negative — confirming the germline mutation) and thyroid papillary microcarcinoma. Within 24 hours of surgery, catecholamines normalised, blood glucose returned to normal without insulin, and thyroid function normalised. At three-month follow-up, 68Ga-DOTATATE PET/CT confirmed no residual or recurrent disease.

Patient Background

• Name / Nationality: Ms. Claire Beaumont (pseudonym) — French; financial analyst based in Shanghai
• Age / Sex: 32-year-old female
• Chief Complaint: Paroxysmal headache, palpitations, and diaphoresis for 3 years; worsening with 10 kg weight loss over 6 months
• Paroxysmal Episodes: Blood pressure peaks to 220/120 mmHg; pallor; profuse sweating; duration 10–20 minutes; spontaneous resolution; frequency increasing to 3–4 per day
• Recent Symptoms: Weight loss 10 kg; tremor; anxiety; heat intolerance — attributed externally to hyperthyroidism
• External Diagnoses: New-onset diabetes (fasting glucose 9.8 mmol/L); apparent hyperthyroidism (FT3/FT4 elevated, TSH suppressed, TRAb negative)
• Family History: Mother with papillary thyroid carcinoma — raising suspicion for hereditary endocrine tumour syndrome
• Examination: BP 160/95 mmHg; HR 110 bpm; mild proptosis (±); hand tremor (+); thyroid Grade II enlargement without bruit; no Cushingoid features

Biochemical and Imaging Workup

Catecholamine Excess Confirmation

• 24-hour urinary VMA: Elevated 3-fold above upper limit of normal — catecholamine excess confirmed
• Plasma free normetanephrine (NMN): Elevated 5-fold — highly specific for pheochromocytoma/paraganglioma
• Plasma free metanephrine (MN): Mildly elevated — consistent with predominantly norepinephrine-secreting tumour

Thyroid and Metabolic Assessment

• Thyroid function: FT3 12.5 pmol/L; FT4 35 pmol/L; TSH <0.01 mIU/L; TRAb negative — hyperthyroidism pattern without Graves' autoimmunity; consistent with catecholamine-driven hypermetabolism
• HbA1c: 8.2%; C-peptide release test low-flat — consistent with catecholamine-mediated insulin secretion suppression and insulin resistance, not primary diabetes
• Adrenal CT: Bilateral adrenal glands normal — extra-adrenal disease confirmed; conventional imaging insufficient for localisation
• Neck ultrasound: Multiple thyroid nodules; right lower pole nodule TI-RADS 4 — suspicious for malignancy

68Ga-DOTATATE PET/CT — Molecular Localisation

• Retroperitoneal nodule: Left para-aortic region; 2.5 x 2.0 cm; SUVmax 25.6 — intense somatostatin receptor expression; diagnostic of paraganglioma
• Thyroid right lower pole: High-uptake nodule — suspicious for synchronous neuroendocrine lesion or thyroid malignancy
• Adrenal glands: No abnormal uptake bilaterally — extra-adrenal origin confirmed
• Distant sites: No metastatic uptake — localised disease

Genetic Diagnosis — Whole-Exome Sequencing

• Finding: SDHB (succinate dehydrogenase complex subunit B) germline pathogenic variant — confirmed hereditary paraganglioma-pheochromocytoma syndrome type 4 (PGL4)
• Clinical implications: Extra-adrenal location explained (SDHB mutations preferentially cause retroperitoneal and thoracic paragangliomas); elevated malignant potential (SDHB-mutant tumours carry 30–40% lifetime metastasis risk); synchronous thyroid and other neuroendocrine tumour risk; autosomal dominant inheritance — 50% transmission risk to offspring

Clinical Decision Making

Three compounding risks defined the pre-operative period: catecholamine crisis risk during anaesthesia induction and tumour manipulation — potentially fatal without adequate alpha-adrenergic blockade; the apparent hyperthyroidism creating a hypermetabolic state that amplified cardiovascular risk; and the new-onset diabetes requiring metabolic stabilisation before surgery. The conventional approach — treating hyperthyroidism with antithyroid drugs and diabetes with insulin independently — would have delayed surgery and exposed the patient to ongoing catecholamine toxicity.

Dr. Liu Jianmin's precision strategy: This patient does not have three diseases. She has one disease — an SDHB-mutant paraganglioma — that is causing three metabolic consequences. The hypertension is catecholamine-driven. The apparent hyperthyroidism is catecholamine-driven hypermetabolism, not Graves' disease — TRAb is negative. The diabetes is catecholamine-mediated insulin suppression and insulin resistance, not primary diabetes. If we treat each consequence separately, we will never cure the patient. We must remove the source. But we cannot remove the source safely until we have blocked the catecholamine receptors completely. Alpha blockade first. Then surgery. Then watch everything normalise simultaneously.

Treatment Sequence

Phase 1 — Genetic Confirmation and Alpha-Adrenergic Blockade (2 Weeks)

Genetic result: SDHB germline pathogenic variant confirmed within 10 days of whole-exome sequencing — establishing hereditary PGL4 syndrome and guiding surgical strategy toward complete resection with aggressive margins.

Alpha-adrenergic blockade: Phenoxybenzamine initiated at 10 mg twice daily and titrated over two weeks to 40 mg twice daily — targeting blood pressure below 130/80 mmHg and heart rate below 90 bpm. Nasal congestion developed at day 10 — a reliable clinical marker of complete alpha-receptor blockade. Beta-blockade (propranolol) was added only after adequate alpha blockade was established — preventing the paradoxical hypertensive crisis that occurs when beta-blockade is initiated first in catecholamine excess states.

Metabolic management: Insulin initiated for glycaemic control during the pre-operative period; antithyroid drugs deliberately withheld — the apparent hyperthyroidism was assessed as catecholamine-driven hypermetabolism that would resolve with tumour removal, not primary Graves' disease requiring independent treatment.

Dr. Liu's clinical note: The nasal congestion is not a side effect we tolerate — it is the sign we are waiting for. It tells us the alpha receptors in the nasal mucosa are blocked. If they are blocked there, they are blocked in the blood vessels. The patient is now safe for anaesthesia. Without this sign, we do not proceed to the operating theatre.

Phase 2 — Single-Stage Multidisciplinary Surgery

Anaesthesia strategy: Total intravenous anaesthesia; short-acting vasoactive agents prepared and immediately available — sodium nitroprusside and urapidil for hypertensive surges; esmolol for tachyarrhythmia; norepinephrine and rapid volume expansion for post-resection hypotension. Long-acting agents deliberately avoided to prevent refractory post-operative hypotension. Glucose infusion prepared for post-resection hypoglycaemia — catecholamine withdrawal restores insulin sensitivity abruptly.

Laparoscopic retroperitoneal paraganglioma resection: The retroperitoneal approach was selected to avoid peritoneal contamination and provide direct access to the para-aortic tumour. The tumour was identified adjacent to the left renal vein and aorta. Minimal manipulation technique was employed — dissecting the vascular pedicle before any tumour mobilisation to minimise catecholamine release.

Intraoperative catecholamine crisis: At the moment of tumour pedicle manipulation, blood pressure surged to 250/140 mmHg. Sodium nitroprusside was immediately infused; the surgical team accelerated vascular pedicle ligation. The tumour was completely resected en bloc within 4 minutes of the hypertensive surge.

Post-resection hypotension: Immediately following tumour removal, blood pressure fell to 60/40 mmHg — the classic catecholamine withdrawal hypotension as peripheral vascular resistance collapsed with the removal of the catecholamine source. Rapid crystalloid and colloid infusion combined with norepinephrine infusion restored haemodynamic stability within 15 minutes.

Synchronous thyroid surgery: Intraoperative frozen section of the right thyroid lower pole nodule confirmed papillary thyroid microcarcinoma. Right thyroid lobectomy with central compartment lymph node dissection was performed in the same anaesthetic session — avoiding a second surgical procedure and anaesthetic exposure.

Phase 3 — Post-operative Precision Management

Pathology: Retroperitoneal paraganglioma — SDHB immunohistochemistry negative (confirming germline mutation at the protein level); no capsular invasion; complete resection margins. Thyroid: papillary microcarcinoma, unifocal, no lymphovascular invasion, 0/6 central lymph nodes positive.

Biochemical cure — within 24 hours: Plasma catecholamines normalised; blood glucose returned to normal range without insulin (catecholamine-mediated insulin suppression resolved); thyroid function normalised (confirming the hyperthyroidism was catecholamine-driven hypermetabolism, not primary Graves' disease). All three metabolic abnormalities resolved simultaneously with removal of the single causative lesion.

Thyroid hormone replacement: Levothyroxine initiated post-operatively for thyroid hormone replacement following right lobectomy; TSH target set at low-normal range given the papillary carcinoma diagnosis.

Family cascade screening: Genetic counselling initiated; first-degree relatives (mother and children) referred for SDHB germline testing — enabling pre-symptomatic identification of mutation carriers before tumour development.

Follow-up and Outcomes

1-Month Follow-up

• Blood pressure: 120/75 mmHg — all antihypertensive medications discontinued
• Blood glucose: Fasting 5.2 mmol/L; HbA1c trending toward normal — insulin discontinued
• Thyroid function: Normal on levothyroxine replacement
• Symptoms: No paroxysmal episodes; weight stabilising; tremor resolved; anxiety resolved

3-Month Follow-up

• 68Ga-DOTATATE PET/CT: No residual tumour uptake; no new lesions; complete biochemical and imaging remission confirmed
• Plasma metanephrines: Within normal range — biochemical cure sustained
• Family screening: Mother's SDHB testing pending; children referred for paediatric genetic counselling

Long-term Surveillance Protocol

• Annual plasma metanephrine measurement and 68Ga-DOTATATE PET/CT — SDHB-mutant tumours carry 30–40% lifetime metastasis risk requiring lifelong surveillance
• Annual renal ultrasound and abdominal MRI — SDHB mutations associated with renal cell carcinoma and gastrointestinal stromal tumour risk
• Annual thyroid ultrasound and thyroglobulin measurement — papillary carcinoma surveillance
• Genetic counselling for all first-degree relatives

Expert Commentary — Dr. Liu Jianmin

1. Recognising the Catecholamine Excess Syndrome: One Disease, Three Faces

The most dangerous error in this case would have been to treat three separate diseases: hypertension with antihypertensives, hyperthyroidism with antithyroid drugs, and diabetes with insulin. Each treatment would have been partially effective, the underlying cause would have remained, and the patient would have faced an unrecognised catecholamine crisis during any future surgical or anaesthetic procedure. The key diagnostic insight is that paroxysmal hypertension in a young patient — particularly when accompanied by the triad of headache, palpitations, and diaphoresis — is a pheochromocytoma or paraganglioma until proven otherwise. Catecholamine measurement is not an optional test in this presentation. It is the first test. The apparent hyperthyroidism — elevated FT3/FT4 with suppressed TSH but negative TRAb — is a classic catecholamine-driven hypermetabolic state, not Graves' disease. The diabetes is catecholamine-mediated insulin suppression, not primary pancreatic failure. Remove the tumour. Watch everything normalise. That is the power of the correct diagnosis.

2. Molecular Imaging as the Localisation Standard for Extra-Adrenal Disease

Conventional CT and MRI have sensitivity below 70% for extra-adrenal paraganglioma — particularly for small retroperitoneal tumours adjacent to major vessels where anatomical imaging cannot distinguish tumour from lymph node or vascular structure. 68Ga-DOTATATE PET/CT exploits the high somatostatin receptor expression of paraganglioma tissue to generate a functional signal that is independent of tumour size or anatomical location. The SUVmax of 25.6 in this case is unambiguous — no benign retroperitoneal structure generates that level of somatostatin receptor uptake. This is not a research tool. At Ruijin Hospital, 68Ga-DOTATATE PET/CT is the standard localisation investigation for all patients with biochemically confirmed catecholamine excess and negative conventional imaging. It is the reason we find tumours that other centres miss.

3. Genetic Diagnosis as the Foundation of Surgical Strategy

The SDHB germline mutation changed every aspect of the management plan. It explained the extra-adrenal location — SDHB mutations preferentially cause retroperitoneal and thoracic paragangliomas rather than adrenal pheochromocytomas. It explained the synchronous thyroid lesion — SDHB-associated PGL4 syndrome carries elevated risk of thyroid and renal malignancy. It established the malignant potential — SDHB-mutant tumours carry a 30–40% lifetime risk of metastasis, mandating complete resection with adequate margins and lifelong surveillance. And it identified the family risk — autosomal dominant inheritance means 50% of first-degree relatives carry the mutation. The genetic diagnosis did not change the operation. It changed the meaning of the operation: from removing a tumour to protecting a family.

4. Perioperative Catecholamine Crisis Management: The Endocrinologist's Responsibility

Pheochromocytoma and paraganglioma surgery is the highest-risk endocrine surgical procedure. The perioperative mortality in inadequately prepared patients approaches 3–5%. In adequately prepared patients at experienced centres, it is below 1%. The difference is alpha-adrenergic blockade. Phenoxybenzamine must be titrated to clinical endpoints — not to a fixed dose. The clinical endpoints are: blood pressure below 130/80 mmHg for 24 hours pre-operatively; heart rate below 90 bpm; nasal congestion (confirming mucosal alpha-receptor blockade); and orthostatic hypotension (confirming volume expansion from alpha-receptor-mediated vasodilatation). Beta-blockade must never precede alpha-blockade — blocking beta-2 vasodilatory receptors before alpha receptors are blocked leaves alpha-mediated vasoconstriction unopposed, precipitating hypertensive crisis. These are not guidelines. They are rules. Violating them kills patients.

How CMCS Shanghai Coordinated This Case

China Medical Concierge Shanghai (CMCS) supported Ms. Beaumont's care pathway from initial overseas inquiry through three-month post-operative surveillance and family genetic counselling coordination. Our coordination included:

• Pre-arrival review of external workup including blood pressure records, catecholamine measurements, thyroid function tests, adrenal CT, and neck ultrasound; specialist referral to Dr. Liu Jianmin's endocrinology team at Ruijin Hospital
• Arrangement of comprehensive diagnostic workup at Ruijin Hospital: plasma free metanephrines, 24-hour urinary VMA, repeat thyroid function with TRAb, HbA1c and C-peptide release test, whole-exome sequencing, and 68Ga-DOTATATE PET/CT — with results reviewed by Dr. Liu's team and the unified diagnosis established prior to any treatment initiation
• Bilingual interpretation during the diagnostic consultation — including detailed explanation of the paraganglioma diagnosis, the SDHB germline mutation and its implications for the patient and her family, the catecholamine-driven mechanism of the apparent hyperthyroidism and diabetes, the alpha-blockade protocol and its clinical endpoints, and the single-stage surgical strategy
• Facilitation of informed consent for both the paraganglioma resection and the synchronous thyroid lobectomy — ensuring Ms. Beaumont fully understood the intraoperative catecholamine crisis risk, the post-resection hypotension protocol, the expected simultaneous normalisation of all three metabolic abnormalities, and the long-term surveillance requirements
• Two-week alpha-blockade monitoring coordination: daily blood pressure and heart rate recording; phenoxybenzamine dose titration communication between Ms. Beaumont and Dr. Liu's team; clinical endpoint assessment (nasal congestion, orthostatic hypotension) with results relayed to the surgical team for operative clearance
• Surgical admission logistics: laparoscopic retroperitoneal suite scheduling, intraoperative vasoactive agent preparation confirmation, anaesthesia pre-assessment, and ICU bed reservation for post-operative haemodynamic monitoring
• On-site medical interpretation throughout the surgical admission — including intraoperative findings communication, post-resection hypotension explanation, frozen section results relay, and post-operative metabolic normalisation explanation
• Post-operative monitoring coordination: daily catecholamine and glucose measurements in the first 48 hours; thyroid function assessment at 2 weeks; results translation and communication to Ms. Beaumont's endocrinologist in France
• Long-term surveillance scheduling: annual plasma metanephrine measurement, 68Ga-DOTATATE PET/CT, renal ultrasound, abdominal MRI, and thyroid surveillance protocol; results communication to the French endocrinology team
• Family genetic counselling coordination: referral of Ms. Beaumont's mother and children for SDHB germline testing; explanation of autosomal dominant inheritance and 50% transmission risk; pre-symptomatic surveillance protocol for confirmed mutation carriers

For international patients presenting with complex, multi-system endocrine disorders — particularly young patients with paroxysmal hypertension, unexplained metabolic dysregulation, or a family history of endocrine tumours — the combination of biochemical precision, 68Ga-DOTATATE molecular imaging, whole-exome genetic diagnosis, and perioperative catecholamine crisis expertise at Ruijin Hospital represents a standard of endocrine oncology care genuinely at the international frontier. CMCS exists to connect patients with that expertise: ensuring the correct diagnosis is established before any treatment begins, every genetic implication is explained in their language, and every step from molecular imaging to family cascade screening is coordinated across borders with precision and care.

This case report is de-identified and published for educational purposes. All clinical details have been anonymized in accordance with patient privacy standards. CMCS Shanghai is a medical concierge service and does not provide direct medical care.