Young-Onset Hypertension (MEN2A Syndrome)
Secondary Hypertension • Pheochromocytoma • Medullary Thyroid Carcinoma • MRCP (UK) PACES
A structured MRCP (UK) PACES approach to young adults presenting with hypertension. Learn how to recognise endocrine causes of secondary hypertension, identify pheochromocytoma, screen for MEN2A syndrome and counsel patients regarding investigation, treatment and family screening.
At a Glance
Red Flags
PACES Approach
Secondary Hypertension Framework
Kidney disease
Conn's • Phaeochromocytoma • Cushing's
Renal artery stenosis
NSAIDs • Steroids • OCP
Obstructive sleep apnoea
MEN2A syndrome
Overview
Young adults presenting with severe or resistant hypertension should always be evaluated for secondary causes. In the MRCP (UK) PACES examination, the combination of hypertension, episodic headaches, palpitations, sweating and a thyroid nodule should immediately raise suspicion of MEN2A syndrome, an inherited disorder caused by a mutation in the RET proto-oncogene. The syndrome classically comprises medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. :contentReference[oaicite:1]{index=1}
Focused History
Assess the Hypertension
- When was hypertension first diagnosed?
- Highest recorded blood pressure.
- Persistent or episodic hypertension.
- Previous antihypertensive treatment.
- Medication adherence.
- Previous hypertensive emergencies.
Symptoms of End-organ Damage
- Headache.
- Visual disturbance.
- Chest pain.
- Breathlessness.
- Stroke or transient neurological symptoms.
- Urinary symptoms suggesting renal disease.
Screen for Phaeochromocytoma
- Paroxysmal headaches.
- Palpitations.
- Profuse sweating.
- Tremor.
- Anxiety or panic-like episodes.
- Weight loss.
- Attacks triggered by stress, exercise or surgery.
Screen for MEN2A Components
- Neck swelling or thyroid lump.
- Persistent diarrhoea (calcitonin excess).
- Symptoms of hypercalcaemia (thirst, constipation, renal stones).
- Previous thyroid or parathyroid surgery.
Screen for Other Secondary Causes
- Hypokalaemia or muscle weakness (Primary hyperaldosteronism).
- Weight gain and easy bruising (Cushing syndrome).
- Acromegalic features.
- Symptoms of thyroid disease.
- Haematuria or renal disease.
- Obstructive sleep apnoea symptoms.
Drug, Family and Social History
- NSAIDs, corticosteroids or oral contraceptives.
- Recreational drug use.
- Family history of endocrine tumours or early hypertension.
- Smoking and alcohol intake.
- Impact on work and quality of life.
Focused Examination
- Repeat blood pressure in both arms.
- Measure pulse rate and rhythm.
- Assess body mass index.
- Inspect for diaphoresis and tremor.
- Palpate the thyroid for nodules.
- Look for thyroidectomy or neck scars.
- Perform fundoscopy for hypertensive retinopathy.
- Assess for features of Cushing syndrome or acromegaly.
- Examine the cardiovascular system.
- Look for features of chronic kidney disease.
Differential Diagnosis
Investigations
Baseline Investigations
- Full blood count.
- Urea, electrolytes and creatinine.
- Serum calcium.
- Liver function tests.
- Thyroid function tests.
- Urinalysis.
- ECG.
Investigations for Phaeochromocytoma
- Plasma free metanephrines.
- 24-hour urinary fractionated metanephrines.
- CT or MRI of the adrenal glands.
- MIBG scan when indicated.
Investigations for MEN2A
- Serum calcitonin.
- Carcinoembryonic antigen (CEA).
- Neck ultrasound.
- Parathyroid hormone level.
- RET proto-oncogene mutation testing.
PACES Tip: Before surgery for medullary thyroid carcinoma, always exclude and treat a phaeochromocytoma first to avoid a potentially life-threatening hypertensive crisis during anaesthesia. :contentReference[oaicite:1]{index=1}
Diagnosis
Secondary Hypertension due to MEN2A Syndrome
The combination of severe hypertension, symptoms suggestive of phaeochromocytoma and a thyroid nodule should raise strong suspicion of MEN2A syndrome. Confirmation requires biochemical testing for phaeochromocytoma, assessment for medullary thyroid carcinoma and hyperparathyroidism, together with genetic testing for a RET proto-oncogene mutation. :contentReference[oaicite:2]{index=2}
Explaining to the Patient
"Your high blood pressure may be due to an underlying condition affecting several hormone-producing glands rather than ordinary hypertension. We are particularly concerned about a condition called MEN2A syndrome, which can affect the thyroid gland, adrenal glands and parathyroid glands. We will arrange specialised blood tests, scans and genetic testing to confirm the diagnosis. If confirmed, treatment is available, and because this condition can run in families, we would also recommend genetic counselling and screening for close relatives."
Management
Examiner's Corner
What is MEN2A syndrome?
- An autosomal dominant endocrine tumour syndrome.
- Caused by pathogenic mutations in the RET proto-oncogene.
- Classically comprises:
- Medullary thyroid carcinoma.
- Phaeochromocytoma.
- Primary hyperparathyroidism.
Why must phaeochromocytoma be treated before thyroid surgery?
- Undiagnosed phaeochromocytoma may precipitate a catastrophic hypertensive crisis during anaesthesia.
- Alpha-blockade is required before adrenalectomy.
- Only after phaeochromocytoma has been treated should thyroid surgery proceed.
How is phaeochromocytoma diagnosed?
- Plasma free metanephrines.
- 24-hour urinary fractionated metanephrines.
- CT or MRI adrenal imaging.
- Functional imaging (e.g. MIBG) where indicated.
How should family members be managed?
- Offer genetic counselling.
- RET mutation testing for first-degree relatives.
- Early endocrine screening if mutation-positive.
- Long-term surveillance for endocrine tumours.
Common PACES Viva Questions
- Which patients should be investigated for secondary hypertension?
- What is the classic triad of phaeochromocytoma?
- Which gene is responsible for MEN2A?
- What endocrine tumours occur in MEN2A?
- Why is alpha-blockade essential before surgery?
- How do MEN2A and MEN2B differ?
- Which relatives require screening?
MEN2A vs MEN2B
| Feature | MEN2A | MEN2B |
|---|---|---|
| Medullary thyroid carcinoma | ✓ | ✓ |
| Phaeochromocytoma | ✓ | ✓ |
| Hyperparathyroidism | ✓ | Rare |
| Mucosal neuromas | Absent | Present |
| Marfanoid habitus | Absent | Present |
Important Clinical Pearls
- Always suspect secondary hypertension in young adults.
- The combination of headache, sweating and palpitations strongly suggests phaeochromocytoma.
- Think MEN2A whenever phaeochromocytoma coexists with a thyroid lesion.
- RET mutation testing has major implications for family members.
- Phaeochromocytoma must be treated before thyroid surgery.
Pathfinder Pearls
Common Pitfalls
- Assuming hypertension in a young patient is essential hypertension without investigating secondary causes.
- Missing the classic episodic symptoms of phaeochromocytoma.
- Starting beta-blockers before adequate alpha-blockade in phaeochromocytoma.
- Overlooking a thyroid nodule during examination.
- Failing to screen for hyperparathyroidism.
- Not arranging genetic counselling for the patient and first-degree relatives.
- Proceeding to thyroid surgery before excluding phaeochromocytoma.
Key Take-home Messages
- Always investigate secondary causes in young-onset or resistant hypertension.
- Phaeochromocytoma should be suspected in patients with episodic headaches, palpitations and sweating.
- MEN2A consists of medullary thyroid carcinoma, phaeochromocytoma and primary hyperparathyroidism.
- RET mutation testing confirms the inherited syndrome and guides family screening.
- Treat phaeochromocytoma before undertaking thyroid surgery.
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