Phaeochromocytoma and endocrine hypertension — formative SAQs

SAQ 1 — The hypertensive adolescent with spells (20 marks, ~15 minutes)

A 14-year-old boy presents with a six-month history of episodes of severe headache, generalised sweating, palpitations and anxiety lasting minutes, with pallor noted by his mother. Between episodes he feels well. His blood pressure is 160/100, sustained on repeat measurement, and his heart rate is 96. A catecholamine-secreting tumour is suspected. [4]

Questions

1. State the best first-line biochemical test and explain why it is preferred over a random catecholamine level. (4 marks) [3]
2. Outline the imaging strategy once biochemistry is positive, including functional imaging. (5 marks) [1]
3. Describe the mandatory preoperative pharmacological preparation, stating the sequence and the consequence of getting it wrong. (6 marks) [1]
4. Explain why every child with this diagnosis needs a hereditary gene panel, and name the gene that flags metastatic extra-adrenal disease. (5 marks) [2]

Model answer (must-hit)

1. Measure plasma free metanephrines or a twenty-four-hour urine fractionated metanephrines collection. These are preferred because the tumour cell continually converts catecholamines to metanephrines (noradrenaline to normetanephrine, adrenaline to metanephrine), which leak into the bloodstream continuously, whereas catecholamine release is episodic from stored vesicles. A random catecholamine level drawn between spells reads normal and misses the tumour; metanephrines do not. [3]
2. Start with CT or MRI of the abdomen and pelvis (MRI preferred in children to avoid radiation) because most tumours lie in the adrenal gland or the organ of Zückerkandl. Then characterise and stage with functional imaging — iodine-123 MIBG scintigraphy or, increasingly, gallium-68 DOTATATE PET, which is more sensitive for metastatic and hereditary disease. [1]
3. Alpha-blockade first, then beta-blockade. Start phenoxybenzamine at around 0.5 mg per kilogram per day in divided doses and titrate over ten to fourteen days until the child is normotensive or mildly hypotensive with an orthostatic drop and nasal stuffiness — the block-and-fill end-point. Add a beta-blocker only once the child is fully alpha-blocked, to control reflex tachycardia. Giving a beta-blocker first removes beta-two vasodilator tone and leaves unopposed alpha-one vasoconstriction, precipitating a fatal hypertensive crisis. [1]
4. Around forty percent of paediatric phaeochromocytomas and paragangliomas carry a pathogenic germline mutation, far above adults, so every child earns a gene panel covering SDHx, VHL, RET, NF1, TMEM127, MAX and FH. Identifying the mutation predicts tumour behaviour, sets the surveillance schedule and enables cascade testing of relatives. An SDHB mutation flags extra-adrenal paraganglioma with metastatic potential. [2]

SAQ 2 — The hypertensive child with hypokalaemia (20 marks, ~15 minutes)

A 10-year-old girl is found to be hypertensive at 150/95 on a routine examination. Her serum potassium is 2.9 mmol per litre, her plasma renin is suppressed and her plasma aldosterone is also suppressed. Her father and paternal aunt were diagnosed with hypertension in their twenties; her grandfather died of a stroke at 45. [11]

Questions

1. Give the diagnostic category and the renin–aldosterone pattern that defines it. (4 marks) [11]
2. Name the two most likely monogenic diagnoses and state the rational first-line therapy for each. (6 marks) [12]
3. Explain why spironolactone is the wrong first drug for Liddle syndrome, and name the correct drug and its mechanism. (5 marks) [11]
4. Describe the family evaluation that should follow a confirmed monogenic diagnosis. (5 marks) [12]

Model answer (must-hit)

1. This is a monogenic mineralocorticoid cause of low-renin, low-aldosterone hypertension. The defining pattern is hypokalaemia with both renin and aldosterone suppressed, indicating sodium retention at the distal nephron driven from below the adrenal gland, independent of aldosterone. [11]
2. The two most likely diagnoses are Liddle syndrome (an epithelial sodium channel gain-of-function mutation in SCNN1B or SCNN1G) and apparent mineralocorticoid excess (loss of 11-beta-hydroxysteroid dehydrogenase type 2, which normally shields the mineralocorticoid receptor from cortisol). Liddle responds to amiloride or triamterene; apparent mineralocorticoid excess responds to mineralocorticoid-receptor blockade with spironolactone or eplerenone, or glucocorticoid replacement. [12]
3. Spironolactone blocks the mineralocorticoid receptor, but in Liddle syndrome the receptor is not the problem — the epithelial sodium channel is constitutively open because of the gain-of-function mutation, so aldosterone-receptor blockade under-controls the blood pressure. The rational drug is amiloride, which blocks the epithelial sodium channel directly and corrects both the hypertension and the hypokalaemia. [11]
4. Offer cascade genetic testing to first-degree relatives, because a confirmed monogenic diagnosis identifies affected relatives who may have unrecognised hypertension and hypokalaemia. Screen parents and siblings with blood pressure, electrolytes and targeted gene testing, and counsel the family on the autosomal dominant inheritance and the lifelong but highly treatable nature of the condition. [12]