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Stem
A 30-year-old woman is referred by her GP after presenting with episodic severe headaches, sweating and palpitations over three months, during which her blood pressure has ranged from 150/95 to 210/120. She also reports a six-month history of a painless left-sided neck lump. Her father died suddenly at 45 from a "thyroid cancer" and her paternal aunt has hyperparathyroidism. On examination, BP 180/110, pulse 96, a 2 cm firm left thyroid nodule with a palpable left cervical node. Twenty-four-hour urine fractionated metanephrines are markedly elevated.
Questions
a) What is the most likely syndromic diagnosis? Give two features from the stem that support it and name the mutated gene and chromosome. (3 marks)
Model answer: MEN 2A (Sipple syndrome) (1). Any two of: phaeochromocytoma (episodic headache, sweating, palpitations, hypertension, raised urinary metanephrines), medullary thyroid carcinoma (neck lump with cervical node - typical first manifestation), family history of thyroid cancer and hyperparathyroidism (autosomal dominant) (1). Gene: RET proto-oncogene on chromosome 10q11.2 (gain-of-function; codon 634 typical of MEN 2A) (1).
b) Outline the immediate pre-operative management priority before any surgery in this patient, naming the drug, dose and the cardinal rule of beta-blockade. (3 marks)
Model answer: ALWAYS EXCLUDE AND TREAT PHAEOCHROMOCYTOMA BEFORE ANY (THYROID) SURGERY (1) — an undiagnosed phaeo under anaesthesia is fatal. Pre-operative ALPHA-blockade with phenoxybenzamine 10 mg twice daily, titrated over 10 to 14 days with intravascular volume expansion (liberal salt and fluid) (1). A beta-blocker (e.g. propranolol) is added ONLY AFTER adequate alpha-blockade — giving a beta-blocker first precipitates unopposed alpha vasoconstriction and catastrophic hypertension/pulmonary oedema (1). Laparoscopic (cortical-sparing, given likely bilaterality) adrenalectomy precedes thyroidectomy.
c) Outline the surgical management of her medullary thyroid carcinoma, including the tumour markers used for surveillance and why radioiodine is not used. (2 marks)
Model answer: Total thyroidectomy with central (level VI) neck dissection (lateral neck dissection if nodal disease) (1). Surveillance markers are calcitonin and CEA (NOT thyroglobulin, which tracks papillary/follicular cancer from follicular cells); calcitonin doubling time (under 6 months poor, over 24 months good) is the best prognostic marker. Radioiodine is useless because parafollicular C cells do not take up iodine (1).
d) Describe the family screening programme that should follow her genetic diagnosis. (2 marks)
Model answer: Confirm the pathogenic RET mutation in the proband by germline sequencing, then offer predictive genetic testing of all first-degree relatives FROM BIRTH (autosomal dominant, 50 percent risk per child) (1). RET-positive relatives enter the ATA risk-adapted programme: prophylactic thyroidectomy timed by mutation risk (highest MEN 2B codon 918 in infancy; high MEN 2A codon 634 by about age 5) with annual basal calcitonin/CEA, plasma or 24-hour urine fractionated metanephrines, and serum calcium/PTH surveillance; MEN 1 relatives are screened from age 5 (1).