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A 52-year-old woman presents to her GP with a 6-month history of progressive fatigue, cold intolerance, a 4 kg weight gain, constipation, and menorrhagia. On examination she is bradycardic (pulse 52/min) with cool, dry skin, periorbital puffiness, a firm rubbery diffuse goitre, and slow-relaxing ankle reflexes. Her TSH is 18 mIU/L (reference 0.4 to 4.5) and free T4 is 6 pmol/L (reference 10 to 20).
Questions
a) What is the diagnosis, the most likely underlying cause, and the expected antibody? (2 marks)
Primary overt hypothyroidism, with the firm rubbery diffuse goitre pointing to chronic autoimmune (Hashimoto) thyroiditis — the commonest cause in iodine-sufficient regions. The expected antibody is anti-thyroid peroxidase (anti-TPO), positive in about 90% of cases.
b) Outline the pathophysiology of her symptoms, with two molecular mechanisms. (2 marks)
Loss of T3 action at the nuclear thyroid-hormone receptor reduces transcription of target genes: (1) reduced Na-K-ATPase lowers basal metabolic rate (fatigue, cold intolerance, weight gain) and (2) reduced beta-adrenergic receptor density/coupling produces bradycardia and reduced inotropy. Accumulation of hyaluronic acid glycosaminoglycans in the dermis causes the non-pitting periorbital puffiness (myxoedema). Hashimoto itself is driven by CD8+ cytotoxic T cells and anti-TPO antibodies with Th1 cytokines (IFN-gamma, TNF-alpha) causing follicular-cell apoptosis.
c) Give three relevant associated laboratory abnormalities and explain each. (3 marks)
- Raised LDL cholesterol — downregulated hepatic LDL receptor.
- Hyponatraemia — impaired free-water clearance and inappropriate ADH.
- Raised creatine kinase — from hypothyroid myopathy (not infarction).
- (Also acceptable: macrocytic anaemia from coexisting pernicious anaemia; raised prolactin from TRH-driven stimulation.)
d) Outline the definitive management with drug, dose, route, and monitoring plan. (2 marks)
Oral levothyroxine started at the full adult replacement dose of about 1.6 mcg/kg/day (roughly 100 to 125 mcg daily for this 60 kg woman), taken fasting 30 to 60 minutes before breakfast, separated from calcium/iron by 4 hours. Recheck TSH at 6 to 8 weeks, titrate by 12.5 to 25 mcg, then monitor TSH every 6 to 12 months lifelong once stable. Patient education on adherence and lifelong therapy.
e) Two complications of over-treatment and one situation where the starting dose must be much lower. (1 mark)
Over-treatment causes iatrogenic (subclinical) hyperthyroidism — atrial fibrillation and osteoporosis. Start at 25 mcg and titrate slowly (by 25 mcg every 2 to 4 weeks) in the elderly and in those with ischaemic heart disease, because rapid replacement can precipitate angina or infarction.