A 41-year old lady with hypothyroidism for 20 years attended the endocrinology clinic for persistently raised TSH levels despite high dose levothyroxine. Past medical problems depression, psoriasis, obesity, cholecystectomy. Her hypothyroidism was well-controlled until 2016 but since then, her TSH concentration had risen significantly to >100 mU/l with normal free T4. Levothyroxine had been increased in steps to 200 mcg/day. Despite the increased dose, the TSH concentration varied between 8.4 and 11.7 mU/l with normal free T4 levels. Clinically, she did not have significant symptoms of hypothyroidism, examination was unremarkable apart from her weight of 109 kg. She denied poor compliance with her medication. Her medications did not include any drugs which interact significantly with levothyroxine. Investigations including B12, folate, iron studies, calcium, transglutaminase antibodies, HbA1C unremarkable. Short Synacthen test normal. TSH measurements repeated on different platforms but were still high. Macro-TSH assay approximately 80% of the total TSH.
Conclusion: It is not unusual to see patients who have normal free T4 levels with raised TSH level in the context of subclinical hypothyroidism. There are many causes of persistent TSH elevation in patients on thyroxine replacement. These include poor compliance with treatment, drugs that interfere with absorption and other causes of malabsorption. Assay interference including macro-TSH should be considered in the differential diagnosis. Macro-TSH is a large TSH molecule which is formed between anti-TSH antibody and TSH which has low bioactivity. It can cause falsely elevated TSH.