Resistance to thyroid hormones (RTH) is a genetic syndrome characterized by reduced responsiveness of target tissues to thyroid hormones (TH) and accompanied by normal or slightly high TSH values with high serum concentrations of fT4 or fT3. We present two cases of RTH, one pituitary and one generalised resistance.
Case 1: A 31 y.o. male presented with thyrotoxicosis symptoms and a biochemical profile showing increased serum fT4 28.02 pmol/l (N 1222) and T3 209.7 ng/dl (80200) but normal TSH (4.33 mUI/l); he had a small goitre, increased SHBG and ATPO was negative. His CT scan revealed a pituitary microadenoma of 7/4 mm, but TRH test documented increasing TSH with 10 mUI/l from baseline to a maximum at 20 min. He was diagnosed with RTH syndrome with hyperthyroidism and started on Methimazole and beta blockers, with good clinical and biochemical response at follow-up.
Case 2: A female aged 57 with a small goiter, obesity, dyslipidaemia, glucose intolerance, infiltrated skin was diagnosed with subclinical hypothyroidism TSH 7.41 mUI/l, normal fT4, and negative ATPO. She was given 50 μg/day L-thyroxine and had normal thyroid profile for one year, when she presented with very high fT4 values (61.96 pmol/l-N 10.619.4) and a TSH in the upper limit, with the same clinical and biochemical features, suggestive of hypothyroidism. TRH test confirmed RTH syndrome, in a generalized form considering the clinical and biochemical profile. She is well under L-thyroxine treatment in the same dose. The genetic determination was not available in the two cases.
Conclusion: Despite rare, RTH syndrome should be considered when there are mismatches between the clinical and the thyroid functional profile.