Abnormal thyroid hormone response to TRH in a case of macro-TSH and the cut-off value for screening cases of inappropriate TSH elevation

A 74-year-old asymptomatic Japanese man with suspected thyroid dysfunction was referred to our hospital. He had an elevated TSH (53.8 mIU/L; reference interval: 0.5-5.0) despite a free T4 (FT4) level (1.4 ng/dL; reference interval: 0.9-1.6). Further analysis revealed macro-TSH. A notable finding was that a 500-mu g TRH stimulation test revealed a blunted free T3 (FT3) response despite a prolonged TSH response. Macro-TSH typically presents with inappropriately marked elevation of serum TSH levels compared with other thyroid hormones, as exhibited in our case. However, the level of TSH elevation that might differentiate macro-TSH from subclinical hypothyroidism is poorly known. We retrospectively analyzed 8,183 concurrent measurements of TSII and FT4 in individuals previously examined in our hospital to define the cut-off value for screening cases of inappropriate TSH elevation. FT4 values were rounded off to one decimal place, and the 97.5th percentile of TSH against each FT4 value was calculated. The data of our patient and that of 30 cases of macro-TSH extracted from the English literature were then assessed. When the approximate curve obtained from the 97.5th percentile of TSII values was defined as the cut-off value [Log(10)TSH = 0.700 + 1.549/{1 + (FT4/0.844)(6.854)}], 25 of the 31 (80.6%) macro-TSH cases were identified. In conclusion, we report for the first time a case of macro-TSH demonstrating an abnormal FT3 response to TRH. A cut-off value of TSH adjusted to the FT4 level may be a good method of screening for inappropriate TSH elevation (or inappropriate hyperthyrotropinemia) including those caused by macro-TSH.