FRI480 Uncovering The Mystery Of Macro TSH

Abstract Disclosure: F. Anwar: None. Z.I. Saeed: None. Introduction: An isolated elevation in TSH level, while uncommon, may result in incorrect diagnosis and improper treatment. We present a case of suspected hypothyroidism that was later found to be caused by macroTSH in the blood. Clinical Case: A 21-year-old asymptomatic female was diagnosed with hypothyroidism and started on levothyroxine at age 16 when routine lab work revealed TSH of 34.2 MCU (0.550-4.780 MCU) and free T4 of 1.1 ng/dl (0.89-1.76 ng/dl). She denied any personal or family history of thyroid disorders in the past. Patient later reported symptoms including palpitations and weight loss leading to discontinuation of levothyroxine. Repeat lab work showed TSH of 0.112 MCU and free T4 of 1.71 ng/dl. After discontinuing levothyroxine, TSH levels were found in range of 89.26 MCU to 106 MCU (0.550-4.780 MCU). Free T4 levels remained normal, even when tested using dialysis method. Total T3 level also remained normal at 87 ng/dl (80-200 ng/dl). TPO antibodies were slightly elevated at 9.3 IU/mL (0.0-9.0 IU/ml), TSI and TSH receptor antibodies were negative. Patient's high TSH level, lack of symptoms, and normal free T4 levels prompted the use of different assays to test TSH. We contacted Mayo Clinic Lab for further testing. One assay (Roche Elecsys) showed TSH level of 90.8 mIU/L, but this result was not significantly changed when sample was incubated with a commercial heterophile antibody blocking reagent. Another assay (Beckman Coulter Access TSH) produced a significantly different but still elevated result of 43.1 mIU/L. For research purposes, the sample was further tested for macroTSH using polyethylene glycol (PEG) precipitation, which resulted in TSH level of 5.8 mIU/L which was reduced from 90.8 mIU/L (94% reduction). These results were higher than the mean +/- 2 standard deviations of the control group (range 0% to 65% reduction in TSH with PEG in controls). This suggested presence of macroTSH, although the assay's performance characteristics and reference ranges had not been established at the time of testing for this patient. Patient's TSH levels remain high and she was advised not to begin the medication unless circulating thyroid hormone levels are abnormal. Conclusion: Macro TSH is a combination of monomeric TSH and anti-TSH antibodies, similar to macro-prolactin. It is considered inactive and has an estimated prevalence of 0.6-1.6%. In a review of over 150 patients, more than 50% of documented thyroid interferences, including macro TSH, led to incorrect diagnosis and improper treatment. This case demonstrates the significance of identifying macro TSH to avoid misdiagnosis and inappropriate management of euthyroid patients with isolated TSH elevation. Presentation: Friday, June 16, 2023