Endocrine Abstracts

Introduction: MacroTSH or macrothyrotropin is a complex of TSH with IgG, resulting in a molecule with large molecular mass (>150 kDa) but low bioactivity. It can result in falsely elevated TSH levels due to persistence in the circulation, whilst T4 levels remain in normal range and the patient is clinically euthyroid. The clinical and biochemical picture mimics that of subclinical hypothyroidism. Failure to identify macroTSH may result in unnecessary hormone replacement.

Case Description: A 94 year old gentleman with a background of chronic lymphocytic leukaemia, treated with ibrutinib underwent a thyroid function test as part of a screen for weight gain and lethargy. Unexpectedly, as he was clinically euthyroid, the TSH was markedly elevated at 98.0. T4, however, was in the normal range at 14.4. Initially, he was presumed to have subclinical hypothyroidism above the threshold requiring levothyroxine therapy. The possibility of macro-TSH was raised by the clinical chemistry team and a MACROTSH-PEG precipitation study was performed which confirmed the presence of large molecular weight proteins. As the TSH was raised (29 mIU/l) even on the PEG precipitation study, the patient was presumed to have a degree of subclinical hypothyroidism in addition. He was commenced on levothyroxine 25 micrograms once daily. Follow up thyroid function tests demonstrated a decrease in TSH. A second case concerns as a 62 year old female with a background of type 2 diabetes AF and fatty liver, admitted with weakness. TFTs were performed as part of a neuropathy screen. She was clinically euthyroid at presentation. Initial TSH was 23.0 and T4 17.9. PEG precipitation demonstrated 38% recovery (TSH 8.74). The patient was not treated due to the corrected TSH <10 and normal T4. She was diagnosed with a sensory motor axonal polyneuropathy and following a course of prednisolone for vasculitis, TSH fell back to normal range.

Discussion: The polyethylene glycol precipitation method is used in order to remove high molecular weight proteins that could falsely elevate TSH readings. A low post-PEG TSH recovery indicates the presence of high molecular weight molecules interfering with the assay (including macro-TSH or interfering antibodies). This method was utilised in order to differentiate possible macro-TSH from subclinical hypothyroidism in our patients.