Endocrine Abstracts

Case history: A 47 year old male presented to his GP with non-specific symptoms of fatigue and weight gain. Thyroid function tests revealed elevated TSH (28.4 mU/l) with normal Free T4 (14.3 pmol/l). Anti-TPO antibodies were undetectable. A presumptive diagnosis of subclinical hypothyroidism was made and he was commenced on Levothyroxine which was titrated over 9 months to 150 mcg/d given a persistently elevated TSH. The patient was unable to tolerate this dose due to the development of sweating, palpitations, heat intolerance and insomnia. His dose was then reduced to 125 mcg/d and he was referred to his local Endocrinology service.

Investigations: On examination he appeared clinically euthyroid with no goitre and no eye signs. Repeat thyroid function demonstrated Free T4 26.9 pmol/l and TSH 11.67 mU/l. SHBG was elevated at 88 nmol/l. Alpha-subunit was normal at 0.2 U/l. The clinical impression was of iatrogenic thyrotoxicosis with possible underlying thyroid hormone resistance, TSHoma or assay interference. Levothyroxine was discontinued and the patient re-evaluated after 6 weeks.

Results and treatment: The patient’s free T4 normalised on cessation of Levothyroxine (13.2 pmol/l) however TSH remained elevated (20.26 mU/l). There was a normal response to TRH testing. T3 suppression testing demonstrated appropriate Free T4 suppression but a persistently high TSH of 12.08 mU/l. THRβ sequencing was normal. Given the persistence of TSH elevation despite various concentrations of thyroid hormone, the suspicion was of MacroTSH or heterophilic antibody interference. TSH measurement by alternative assays revealed discrepant results; 12.21 mU/l (Roche Cobas) and 1.7 (Abbott Architect). PEG extraction of TSH yielded a recovery 15.7%. Sephadex gel filtration chromatography was performed and confirmed the presence of high molecular weight TSH variant alongside normal TSH. Displacement of this high molecular weight variant was seen on acidification in keeping with IgG bound macroTSH. The patient remained well to follow up in the absence of any treatment.

Conclusions and points for discussion: MacroTSH is a rare phenomenon that presents as a spuriously elevated TSH and which may mimic subclinical hypothyroidism. Careful history and examination should alert the clinician to thyroid function tests that are discordant with the clinical picture. Non-specific symptoms should not be automatically ascribed to abnormal thyroid function. Recognition of macroTSH avoids misdiagnosis and prevents inappropriate treatment.