Endocrine Abstracts

Background: Elevated TSH concentration should be assessed and treated with caution because of the possibility of transient thyroid dysfunction, or, in rare cases, measurement interference. We describe a case with a rare cause of elevated TSH level in a 39-year-old mother and her four children.

Case Summary: A 39-year-old lady was referred with a long history of high serum TSH ranging between 18.9 to 38.7 (reference interval 0.4-4.0 mU/l) with FT4 concentration ranging between 12.0-15.6 but within reference interval 12.0-22.0 pmo/l using Roche Elecsys thyroid assays. There were no associated significant hypothyroid symptoms or signs and no family history of thyroid disorder. Serum TSH concentration was also elevated using assays from Abbott and Perkin Elmer DELFIA. Despite this, she never required levothyroxine therapy. Mutations associated with thyroid hormone resistance were not detected by THRβ gene sequencing. She has four male children aged 10, 8, 3 years, and 8 months. All had elevated TSH concentration noted at birth, and all were commenced on levothyroxine replacement. However, the older three children were successfully weaned off levothyroxine by age of 30 months. Recovery of TSH immunoreactivity following polyethylene-glycol precipitation (PEG) was low at 17 (27-70) % suggesting immunoglobulin-based TSH assay interference. Gel filtration chromatography confirmed the presence of high molecular mass TSH immunoreactivity in the samples of the mother and PEG recovery was also abnormal at 21 (27-20) % in her youngest child.

Discussion: Increased immunoreactive TSH, in this case, is likely to be due to Macro-TSH, an immunoglobulin TSH complex. This can accumulate in circulation, simulating a laboratory picture of subclinical hypothyroidism. Multiple TSH assays can be affected. Macro-TSH can be detected by immunosubtration and dilution studies and confirmed by gel filtration chromatography. As transplacental transmission of Macro-TSH can occur. Maternal TSH should be checked following all positive Guthrie tests to prevent inappropriate diagnosis and treatment.