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      Macro-TSH: A Diagnostic Challenge

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          Introduction: Analytical problems should be considered in case of a discrepancy between the results of biochemical tests and the clinical findings. Macro-hormones often artefactually elevate biochemical tests. Case Presentation: A young male was referred with persistently elevated TSH (148 mIU/L) measured by a sandwich electrochemiluminescence immunoassay, ECLIA (Cobas; Roche, Basel, Switzerland). The patient’s complaints were unspecific, and he appeared clinically euthyroid. The plasma levels of free T4 and free T3 were within the normal range, thyroid autoantibodies were negative, and thyroid ultrasonography was normal. During a short trial of thyroid hormone substitution, the level of TSH decreased to near-normal levels, but hyperthyroid symptoms emerged. TSH analysed by a different immunoassay (Architect; Abbott, Chicago, IL, USA) yielded similar results. In addition, serial dilutions were performed showing linearity, without detection of heterophilic antibody interference. Gel filtration chromatography confirmed the presence of macro-TSH. Conclusion: The patient harboured macro-TSH, which is a rare condition. The complex binding of TSH to other plasma proteins, most often immunoglobulins, results in elevated plasma TSH. However, the biologically active fraction of TSH is normal, reflected by clinical and biochemical euthyroidism.

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          Most cited references 10

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          Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm

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            Macro-thyrotropin: a case report and review of literature.

            Isolated elevation of TSH in the absence of thyroid symptoms can be very rarely caused by a macromolecule formed between TSH and Ig (macro-TSH), confounding the interpretation of thyroid function test results. We described the use of several commonly available laboratory-based approaches to investigate an isolated TSH elevation [232 mIU/liter; free T(4), 10 pmol/liter (reference interval, 10.0-23.0 pmol/liter), Vitros platform] in a clinically euthyroid elderly gentleman, which led to the diagnosis of macro-TSH. TSH concentration of the patient was significantly lower (122 mIU/liter) when measured on the Advia Centaur platform. Serial dilution of the patient's sample showed a nonlinear increase in TSH recovery at increasing dilution (nonlinearity). Polyethylene glycol precipitation and mixing the patient's sample with a hypothyroid patient sample showed reduced TSH recovery, suggesting the presence of a high molecular weight interfering substance and excess TSH binding capacity, respectively. Heterophile blocking tube studies and rheumatoid factors were negative. Gel filtration chromatography demonstrated a TSH peak fraction that approximated the molecular size of IgG; together with the excess TSH binding capacity, this indicated the presence of TSH-IgG macro-TSH. A review of 12 macro-TSH case reports showed that samples with macro-TSH produce over-recovery with dilution, return negative results on anti-animal and anti-heterophile blocking studies, and commonly have recovery of less than 20% when subjected to polyethylene glycol precipitation. Macro-TSH is an underrecognized laboratory interference. Routine laboratory techniques described above can help diagnose this rare entity. A close dialogue between the physician and the laboratory is important in approaching such cases.
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              Macro TSH in patients with subclinical hypothyroidism.

              TSH is a sensitive indicator of thyroid function. In subclinical hypothyroidism, however, serum TSH concentrations are elevated despite normal thyroid hormone levels, and macro TSH is one of the causes. This study aimed to clarify the prevalence and nature of macro TSH in patients with subclinical hypothyroidism.

                Author and article information

                European Thyroid Journal
                S. Karger AG
                March 2021
                21 August 2020
                : 10
                : 1
                : 93-97
                aDepartment of Endocrinology, Odense University Hospital, Odense, Denmark
                bDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark
                cDepartment of Clinical Biochemistry and Immunology, Hospital of Southern Jutland, Aabenraa, Denmark
                dDepartment of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark
                Author notes
                *Camilla Bøgelund Larsen, Department of Endocrinology, Odense University Hospital, Kløvervænget 6, DK–5000 Odense C (Denmark), Camilla.Bogelund.Larsen@rsyd.dk
                509184 Eur Thyroid J 2021;10:93–97
                © 2020 European Thyroid Association Published by S. Karger AG, Basel

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                Page count
                Figures: 2, Pages: 5
                Clinical Thyroidology / Case Report


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