Valores inesperadamente elevados de TSH: a presença de formas de alto peso molecular ("macro TSH") deve ser investigada

Abstract

The laboratory methods usually employed for the measurement of serum TSH present sensitivity and specificity levels, both analytical and clinical, are highly satisfactory. Additionally, the methodologies are quite robust, so that false-positive and false-negative results are rare and unexpected. In this paper we describe two individuals quoted as euthyroid clinically, with no reference to autoimmune diseases, and no reference to the use of exogenous TSH, that presented with normal to extremely high serum TSH levels, depending on the method employed for analysis. In the three tested methods, serial dilution showed that the real TSH levels were between 250 and 300 mUI/L. In both cases the increment in TSH levels were due to the presence of TSH-binding proteins, forming high molecular weight complexes ("macro TSH"), well characterized by gel filtration chromatography on Superdex S-200 column. In one of the patients the binding protein was characterized as being IgG by protein-G binding study. In the other case, protein-G binding as well as anti-IgM binding failed to characterize the protein. These two cases call attention to the importance of the clinical-laboratory correlation and suggest the need that the presence of "macro TSH" must be investigated in patients with unexpectedly high TSH values.

Tissue-Specific Posttranslational Modification Allows Functional Targeting of Thyrotropin

“…Although the immunoreactive band of IgG-TSH was shifted by the DTT treatment, detection of IgG2b at same molecular weight confirmed the existence of IgG-TSH complex even after DTT treatment (Figure 3J). In contrast to aforementioned treatments, only acidification below pH 3 has been reported to dissociate the macro-TSH complex in humans (Sakai et al, 2009; Vieira et al, 2006). Therefore, we also examined the effect of acidification on the stability of the mouse IgG-TSH complex.…”

“…These results indicated that PT-TSH forms macro-TSH with IgG or albumin. It is suggested that the binding of TSH to IgG is extremely high in humans and rats (Erhardt and Scriba, 1977; Kourides et al, 1978; Mori et al, 1984; Sakai et al, 2009; Vieira et al, 2006). For example, incubations with the surfactant Triton-X, the strong denaturants; mercaptoethanol and quinidine hydrochloride, or the enzyme trypsin do not dissociate the IgG-TSH complex.…”

TSH de alto peso molecular ou "macro TSH": importância do diagnóstico

“…Entretanto, ao solicitarmos um exame complementar jamais devemos esquecer a correlação clínico-laboratorial tão bem discutida no estudo de Vieira e cols. (6).…”

“…Há dados sugerindo que o TSH ligado a anticorpos também seja incapaz de se ligar às células tireóideas, o que corrobora os achados clínicos de Vieira e cols. (6), pois os pacientes não têm sinais e sintomas de hipertireoidismo ou bócio, apesar de apresentarem TSH elevado. Por outro lado, também não há características clínicas de hipotireoidismo, ou seja, uma fração do TSH sérico deve ser biologicamente ativa o que é fundamental para manter a função tireóidea normal.…”

A mini-review in Thyroid Function Test: More Than Meets Our Eye

“…The TSH did not recover more than 20% when subjected to polyethylene glycol precipitation (14). The Roche and Perkin-Elmer DELFIA assays are more susceptible to macro-TSH interference, whereas the ADVIA Centaur assay is less sensitive to such interference (16,17) Macro-TSH is diagnosed when a macro-TSH/ hypothyroid mixture gives lower TSH values after the incubation in assays known to be adequately sensitive to macro-TSH. The gold standard test for the isolation of macro-TSH is gel filtration chromatography which is costly and not readily available (18).…”