Transient neonatal hyperthyrotrophinaemia: a serum abnormality due to transplacentally acquired antibody to thyroid stimulating hormone.

Lazarus, John; John, Rhys; Ginsberg, Jody; Hughes, Ieuan A.; Shewring, Gerald; Smith, B. R.; Woodhead, J. S.; Hall, R.

doi:10.1136/bmj.286.6365.592

Cited by 45 publications

(23 citation statements)

References 14 publications

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“…However, there are almost no reports on the formation of macro-TSH except in cases of neonates and their mothers both of whom had the anti-TSH autoantibody [11][12][13]. In the present case we were able to clearly demonstrate that the majority of TSH in the patient serum was present in the form of macro-TSH consisting of the immune complex bound to the anti-TSH autoantibody.…”

Section: Discussionsupporting

confidence: 52%

Falsely Elevated Thyroid-Stimulating Hormone (TSH) Level Due to Macro-TSH

et al. 2009

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trochemiluminescence immunoassay (ECLIA). These latter immunoassays provide greater precision, accuracy and a wider range of measurement [5].A high level of TSH generally indicates hypothyroidism. However, we should consider the cases of TSH-producing tumor, resistance to thyroid hormone (RTH: Refetoff syndrome), and false elevation of TSH due to heterophile antibodies specific to the reagents [6]. Autoimmunity against TSH is rare and has not been evaluated in sufficient detail, although several reviews have been published on heterophile antibodies.We examined a case with extremely high TSH levels. We decided to perform the polyethylene glycol (PEG) precipitation test. Furthermore, the TSH value was shown to be markedly low by PEG precipitation test. We eventually found macro-TSH, a unique anti-TSH autoimmune complex which may have caused the unexpectedly high elevation of TSH. Abstract. We encountered a 60-year-old woman with remarkably elevated thyroid-stimulating hormone (TSH) level as measured by electrochemiluminescent immunoassay (ECLIA), but with no specific symptoms, and with normal levels of free T3 and free T4. We performed the following investigations: polyethylene glycol (PEG) precipitation test, human antimouse IgG antibody (HAMA) interference test, and 3 additional TSH measurements by chemiluminescent immunoassay (CLIA). We then performed 2 gel filtration chromatography (GFC) procedures; one was at pH 7.2, and the other was at pH 3.0. Although the recovery of TSH shown by the PEG precipitation test was 4% which was extremely low, no HAMA interference was observed. Moreover, 3 CLIA instruments also showed various high values. The first GFC showed that the main peak of TSH immunoreactivity by ECLIA was located at a slightly larger molecular weight position than that of IgG. By the second GFC, the sample from the peak fraction of the first GFC showed that the TSH peak disappeared completely at the previous retention time but newly appeared at the same retention time as the TSH monomer. Protein G-Agarose gel removed the majority of the TSH complex. In conclusion, the majority of TSH in her serum was macro-TSH; TSH and anti-TSH IgG autoantibody complex. We should keep the possibility of macro-TSH in mind in cases with unexpectedly high TSH values, especially in autoimmune thyroidal disorders.

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Section: Discussionsupporting

confidence: 52%

Falsely Elevated Thyroid-Stimulating Hormone (TSH) Level Due to Macro-TSH

et al. 2009

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“…In some this is indicative of an ectopic thyroid [4,5]. In others, the increased plasma TSH may be transient and of an unknown cause [8] or artefactual arising from the transplacental transfer of maternal antibodies [3,6,7].…”

Section: Introductionmentioning

confidence: 94%

Persistent hyperthyrotropinaemia since the neonatal period in clinically euthyroid children

et al. 1991

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We describe three children, now aged between 5 and 6 years, with a persistent mild hyperthyrotropinaemia since the neonatal period and normal levels of thyroid hormones. The increased thyroid stimulating hormone concentration is not artefactual and is not caused by antibody interferences. Their growth and development is normal and none has received thyroid hormone replacement. We believe that they have compensated hypothyroidism, and that before the advent of screening for congenital hypothyroidism these children would have presented in mid-childhood with juvenile hypothyroidism.

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“…There are neonates having congenital hypothyroidism due to antibodies with macro-TSH reported in the literature, in whom it was shown that the macro-TSH passed from the mother across the placenta [8,9]. This point may be important and should be kept in mind in women who are diagnosed with macro-TSH in their child-bearing age, like our patient.…”

Section: Discussionmentioning

confidence: 54%