Factitious Increase in Thyrotropin in a Neonate Caused by a Maternally Transmitted Interfering Substance

Newman, Julie; Bergman, Philip; Doery, James C.G.; Balazs, N.D.H.

doi:10.1373/clinchem.2005.064832

Cited by 21 publications

(20 citation statements)

References 15 publications

(7 reference statements)

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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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“…Because macro TSH is a complex of TSH and IgG in most cases (3,4,5,6,7,8,9,10,11), increased ratios of PEG-precipitable TSH may indicate the presence of macro TSH. In macroprolactinemia, PEG-precipitable PRL O60% (recovery !40%) is usually used for the screening, and the diagnosis is confirmed using gel filtration chromatography (16,17,18,19,20,21,22).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

“…The prevalence of subclinical hypothyroidism has been reported as being present in 4-10% of the adult population, depending on the TSH cut-off and assay platform (1). However, the prevalence might be lower, since it has been reported that the direct analogue immunoassay for free thyroxine (T 4 ) measurement results in a significant proportion of patients being misclassified as having subclinical hypothyroidism (2).…”

Section: Introductionmentioning

confidence: 99%

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Variability in the detection of macro TSH in different immunoassay systems

Hattori

Ishihara

Shimatsu

2016

European Journal of Endocrinology

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Design: Macro TSH is a large molecular-sized TSH that is mostly a complex of TSH and IgG. Patients with macro TSH have elevated serum TSH and normal free thyroxine levels, mimicking subclinical hypothyroidism. The aim of this study was to clarify the degree of cross-reactivity of macro TSH to different commercial immunoassay systems. Methods: Screening for macro TSH was done using a polyethylene glycol (PEG) method and confirmed with gel filtration chromatography in serum samples from 1901 patients with subclinical hypothyroidism. Interference due to human anti-mouse antibodies (HAMA) was examined using HAMA blockers. TSH was measured with an enzyme immunoassay for the analysis of macro TSH. Serum TSH values in patients with macro TSH were also determined with the widely used commercial immunoassay platforms Elecsys, Centaur and Architect, and the detectability of macro TSH was compared among them. Results: Gel filtration chromatography was performed with 174 serum samples with PEG-precipitable TSH ratios O75%. Twenty serum samples were found to contain large molecular-sized TSH, five of which were due to interference by HAMA. The prevalence of macro TSH was eventually 0.79% (15/1901). Commercial immunoassay systems variably recognized macro TSH. The Architect TSH immunoassay platform was the least reactive to macro TSH, but still recognized it in 60% of macro TSH-containing serum samples. Conclusions: There were no commercial TSH immunoassay platforms that did not cross-react with macro TSH. Screening for macro TSH should be performed before hormone replacement therapy is initiated for subclinical hypothyroidism.

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“…This has already been described in cases of macro-TSH complexes detected in both maternal and neonatal sera. This shows that it is possible for interfering antibodies to be passed from mother to child resulting in interference affecting hormone measurement from the newborn's blood [5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

The Risk from Anti-Thyroid Hormone Antibody Interference in Neonatal Congenital Hypothyroidism Screening

Brincat

Buhagiar

2017

IJNS

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Neonatal congenital hypothyroidism screening is considered to be one of the most effective newborn screening strategies. Neonatal screening for congenital hypothyroidism involves the analysis of thyroid hormone and thyrotropin levels using an immunoassay based technique. Immunoassays are also prone to analytical problems such as assay interference. Immunoassays used for thyroid hormone measurement are known to be affected from anti-thyroid hormone antibody interference. This is the first reported case of interference presumably caused by anti-thyroid hormone antibodies transferred from mother to child during pregnancy, affecting the measurement of free-thyroxine in a cord-blood sample. We report a case of a full-term newborn with presumed anti-thyroid hormone antibody interference present in both cord blood and subsequent venous blood samples. In the context of a newborn screening programme based solely on thyroxine measurement, this is an important finding, since it has the potential to cause false negative screening results.

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Factitious Increase in Thyrotropin in a Neonate Caused by a Maternally Transmitted Interfering Substance

Cited by 21 publications

References 15 publications

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

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

Variability in the detection of macro TSH in different immunoassay systems

The Risk from Anti-Thyroid Hormone Antibody Interference in Neonatal Congenital Hypothyroidism Screening

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