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Letters to the Editor |
1 Biochemistry Unit, Southern Cross Pathology Australia, 2
Diabetes Ambulatory Care Service, Monash Medical Centre, Clayton, Victoria, Australia
3 Departments of Paediatrics, and 4
Immunology, Monash University, Monash Medical Centre, Clayton, Victoria, Australia
aAddress correspondence to this author at: Biochemistry Unit, Southern Cross Pathology Australia, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 3168, Australia. Fax 061-03-9594-6619; e-mail julie.newman{at}southernhealth.org.au.
To the Editor:
Falsely increased thyrotropin (TSH) results caused by heterophile antibodies have been well documented in the literature. Although demonstration of macro forms of hormones (especially macroprolactin) is well known, there have been very few reports in the literature of factitious TSH increases caused by macro TSH in euthyroid patients.
Halsall and colleagues, in their letter above, are to be commended for their elegant use of Sephacryl S-300 chromatography to analyze macro TSH in the serum of a mother and her neonate.
Unfortunately, it is unclear whether the maternally transmitted interfering substance that we detected in our study (1) is similar to the macro TSH reported by Halsall et al. In the neonate investigated by Halsall et al., the increase in neonate TSH values was an order of magnitude greater than in our patient (Roche Elecsys result of 826 mIU/L compared with 60.9 mIU/L, measured on the Dade Dimension in our study). Like Halsall et al., we believe that we excluded the presence of heterophile antibodies, but there remains a possibility that we were also dealing with a macro TSH. Protein A-sepharose did not decrease the high maternal serum TSH concentrations in our study, in marked contrast to the protein G-sepharose in the study of Halsall et al. Two possible explanations are the presence of an IgG3-TSH binding antibody not bound by protein A-sepharose but bound by protein G-sepharose; or dissociation of an IgG-TSH complex under the conditions of the protein A-sepharose separation, perhaps a result of the ionic strength, as demonstrated by Tamaki et al. (2).
We reiterate the importance of following up abnormal TSH results for which clearly increased TSH is inconsistent with the clinical state of the patient and/or the normal free thyroxine (FT4). This precaution is particularly important in newborn screening, but will apply generally to any situation. In the case of neonates, confirmation of the abnormality in maternal serum (by measuring both TSH and FT4) will support the conclusion that the interference is caused by a maternally derived Ig. Alternative assays may confirm the artifactual nature of the TSH. It may be necessary, however, to provide more than 1 alternative assay, because we found that 4 of 7 TSH assays were affected in our study (1), and Halsall et al. found that 3 of 4 assays were affected. Other tests to elucidate whether the interference is a result of a heterophile antibody or macro TSH should include measurement of dilutions of sample with manufacturers diluent, sample pretreatment with protein A-sepharose, and addition of heterophile blocking agents such as Scantibodies.
We would support the approach of Halsall et al. in definitively demonstrating the presence of a macro TSH by the use of gel filtration. In conclusion, the presence of macro TSH has been poorly recognized but may be more common than is currently appreciated.
References
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