The most frequently ordered test to screen patients for thyroid disease is the TSH. This hormone is released by the pituitary gland in response to the blood levels of active thyroid hormones (free T4 and free T3). TSH levels are opposite the thyroid hormone levels. Therefore, if the blood thyroid hormone levels are low, the TSH will be elevated and vice versa.
Occasionally, when screening a person who does not appear to have obvious thyroid disease, a TSH will be found to be very low or not detectable. In those cases, if the free T4 is low, one might consider the diagnosis of central hypothyroidism (a problem with the pituitary gland) or the effect of another illness on TSH levels. If the free T4 is normal or high, then a diagnosis of hyperthyroidism might be considered. However, this study illustrates a different diagnostic possibility, showing that the physician must keep an open mind when evaluating thyroid tests, especially when the patient does not have any symptoms.
In a prior study, a group of 20 patients who had a TSH that was not detectable by the commonly used assays, was found to have a mutation involving one of the chains that make up the TSH molecule. The TSH with this mutation was found to have normal function, but almost half of the patients were inappropriately treated because their TSH levels were not detectable.
The current article describes all studies done on a new family carrying the same mutation, and reports results that indicate that the mutation described changes only a very small portion of the molecule that is needed for the attachment of the TSH to the antibodies used in the assays, therefore TSH is not detected although is present in normal quantities and has normal function.
THE FULL ARTICLE TITLE:
Pappa T et al TSHβ variant with impaired immunoreactivity but intact biological activity and its clinical implications. Thyroid 2015;25:869-75. Epub June 15, 2015.
SUMMARY OF THE STUDY
The first member of the family that was studied was a 4 year old boy. He had a TSH that was not detectable, a free T4, free T3 and total T4 that were normal. His 10 year old brother had identical thyroid tests. Their mother, older brother and sister had a normal TSH. The father declined testing. None of them had evidence of thyroid disease.