Pituitary disease unlikely in adults with low free T4 and normal free T4 index
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Most adults with free thyroxine levels slightly below the reference range have normal free T4 index values and did not have abnormal findings on pituitary imaging or functional tests, according to a study published in Endocrine Practice.
“Free T4 immunoassays have inherent limitations, and abnormal values often lead to further testing, including expensive imaging studies,” Gregory Westcott, MD, staff endocrinologist at Beth Israel Deaconess Medical Center, told Healio. “In our study population, those with a slightly low free T4 but normal free T4 index did not have evidence of structural or biochemical pituitary disease. The free T4 index was also more consistent than free T4 with free T4 by direct dialysis in a subset of patients who had all three tests performed.”
Westcott and colleagues reviewed 155 laboratory results from 118 adults (mean age, 53.2 years; 84% women) who had thyroid-stimulating hormone levels in the normal reference range, free T4 immunoassay levels below the reference range of 0.93 ng/dL to 1.7 ng/dL, and free T4 index measured at Beth Israel Deaconess Medical Center from June 2014 to October 2016. Radiographic reports were reviewed manually from electronic medical records. Head imaging was collected, with pituitary MRIs classified separately from other imaging. Records were also reviewed for biochemical evidence of abnormal pituitary function.
In the study population, a free T4 of 0.89 ng/dL or greater was associated with a normal free T4 index. The positive predictive value in which low free T4 index was designated as a true positive increased from 20.7% with a free T4 lower limit of 0.93 ng/dL to 31.1% when the lower limit was 0.89 ng/dL. Free T4 index values were low for all participants with a free T4 level of 0.67 ng/dL or lower.
Of adults with a lower free T4 and normal free T4 index, none had head imaging performed for secondary hypothyroidism. In four people who had head imaging for other reasons, one had small pars intermedius cyst that was not clinically significant, and three had normal findings.
In biochemical pituitary testing, the rate of pituitary axis abnormality generally decreased as free T4 increased, although only 34% of the study population underwent testing. Researchers said this may have been due to the exclusion of testing done more than 1 year before thyroid function testing, the inability to capture additional clinical history, and the impact of normal free T4 index reassuring providers.
“The free T4 index may be useful as an adjunct to evaluate patients with a normal TSH but slightly low free T4 by immunoassay to further evaluate the thyroid axis,” Westcott said. “Patients with a normal free T4 index may not require further workup for pituitary disease in the absence of other clinical indicators. Note that free T4 reference ranges are lab-specific, so the particular levels indicated in our study may not apply to every institution.”
Westcott said a future prospective study with a larger sample might identify free T4 cutoffs that are likely to indicate structural pituitary disease.
For more information:
Gregory Westcott, MD, can be reached at gwestcot@bidmc.harvard.edu.
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