Use of the Free Thyroxine Index to Refine the Lower Limit of a Free Thyroxine Immunoassay for Detection of Secondary Hypothyroidism

ObjectiveTo determine the utility of measuring free T₄ index (FT₄I) in patients with low free T₄ (FT₄) levels using immunoassay and normal thyroid-stimulating hormone for the evaluation of secondary hypothyroidism.MethodsWe performed a retrospective medical chart review of patients seen at a single institution as outpatients who had a simultaneously normal thyroid-stimulating hormone level, low FT₄ level, and any FT₄I measured between June 2014 and October 2016. Demographic, laboratory, and imaging data were collected. Using FT₄I as the reference for diagnosis of hypothyroidism, the sensitivity and specificity of the FT₄ immunoassay’s lower-limit thresholds were determined. Within each threshold group, available brain imaging and biochemical evaluation were categorized according to the presence or absence of pituitary disease.ResultsA total of 155 sets of result pairs (FT₄ and FT₄I) performed on 118 subjects were analyzed. The lower limit of a normal FT₄ level by immunoassay at this institution was 0.93 ng/dL, though all pairs with FT₄ ≥0.89 ng/dL had a normal FT₄I. All pairs with FT₄ ≤0.67 ng/dL had a low FT₄I. No pituitary macroadenomas were identified in any subject, though the rates of pituitary imaging in this patient sample were low.ConclusionPatients with a borderline low FT₄ level by immunoassay often have normal FT₄I. In such patients at our center, significant structural and biochemical pituitary pathology was uncommon.