Raised serum FT4 and inappropriately detectable serum TSH: evaluation of recommendations from the UK TFT guidelines
T S Han1, E Woolman2, K Marshall2, M Thomas2 & M Vanderpump1
Objectives: The UK TFT Guidelines (2006) recommend screening for heterophilic antibodies (HA), thyroid hormone resistance (THR) and TSHoma in samples with raised FT4 and detectable or raised TSH levels. The aim was to determine the frequency and aetiology of such abnormal thyroid function tests (TFTs) and to evaluate the use of further analyses for this common biochemical abnormality.
Design: Six-month retrospective study (1/08/0628/2/07) of TFTs with raised serum FT4 (>22 pmol/l) and detectable (0.34.2 mU/l) or raised (>4.2 mU/l) serum TSH concentrations, followed by a three-week prospective study (21/1011/11/07) of TFTs that met these criteria, in which all samples were further assayed for FT3, SHBG and HA.
Results: In the retrospective study 756 samples from 635 patients had raised FT4 and detectable TSH (2% of total requested), of which 10% (53 single and 11 multiple) were repeated. There were 88 samples from 66 patients with raised FT4 and raised TSH (0.2% of all TFTs requested), of which 18% (9 single and 3 multiple) were repeated. In the prospective study of the 56 abnormal TFTs, 9 were on T4 therapy (FT3 between 3.2 and 5.5 pmol/l). Of the remaining 47 samples, no sample was positive for HA or had SHBG >120 mmol/l. Three samples had a raised FT4 (26.940.3 pmol/l), detectable TSH (0.971.27 mU/l) and raised FT3 (6.510.2 pmol/l) with SHBG between 9.6 and 72.2 nmol/l. One has been confirmed to have THR and other two are currently being investigated. In the remaining 44 samples of raised FT4 and detectable TSH, 42 (96%) had FT3 below and two (4%) above 6.0 pmol/l, 27 (61%) had SHBG below 60 mmol/l and 17 (39%) between 60 and 120 mmol/l. None had a combination of FT3 above 6.0 pmol/l and SHBG between 60 and 120 mmol/l.
Conclusions: The lack of follow up on abnormal TFTs could potentially misclassify a thyroid condition. FT3 measurements in samples with raised serum FT4 and detectable serum TSH appears to be of predictive value for detecting THR and for reassurance that either T4 therapy or antibody interference was likely. Measurement of SHBG and HA appear redundant in further investigation of this TFT abnormality.