Occurrence and management of an aberrant free T4 in combination with a normal TSH

Thyroid function tests may show the combination of a normal concentration of serum thyroidstimulating hormone (TSH) and an increased or decreased level of free thyroxine (free T4). How often this occurs is unclear and not everyone is familiar with how it should be adressed.

We conducted a retrospective cohort study of all adult patients who presented at a non-academic general hospital in the Netherlands between 1 January 2010 and 31 December 2014 and yielded an increased or decreased free T4 in combination with a normal TSH. Exclusion criteria included the use of thyroid medication, pregnancy, a history of thyroid surgery and treatment with radioactive iodine. The medical records of the patients included were retrieved and evaluated.

Of the 30,143 combined TSH and free T4 measurements in 23,199 individual patients, 1005 measurements (3.33%) in 775 patients (3.34%) yielded an aberrant free T4 in combination with a normal TSH. 398 patients (1.72%) had a persistent aberrant free T4, 349 (87.7%) of whom had a decreased free T4 and 49 (12.3%) an increased free T4. In 58 of the 398 patients (14.6%) with a persistent abberant free T4 a possible cause was established by the treating physician. However, upon re-examination of medical files a possible causative factor could be identified in 123 patients (30.9%).

In our study population the prevalence of hyperthyroxinemia or hypothyroxinemia in combination with a normal TSH was 334 per 10.000 patients. When records were thoroughly searched, identification of potential causative factors increased substantially. Clinicians should be encouraged to check for underlying causes.