Endocrine Abstracts

Familial Dysalbuminemic Hyperthyroxinemia is an autosomal dominant condition that is caused by a mutant albumin molecule with an increased affinity for serum thyroxine (T4). Assay interference occurs because the increased affinity leads to spuriously high T4 readings in many immunoassay methods, despite a normal thyroid status. This creates a misleading biochemical profile that mimics true hyperthyroidism and can be misdiagnosed leading to inappropriate treatment. (Khoo et al., 2020) A 68-year-old male presented to his GP in 2020 with a UTI. During routine investigations, a mildly elevated total T4 of 23.7 (NR 12-22 pmol/l) was noted, with a normal TSH 0.87 (NR 0.27-4.2 uIU/ml). Previous T4 and TSH were normal in 2012. Repeat thyroid function tests in 2022 demonstrated a further increase in total T4 to 26.7 pmol/l, with persistently normal TSH. This discordant thyroid function raised concerns for secondary hyperthyroidism, prompting referral to endocrinology. His past medical history included benign prostatic hyperplasia and a tonsillectomy. Family history was not significant of any endocrinology disorders. Given persistent biochemical discrepancies and lack of clinical correlation, advanced thyroid studies were performed. These confirmed a diagnosis of Familial Dysalbuminemic Hyperthyroxinaemia (FDH) via ligand binding assay. FDH is a rare, benign and non-thyrotoxic condition, explaining the patient’s asymptomatic status despite abnormal thyroid biochemistry. The effect is assay-dependent, with certain platforms known to over-read in FDH. In 2012 the Abbott Architect Free T4 Assay with the Chemiluminescence method was used in our lab, this assay was changed in 2020 to Roche Cobas Pro Elecsys FT4. Abbott Architect was less susceptible when compared to Roche which might explain the normal thyroid tests in 2012. Immunoassay methods are susceptible to interference from FDH, indicating that it is not only a major cause of discordant thyroid function results, but may also lead to significant misdiagnosis, unnecessary investigations and inappropriate treatment. (Khoo et al., 2020) ReferenceKhoo, S., Lyons, G., McGowan, A., Gurnell, M., Oddy, S., Visser, W.E., van den Berg, S., Halsall, D., Taylor, K., Chatterjee, K. and Moran, C. (2020). Familial dysalbuminaemic hyperthyroxinaemia interferes with current free thyroid hormone immunoassay methods. European Journal of Endocrinology, [online] 182(6), pp.533–538. doi: https://doi.org/10.1530/eje-19-1021.