Newer analogue free T4 methods, despite claims to the contrary, are still prone to interference by commonly occurring polymorphic albumin variants. These albumin variants bind T4 with increased affinity. Free T4 methods typically return high values for free T4, usually with normal values for TSH. The degree of elevation is method dependant, although most methods can show some degree of interference. As three common genetic variants in the albumin gene are associated with increased affinity for T4, these can be simply detected using genetic methods.
Suspected thyroid hormone assay interference particularly unexpectedly raised free T4 with normal TSH.
See also ‘Anomalous thyroid function tests’ for screening test.
PCR and Dideoxy terminator sequencing of DNA extracted from peripheral leukocytes. Exon 3 and 7 are amplified and sequenced to detect p.R242H, p.R242P and p.L90P. Reference sequence NM_000477.3. +1 = ATG translation initiation codon.
As for all genetic tests patients need to be counselled. Dysalbuminaemic hyperthyroxinaemia is doinnantly inherited, so first degree relatives may also be affected. The requesting clinician is responsible for provision of appropriate counselling.
5mls of EDTA anti-coagulated blood are required.
Please send the sample via first class post from UK locations
The laboratory will provide interpretation
Centres offering this assay
Cambridge Addenbrooke’s Hospital Endocrine Laboratory
Sapin R, Gasser F, Schlienger JL. Familial dysalbuminemic hyperthyroxinemia and thyroid hormone autoantibodies: interference in current free thyroid hormone assays. Horm Res. 1996;45(3-5):139-41.