SFEBES2008 Poster Presentations Thyroid (68 abstracts)
Familial dysalbuminaemic hyperthyroxinaemia: a persistent diagnostic problem
David Cartwright 1 , Paula O’Shea 2 , Odelia Rajanayagam 3 , Carla Moran 4 , Rhys John 5 , Amar Agha 4 , Krishna Chatterjee 3 & David Halsall 1
1Department of Chemical Pathology, Addenbrookes Hospital, Cambridge, UK; 2Department of Chemical Pathology, Beaumont Hospital, Dublin, Ireland; 3Department of Medicine, Addenbrookes Hospital, Cambridge, UK; 4Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin, Ireland; 5Department of Medical Biochemistry, University Hospital of Wales, Cardiff, UK.
The differential diagnosis of raised circulating thyroid hormones with normal TSH includes familial dysalbuminaemic hyperthyroxinaemia (FDH), a benign, inherited disorder caused by a variant albumin with increased affinity for thyroxine (T4) or triiodothyronine (T3). Three different albumin gene mutations, generating mutant proteins with increased affinity for either T4 (R218H,R218P) or T3 (L66P) have been commonly described. Typically, serum total T4 is raised and free T4 measured by analogue assays is susceptible to positive interference, whereas two-step FT4 assays are reputedly not susceptible. Assay interference is surmountable with measurement of FT4 by equilibrium dialysis, but no commercial assay for this method exists currently in the UK. Here, we report three unrelated cases of FDH presenting with elevated circulating free T4, including one patient whose fT4 was raised in two different analogue and four types of two-step free hormone assay as tabulated below. In each case, TSH levels were within the reference range.
| Test | Abbott Architect i8100a | Beckman Accessa | PE-Delfiaa | DPC Immulite | Tosoha | Roche E170 |
| Serum TSH mU/l | 0.94 (0.35–5) | 1.18 (0.5–4.2) | 1.17 (0.4–4) | 1.25 (0.4–4) | 1.23 (0.34–3.81) | 1.19 (0.3–4) |
| Serum fT4 pmol/l | 22.7 (10.8–18.2) | 37.2 (7–16) | 21.0 (9–20) | 43.1 (10–25) | 37.0 (10–25) | 27.4 (10–21) |
| Local reference ranges in brackets. | ||||||
| *Two-step assay | ||||||
Sequencing of the albumin gene revealed the same mutation (R218H) in all three cases. As individuals can be genotyped for the three albumin gene mutations which commonly cause this disorder readily, we suggest that genetic testing is useful in making a positive diagnosis of FDH. This avoids ongoing investigation or even inappropriate treatment of cases with raised FT4 and normal TSH for alternative causes including thyrotrophinoma or resistance to thyroid hormone.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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