Endocrine Abstracts

Background: Familial dysalbuminaemic hyperthyroxinaemia (FDH) is an interesting autosomal dominant condition that is associated with euthyroid hyperthyroxinaemia, whereby patients remain euthyroid but laboratory value will show high free thyroxine (fT₄) level. It is caused by mutations in ALB (albumin) gene that increase affinity of albumin for thyroxine (T₄). The usual thyroid assay will show a spuriously high level of thyroxine. This interference could be excluded when the free hormone is extracted from serum and analysed separately. We present a case of a Caucasian lady who was referred to endocrinology team for deranged thyroid function test.

Case: A 50-year-old lady with polycystic ovarian syndrome presents with elevated fT₄, 30.4 pmol/l and triiodothyronine (T₃) level of 5.5 pmol/l with a normal thyroid stimulating hormone (TSH), 4.47 mU/l. Symptoms on presentation include one month history of hot flushes, palpitations and lethargy. Examination findings revealed normal thyroid gland. US thyroid and thyroid uptake scan were unremarkable. Her TSH receptor and thyroid peroxidase antibodies were negative. Her maternal aunt has suffered from thyroid disorders. She was commenced on carbimazole 15 mg once a day. TSH level went up to 6.69 with a T₄ level of 23 and T₃ level of 5.5. She continued to have palpitations and anxiety. Her carbimazole was further increased to 20 mg. Her repeat blood test then showed a TSH and fT₄ of 9.42 and 22. Her case was discussed with Cambridge team who suggested TRH stimulation tests and MR pituitary which were normal. In the meanwhile patient was advised to take alternating dose of carbimazole 20 and 25 mg. Her symptoms remained the same throughout. We sent her blood sample to Cambridge for FDH testing. DELFIA assay in Cambridge showed TSH 3.85 and T₄ 19.3. Genetic testing at Cambridge showed a positive mutation in the albumin gene, R242H in keeping with FDH. We stopped carbimazole and commenced propranolol for anxiety. Her repeat results show TSH 3.28 and T₄ 26.8 with our laboratory values but normal values with DALFIA analyser.

Conclusion: Euthyroid hyperthyroxinemia is a common condition with several causes. Although rare, FDH should always be one of the differentials. When there is mismatch between the clinical picture and biochemical results, we should establish possible differentials and resist the temptation to treat high free thyroxine as this could potentially lead to unpleasant consequences. It is also important to screen the immediate family members of FDH to avoid unnecessary treatment in similar individuals.