Endocrine Abstracts

Case history: A 44 year old black African woman was referred to the endocrinology clinic for investigation of abnormal thyroid function tests. She had initially presented with palpitations and sweats. She had no significant past medical history and was not taking any prescribed medications or over the counter preparations. On examination, she was clinically euthyroid and did not have any abnormal findings of note.

Investigations: Biochemical investigations revealed a normal TSH of 3.75 iU/ml (0.38–5.33 iU/ml) with a raised free T4 of 24.2 pmol/l (7.0–16.0 pmol/l) and a normal free T3 of 5.6 pmol/l (3.8–6.0 pmol/l). TSH-receptor antibodies were not detected and anterior pituitary hormones were normal. Measurement of thyroid function tests using a second assay at another laboratory yielded similar results, excluding assay interference. Thyroxine binding globulin level was normal at 17.0 ug/ml (14.0–31.0 ug/ml).

Results and treatment: Her total T4 was found to be raised at 195.0 nmol/l (69.0–141.0 nmol/l) by immunoassay, raising suspicion of familial dysalbuminaemic hyperthyroxinaemia (FDH). Radioligand binding assay demonstrated enhanced binding of the patient’s albumin to T4, confirming FDH. Furthermore, mutational analysis of the albumin gene ALB revealed a heterozygous change for c.725G>A, (p.Arg242His).

Conclusions and points for discussion: Approximately 99.98% of circulating T4 is protein bound. FDH is an autosomal dominant condition of euthyroid hyperthyroxinaemia caused by mutations in the gene encoding albumin that increase the affinity of albumin for T4. Analogue fT4 assays, commonly used to measure free T4 in clinical practice, work on the assumption that approximately 10% of thyroxine is bound to albumin; in FDH abnormal albumin protein binds up to 30% of thyroxine. ‘True’ free thyroxine levels remain normal; hence the patient is clinically euthyroid. In addition, as T3 is mostly unbound, it remains normal. The condition does not require treatment. Screening of relatives should be offered. Patients with FDH may be mistakenly treated for thyrotoxicosis, and so a high degree of suspicion is warranted in patients presenting with a raised free T4 in the context of a normal TSH and free T3. Depending on the mutation, the levels of T4 can be 1.2 to 15 times the upper levels of normal. The mutation found in our patient is associated with a milder hyperthyroxinaemia compared to other mutations. FDH has been reported predominantly in Caucasian and Hispanic subjects with only three other cases described in individuals of African (Somali) origin. To our knowledge, this is the first report of the Arg242His mutation in a person of African origin.