Endocrine Abstracts

Section 1: Case history: A 61-year-old lady was referred by her GP to our endocrine clinic with abnormal thyroid function tests (TFTs) incidentally identified in routine blood tests. She had no symptoms suggestive of thyrotoxicosis apart from occasional palpitations when using inhalers for asthma. She had no family history of endocrine significance. She was on salbutamol, salmeterol, fluticasone inhalers and laxatives. Physical examination was unremarkable with no goitre.

Section 2: Investigations: Initial TFTs showed a free T4- 23.8 pmol/l (NR- 11-22) and TSH- 6.41 miU/l (NR- 0.3-5). Thyroid receptor antibodies and anti TPO antibodies were negative. Subsequent TFTs in next clinic visits showed persistent mildly elevated free T4 ranging between 21.4-29.8 pmol/l. Free T3 was normal. TSH measurements after the initial visit were normal. Pituitary function tests showed normal prolactin, growth hormone and IGF-1 measurements with post-menopausal pattern gonadotrophins along with a normal alpha-subunit. Her short synacthen test was normal. Pituitary MRI showed no pituitary adenoma.

Section 3: Results and treatment: She subsequently underwent genetic testing. She was found to be heterozygous for the c.725G>A p.(Arg242His) albumin gene variant which confirmed the diagnosis of familial dysalbuminaemic hyperthyroxinemia (FDH). She was not given any antithyroid medications at any point. Patient was discharged back to the GP with reassurance as FDH does not need any treatment. Her family members were advised to check TFTs to avoid unnecessary investigations in the future.

Section 4: Conclusions and points for discussion: FDH is an autosomal dominant disorder characterized by mutations in the human serum albumin causing increased affinity of thyroxine to albumin. Prevalence is about 0.2 percent in Hispanics and 0.01 percent in Caucasian population. Affected individuals have high total T4 +/- free T4 but normal T3 and TSH and are clinically euthyroid. Serum albumin is quantitively normal. Although in theory, free T4 measurements should be normal in FDH, many T4 assays are adversely affected by changes in albumin concentration and give spuriously high values. Free T4 assays used in our hospital were not sensitive enough to correct albumin changes seen in FDH, they are better at correcting for thyroid binding globulin alterations. FDH cases can be confused with hyperthyroidism, thyroid hormone resistance or TSH-oma and may cause unnecessary treatment with antithyroid medications. Knowledge about FDH will allow clinicians to avoid complicated laboratory testings and inappropriate treatment.