Endocrine Abstracts

Familial Dysalbuminaemic Hyperthyroxinaemia (FDH) is a benign inherited disorder caused by mutations in the albumin gene that increase the affinity of albumin for thyroxine, leading to elevated total thyroxine (T4) levels with normal free hormone concentrations. This biochemical anomaly can complicate the interpretation of thyroid function tests (TFTs) and, if unrecognised, may result in misdiagnosis and inappropriate treatment. We present a case illustrating the long-term clinical and therapeutic implications of undiagnosed FDH. (Kragh-Hansen et al., 2017) An 84 year old woman had been diagnosed with presumed “thyrotoxicosis” in 1983, underwent radioiodine treatment in 1989. Over subsequent decades, she was managed for iatrogenic hypothyroidism with levothyroxine replacement. Her clinical course was marked by substantial fluctuations in TFTs, with T4 levels ranging from 24.4 to 47.6 pmol/l (6.5 – 17.0) and TSH ranging from 0.46 to 100 mU/l (0.34 – 4.94). Notably, there were multiple periods where she was clinically euthyroid despite marked biochemical variation, prompting repeated adjustments in levothyroxine dosing. Patient reported feeling symptomatically well when her TSH was within target range with accompanying high T4 level. These fluctuations led to concerns regarding medication adherence. In 2020, in view of these marked fluctuations in her TFTs her serum sample was sent to Addeenbrooks hospital which confirmed FDH, finally resolving the long-standing diagnostic uncertainty. The diagnosis was communicated to the patient, with reassurance that FDH is a benign, inherited condition requiring no specific therapy. The patient was discharged from specialist endocrine care, with advice that any future levothyroxine dose adjustments should be guided by clinical assessment and TSH levels. Retrospective review of the patient’s initial presentation in the 1980 s suggested that FDH may have contributed to the apparent hyperthyroxinaemia and possible misclassification as thyrotoxicosis, though this could not be confirmed due to destruction of historical records. The case underscores the importance of considering FDH in patients with discordant TFTs—particularly elevated total T4 with non-suppressed TSH—and stable clinical status. Recognition of FDH can prevent unnecessary investigations, inappropriate treatments, and prolonged diagnostic uncertainty. This case highlights the need for increased awareness of rare binding protein abnormalities in the interpretation of thyroid biochemistry. Early use of specialist assays or referral to reference laboratories can facilitate timely diagnosis, reducing the risk of overtreatment and improving patient confidence in their care.

Reference: Kragh-Hansen U, Galliano M, Minchiotti L. Clinical, Genetic, and Protein Structural Aspects of Familial Dysalbuminaemic Hyperthyroxinaemia and Hypertriiodothyroninemia. Front Endocrinol (Lausanne). 2017;8:297. doi:10.3389/fendo.2017.00297