A Yet Unrecognized Cause of Unusually High Levothyroxine Replacement Dose: Protein-Losing Enteropathy

Large amount of protein wasting such as in nephrotic syndrome is a rare cause of high levothyroxine (LT4) replacement dose requirement. A case has been reported here that demonstrates that protein-losing enteropathy is a novel and yet unrecognized cause of high LT4 replacement dose requirement.

A 21-year-old man with congenital heart disease was found to have primary hypothyroidism and started LT4 replacement. His weight was approximately 60 kg. Nine months later, while he was taking LT4 100 μg daily, thyroid-stimulating hormone (TSH) level was >200 μIU/mL (normal range, 0.3-4.7 μIU/mL) and free thyroxine level was 0.3 ng/dL (normal range, 0.8-1.7 ng/dL). The patient had excellent medication compliance. LT4 dose was increased to 200 μg daily and then 200 and 300 μg every other day. Two months later, TSH level was 3.1 μIU/mL and free thyroxine level was 1.1 ng/dL. He did not exhibit malabsorption or proteinuria. His albumin levels had been low since the age of 18 years (mostly <2.5 g/dL). Stool α-1-antitrypsin levels and calprotectin levels were elevated on multiple occasions. Protein-losing enteropathy was diagnosed.

As most circulating LT4 is protein-bound, loss of protein-bound LT4 due to protein-losing enteropathy is the most plausible cause of the large LT4 dose requirement in this case.

This case demonstrates that protein-losing enteropathy, through loss of protein-bound thyroxine, is a novel and yet unrecognized cause of high LT4 replacement dose requirement. In patients who require high LT4 dose for unclear reasons, albumin levels should be examined and protein wasting be suspected in those with low albumin levels.