Stimulation of the thyroid epithelial cells by thyroid hormone receptor antibodies (TRAb) in Graves’ disease, usually leads to hyperthyroidism1. TRAb is crucial not only in the diagnosis but also for the prognosis and management2. TRAb can be functionally characterised by bioassays. We present a case of “antibody switch” resulting in challenging management.
A 60-year-old woman presented with thyrotoxicosis in January 2018. She had a diffuse goitre without eye signs or brisk reflexes. Her thyroid function tests were consistent with thyrotoxicosis. Both elevated TRAb and diffuse uptake on the technetium scan support Graves’ disease. Thyroid ultrasound showed mildly enlarged thyroid gland with increased vascularity without nodules. Carbimazole 10 mg tds was commenced, causing biochemically hypothyroid, 6 weeks later. She stabilized on carbimazole 15 mg/day. In December 2018, she had mild orbitopathy despite normal TRAb with euthyroidism. Later, she was well on carbimazole 5 mg/day.
In October 2020, she developed significant fatigue. Surprisingly, TRAb was highly positive but she was hypothyroid clinically and biochemically. Carbimazole was stopped. Thyroxine 100 mcg per day was started. Because of discordant results, heterophile Ab and dilutional studies were excluded. TRAb positivity was again confirmed by thyroid-stimulating immunoglobulin (TSI). All results are in table 1.
2 months later, she became hyperthyroid and thyroxine was reduced to 300 mcg/week with good response. TRAb and TSI remained elevated. Functional characterization of TRAb was requested using Thyretain assay. Blocking antibodies was positive (71.8%), triggering “Ab switch”3.
Presence of predominantly blocking antibodies resulted in hyperthyroidism switching to hypothyroidism and is potential for further oscillations. Block and replace regimen can be considered but this requires close monitoring4. Definitive therapies are preferred for stability of thyroid function. Radioactive iodine is not ideal given Graves’ orbitopathy. Our patient had total thyroidectomy without complications and is currently euthyroid on thyroxine.
Table 1: Thyroid functions