Treatments for Medial Temporal Lobe Volume Loss Caused by Graves Disease

People with Graves disease can experience volume loss in the medial temporal lobe (MTL), but  treatment with antithyroid drugs (ATD) and/or surgery leads to partial recovery of these regions, according to a study in the Journal of Clinical Endocrinology and Metabolism.

Findings were extracted from the CogThy study and based on 62 female patients (mean age, 32.3±9.1 years) with newly diagnosed Graves disease treated at a hospital in Göteborg, Sweden, from September 2011 to October 2019. Patients were included within 2 weeks from the start of treatment with ATD, receiving ATD in a block-and-replacement regimen (the addition of 50 mcg levothyroxine after 2 weeks and an increased does to 100 mcg after 4 weeks), or underwent surgery with previous ATD treatment. They were matched with 56 control participants (mean age, 33.7±8.8 years).

Both patients and controls had a comprehensive multimodal assessment battery, including neuropsychological testing and magnetic resonance (MR) imaging. Control participants (n=56) and a subset of patients (n=48) had MR segmentation results at 15 months; 22 follow-up MR scans in controls were also included.

At baseline, the patients had smaller volumes of amygdalae and hippocampi compared with control individuals. The mean differences in volume percentage were –10.4% for the left amygdala (P = 2.8e-6), –13.3% for the right amygdala (P = 5.0e-8), –4.4% for the left hippocampus (P = .013), and –4.8% for the right hippocampus (P = .009).

After ATD and/or surgical treatment, amygdalae and hippocampi volume in patients showed a mean increase of +6.7% for the left amygdala (P = 3.0e-4), +11.1% for the right amygdala (P = 1.7e-6), +5.6% for the left hippocampus (P = 1.3e-4), and +5.8% for the right hippocampus (P = 1.2e-5). The left amygdala was the only region that remained significantly smaller in patients vs controls at follow-up (–5.0%, P = .029).

In 22 control participants who were evaluated after a mean (SD) interval of 15.5±1.5 months, the differences in non-intracranial volume (ICV) normalized volumes were 0.9% for the left amygdala (95% CI, –4.3 to 3.9), –1.6% for the right amygdala (95% CI, 6.7-3.5), –0.2% for the left hippocampus (95% CI, –2.6 to 2.2), and –0.6% for the right hippocampus (95% CI, –4.2 to 3.0).

A negative correlation was found between the longitudinal difference from inclusion to follow-up in the level of free triiodothyronine (FT3) and the difference in volumes of the left MTL but not for the right MTL. A negative correlation was observed between the difference in thyroid-stimulating hormone receptor antibodies (TRAb) and the difference in the volume of the left and right amygdala and the left hippocampus. There were no correlations between the difference in free thyroxine (FT4) and the difference in MTL volumes.

No significant correlations were observed between any of the mental symptom scores or the neuropsychological test results and amygdalae and hippocampi volumes in patients at inclusion or follow-up.

The investigators noted that their results may be limited by the inclusion of patients with severe hyperthyroidism, the inclusion of only women, and the long inclusion time, which may have introduced MR-related biases due to software upgrades or scanner drift.

“The finding of dynamic alterations in the amygdalae and hippocampi in Graves disease reflects a previously unknown level of brain involvement both in the development of the condition and its response to treatment,” the researchers concluded.  “Although no correlations between symptom severity and brain volumes were found, on a group level MTL volumes were reduced in hyperthyroid GD patients and became larger after treatment, at the same time as symptom severity on all scales diminished. This parallelism indicates that the existence of mental symptoms as a disease consequence deserves further attention.”

Disclosure: One of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Holmberg M, Malmgren H, Heckemann RA, et al. A longitudinal study of medial temporal lobe volumes in Graves’ disease. J Clin Endocrinol Metab. Published online November 9, 2021. doi:10.1210/clinem/dgab808