Thyroid hormone in patients with insulin receptor mutations

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

Patients with homozygous (n=5) or heterozygous (n=2) INSR mutation participated in a single-arm, open-label study of liothyronine at the National Institutes of Health. Subjects received liothyronine q8 hours for 2 weeks (n=7)and an additional 6 months treatment in those with HbA1c>7% (n=4). There was no change in whole-body, muscle, or WAT glucose uptake from baseline to 2 weeks of liothyronine. After 6 months, there was no change in HbA1c (8.3 +/- 1.2 vs 9.1 +/- 3.0%, p=0.27), but there was increased whole-body glucose disposal (22.8 +/- 4.9 vs 30.1 +/- 10.0 mol/kgLBM/min, p=0.02), and muscle (0.7 +/- 0.1 vs 2.0 +/- 0.2 mol/min/100ml, p<0.0001) and WAT glucose uptake (1.2 +/- 0.2 vs 2.2 +/- 0.3 mol/min/100ml, p<0.0001). BAT glucose uptake could not be quantified due to small volume. There were no signs or symptoms of hyperthyroidism. In conclusion, liothyronine administered at well-tolerated doses did not improve HbA1c. However, the observed increases in muscle and WAT glucose uptake support the proposed mechanism that liothyronine increases tissue glucose uptake. More selective agents may be effective at increasing tissue glucose uptake without thyroid-hormone-related systemic toxicity. The primary results of this study were published in the Journal of Clinical Endocrinology and Metabolism. An ancillary analysis from this study of thyroid hormones measured by mass spectrometry versus immunoassay was presented at the Endocrine Society annual meeting in 2018, and a manuscript including these results has been published.