Pilot Project Abstract - Kathryn Schuff, MD

Kathryn Schuff, MD, Associate Professor of Endocrinology at OHSU: “3-Monoiodothyronamine: A novel thyroid hormone metabolite with a potential role in thyroid hormone regulation of metabolism”

Obesity is one of the most significant public health problems and thyroid hormone is a major regulator of basal metabolism. The mechanism of this is unclear and may not be mediated via direct effects of the classic thyroid hormone, T3. Thyroid hormones are metabolized by deiodination and decarboxylation to iodothyronamines. 3-monoiodothyronamine (T1AM) is found endogenously, correlates with thyroid hormone levels, and has profound metabolic effects when administered to rodents, suggesting it may be involved in thyroid hormone regulation of energy expenditure and nutrient flux. Our objective is to evaluate the role of T1AM in mediating energy expenditure and nutrient flux. We hypothesize that thyroid hormone levels correlate with T1AM, and T1AM levels correlate with resting energy expenditure (REE) and respiratory quotient (RQ) across a range of TSH levels. To evaluate this, we propose two studies: 1) A cross-sectional baseline study of patients with overt hyperthyroidism (TSH <0.01, elevated FT4 and/or T3), subclinical hyperthyroidism (TSH 0.01-0.28, normal FT4 and T3), euthyroid (TSH 0.28-4.5), subclinical hypothyroidism (TSH 4.5-20), and overt hypothyroidism (TSH > 20). 2) A longitudinal, parallel arm, randomized, double blind interventional study of experimentally manipulated thyroid hormone dosing to target TSH levels to induce euthyroidism, subclinical hypo- or hyperthyroidism. In both studies, predictor variables are final thyroid hormone levels; outcome variables are T1AM, REE and RQ. Demonstration of the hypothesized association will support the involvement of T1AM in thyroid hormone regulation of metabolism. Further mechanistic studies will support this pathway as a pharmacologic target for treatment of obesity.

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