SUN-309 Cytokine Signaling by Thyronine and NAD in Colon and Pancreas - Case reports Highlighting Stem Cell Differentiation and Insulin Regulation

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Abstract Disclosure: T. Bilash: None. There has been an explosion of interest in Thyroid dysfunction since the chemiluminescent free hormone assays, advanced imaging and biophysical techniques (Phasor FLIM) have evolved over the last 15 years. Research now identifies peripheral metabolism as intimate to Thyroid Physiology, adding cellular (non-genomic/cytoplasmic) to well studied nuclear (genomic) processes. Carrier proteins, Enzyme Converters (Deiodinase), and Trans-membrane Transport Proteins create a complex web communicating across distinct Thyroid compartments. Feedback, conversion, local accommodation among and inside cells results in precise control. There is currently not one Thyroid test accurate enough to define Thyroid Status, although Thyroid Stimulating Hormone (TSH), Thyroxine (T4 - Total and Free), and Triiodothyronine (T3 - Total and Free) are shown to be clinically determinant in function. This work reports case studies for two patients with distinct, serious medical issues in the presence of Hypothyroxinemia: Diabetes Mellitus in a Pregnant female treated with Levothyroxine, and Advanced Stage Adenocarcinoma of the Colon in a male treated with Levothyroxine and Liothyronine, leading to successful clinical outcomes. T4 vs T3 and NAD vs NADP impact sources of cellular energy; in gradient for Colon stem cell differentiation (Wnt/b-catenin/PDK-1/NF-κB/STAT3) and for Insulin production in Pancreatic Beta Cells (MAPK/ERK). Support for the Serum FreeT3/FreeT4 Ratio as an important clinical parameter is offered. References 1 Kira T. Pate et al., Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer, The EMBO Journal 2014, Vol 33, No 13, 1454-1473 (doi/10.15252/embj.201488598) 2 Maria Virginia Giolito, Michelina Plateroti, Thyroid hormone signaling in the intestinal stem cells and their niche, Cell Mol Life Sci 2022 Aug 10;79(9):476 (doi/10.1007/s00018-022-04503-y) 3 T. Oda et al., Positive association of free triiodothyronine with pancreatic β-cell function in people with prediabetes, Diabetic Medicine 2014, Vol 32, Issue 2, p. 213-219 2014 (doi.org/10.1111/dme.12589) 4 Xing Zaou et al., Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblasoma cells, Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4890-5. (doi/10.1073/pnas.0501042102) Presentation: Sunday, July 13, 2025