Our group discovered that infantile hemangiomas express high levels of the thyroid hormone-inactivating enzyme type 3 deiodinase and that children with large tumor burden can succumb to severe hypothyroidism from the rapid inactivation of circulating thyroid hormone at rates which exceed the synthetic capacity of the normal thyroid axis. Because 3-4 IQ points are lost for each month of untreated hypothyroidism during infancy, we provided screening guidelines for children with large hemangiomas and treatment recommendations to use supernormal doses of exogenous thyroid hormone in severe cases. This has led to the diagnosis and treatment of hundreds of affected infants, and we named this condition consumptive hypothyroidism. My group has recently discovered that this mechanism of pathophysiology extends to adults with gastrointestinal stromal tumors, the most common mesenchymal tumor of the alimentary canal, and that their tumoral deiodinase activity is stimulated by treatment with tyrosine kinase inhibitors.
The goals of my current research are to determine the clinical consequences of D3 expression in hemangiomas and in other tumors, to understand the molecular explanation for its expression in consumptive hypothyroidism, and to determine if there are other conditions in which D3 causes hypothyroxinemia due to the accelerated degradation of thyroid hormones.
In addition to my studies of deiodinase regulation, I am a clinical thyroidologist with a special focus in the care of children with thyroid cancer. In collaboration with clinical researchers from numerous disciplines, including radiology, surgery, pathology, oncology, and genetics, we are performing clinical and translational studies of this rare pediatric cancer population.