UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES

Thyroid Pathophysiology

Thyroid cancer: We are investigating re-differentiation therapy in advanced thyroid cancer. Progression of follicular cell thyroid cancer is accompanied by loss of cell differentiation. As a result, advanced follicular cell thyroid cancer accumulates little if any iodine, rendering radioiodine ineffective as ablative therapy. Several common drugs have been shown to induce differentiation of thyroid cancer cells in vitro. They include retinoic acids, thiazolodinediones, and valproic acid. We recently completed a study with a retinoic acid, isotretinoin, which resulted in an increase in radioiodine uptake in 3 of 10 patients with advanced thyroid cancer. A second study with a thiazolodinedione, rosigltazone, is currently underway. A third study with valproic acid is currently being reviewed.

Subclinical hyperthyroidism : This is a state characterized by a subnormal serum thyroid stimulating hormone (TSH) in association with normal serum thyroxine and triiodothyronine levels with a prevalence of ~2%. The incidence with which subclinical hyperthyroidism progresses to overt disease is uncertain. Moreover, it is uncertain whether the incidence varies depending on the initial serum TSH value and on whether the disorder is due to Graves' disease or to multinodular goiter. Accordingly, retrospective analysis of our patients was recently undertaken. This study suggests that the natural history of subclinical hyperthyroidism is variable, resolving or occasionally evolving in Graves' disease and persisting unchanged in multinodular goiter. A prospective study is being designed to confirm and extend these observations and to identify other potential predictors of outcome.

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