Thyroid calcitonin and C‐cell hyperplasia increase with exenatide use: a rat model

Liver steatosis is a serious health problem with few treatment options. To evaluate effects on hepatic steatosis of the drug exenatide (a GLP‐1 receptor agonist), rat models were created by a methionine‐choline deficient (MCD) diet, matched to a control diet. Both groups were treated or untreated with 10 μg/day exenatide. Recent reports suggest that GLP‐1 agonists may also have distant effects including C‐cell thyroid hyperplasia. This report details thyroid histology and measurements of an adipocytokine suspected of regulating thyroid function, adiponectin. Rat thyroids were stained for calcitonin, H&E and for carcinoembryonic antigen (CEA), present in medullary carcinomas. Thyroid C‐cell hyperplasia was graded on H&E stained slides using cell size and secretory granule numbers. Counts of stained cells/high power field and intensity of staining were recorded by three pathologists. Serum was measured for rat adiponectin by ELISA. Data were analyzed by ANOVA/post‐tests. C cell hypertrophy was elevated in exenatide‐treated vs untreated (22.5±8.7 vs 10.5±2.7 cells/HPF). CEA staining failed to show effects by exenatide. Calcitonin staining was significantly elevated in exenatide treated controls (P<0.001) with a trend in the MCD + exenatide group (p=0.055). Although adiponectin was elevated in both MCD groups, no exenatide –related effects were seen. In summary, exenatide was associated with C cell hyperplasia and increased calcitonin staining of thyroids, but was unrelated to CEA and serum adiponectin levels. Sponsor: St. Luke's Hospital Foundation