Investigation of adrenal and thyroid gland dysfunction in dogs with ultrasonographic diagnosis of gallbladder mucocele formation

Gallbladder mucocele formation is an emerging disease in dogs characterized by increased secretion of condensed granules of gel-forming mucin by the gallbladder epithelium and formation of an abnormally thick mucus that can culminate in obstruction of the bile duct or rupture of the gallbladder. The disease is associated with a high morbidity and mortality and its pathogenesis is unknown. Affected dogs have a significantly increased likelihood of concurrent diagnosis of hyperadrenocorticism, hypothyroidism, and hyperlipidemia. Whether these endocrinopathies represent coincidental primary disease processes that exacerbate gallbladder mucocele formation in predisposed dogs or reflect a concurrent disruption of endocrine and lipid metabolism is unclear. In this study, we investigated a hypothesis that dogs with gallbladder mucocele formation would have a high prevalence of occult and atypical abnormalities in adrenal cortical and thyroid gland function that would suggest the presence of endocrine disruption and provide deeper insight into disease pathogenesis. We performed a case-control study of dogs with and without ultrasonographic diagnosis of gallbladder mucocele formation and profiled adrenal cortical function using a quantitative mass spectrometry-based assay of serum adrenal-origin steroids before and after administration of synthetic cosyntropin. We simultaneously profiled serum thyroid hormone concentrations and evaluated iodine sufficiency by measurement of urine iodine: creatinine ratios (UICR). The studies were complemented by histological examination of archival thyroid tissue and measurements of thyroid gland organic iodine from dogs with gallbladder mucocele formation and control dogs. Dogs with gallbladder mucocele formation demonstrated an exaggerated cortisol response to adrenal stimulation with cosyntropin. A prevalence of 10% of dogs with gallbladder mucocele formation met laboratory-based criteria for suspect or definitive diagnosis of hyperadrenocorticism. A significantly greater number of dogs with gallbladder mucocele formation had basal serum dehydroepiandrosterone (DHEAS) increases compared to control dogs. A high percentage of dogs with gallbladder mucocele formation (26%) met laboratory-based criteria for diagnosis of hypothyroidism, but lacked detection of anti-thyroglobulin antibodies. Dogs with gallbladder mucocele formation had significantly higher UICRs than control dogs. Examination of thyroid tissue from an unrelated group of dogs with gallbladder mucocele formation did not demonstrate histological evidence of thyroiditis or significant differences in content of organic iodine. These findings suggest that dogs with gallbladder mucocele formation have a greater capacity for cortisol synthesis and pinpoint DHEAS elevations as a potential clue to the underlying pathogenesis of the disease. A high prevalence of thyroid dysfunction with absent evidence for autoimmune thyroiditis suggest a disrupted thyroid hormone metabolism in dogs with gallbladder mucocele formation although an influence of non-thyroidal illness cannot be excluded. High UICR in dogs with gallbladder mucocele formation is of undetermined significance, but of interest for further study.