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.