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

Abstract

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 ...

Prevalence and risk factors associated with systemic hypertension in dogs with spontaneous hyperadrenocorticism

“…2 Chronic hypercortisolism might lead to several complications such as diabetes mellitus (DM), systemic hypertension (SH), proteinuria, glomerulosclerosis, pancreatitis, gallbladder mucocele, increased susceptibility to infections, or pulmonary thromboembolism among others, both in humans and dogs. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Systemic hypertension associated with hypercortisolism is common in people, affecting 70%-85% of the patients. [4][5][6][7][8] The pathophysiological mechanisms for hypertension in HAC are incompletely understood, but in people a multifactorial model has been proposed with many pathways involved: the renin-angiotensin system, an increased mineralocorticoid activity, the sympathetic nervous system, the vasoregulatory system, metabolic factors, vascular remodeling and sleep apnea.…”

“…Cortisol excess can result from an ACTH producing pituitary tumor (pituitary‐dependent hyperadrenocorticism; PDH), secondary to an adrenal tumor (adrenal‐dependent hyperadrenocorticism; ADH) or, less frequently, because of an ectopic ACTH secretion 1 or food dependent hypercortisolemia 2 . Chronic hypercortisolism might lead to several complications such as diabetes mellitus (DM), systemic hypertension (SH), proteinuria, glomerulosclerosis, pancreatitis, gallbladder mucocele, increased susceptibility to infections, or pulmonary thromboembolism among others, both in humans and dogs 3‐21 …”

Proteinuria in dogs with gallbladder mucocele formation: A retrospective case control study

“…Dogs with gallbladder mucocele formation are at increased risk for concurrent diagnoses of hypertriglyceridemia, hypercholesterolemia, and hypothyroidism. 7,9,12,30 Dyslipidemia also is associated with proteinuria in people and dogs. 4,5,31,32 We did not identify an association between proteinuria and median serum cholesterol concentration or number of dogs having high serum cholesterol concentrations.…”

“…Medical records of dogs that were included in a prior case‐control study of gallbladder mucocele formation 12 were retrospectively reviewed. Case and control dogs were selected for inclusion in the present study if both dogs had results of CBC, serum biochemical profile, and urinalysis reported within 1 month of gallbladder ultrasound examination.…”

“…Case-control study populationA total of 30 case-control pairs of dogs from the previously published study12 had medical records screened for inclusion in the present study. Five case-control pairs were excluded because of lack of urinalysis in 1 or both dogs.…”