Investigation of the Pathophysiological Mechanism for Altered Calcium Homeostasis in Hyperthyroid Cats

Williams T., Elliott J. and Syme H.M.


Conference Proceedings, (2013). American College of Veterinary Internal Medicine, Seattle: p.686



Hyperthyroid cats are reported to have reduced blood ionised calcium concentrations (iCa) and elevated plasma parathyroid hormone (PTH) concentrations, however, the pathophysiological mechanism for these changes is unknown. Intestinal absorption of calcium is regulated by calcitriol, and reduced plasma calcitriol concentrations are reported in human Graves’ disease patients. Therefore, if hyperthyroidism was associated with calcitriol defi- ciency in cats, this could be the pathophysiological mechanism for hypocalcemia and elevated plasma PTH concentrations. The aim of this prospective study was to investigate the association between iCa and plasma concentrations of PTH and calcitriol in hyperthyroid cats. Newly diagnosed hyperthyroid cats (plasma total thyroxine (TT4)>55 nmol/l) from two London-based first opinion prac- tices were prospectively recruited into the study in 2011-12. A group of non-azotemic euthyroid (TT4 < 40 nmol/l) geriatric (>9 years old) cats (control) were also recruited into the study for comparison of iCa and plasma calcitriol concentrations. The Mann-Whitney U test was used to compare baseline vari- ables between hyperthyroid and control cats. Multivariable lin- ear regression analysis was used to identify independent predictors of iCa in hyperthyroid cats. The first multivariable model included variables associated with iCa at the 10% level (P < 0.1) in the univariable analysis. The second model included TT4, PTH and calcitriol. Data are presented as med- ian [25th, 75th percentile] and statistical significance defined as P < 0.05.  Hyperthyroid cats had significantly lower iCa than control cats(1.24[1.21,1.27]mmol/l,n = 45vs. 1.2  [1.23, 1.29] mmol/l, n = 52; P = 0.003). Hyperthyroid cats also had signifi- cantly higher plasma calcitriol concentrations than control cats (115 [99, 144] pmol/l, n = 20 vs. 89 [61, 108] pmol/l, n = 10; P = 0.037). Linear regression analysis identified TT4 (P < 0.001), venous pH (P = 0.019), and plasma globulin con- centration (P = 0.002) as being associated with iCa at the 10% OFTHE PATHOPHYSIOLOGICAL level. Plasma concentrations of creatinine (P = 0.109), albumin (P = 0.125), PTH (P = 0.691) and calcitriol (P = 0.646) were not associated with iCa at the 10% level in the univariable analyses. In the first multivariable model, TT4 (P = 0.003) and venous pH (P = 0.026) were independently associated with ion- ised calcium concentration, and plasma globulin concentration tendedtowardsanindependent association with iCa (P = 0.084). In the second multivariable model, only TT4 was an independently associated with iCa (P = 0.003). Plasma con- centrations of PTH (P = 0.442) and calcitriol (P = 0.492) were not independently associated with iCa after adjustment for TT4. Hyperthyroid cats have increased plasma calcitriol concentra- tions, therefore calcitriol deficiency does not appear to be the pathogenetic mechanism for altered calcium homeostasis in hyperthyroid cats. One interpretation of these data is that thyroid hormones cause hypocalcemia either directly or through another currently undetermined mechanism that is independent of control by PTH and calcitriol.