(1) Determine if a relationship exists between ionized calcium (iCa) and pancreatic lipase (cPLI) concentration in dogs, and (2) assess for correlation between resolving hypercalcemia and cPLI concentrations in dogs after treatment for primary hyperparathyroidism (PHPT). Phase I, 44 residual serum samples (collected April 2023) from client-owned dogs with a clinical indication for cPLI quantification. Phase II, 24 residual serum samples (collected August 2022 through February 2023) from client-owned dogs with PHPT pre- and postcorrection of hypercalcemia. Serum cPLI and iCa concentrations were measured via the Spec cPL assay and a spectrophotometric method respectively. Spearman's rank correlation coefficients were used to investigate if there was a correlation between serum calcium and cPLI concentrations. A paired t-test was used to investigate the effect of the resolution of hypercalcemia on serum cPLI concentrations. Phase I, serum cPLI concentrations were negatively correlated with serum iCa concentrations (r = -.429, 95% CI [-.64, -.14], P = .005) in dogs with a clinical indication for cPLI quantification. Phase II, median serum cPLI concentrations were higher before (median: 228.5 μg/L, IQR: 351.3 μg/L) than after (median: 141.0 μg/L, interquartile ranges (IQR): 279.5 μg/L) management of hypercalcemia (PHPT model). However, the decrease in cPLI concentration was not statistically significant (P = .70). Calcium depletion may result in an inverse relationship between serum cPLI and iCa concentrations in dogs with a clinical indication for cPLI quantification. Hypercalcemia may be associated with an above reference interval cPLI concentration in some dogs.

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