Hypercalcemia: a quick reference.

This article serves as a quick reference for hypercalcemia. Guidelines for causes, clinical signs, analysis, and diagnosis are presented in a stepwise approach.

Hypocalcemia: a quick reference.

This article serves as a quick reference for hypocalcemia. Guidelines for causes, clinical signs, and diagnosis are presented in a stepwise approach.

Calcium: total or ionized?

Measurement of serum total calcium (tCa) has been relied on for assessment of calcium status, despite the fact that it is the ionized calcium (iCa) fraction that has biologic activity. Serum tCa does not accurately predict iCa status in many clinical conditions. For accurate assessment of iCa status, iCa should be directly measured. Anaerobic measurement of serum iCa under controlled conditions provides the most reliable assessment of calcium status; aerobic measurement of iCa with species-specific pH correction is highly correlated with anaerobic measurements.

Dietary Fatty Acids Differentially Regulate Secretion of Adiponectin and Interleukin-6 in Primary Canine Adipose Tissue Culture.

The aim of this study was to determine the effect of n3 polyunsaturated fatty acids (PUFA) on canine adipose tissue secretion of adiponectin, interleukin-6 (IL6), and tumor necrosis factor-α (TNFα). Subcutaneous and omental visceral adipose tissue samples were collected from 16 healthy intact female dogs. Concentrations of adiponectin were measured in mature adipocyte cultures, and concentrations of IL6 and TNFα were measured in undifferentiated stromovascular cell (SVC) cultures following treatment with eicosapentaenic acid (EPA, 20:5n-3), arachidonic acid (ARA, 20:4n-6), or palmitic acid (PAM, 16:0) at 25, 50, or 100 µM. Secretion of adiponectin from mature adipocytes was higher (p < 0.001) following EPA treatment at 50 µM compared to control in subcutaneous tissue, and higher following EPA treatment compared to PAM treatment at 25 µM in both subcutaneous (p < 0.001) and visceral tissues (p = 0.010). Secretion of IL6 from SVC derived from subcutaneous tissue was lower following EPA treatment and higher following PAM treatment compared to control both at 50 µM (p = 0.001 and p = 0.041, respectively) and 100 µM (p = 0.013 and p < 0.001, respectively). These findings of stimulation of adiponectin secretion and inhibition of IL6 secretion by EPA, and stimulation of IL6 secretion by PAM, are consistent with findings of increased circulating concentrations of adiponectin and decreased circulating concentration of IL6 in dogs supplemented with dietary fish oil, and show that the effect of fish oil on circulating concentrations of adiponectin and IL6 is, at least partially, the result of local effects of EPA and PAM on adipose tissue.

Calcium homeostasis in thyroid disease in dogs and cats.

Hyperthyroidism is the most common endocrine disorder of cats, and hypothyroidism is the most common endocrine disorder of dogs. Little is known regarding the effects of hyperthyroidism, hypothyroidism, or treatment of these disorders on calcium metabolism in the dog or cat, however, especially any potential effects on bone. With better diagnostic tools, better treatments, and increased longevity of pets, the clinical impact of thyroid disorders on calcium metabolism and bone may be uncovered.

A Quick Reference on Hypocalcemia.

Primary hypoparathyroidism should be considered in dogs with vague signs, including tremors, facial rubbing, and seizures. Ionized hypocalcemia should be considered in dogs with protein-losing enteropathy, especially lymphangiectasia caused by hypovitaminosis D. Ionized hypocalcemia typically occurs only in advanced chronic kidney disease.

A Quick Reference on Hypercalcemia.

In dogs, neoplasia is the most common cause of hypercalcemia, followed by primary hyperparathyroidism, chronic kidney disease, and hypoadrenocorticism. In cats, idiopathic hypercalcemia is the most common cause, followed by chronic kidney disease and then neoplasia. Prognosis and treatment ultimately depend on the cause of the hypercalcemia.

Update on Feline Ionized Hypercalcemia.

Hypercalcemia in cats is recognized with increased frequency, especially idiopathic hypercalcemia, which is the most common cause. Idiopathic hypercalcemia seems to be unique to the cat, not occurring in the dog as a specific syndrome. There are many causes of hypercalcemia, and diagnosis relies on evaluation of clinical signs, physical examination, diagnostic imaging, serum biochemistry, urinalysis, and evaluation of calcium metabolic hormones. With an accurate diagnosis, treatment options can be tailored to the individual.

Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure.

BACKGROUND: Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy. HYPOTHESIS: Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia. ANIMALS: Ten normal cats; 10 cats with chronic renal failure. METHODS: Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration. RESULTS: Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated. CONCLUSIONS AND CLINICAL IMPORTANCE: At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and cats with chronic renal failure. With these dosages, adverse affects of calcitriol administration were not seen. Potential reasons for lack of apparent effect include small sample size, insufficient duration of study, insufficient dosage of calcitriol, problems with formulation or administration of calcitriol, and variable gastrointestinal absorption of calcitriol.

Prediction of serum ionized calcium concentration by use of serum total calcium concentration in dogs.

OBJECTIVE: To determine whether total serum calcium (tCa) or adjusted tCa concentrations accurately predict ionized calcium (iCa) status in dogs. SAMPLE POPULATION: 1,633 canine serum samples. PROCEDURE: The tCa concentration was adjusted for total protein (TP) or albumin concentration by use of published equations. Correlations between iCa and tCa or adjusted tCa, tCa and TP, and tCa and albumin were calculated. Diagnostic discordance between tCa or adjusted tCa and iCa was determined. Diagnostic discordance in predicting iCa was also determined for 490 dogs with chronic renal failure (CRF). Sensitivity, specificity, positive and negative predictive values, and positive and negative diagnostic likelihood ratios were calculated for tCa, tCa adjusted forTP, and tCa adjusted for albumin. RESULTS: Diagnostic discordance was 27% when tCa concentration was used to predict iCa status. Use of adjusted tCa increased diagnostic discordance to approximately 37% for all dogs and 55% for dogs with CRF. Positive predictive value and positive diagnostic likelihood ratios were poor when tCa concentration was used to predict iCa status. The tCa concentration overestimated normocalcemia and underestimated hypocalcemia. Adjusted tCa overestimated hypercalcemia and underestimated hypocalcemia. CONCLUSIONS AND CLINICAL RELEVANCE: Adjusted tCa or tCa concentrations are unacceptable for predicting iCa status in dogs. Use of adjustment equations is not recommended. Direct measurement of iCa concentration is necessary for accurate assessment of calcium status. Use of tCa or adjusted tCa concentrations to predict iCa status in dogs could cause serious mistakes in diagnosis and case management, especially in dogs with CRF.

Fractionation of canine serum magnesium.

BACKGROUND: Serum total magnesium (tMg) consists of 3 fractions: ionized magnesium (iMg), protein-bound magnesium (pbMg), and complexed magnesium (cMg). Serum iMg may be measured by an ion-selective electrode, but determination of pbMg and cMg has not been attempted in dogs. OBJECTIVES: The objectives of this study were to assess the validity of a micropartition system to fractionate serum tMg and to establish reference intervals for pbMg, cMg, and iMg in clinically normal dogs using this method. METHODS: Serum samples from 10 clinically healthy dogs were fractionated using a micropartition system (Centrifree YM-30, Amicon Corp, Lexington, MA, USA). Serum tMg and iMg were measured in whole serum, and tMg was also measured in the ultrafiltrate. Concentration of cMg was obtained by the subtraction of iMg from tMg concentrations of the ultrafiltrate. Protein-bound Mg was calculated by subtracting the tMg concentration of the ultrafiltrate from the tMg concentration of whole serum. RESULTS: Results for pbMg and cMg using the micropartition system showed good reproducibility. Determination of tMg and iMg had acceptable inter- and intra-assay precision. Concentrations of iMg, cMg, and pbMg were 0.50 +/- 0.05 mmol/L, 0.05 +/- 0.04 mmol/L, and 0.24 +/- 0.04 mmol/L, representing 63%, 6%, and 31% of the tMg concentration, respectively. CONCLUSIONS: The micropartition system was a reproducible means to accurately assess cMg and pbMg concentrations in dogs.

Increased serum concentrations of adiponectin in canine hypothyroidism.

Serum concentrations of adiponectin were compared between sex-matched hypothyroid (n = 18) and euthyroid (n = 18) client-owned dogs with comparable ages and body condition scores (BCS). Concentrations of adiponectin (mean; 95% confidence interval) were significantly (P < 0.01) higher in hypothyroid (17.2 µg/mL; 12.1-20.5 µg/mL) than healthy (8.0 µg/mL; 5.6-11.4 µg/mL) dogs following adjustment for potential confounders (BCS, age and sex). Serum concentrations of adiponectin were significantly negatively associated with concentrations of total thyroxine (P <0.05) and positively correlated with concentrations of cholesterol (r = 0.6, P <0.01) in hypothyroid dogs. In conclusion, this study demonstrated increased serum concentrations of adiponectin in dogs with hypothyroidism. Suggestive of the presence of resistance to adiponectin that could have contributed to development of hyperlipidemia and insulin resistance in these dogs or alternatively, could be a consequence of these metabolic alterations.

Determination of calcium fractionation in dogs with chronic renal failure.

OBJECTIVE: To determine concentrations of calcium (total [tCa], ionized [iCa], protein-bound [pCa], and complexed [cCa]) in dogs with chronic renal failure (CRF). ANIMALS: 23 dogs with CRF. PROCEDURE: Serum calcium was fractionated by use of a micropartition system. Total calcium and iCa concentrations and pH were measured in unfractionated serum, and tCa concentration was measured in the ultrafiltrate. The pCa fraction was calculated by subtracting tCa of the ultrafiltrate from tCa concentration of unfractionated serum. The iCa concentration in unfractionated serum was subtracted from tCa concentration in the ultrafiltrate to determine the concentration of cCa. RESULTS: Concentrations of tCa, iCa, pCa, and cCa had wide ranges among dogs with CRF Dogs with significantly low tCa concentration (770 +/- 1.73 mg/dL) had cCa concentration (0.76 +/- 0.38 mg/dL) within reference range, whereas dogs with reference range to high tCa concentration (10.85 +/- 1.13 mg/dL) had significantly high cCa concentration (2.62 +/- 1.04 mg/dL). There was no significant difference in iCa or pCa concentrations between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of tCa, iCa, cCa, and pCa varied widely in dogs with CRF Overall, cCa concentration was high, although subpopulations differed in cCa and tCa concentrations. Differences in tCa concentration were primarily attributable to differences in cCa fraction.

Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor-23 interactions in chronic kidney disease.

OBJECTIVE: To review the inter-relationships between calcium, phosphorus, parathyroid hormone (PTH), parent and activated vitamin D metabolites (vitamin D, 25(OH)-vitamin D, 1,25(OH)2 -vitamin D, 24,25(OH)2 -vitamin D), and fibroblast growth factor-23 (FGF-23) during chronic kidney disease (CKD) in dogs and cats. DATA SOURCES: Human and veterinary literature. HUMAN DATA SYNTHESIS: Beneficial effects of calcitriol treatment during CKD have traditionally been attributed to regulation of PTH but new perspectives emphasize direct renoprotective actions independent of PTH and calcium. It is now apparent that calcitriol exerts an important effect on renal tubular reclamation of filtered 25(OH)-vitamin D, which may be important in maintaining adequate circulating 25(OH)-vitamin D. This in turn may be vital for important pleiotropic actions in peripheral tissues through autocrine/paracrine mechanisms that impact the health of those local tissues. VETERINARY DATA SYNTHESIS: Limited information is available reporting the benefit of calcitriol treatment in dogs and cats with CKD. CONCLUSIONS: A survival benefit has been shown for dogs with CKD treated with calcitriol compared to placebo. The concentrations of circulating 25(OH)-vitamin D have recently been shown to be low in people and dogs with CKD and are related to survival in people with CKD. Combination therapy for people with CKD using both parental and activated vitamin D compounds is common in human nephrology and there is a developing emphasis using combination treatment with activated vitamin D and renin-angiotensin-aldosterone-system (RAAS) inhibitors.

Effect of omega-3 polyunsaturated fatty acids and body condition on serum concentrations of adipokines in healthy dogs.

OBJECTIVE: To determine associations between serum concentrations of omega-3 polyunsaturated fatty acids or body condition and serum concentrations of adiponectin, leptin, insulin, glucose, or triglyceride in healthy dogs. ANIMALS: 62 healthy adult client-owned dogs. PROCEDURES: Body condition score and percentage of body fat were determined. Blood samples were collected after food was withheld for 12 hours. Serum was harvested for total lipid determination, fatty acid analysis, and measurement of serum concentrations of adiponectin, leptin, insulin, glucose, and triglyceride. Associations between the outcome variables (adiponectin, leptin, insulin, glucose, and triglyceride concentrations) and each of several variables (age, sex, percentage of body fat, and concentrations of total lipid, α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) were determined. RESULTS: Serum concentrations of docosapentaenoic acid were significantly positively associated with concentrations of adiponectin and leptin and negatively associated with concentrations of triglyceride. Serum concentrations of α-linolenic acid were significantly positively associated with concentrations of triglyceride. No significant associations were detected between serum concentrations of eicosapentaenoic acid or docosahexaenoic acid and any of the outcome variables. Percentage of body fat was significantly positively associated with concentrations of leptin, insulin, and triglyceride but was not significantly associated with adiponectin concentration. Age was positively associated with concentrations of leptin, insulin, and triglyceride and negatively associated with concentrations of adiponectin. Sex did not significantly affect serum concentrations for any of the outcome variables. CONCLUSIONS AND CLINICAL RELEVANCE: Docosapentaenoic acid may increase serum concentrations of adiponectin and leptin and decrease serum triglyceride concentration in healthy dogs.

Effect of omega-3 fatty acids on serum concentrations of adipokines in healthy cats.

OBJECTIVE: To determine associations between serum concentrations of omega-3 polyunsaturated fatty acids and concentrations of adiponectin, leptin, and insulin in healthy cats. ANIMALS: 56 healthy adult client-owned cats. PROCEDURES: Body condition score (BCS) was determined, and blood samples were collected after food was withheld for 12 hours. Serum was harvested for fatty acid analysis and measurement of serum concentrations of adiponectin, leptin, insulin, glucose, triglyceride, and cholesterol. RESULTS: 1 cat was removed because of hyperglycemia. Significant interaction effects between BCS and serum concentrations of eicosapentaenoic acid (EPA) were detected for the analyses of associations between EPA and serum concentrations of adiponectin, insulin, and triglyceride. Cats were categorized into nonobese (BCS, 4 to 6 [n = 34 cats]) and obese (BCS, 7 to 8 [21]) groups; serum concentrations of EPA were directly associated with concentrations of adiponectin and inversely associated with concentrations of insulin and triglyceride in obese cats and were directly associated with concentrations of leptin and inversely associated with concentrations of adiponectin in nonobese cats. Additionally, serum concentrations of docosahexaenoic acid were directly associated with concentrations of adiponectin in obese cats. No significant associations between serum concentrations of docosahexaenoic acid or α-linolenic acid were detected in the analyses for all cats. Female cats had higher serum concentrations of adiponectin and lower concentrations of glucose than did male cats. Increased age was associated with a small increase in serum concentrations of leptin. CONCLUSIONS AND CLINICAL RELEVANCE: EPA may ameliorate the decrease in adiponectin and the increase in insulin and triglyceride concentrations in obese cats.

Prediction of serum ionized calcium concentration by serum total calcium measurement in cats.

Feline serum samples (n = 434) were classified as hypercalcemic, normocalcemic, or hypocalcemic based on both total calcium (tCa) and ionized calcium (iCa) concentrations. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive diagnostic likelihood ratio (PDLR), and negative diagnostic likelihood ratio (NDLR) were calculated for prediction of hypercalcemia and hypocalcemia in all samples, in hypoalbuminemic cats, and in those with chronic renal failure (CRF) as compared with cats that had other conditions. Diagnostic discordance in prediction of iCa using tCa was 40%. Sensitivity of tCa in prediction of ionized hypercalcemia was low and specificity was high. The PDLR for prediction of ionized hypercalcemia or hypocalcemia was low in all cats, especially in those with CRF. Due to the high level of diagnostic discordance, tCa should not be used to predict iCa concentration. Concentration of iCa should be measured directly when accurate assessment of calcium status is needed.

Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats.

Nineteen cats with abnormally high serum T4 concentrations underwent thyroid scintigraphy using technetium-99m pertechnetate (99mTcO4) before and after 36 +/- 6 days of methimazole administration (approximately 2.5mg PO q 12 h). Thyroid-to-salivary gland ratios (T:S ratios) and percentage thyroidal uptake of injected radioactivity at 20 and 60min after injection of 99mTcO4 were compared before and after methimazole treatment. Serum thyroid stimulating hormone (TSH) concentration was measured before and after methimazole treatment. Quantitatively, there was a positive association between the thyroid uptake of 99mTcO4 and the serum T4 before treatment (r = 0.74-0.83). TSH suppression was present when cats were first evaluated for hyperthyroidism. Methimazole treatment did not relieve TSH suppression in 17 cats. Two cats with unilateral thyroid uptake developed bilateral, asymmetric thyroid uptake of 99mTcO4 after treatment and had the greatest increase in TSH concentration after treatment. Quantitatively, thyroid scintigraphy did not significantly change after methimazole treatment (P>0.1). Evaluation of serum TSH concentration may be helpful in identifying methimazole-induced changes in the scintigraphic features of hyperthyroidism in mildly hyperthyroid cats.

Effects of storage on serum ionized calcium and pH from horses with normal and abnormal ionized calcium concentrations.

It has been previously shown that Ca(I) concentration is stable in serum collected from healthy horses for 10 days if stored at 40 degrees C. This may not be true for horses with abnormal Ca(I) concentrations. Thus the stability of ionized calcium (Ca(I)) concentration and pH measurement in serum from horses with both normal and abnormal Ca(I) concentrations stored for various times at 40 degrees C and -10 degrees C was evaluated. Our results indicated that serum Ca(I) concentration was stable throughout 7 days of cold or frozen storage, after being received by the Clinical Chemistry Laboratory. Serum Ca(I) concentration showed a significant decrease by 14 days of frozen storage (-10 degrees C). Serum pH showed a statistically significant increase by 7 days of cold storage, and within 3 days of frozen storage. If equine serum is collected, handled and stored anaerobically, and kept cold or frozen, Ca(I) concentration can be accurately measured for approximately 7 days after collection, regardless of the health status of the animal. An accurate measurement of pH may be made within 3 days of cold or 1 day of frozen storage.