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1 The Case of Kensington s Calcium Gregory K. Ogilvie, DVM Diplomate ACVIM (Specialties of Internal Medicine, Oncology) Diplomate ECVIM-CA (Oncology) CVS Angel Care Cancer Center University of California San Diego Key Questions: What are the Signs/Causes/Diagnostics/Rx s: Hyper- Hypocalcemia? Times to evaluate PTH/PTHrp? Best-iCa vs tca vs adjusted Ca? Pathogeneses/Diagnostics/Rx/ Prognosis for AGASACA? "Kensie" 7 yr SF Border Collie Problem List: Wt loss, BCS: 3/9 PU/PD Thickened Anal Sac Mildly Elevated tca, Low Phosphorus
2 Hypercalcemia: Clinical Signs Clinical Signs: Elevated ica Polyuria, Polydipsia Vomiting, Constipation Bradycardia Weakness, Depression Stupor, Coma, and Seizures
3 Hypercalcemia: Causes Top 3 Causes for Hypercalcemia? A. Cancer B. Renal Failure C. Hyperparathyroidism D. Hypoadrenocorticism E. Hypervitaminosis D F. Granulomatous Disease Elevated icalcium 109 Hypercalcemic Dogs Lymphoma>Renal Failure>Hyperparathyroidism> Hypoadrenocorticism J Vet Intern Med May-Jun;23(3):514 Jun;23(3):514-9.
4 Hypercalcemia: Diagnostics Hypercalcemia: Diagnostics tca vs ica vs adjusted Ca BUN, Creatinine, USG Chest Radiograph/Ultrasound PTH/PTHrp ACTH Stimulation Bone Marrow Which is LEAST Accurate? A. Total Ca (tca) B. Ionized Ca (ica) C. Adjusted Ca-Albumin D. Adjusted Ca-TP
5 ica vs tca vs adjusted tca 1,633 Hypercalcemic Dogs ica vs tca vs adjusted tca (TP vs albumin) Adjusted tca or tca: unacceptablefor predicting ica & should not be used Am J Vet Res Aug;66(8): ica vs tca vs adjusted tca 434 Feline Samples ica vs tca tca: unacceptablefor predicting ica tca should not be used to predict ica concentration Can J Vet Res Jul;74(3): Which has higher ica? A. ica in Lymphoma & AGASACA? B. Renal Failure? J Vet Intern Med May-Jun;23(3):514-9.
6 Elevated icalcium 109 Hypercalcemic Dogs ica in Lymphoma & AGASACA> Renal Failure J Vet Intern Med May-Jun;23(3): How often is PTHrp Elevated in hypercalcemia of AGASACA A. ~100% B % C % D % J Vet Intern Med May-Jun;23(3): PTHrp Levels Elevated PTHrp 12/14 hypercalcemic dogs with lymphoma & AGASACA, but WNL in controls, normocalcaemic dogs with lymphoma Vet Rec Dec 16;159(25):833-8
7 "Kensie" 7 yr SF Border Collie Problem List: Wt loss, BCS: 3/9 PU/PD Thickened Anal Sac Mildly Elevated tca, Low Phosphorus "Kensie" 7 yr SF Border Collie How do phosphorus levels help determine causation when the ica is elevated? "Kensie" 7 yr old SF Border Collie
8 "Kensie" 7 yr old SF Border Collie Probable Carcinoma Anal Sac Adenocarcinoma Spayed Females? 25-90% (25%) Elevated ica 25% Elevated PTHrp Hypophosphatemic Ipsilateral External Iliac Nodes Chest Metastases? "Kensie" 7 yr SF Border Collie Revised diagnostic plan: 3 View Chest, 2 View Abdominal Radiographs PTH and PTHrp? Ultrasound (declined due to $)
9 "Kensie" 7 yr SF Border Collie "Kensie" 7 yr SF Border Collie "Kensie" 7 yr SF Border Collie Pertinent results: Radiographs: WNL Hypercalcemia of Malignancy Recommendations: Ultrasound (declined due to $) Anal sacculectomy
10 Treatment and Prognosis The Single Most Important Thing in all of Veterinary Medicine is:
11 The Commandments Don t Let them Hurt! Don t Let them Vomit (or have diarrhea)! Don t Let them Starve! 113 Cases of AGASACA 53 hypercalcemia, 79% mets Median survival (treated): 544 days (surgery, RT, chemo) 33% PR to Carboplatin J Am Vet Med Assoc Sep 15;223(6): Prognosis: AGASACA Median survival 544 days
12 Prognosis: AGASACA Median survival 544 days Postop RT/mito: AGASACA 15 Cases 4 Hypercalcemic, 7 to nodes Surgery (nodes) Postop RT, 5 Mitoxantrone Rx Overall survival 956 days Vet Comp Oncol Jun;1(2): Postop Melphalan: AGASACA 19 AGASACA 2 Bilateral, 10 Mets to Nodes Surgery (nodes) Postop Melphalan Rx Node+ Survival: 20 Months Node- Survival: 29.3 Months Aust Vet J. J Jun;83(6): Jun;83(6):340-3.
13 Palladia (Toceranib Phosphate) Tyrosine Kinase Inhibitor Inhibits Angiogenesis, Inhibits Tyrosine Kinases First Approved in USA (>1000 Dogs Treated) Broad Anticancer Effects: Sarcomas, Carcinomas, Melanomas, Myeloma, and MCTs Approved for Mast Cell Tumors Palladia (Toceranib Phosphate) Labeled Dosage, Frequency of Administration (3.25 mg/kg q48 hrs): Not Recommended Recommended Dosage: mg/kg Recommended Frequency: Monday, Wednesday, Friday Palladia & AGASACA 33 Cases of AGASACA 88% Biological Activity Median Duration for PR of 25 weeks Median Duration for SD of 19 weeks
14 Hypercalcemia: Rx Mild Hypercalcemia: Rx Restore, maintain hydration & ensure calciuresis Monitor ica, PO4, creatinine until the hypercalcemia, clinical signs resolve Avoid nephrotoxic drugs Moderate Hypercalcemia: Rx 0.9% NaCl+KCl: Urine Output > 2 mls/kg/hr Monitor ica, PO4, creatinine, electrolytes Furosemide? Steriods!?
15 Severe Hypercalcemia: Rx 0.9% NaCl+KCl: Urine Output > 2 mls/kg/hr Monitor ica, PO4, creatinine, electrolytes Calcitonin, Bisphosphonates Which Rx is LEAST Effective? A. 0.9% NaCl Diuresis B. Furosemide C. Prednisone D. Calcitonin E. Bisphosphonates Furosemide & Hypercalcemia 0.9% NaCl + Furosemide: Std??? Since 1950: 9 Pubs, 37 Patients 14/37 Normalized, 2< 24 hrs Complications: hypernatremia, coma, metabolic acidosis, hypophosphatemia, death Ann Intern Med 2008 Aug 19; 149:259
16 Hypercalcemia Saline, bisphosphonates+/- calcitonin: Std of Care Bisphosphonates: 56 Pubs, 34 Randomized 70% Normocalcemic Anal Sacculectomy "Kensie" 7 yr SF Border Collie Postoperative Recovery Uneventful Histopathology: Apocrine gland anal sac adenocarcinoma Margins clean 0.1 cm PU/PD 3 days post-op
17 "Kensie" 7 yr SF Border Collie Revised diagnostic plan: Blood work including ionized calcium Abdominal ultrasound Ultrasound: MLN 38 Dogs: AGASACA, Lymphoma Ultrasound proved to be useful to assess canine medial iliac lymph nodes Vet Radiol Ultrasound Mar-Apr;45(2): "Kensie" 7 yr SF Border Collie Pertinent results: Elevated Ionized Calcium Enlarged Medial Iliac Node L
18 "Kensie" 7 yr SF Border Collie Recommendations: Diurese 0.9% NaCl Normalize Calcium Surgical Lymphadenectomy Monitor Calcium Postop Lymphadenectomy: Complications AGASACA Lymphadenectomy Node Almost Always Ipsilateral No Postoperative Complications Bleeding, Neuro Impairment Median Survival 20.6 Months Vet Surg Apr;35(3):267-70
19 "Kensie" 7 yr SF Border Collie Postop Recovery Uneventful Dramatic Improvement: Acting Like a Puppy Plan: Outpatient Monitoring of ionized calcium "Kensie" 7 yr SF Border Collie Represented Lethargic, anorexic, 2 brief seizures Hypocalcemia Ventricular arrhythmias
20 "Kensie" 7 yr SF Border Collie Hypocalcemia: Clinical Signs Clinical Clinical Signs: Signs: Hypocalcemia Hypocalcemia
21 Hypocalcemia: Causes Primary (Surgically Induced) Hypoparathyroidism Eclampsia Ethylene Glycol Toxicity Mg Deficiency TPN, Cisplatin Rx, etc Calcium-Sensing Calcium-Sensing Receptor Receptor Hypocalcemia: Vitamin D Therapy
22 Which Vitamin D is Best? A. Ergocalciferol B. Dihydrotachysterol C. Calcifediol D. Calcitriol Vitamin D Therapy Vitamin D Analog Maximum Action Duration of Action Ergocalciferol 6 weeks 6 months Dihydrotachysterol: 2 weeks 2 months Calcifediol 1 week days Calcitriol 1-2 hours 1-2 days
23 "Kensie" 7 yr SF Border Collie Recommendations/Plan: CRI Calcium Gluconate 1, 25 Dihydroxycholicalciferol Oral Calcium "Kensie" 7 yr SF Border Collie Rapid Improvement within 24 hours (ica Monitoring q12hrs) Discharged Vitamin D, oral calcium weaned and discontinued as calcium normalized "Kensie" 7 yr SF Border Collie Carboplatin IV q 3wks 5 Treatments Doing GREAT!
24 Key Questions: What are the Signs/Causes/Diagnostics/Rx s: Hyper- Hypocalcemia? Times to evaluate PTH/PTHrp? Best-iCa vs tca vs adjusted Ca? Pathogeneses/Diagnostics/Rx/ Prognosis for AGASACA? To complete the evaluation, please go to the following website: Thank you for your participation!
David Bruyette, DVM, DACVIM
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