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Tips for diagnostic investigation of the hypercalcaemic cat
↑tCa is confirmed by repeat testing on a fasted, non-haemolysed sample in a well-hydrated patient. Information from the history and physical examination helps to rank the differentials. CKD and neoplasia should be ruled out early on in the investigation.
Where ↑tCa is persistent then iCa should be measured concurrently. Where tCa is elevated and iCa is normal, no further investigation is necessary. If iCa is elevated consider the following;
- the age and signalment of the cat primary hyperparathyroidism is a rare disease of older cats. Long-haired cats are overrepresented for idiopathic hypercalcaemia
-potential for vitamin D toxicity review diet history, access to rodenticides, medications, houseplants
-review physical examination findings for evidence of neoplasia, cervical lesions, bone pain.
- is there physical or laboratory evidence of renal disease? This is the most common cause of ↑tCa
- what is the phosphate level? phosphate is typically
low in PTH and PTHrP-mediated hypercalcaemia. Elevated phosphate occurs with renal disease, vitamin D intoxication and osteolysis.
- imaging may show evidence of neoplasia, urolithiasis or bony lesions (multiple myeloma, other neoplasia, osteomyelitis) Cervical ultrasonography can help to rule in primary hyperparathyroidism.
12 hour fast is recommended.
- adjustment of tCa to TP or albumin is not recommended in cats
- iCa can be measured in-house or submitted to a commercial laboratory.
- for iCa assay, anaerobic collection, the use of dry heparinised syringes and storage at 4oC (if not processed immediately) reduce errors.
- the availability of PTH and PTHrP should be investigated locally. These tests are currently available at www.dcpah.msu.edu. Sample handling requirements as per website should be followed carefully.
Treatment for idiopathic hypercalcaemia
The long term consequences of hypercalcaemia include renal damage, urolithiasis and soft tissue calcification. Diet change may be helpful and should be individualized. If the iCa elevation is minimal, phosphate is not elevated and diet change has not been effective, then regular monitoring may be all that is required. Glucocorticoids reduce intestinal calcium absorption and bone resorption and may increase calciuresis. The use of frusemide or glucocorticoids long term is not recommended.
Bisphosphonates inhibit bone resorption by
promoting osteoclast apoptosis at sites of active bone turnover. Oral alendronate is effective for treatment
of idiopathic hypercalcaemia but dosing precautions
are necessary and the risks associated with long-term alendronate therapy are not yet fully understood.(1, 2) Food substantially reduces the bioavailability of oral alendronate. Medication must be accompanied by a water swallow because alendronate has the potential to cause drug-induced oesophageal disease (resulting in oesophagitis that may progress to oesophageal stricture formation). We use a starting dose of 10 mg per cat once weekly PO given on an outpatient basis. Medication is administered following a 12 hour fast, with a 5 ml water swallow, and the cat is fed 2 hours later. Once iCa is controlled, the dosing interval is progressively increased to determine the minimum effective dose. Medication- free periods should be considered in the long term. In humans and dogs long term bisphosphonates can cause osteonecrosis of the jaw.(3) Patella fractures and cortical bone thickening in a cat on long term alendronate therapy are reported.(4)
References
1. Whitney JL, Barrs VRD, Wilkinson MR, Briscoe KA, Beatty JA. Use of bisphos- phonates to treat severe idiopathic hypercalcaemia in a young Ragdoll cat. Journal of Feline Medicine and Surgery. 2011;13(2):129-34.
2. Hardy BT, Galvao JFD, Green TA, Braudaway SR, DiBartola SP, Lord L, et al. Treatment of Ionized Hypercalcemia in 12 Cats (2006-2008) Using PO-Adminis- tered Alendronate. J Vet Intern Med. 2015;29(1):200-6.
3. Burr DB, Allen MR. Mandibular necrosis in beagle dogs treated with bisphos- phonates. Orthodontics & Craniofacial Research. 2009;12(3):221-8.
4. Council N, Dyce J, Drost WT, de Brito Galvao JF, Rosol TJ, Chew DJ. Bilateral patellar fractures and increased cortical bone thickness associat- ed with long-term oral alendronate treatment in a cat. JFMS Open Reports. 2017;3(2):2055116917727137.
- PTH, PTHrP and vitamin D testing. Assays have
been validated for feline PTH (measured as the intact molecule, iPTH or PTH 1-84) and PTHrP. Vitamin
D metabolites do not differ between species. An inappropriate PTH level (elevated or top half of reference range) in the face of concurrent ↑iCa indicates a parathyroid-dependent process. Whether this results from primary or teritary hyperparathyroidism can be concluded from the rest of the clinical data. Where
PTH is appropriately low (bottom half of reference
range or undetectable) in the face of concurrent ↑iCa, then all other diagnoses should be considered. Where PTHrP is elevated then malignancy becomes the
major differential. Where PTHrP is normal or subnormal malignancy cannot be ruled out.
- idiopathic hypercalcaemia is diagnosed by ruling out all other causes.
Practicalities of laboratory investigation
- EDTA (ethylenediaminetetraacetic acid) chelates calcium so should not be used for samples for calcium measurement
- for tCa, serum or heparinised plasma collected after a
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