Calcium disorders

• Calcium disorder - is the patient normally abnormal?

  Know your laboratory method:

  • Re-test - if the test doesn’t seem correct.
  • Alternative test

  Do you get high calcium results with:

  • Lipaemia
  • Icterus
  • Haemolysis

  Dry chemistry equipment may indicate increased calcium bot confirmed by reference lab.

  Is the sample EDTA contaminated - EDTA stops blood calcium by holding all the calcium in the sample to stop clotting, so if EDTA in blood calcium test then will get a false low calcium.
• Renal secondary hyperparathyroidism

  FGF-23, decreased calcitriol and reduced calcium absorption leads to increased PTH.

  Hyperphosphatemia -> increased complexed fraction of calcium.

  Serum total calcium normal or high.

  Ionised calcium low or low-normal.

  High serum parathyroid hormone.
• How urgent is my Hypercalcaemia investigation?

  Mass actions:

  • Calcium and phosphorous will complex/precipitate when the concentration of both is high.

  In tissues = mineralisation.

  Kidneys, gastric mucosa, other tissue.

  Prediction by calcium phosphate product (Ca xP)

  Estimate of mineralisation risk varies in literature.
• What can go wrong to cause Hypercalcaemia?

  Increased PTH activity - primary hyperparathyroidism

  Activity of PTH like substances - humoral Hypercalcaemia of malignancy - parathyroid related peptide (PTHrP).

  Increased Vitamin D activity - vitamin D toxicity, granulomas or incorrect diet.

  Osteolysis - local destruction of bone (neoplasia).
• Causes of total Hypercalcaemia in dogs

  In order of most common to least:

  Malignancy

  Hypoadrenocorticism

  Priamry hyperparathyroidism

  Chronic renal failure

  Vitamin D toxicosis

  Granulomatous diseases
• Causes of total Hypercalcaemia in cats

  In order of most common to least:

  • Idiopathic Hypercalcaemia
  • Renal failure (total mainly, occ iCa)
  • Malignancy (lymphoma and squamous cell carcinoma)
  • Primary hyperparathyroidism.
• Principle differentials for hypercalcaemia - parathyroid dependant

  Parathyroid adenoma

  Parathyroid adenocarcinoma

  Parathyroid hyperplasia

  Calcium sensor defect
• Principle differentials for hypercalcaemia - parathyroid independent

  Humoral hypercalcaemia of malignancy

  Vitamin D excess

  Granulomatous disease

  Osteolysis

  Feline idiopathic hypercalcaemia

  Hypoadrenocorticism
• Principle differentials for hypercalcaemia - malignancy

  Lymphoma (T-cell)

  Anal sac apocrine gland adenocarcinoma

  Other carcinoma

  Myeloma

  Oesteosarcoma

  Bone metastases

  Histiocytic neoplasia.
• Principle differentials for hypercalcaemia - vitamin D excess

  Over-supplementation

  Incorrect dietary formulation

  Rodenticide

  Vitamin D analogue

  Plants

  Granulomatous disease

  Immunological (e.g. poly arthritis)
• Hypoadrenocorticism

  Usually mild hypercalcaemia but other signs are used to diagnose the disease.

  Present in ~30% of Addisonian dogs.

  Usually only affects total calcium; ionised calcium is normal

  Exact mechanism unknown:

  • Dehydration and increased protein concentration
  • Decreased renal calcium excretion.
• Idiopathic hypercalcaemia

  Young to middle-aged cats.

  Mild to moderate hypercalcaemia

  No obvious etiology

  • Hypercalcaemia (total and ionised)
  • Normal phosphorous concentration
  • Intact PTH normal or decreased
  • PTHrp undetectable
  • Normal vitamin D3 concentration.
• Hypercalcaemia - investigation first steps

  Diet:

  • Supplements
  • Unusual or unfamiliar brand
  • Access to grapes/ raisins.

  Access to Vitamin D:

  • Supplements
  • Rodenticide (cholecalciferol)
  • Psioriasis medication
  • Certain plants.

  Review signalment:

  • Primary hyperparathyroidism is middle-aged to geriatic disease
  • Breed predisposition
• Hypercalcaemia - clinical review

  Lymph nodes - palpation/imaging

  Anal sac masses - rectal examination may be required. Sublumbar lymph nodes on imaging.

  Other masses - neoplasia, granulomas.

  Parathyroid imaging (ultrasound)

  Angiostrongylus

  • Imaging, faecal examination
  • Haematomas, bleeding
• Hypercalcaemia - clinical pathology review

  Ionised calcium.

  Albumin

  Phosphorous

  Chloride

  Urea and creatinine

  Na:K ratio (+/- ACTH stimulation) - shows of you have Addison’s
• When azotaemia hypercalcaemia - which came first?

  Elevated urea, creatinine, total calcium, phosphorous.

  Renal dysfunction leads to elevated total calcium

  Elevated calcium leads to renal dysfunction.
• Further investigations beyond PTH and iCa

  Most common requirement is:

  • Characterise parathyroid independent hypercalcaemia.
  • Low PTH and high iCa.
  • No initial clinical appearance of neoplasia/ granuloma.

  Relevant lab tests:

  • Parathyroid related peptide (PTHrP).
  • 25 hydroxy-vitamin D (calcidiol)
  • 1,25 dihydroxy-vitamin D (calcitriol)
• Generic treatment for hypercalcaemia

  Determine urgency by Ca x P.

  Fluid/ diuresis

  • 5ml/kg/hr NaCl
  • Furosemide 2mg/kg BID-TID - only once hydrated, the faster the filtrate travels through the nephron the harder to grab onto the calcium.

  Glucocorticoids - Prednisolone 1mg/kg or equivalent.

  Biphsophates - oestoclasts poison (so stop the calcium being taken up by the osteoclasts)
• More specific treatment for hypercalcaemia

  Depends on cause:

  Treat directly:

  • Neoplasia (surgery/chemotherapy)
  • Toxicities - remove and generic treatment.
  • Addison’s (DOCP)
  • Idiopathic (diet, generic therapy)
  • Primary hyperparathyroidism (surgery, percutaneous ablation)
  • Granulomatous (surgery/antimicrobials/ antifungals)
  • Immune mediated - immunosuppression.
• Parathyroid adenoma

  Peri, post surgical considerations

  • Hyperactive nodule -> hypercalcaemia
  • Hypercalcaemia -> negative feedback -> atrophy of normal tissue.
  • Remove nodule -> hypocalcaemia

  Monitor calcium post surgically

  Support with IV calcium

  Vitamin D therapy (calcitriol, Alfacalcidiol)

  Aim for subclinical hypocalcaemia - provide stimulus for remaining tissue to regain function.
• Hypocalcaemia

  Parathyroid dependant:

  • Primary hypoparathyroidism
  • Spontaneous immune mediated
  • Functional hypomagnesic
  • Post-surgical e.g. feline hyperthyroidism

  Demand exceeds supply or mobilisation:

  • Periparturient tetany (eclampsia)
  • Nutritional deficiency of calcium or vitamin D
  • e.g. all meat diets, severe GI disease.
  • Pancreatitis with fat necrosis.

  PTH and calcitriol syndromes.
• Diagnosis of hypocalcaemia

  History

  Routine lab results e.g. phosphorous

  • Also check albumin.

  Rarely PTH, iCa and Mg measurements.
• Short term/ acute therapy for hypocalcaemia

  IV calcium:

  • Gluconate
  • e.g. 0.5-1.5ml/kg over 20-30 minutes
  • Borogluconate
  • Chloride

  Monitor for bradycardia
• Long term therapy for hypocalcaemia

  Aim for subclinical or low normal hypocalcaemia

  • Post - thyroidectomy; wants to stimulate remaining tissue.
  • Primary hypoparathyroidism; reduce risk of iatrogenic vitamin D toxicosis.

  Oral calcium supplement only if diet insufficient - sometimes used in early therapy.

  Vitamin D to promote calcium uptake - initially short acting (lower risk, higher cost)

  Wean to intermediate/ longer acting (higher risk lower cost)
• Hyperparathyroidism - primary overview


  Clinical signs of hypercalcaemia

  Excess (inappropriately high) PTH with hypercalcaemia

  Therapy by surgical removal (temporary medical by bisphophonates)
• Hyperparathyroidism - secondary overview

  Renal:

  • Signs relating to renal disease, rubber jaw in extreme disease.
  • Plasma phosphate, iCa
  • treatment is phosphate restirciton
• Hyperparathyroidism - nutritional overview

  Pathological fractures

  Correct nutritional deficiency (avoid all-meat diets).