HISTORY / CLINICAL SIGNS: 3 month Hx of progressive weakness, weight loss, intermittent inappetance, increased water consumption, urinary accidents, and occasional diarrhea. UTD on vaccines, on monthly flea/tick/heartworm preventive. Medications: none.
PHYSICAL EXAM FINDINGS: QAR, friendly. BCS 3.5/9. mm pink/moist, CRT 2 sec. TPR WNL. Heart & lungs sounds unremarkable. Thin body condition yet mildly distended abdomen. Abdominal palpation: generalized hepatomegaly, mild discomfort upon cranial abdomen palpation. Rectal palpation exam unremarkable. External lymph nodes unremarkable. Bilateral hind limb paresis with muscle trembling after standing for a long period of time. Suspect mild/moderate elbow and hip osteoarthritis. Minor bilateral elbow hygromas. Rough, dull hair coat. Moderate periodontal disease.
What diagnostic tests would you order? Any other questions?
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DIAGNOSTIC TESTS & RESULTS:
- Bloodwork: Mild normocytic, normochromic, non-regenerative anemia. Stress leukogram. TP normal, albumin normal (3.7 g/dL). Slight azotemia. Glu normal. Ca high (21.1 mg/dL). P normal (3.3 mg/dL). Liver enzymes elevated (moderate/high). Electrolytes unremarkable.
- Calculations:
- Correct the Ca (21.1 mg/dL) for the serum albumin concentration (3.7 g/dL): Ca 21.1 mg/dL โ albumin 3.7 g/dL + 3.5 = corrected Ca 20.9 mg/dL.
- Calculate the Ca X P product: corrected Ca 20.9 mg/dL X P 3.3 mg/dL = 20.9 X 3.3 = 68.97.
- Calculations:
- Urinalysis: USG 1.015. Otherwise, unremarkable.
- Thoracic radiographs: unremarkable
- Abdominal radiographs: moderate generalized hepatomegaly, spondylosis between various lumbar vertebrae
- Abdominal ultrasound (with liver FNA): declined by owner
What are differential diagnoses for hypercalcemia?
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DIFFERENTIALS for hypercalcemia: Increased parathyroid hormone: primary hyperparathyroidism, hypercalcemia of malignancy. Increased vitamin D: rodenticide toxicity, excessive dietary supplementation, granulomatous inflammation. Neoplasia: bone cancer, hypercalcemia of malignancy. Primary renal failure. Hypoadrenocorticism (Addisonโs Disease). Osteolytic bone disease. Spurious causes: lipemia, hemolysis, hyperalbuminemia.
Any additional diagnostic testing youโd like to run to rule in/out causes of hypercalcemia in this patient?
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- Ionized calcium: elevated
- PTH: low normal
- PTHrp: elevated
Based on this patientโs signalment, clinical signs, physical exam findings, and test results, what is your diagnosis, recommended treatment, and prognostic outlook?
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DIAGNOSIS: Hypercalcemia of Malignancy (PTHrp-secreting neoplasia) / suspected diffuse Hepatic Lymphoma
Because this geriatric patient had a high Ca and iCa, normal P, normal PTH, and high PTHrp along with an enlarged liver and elevated liver values, a tentative diagnosis of liver cancer (most likely lymphoma) and hypercalcemia of malignancy was made. Certain cancer cells, including lymphoma, can produce parathyroid hormone related peptide (PTHrp), a protein that mimics the effects of the naturally-occurring parathyroid hormone (PTH), which increases calcium (Ca) absorption from bone and the GI tract to raise blood levels of Ca. Therefore, these types of malignant cancers can cause hypercalcemia (or high blood calcium). Not only do we have to worry about the suspected liver cancer in this patient, but we also have to manage the high Ca. Once Ca levels reach 15-18 mg/dL (20.9 mg/dL in this patient) or when the Ca X P product exceeds 60-70 (68.97 in this patient), hypercalcemia can cause severe bodily side effects. Excessive calcium and phosphorus can bind together, causing spontaneous mineral deposits to form in soft tissues, including the heart and kidneys. High calcium also affects cellular functions of the brain, heart, kidneys, and muscles, causing seizures, cardiac arrhythmias, kidney failure, muscle twitching, and weakness. Other clinical signs of hypercalcemia include decreased appetite and increased urination with excessive water consumption (polyuria/polydipsia, or PU/PD, respectively) by inhibiting ADH action. The PU/PD may also be attributed to hepatic dysfunction caused by the suspected neoplasia.
TREATMENT: This patient had not yet exhibited dangerous clinical signs of hypercalcemia, so aggressive emergency treatment was declined in favor of maintenance therapy at home. This patient was prescribed immunosuppressive prednisone to 1) serve as a chemotherapy agent for the suspected lymphoma, and 2) to decrease vitamin D production to lower calcium concentration. This patient was also prescribed oral furosemide to induce diuresis to help excrete excessive Ca from the body. Injectable calcitonin was also discussed with the owners as was additional diagnostics and an oncology consultation to confirm the suspicion of hepatic lymphoma; all were declined due to financial constraints.
PROGNOSIS: This patient initially did very well on the above therapy. Upon rechecks over the first 4 months following treatment, her appetite had improved, and repeated physical exam and bloodwork revealed steadily decreasing calcium with no evidence of cardiac arrhythmias or secondary renal effects. Eventually, calcium concentration and the Ca X P product reached normal values. However, after about 5 months of treatment, she acutely declined; she stopped eating and experienced tremendous weakness in her hind limbs. Because prednisone alone is only effective in ~50% of cases of canine lymphoma, only buying on average an additional lifespan of 2-4 months, it was not surprising that this patient would ultimately succumb to her disease. Due to poor quality of life and likely spread of her suspected neoplasia, her owners requested euthanasia. A necropsy was declined.
Any other questions, comments, or suggestions?
A good rule of thumb for interpreting hypercalcemia diagnostic tests:
| Ionized calcium (iCa) | Parathyroid hormone (PTH) | Parathyroid hormone related peptide/protein (PTHrp) | Phosphorus (P) | BUN / creatinine | |
| Hypercalcemia of malignancy | High | Low or normal | Normal or high | Variable | May be mildly high |
| Primary hyperparathyroidism | High | High normal or high | Normal | Low or normal | May be mildly high |
| Primary renal failure | Normal | Low or normal | Normal | High | Usually very high |
Unless otherwise stated, these clinical cases are real-life cases that I have managed as a veterinarian in general small animal veterinary practice or else assisted with as a student in vet school. These cases are a great real-world learning tool for vet students and other veterinary professionals. They shall be used for learning purposes and collaboration of knowledge only. These cases are not intended to diagnose or treat any disease by pet owners. – Maranda Elswick, DVM
