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A six-year-old male, neutered standard Poodle presented with a three-week history of polydipsia, polyuria, malaise and weight loss. He had more recently cried out in pain while pulling on the lead.

Upon examination the dog appeared slightly underweight and at rest had a slightly lowered head carriage. Rectal temperature was 38.4°C, pulse rate 112/min and respiratory rate 30/min. Abdominal palpation revealed a fullness of the cranial abdomen suggestive of splenomegaly, peripheral lymph nodes were normal. There was some pain on direct palpation of the cervical and thoracic spine and neurological abnormalities were not detected.

Bloods, urinalysis and radiographs of the cervical spine were obtained.

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Fig. 1:  Lateral chest radiograph.

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Fig. 2:  Lateral abdominal radiograph.

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Fig. 3:  Close-up of thoracic dorsal spinous processes

Table 1.  Haematology and biochemistry
ParameterResultRange
Haematocrit29.237–55
Haemoglobin (g/dl)8.612–18
MCV (fL)71.161–80
MCHC (g/dl)36.430–36.9
WBC (×109/L)6.76–16.9
Neuts (×109/L)3.42.8–10.5
Eos (×109/L)0.10.5–1.5
Lymphocytes (×109/L)0.60.5–4.8
Monocytes (×109/L)0.65<0.8
Platelets (×109/L)25175–500
Albumin (g/l)1627–38
Alk Phos (U/L)610–400
ALT (U/L)150–77
Amylase (U/L)1177510–1589
Urea (mmol/l)11.211.79–8.21
Calcium (mmol/l)3.692.12–3.0
Cholesterol (mmol/l)4.53.5–7.3
Creatinine (€mol/l)25235–133
Glucose (mmol/l)6.253.3–6.7
Phosphate (mmol/l)1.770.81–1.77
Total bilirubin (€mol/l)110–12
Globulin (g/l)9817–39
Sodium (mmol/l)142135–155
Potassium (mmol/l)4.83.6–5.6
Table 2.  Urinalysis
ParameterResultRange
Specific gravity1.0111.015–1.045
Protein++zero
Glucose+zero
Ketoneszerozero
Bilirubinzerozero
Bloodzerozero
Culturenegativenegative

QUESTIONS

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  2. QUESTIONS
  3. ANSWERS
  4. REFERENCES
  • 1
    What are the differential diagnoses for polydipsia and polyuria?
  • 2
    What abnormalities are present on the blood and urine screens?
  • 3
    What further laboratory tests would you consider?
  • 4
    Interpret the radiographs.
  • 5
    What is the likely diagnosis?
  • 6
    How would you treat this case?
  • 7
    What are the possible complications associated with this condition?

ANSWERS

  1. Top of page
  2. QUESTIONS
  3. ANSWERS
  4. REFERENCES

1. The differentials for polydipsia and polyuria can be broken down into the following categories according to the pathophysiology responsible:

  • • 
    Reduced response to antidiuretic hormone (ADH) at the renal level: hyperadrenocorticism, hypercalcaemia, hypokalaemia, toxaemia (e.g. pyometra), primary nephrogenic diabetes insipidus and hypoadrenocorticism
  • • 
    Loss of medullary interstitium concentration: chronic renal failure, pyelonephritis, hepatic failure, hyperthyroidism, hyperviscosity syndromes (polycythaemia, myeloma)
  • • 
    Osmotic diuresis: diabetes mellitus, Fanconi's syndrome, nephrotic syndrome, high protein/salt diet
  • • 
    Impaired ADH secretion: central diabetes insipidus (primary/secondary)
  • • 
    Miscellaneous: psychogenic diabetes insipidus.

2. Haematological changes include a non regenerative anaemia, severe thrombocytopenia and mild eosinopenia. Thrombocytopenia may be as a result of reduced production (bone marrow disease, infectious disease), destruction (immune mediated – primary or secondary) consumption (DIC or haemorrhage) or sequestration (splenic pooling). Biochemical changes include hypoalbuminaemia, mild azotaemia, hypercalcaemia and severe hyperglobulinaemia. Urinalysis reveals isosthenuria, proteinuria and mild glycosuria. In the absence of hyperglycaemia these urine results suggest renal tubular damage and also that the azotaemia is renal in origin. Hypoalbuminaemia in this case is likely to be related to urinary loss (although only qualitative measurement of urinary protein was obtained) and decreased production due to preferential production of globulins (negative acute phase proteins) and reduced hepatic function as a response to hyperviscosity syndrome. Hyperglobulinaemia can be polyclonal (as a result of infection, inflammation or immune mediated disease) or monoclonal (as a result of certain infections, neoplasia and monoclonal gammopathy of unknown significance). Hypercalcaemia has many possible causes including neoplasia, hypoadrenocorticism, primary hyperparathyroidism, hypervitaminosis D and chronic renal failure.

3. Further evaluation of the hypercalcaemia would include assessment of parathyroid hormone (PTH), ionised calcium, parathyroid hormone related peptide (PTHrP) and imaging for occult neoplasia. PTH was 1.8 (normal range 2–13 pmol/l) effectively ruling out primary parathyroid disease, PTHrP and ionised calcium were not assessed. Serum electrophoresis should be carried out to further investigate the hyperglobulinaemia. In this case there was a large gamma globulin spike typical of a monoclonal gammopathy (Fig. 4). Electrophoresis can also be carried out on urine but was not done in this case. Further evaluation of a monoclonal gammopathy may also include serological testing for certain exotic diseases (e.g. Ehrlichia spp.).

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Figure 4. Serum electrophoresis.

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4. The lateral thoracic radiograph on close inspection shows the presence of discrete ‘punched out’ lesions suggestive of osteolysis in the dorsal spinous processes. These are more visible on the close-up of the dorsal spinous processes. There is also a larger lytic lesion affecting the ventral edge of the T1 vertebral body. Bony lysis can be caused by osteomyelitis (bacterial/fungal) or neoplasia. The lack of a mixed lytic/sclerotic pattern could be more suggestive of myeloma. The lateral abdominal view is suggestive of splenomegaly.

5. The monoclonal gammopathy, hypercalcaemia and presence of osteolysis are highly suggestive of multiple myeloma (MM). Traditionally the diagnosis of MM requires demonstration of two out of the following criteria: radiographic evidence of osteolytic lesions, a bone marrow biopsy with >5% plasma cells, a serum or urine monoclonal gammopathy and light-chain (Bence-Jones) proteinuria. MM is a disease characterised by the neoplastic proliferation of plasma cells that overproduce a single type of immunoglobulin (M component). Presenting signs may be various since MM is associated with a number of paraneoplastic syndromes and may include skeletal/spinal pain, hypercalcaemia, renal failure, bleeding diathesis, anaemia and hyperviscosity syndrome. Many cases of MM present with spinal pain and approximately 25% have radiographic evidence of lysis as was present in this case. The aetiology of hypercalcaemia present in some cases of MM may be a result of osteolysis or raised PTHrP causing a paraneoplastic hyperparathyroidism. Renal failure in MM has a reported incidence of 30–50%– underlying mechanisms may include neoplastic infiltration, Bence-Jones proteinuria, hypercalcaemia and reduced renal perfusion as a result of hyperviscosity.

6. The presence of hypercalcaemia and azotaemia in this case meant that priority was given to the reduction of serum calcium levels to prevent further deterioration in renal function. Calciuresis was achieved by the use of intravenous normal saline at 60 ml/kg/day along with the initiation of specific therapy. Should this approach have proved inadequate then other therapeutic approach could have included the use of frusemide or bisphosphonate therapy. Chemotherapy is the mainstay of treatment for MM – the protocol of choice is melphalan and prednisolone. Although unusual, melphalan carries the risk of causing thrombocytopenia – in this case close monitoring of platelet count would be prudent and dose alteration or change to cyclophosphamide as an alternative alkylating agent if necessary. Radiotherapy of bone lesions has proved palliative in certain cases but its use is limited to cases with small areas of bone lysis. Despite the fact that complete remission is not achieved in treatment of MM, average survival of 540 days is reported with a response to treatment defined as reduction of M-component immunoglobulin to 50% of pre-treatment values. Follow up electrophoresis was not carried out in this case but significant reduction of globulin levels and normalization of albumin levels was demonstrated within 35 days (Table 3).

Table 3. 
DayAlbuminGlobulin
01698
+72081
+202269
+302854
+352849
Normal 27–38 17–39

7. The multiplicity of clinical presentations with MM has already been mentioned. Clinically significant complications may include hypercalcaemia, renal failure, coagulopathy, hyperviscosity syndrome and pathological fracture. The aetiology of hypercalcaemia and renal failure has already been discussed as they were present in this case. Coagulopathy may be multifactorial and aetiologies may include thrombocytopenia, hyperviscosity syndrome and disseminated intravascular coagulation (DIC). In addition to coagulopathy, hyperviscosity syndrome can be responsible for various neurological and ocular presentations. Pathological fracture results secondary to bony lysis.

In this case the dog re-presented 35 days into treatment quadraparetic and distressed. Cervical palpation was extremely painful, local reflexes were exaggerated in all four limbs and deep pain perception was markedly reduced. A lateral radiograph is shown and demonstrates collapse of T2 (arrowed) and its dorsal displacement into the spinal canal (Fig. 5).

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Figure 5. Lateral radiograph 35 days into treatment.

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This very serious complication led to a grave prognosis and the dog was euthanased.

REFERENCES

  1. Top of page
  2. QUESTIONS
  3. ANSWERS
  4. REFERENCES
  • BREUER, W., et al., (1993) Immunoglobulin-producing tumours in dogs and cats. Journal of Comparative Pathology 109, 203216.
  • BUSH, B. M. (1991) Gammopathies. In: Interpretation of laboratory results for small animal clinicians. 295297.
  • HAMMER, A. S. and COUTO, C. G. (1994) Complications of multiple myeloma. Journal of the American Animal Hospital Association 30, 914.
  • MATUS, R. E., LEIFER, C. E., MACEWAN, E. G., HURVITZ, A. I. (1986) Prognostic factors for multiple myeloma in the dog. Journal of the American Veterinary Medical Association 11, 12881292.
  • MORRISON, W. B. (1979) Paraneoplastic syndromes of the dog Journal of the American Veterinary Medical Association 175(6), 559561.
  • RUSBRIDGE, C., WHEELER, S. J., LAMB, C. R., PAGE, R. L., CARMICHAEL, S., BREARLEY, M. J. and BJORNSON, A. P. (1999) Vertebral plasma cell tumours in 8 dogs. Journal of Veterinary Internal Medicine 13, 126133.
  • VAIL, D. M. (1996) Plasma cell neoplasms. In: Small animal clinical oncology. 2nd ed. Eds Withrow & MacEwan. 509520.
  • VAIL, D. M. (2000) Haematopoietic tumours. In:Textbook of veterinary internal medicine 5th ed. Eds Ettinger SJ and Feldman EC.