Paraneoplastic syndromes (Proceedings)
Paraneoplastic syndromes may develop from the excessive production of hormones from an adenomatous or carcinomatous gland. Feline thyroid carcinomas and insulinomas are examples of excessive hormone production from the cells that normally produce the hormone. Ectopic production of a normal hormone or a hormone look-alike can occur in cells that don't normally produce the hormone. The production of a parathormone-like protein from lymphoma or anal sac carcinoma cells represents this category of paraneoplastic disease. Disruption of normal body function by a tumor product is another form of paraneoplastic syndrome. The development of anorexic due to the production of appetite suppressive agents from tumor cells. The tumor may directly cause paraneoplastic syndromes by excessive consumption of glucose, sequestration of platelets or phagocytosis of erythrocytes or the production of disseminated intravascular coagulopathy (DIC). All these effects can occur away from the primary tumor.
The most common paraneoplastic syndrome is hypercalcemia with secondary anorexia, muscle weakness and shaking and renal tubular calcification with renal failure. The changes may be due to parathormone from a parathyroid tumor or from a parathormone-like hormone produced by t-cell lymphomas, anal sac carcinomas and less commonly by a variety of tumor types such as nasal tumors, mammary carcinomas, etc. These syndromes cause an increase in serum calcium with a decrease in serum phosphorus unless renal failure prevents the phosphorus excretion. Hypercalcemia due to lymphoma tends to be more rapidly damaging to the kidneys than the same degree of hypercalcemia due to a parathyroid adenoma. Hypercalcemia can occur in conditions such as multiple myeloma where tumor cells are destroying bone. There are many conditions associated with hypercalcemia that are not due to neoplasia. Mild hypercalcemia may be a normal physiologic condition in growing dogs. Renal failure with secondary hypercalcemia and hyperphosphatemia can be differentiated from other causes of hypercalcemia by measuring ionized calcium which is usually normal. Vitamin d intoxication as occurs with some rodenticides will cause hypercalcemia without the accompanying decrease in serum phosphorus. Dogs with granulomatous conditions such as fungal infections will occasionally be hypercalcemic.
Differential diagnosis of hypercalcemia requires a good physical examination and history. T-cell lymphomas associated with hypercalcemia often do not have peripheral lymphadenopathy but may have thoracic and mediastinal involvement. A rectal examination to identify anal sac carcinomas is essential. Many anal sac carcinomas also have metastases to the sublumbar lymph nodes that can be found on radiographs. Radiographs and ultrasound examination of the abdomen are helpful in identifying lymphoma. Michigan State University offers a hypercalcemia panel that includes parathormone, parathormone-like protein as well as ionized calcium and an interpretation of the results.Effective treatment of hypercalcemia requires the treatment of the underlying cause. Saline diuresis promotes the excretion of calcium and can be helpful in reducing the severity of the hypercalcemia. In lymphoma cases, the only effective treatment for the hypercalcemia is chemotherapeutic treatment of the lymphoma. In conditions where bone destruction by tumors is increasing blood calcium concentrations, drugs like pamidronate which inhibit the function of osteoclasts will decrease bone destruction thereby reducing bone pain and calcium release from the bone.
Hypoglycemia is associated with weakness, depression, confusion and seizures. An initial consideration in assessing laboratory results indicating hypoglycemia is that the plasma has been separated from the red blood cells soon after obtaining the sample. The primary consideration in true hypoglycemia is an insulinoma. In the face of hypoglycemia, insulin concentrations should be very low. Even normal concentrations of insulin are inappropriate in hypoglycemia. Paired blood samples for insulin and glucose are the initial laboratory evaluation for hypoglycemia. Ultrasound examination of the pancreas may identify a solitary beta-cell nodule but many insulinomas are diffusely distributed throughout the pancreas. Surgical removal of a solitary nodule is helpful and can relieve signs for up to a year. Insulinomas are slow growing tumors in dogs but they metastasize early. A surgical cure would be rare. Medical management of insulinomas with frequent feeding of high protein and complex carbohydrates is helpful and corticosteroids produce an insulin resistance which is helpful in control. Chemotherapy can also be helpful in insulinomas when all else fails but toxicity is likely.