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.