July 1998

Feline Hyperthyroidism

Hyperthyroidism is the most common endocrine disorder of the cat, and increased awareness of the disease has led to earlier diagnosis and treatment. Treatment of feline hyperthyroidism, however, can have complications, some of which are life-threatening and are best averted by careful patient monitoring. The hyperthyroid recheck profile aids veterinarians in monitoring hyperthyroid patients, and includes those values most pertinent to therapy of the uncomplicated patient. This includes: serum T4, BUN, creatinine, SAP, ALT, AST, CBC, and a platelet count. Consider measuring free T4 as well, in cases where concurrent nonthyroidal illness may reduce T4 levels.

Antithyroid drugs are often used for the initial management of hyperthyroid cats. They also may be given to control the condition in preparation for surgical thyroidectomy or radioactive iodine therapy. In cases where additional medical conditions or client preference and cost preclude these latter methods, antithyroid drugs are used on a long-term basis. Treatment complications include side effects of the drugs themselves, or sequelae of the transition to euthyroidism.

Adverse Effects of Antithyroid Drugs

The most commonly used antithyroid drug is methimazole (Tapazole®, Jones Med.), a thioureylene which inhibits synthesis of thyroid hormones. Adverse effects of methimazole range from mild to life-threatening. Less serious reactions including anorexia, vomiting, and lethargy may not necessitate cessation of therapy, if transient, but can be persistent enough to preclude continued use of the drug. Methimazole is bitter tasting, and placing it in a gelatin capsule prior to administration may be helpful. Self excoriation, particularly of the head and neck, is another potential side effect, which requires that the drug be discontinued. Some authors recommend use of glucocorticoids in this situation.

More serious adverse methimazole reactions include hematologic and biochemical changes such as: thrombocytopenia, leukopenia, agranulocytosis, positive Coombs' test, antinuclear antibodies, and milder findings like eosinophilia and lymphocytosis. Hepatic toxicity can occur, with elevation of liver enzymes. Potentially life-threatening abnormalities, particularly hepatopathy, thrombocytopenia and significant leukopenia, require withdrawal of therapy. The possibilities of other bleeding complications is currently under investigation.

Hyperthyroidism and Renal Function

The deterioration of renal function following initiation of antithyroid therapy has become a rising and significant concern. This may reflect a fall in glomerular filtration rate with return to

euthyroidism. Although the relationship is not yet fully understood, monitoring renal function before and following treatment of hyperthyroidism is crucial. Irreversible therapy (e.g., surgical thyroidectomy or radioactive iodine treatment) should be postponed until it has been determined that renal function will be adequate once euthyroidism is achieved. Occasionally, when adverse reaction is severe enough to preclude even short-term administration of antithyroid drugs, owners should be made aware of the risks involved with undertaking other therapies. In some patients, renal failure may prevent use of antithyroid therapy, or necessitate only partial control of hyperthyroidism.

Monitoring Hyperthyroid Patients

Before initiation of therapy, complete baseline data should be collected, including serum biochemical and thyroid profile, CBC with platelet count, and urinalysis. Blood pressure measurement is ideal if equipment is available, and an echocardiogram may be desired if a heart murmur is present. Hematologic changes associated with hyperthyroidism include erythrocytosis, stress leukogram, hyperphosphatemia, and elevation of liver enzymes (ALT, AST, SAP), and should resolve with therapy, if not due to an unrelated condition. The finding of azotemia necessitates proceeding with extreme caution, with frequent monitoring for deterioration of renal function.

In the absence of complicating abnormalities, treatment with methimazole is begun, and the patient is rechecked in about 2 weeks. Then, a hyperthyroid recheck profile is made, along with monitoring for weight gain and improvement in clinical signs. For the azotemic patient or one where renal dysfunction is suspected, kidney values should be measured earlier (e.g., 1 week or sooner if clinical signs develop). Drug dosage is adjusted, as required, and a recheck profile is collected at 2 week intervals until euthyroidism is achieved, and stable on 2 consecutive measurements. Discovery of serious adverse effects, such as thrombocytopenia or significant leukopenia, requires drug withdrawal. Worsening azotemia may require lowering the drug dose or halting therapy.

When euthyroidism has been satisfactorily achieved, more definitive therapy may be undertaken or medical therapy can be continued. If radioactive iodine therapy is planned, the referral center should be consulted regarding withdrawal of antithyroid drugs before treatment. If long term therapy with antithyroid drugs is elected, the hyperthyroid recheck profile should be evaluated approximately every 3 months. More extensive blood work may be indicated. Higher doses of antithyroid drugs may be needed as the disease progresses. With methimazole, this may be associated with an increased risk of serum antinuclear antibodies. Owner compliance and patient cooperation also may vary as dosage requirements escalate.

Feline Hyperthyroid Recheck Profile

Test code #7442 (West); #1135 (East)

Platelet Counts in Cavalier King Charles Spaniels

Recent studies in Sweden, the United Kingdom and North America have established that many healthy Cavalier King Charles Spaniels have low circulating platelet counts, especially when measured with automated cell counters. Manual counting usually reveals a higher number of platelets of relatively large size (megathrombocytes) in some but not all dogs. In the Swedish study, 102 healthy Cavaliers had mean platelet counts of 178,000/µl. However, 32 (31%) of them had platelet counts below 100,000/µl and 4 dogs had counts between 30,000-50,000/µl. The mean count for male dogs was significantly lower (147,000/µl) than that of females (202,000/µl).

In North America, many dogs of this breed are found to have thrombocytopenia during routine health profiling prior to elective procedures or at annual checkups. Typical platelet counts range from 20,000-85,000/µl with some counts as low as 5,000/µl in clinically normal dogs. Ages range from 4 months to 10 years and both sexes are affected. These dogs can be presented for routine wellness exams, dental prophylaxis, or complaints varying from vomiting and diarrhea, coughing, back or joint pain or other illness. Diagnosis can be confusing as petechial or ecchymotic hemorrhages or other signs of bleeding are usually absent and thrombocytopenia is just an incidental finding. However, some Cavaliers have clinically expressed immune-mediated thrombocytopenic purpura, making the diagnosis more complicated.

Dogs with thyroid disease, commonly seen in Cavaliers, may show a greater incidence of thrombocytopenia. Whether the chronic cardiac valvular disease prevalent at a young age in this breed could be a contributing factor is unknown, although no association has been found between the presence of cardiac murmurs and low platelet counts. Splenomegaly is not a feature of the condition. Preliminary evaluation of bone marrow megakaryocytes of severely thrombocytopenic, healthy dogs has shown no structural abnormalities, but functional studies have yet to be performed. The thrombocytopenia has persisted over several years of followup, and treatment with immuno-suppressive drug regimens has not resolved the low platelets counts. Pedigree analysis revealed that the thrombocytopenic tendency can be transmitted to subsequent generations, suggesting that this is a congenital, heritable disorder of the breed. Similar disorders occur in people.

The clinical importance of these findings warrants comment. Cavalier King Charles Spaniels that have thrombocytopenia as an incidental laboratory finding should have platelet counts rechecked by manual methods, and do not need treatment to attempt normalization of platelet numbers. A complete health profile including thyroid function is advised to identify any concurrent abnormality that may need attention.

LAB TIPS

Avian and Exotic Sample Size

One of the most difficult aspects of avian and exotic animal testing is obtaining a large enough blood sample to make a diagnosis without harming the patient. At Antech Diagnostics, this problem is addressed by selecting chemistry analyzers that accurately measure very small specimens and modifying hematology assays.

The ANTECH Services Directory lists the quantity and type of Microtainer® required for each assay. These should be filled completely to minimize effects of anticoagulant dilution, cell degradation and small specimen volume. If the requested specimen volume cannot be obtained, PRIORITIZE THE TESTS REQUESTED! If you do not prioritize, Antech will run the tests in the following order: Abbreviated CBC, Uric Acid, ALT, AST, CK, Ca, Phosphorus, Total Protein, BUN, Creatinine, ALP, Glucose, Total Bilirubin, Cholesterol, Na/K/Cl, Albumin, Globulin, other assays. Small specimen volumes often make it impossible to verify questionable results by repeat analysis.

The following collection devices are available from Antech:

* Fresh Smears: Two well made FRESH blood slides (no anticoagulant added) must be submitted with every avian/exotic CBC request. The smears are used for evaluating cellular morphology, WBC estimate and differential, and blood parasite screen.

* Heparinized Capillary (Microhematocrit) Tube: This specimen can only be used for a spun microhematocrit and nothing else. Please DO NOT place adhesive labels directly on this fragile tube! Instead, slide the tube into a labeled plain red-top Vacutainer® tube.

* Heparinized (Green) Microtainer® SST (with gel): This specimen should be centrifuged at your clinic to separate the plasma from the cells, thus preserving the chemistry constituents. After centrifugation, this specimen CANNOT be used to evaluate the CBC. Immediate refrigeration promotes stability. Please DO NOT attempt to transfer the plasma from this container to another transport tube, as sample recovery will be diminished.