Monday, May 14, 2012

Canine Hyperthyroidism and the Heart


Cardiovascular Manifestations of Iatrogenic Hyperthyroidism
in Two Dogs

by D.M. Fine, A. H. Tobias, and J.D. Bonagura

Background
While hypothyroidism is a common endocrine disorder in dogs, canine hyperthyroidism is rare. Like hyperthyroid cats, most dogs with naturally occurring hyperthyroidism have a functional thyroid tumor (1-3). However, unlike the situation in hyperthyroid cats, where most thyroid tumors are benign, almost all of these hyperthyroid dogs will have thyroid carcinoma. Therefore, the prognosis is generally guarded to poor.

The most common cause of hyperthyroidism in dogs is iatrogenic hyperthyroidism, which results from excessive intake of exogenous thyroid hormones. This is most commonly caused by the chronic administration of too-high a dose of L-thyroxine (L-T4) for treatment of hypothyroidism (1,3-5), but dietary hyperthyroidism secondary to consumption of meat contaminated with thyroid tissue may also rarely occur (6).

In general, most veterinarians consider thyroid hormone replacement to be a very safe and benign treatment. Iatrogenic hyperthyroidism, when it develops, is generally thought to have minimal undue effects. However, some dogs, especially those with underlying cardiac disease, are sensitive to even moderate L-T4 overdosage and will develop clinical complications of thyrotoxicosis (4).

This report by Fine et al (7) illustrates how chronic iatrogenic hyperthyroidism can lead to severe and life-threatening cardiovascular complications (e.g., tachycardia, arrhythmia, syncope) in dogs.

Case reports
Two dogs were diagnosed with iatrogenic thyrotoxicosis as a result of L-T4 overdosage. Both showed clinical signs of agitation, tachypnea, panting, and tachycardia.

One of the dogs (9-year-old, male Golden Retriever) also showed evidence of hyperthermia, polyuria, polydipsia, and polyphagia. The other dog (6-year-old, male castrated Great Pyrenees) also showed signs of severe weakness, syncope, and collapse.

Both dogs had been previously diagnosed with hypothyroidism and had been treated chronically with high doses of L-T4 (i.e., 40 μg/kg, BID, and 25 μg/kg, BID, respectively). On post-pill serum T4 testing, both dogs were confirmed as having severe hyperthyroidism.

Sinus tachycardia with supraventricular ectopy was diagnosed in one dog, whereas and syncope and atrial flutter was diagnosed in the other. Clinical signs and cardiac rhythm abnormalities resolved in both dogs with resolution of the thyrotoxicosis.

Conclusions of report
In both dogs of this report, iatrogenic hyperthyroidism resulted in clinical features and cardiovascular conduction disturbances of sinus tachycardia, supraventricular tachycardia, atrial fibrillation, and atrial flutter. Both dogs also had concurrent cardiac disease (degenerative atrioventricular valve disease) that might have contributed to the severity of their clinical signs. However, clinical signs and rhythm abnormalities resolved in both dogs with resolution of the thyrotoxicosis.

These cases illustrate that thyroid hormone supplementation is not always benign and that appropriate diagnostic studies, proper dosing, and regular post-treatment monitoring are essential to prevent adverse cardiovascular effects. Based on the 2 cases that we report here, this seems especially true for dogs with preexisting cardiac disease.

My Bottom Line:

Over the years, numerous therapeutic strategies have been recommended for the treatment of hypothyroid dogs. Today there is almost general agreement among endocrinologists that a dose of approximately 20–22 μg/kg once daily suffices in most cases, at least for long-term maintenance treatment (7,8).

The clinical response of hypothyroid dogs to once-daily therapy with this dosage is usually excellent. Although the use of divided BID dosing certainly results in less fluctuation of circulating T4 concentrations compared to once-daily administration, the biological action of thyroid hormones far exceeds that of their serum half-life. This presumably explains the clinical success of once-daily therapy. This once-daily dosage approach is also safer, since the total daily dosage administered is almost always less than when BID administration is used (8,9).

Both dogs of this report (7) had been treated chronically for years with high doses of L-T4, administered twice daily, which were at 2-to 4-fold higher than this recommended dose range of approximately 20 μg/kg/day (8,9).

While most dogs are relatively resistant to the thyrotoxic effects of excessive T4 supplementation, some dogs are sensitive to even moderate L-T4 over-dosage (4). If iatrogenic hyperthyroidism does develop in dogs undergoing treatment for hypothyroidism, the most common clinical signs include marked polydipsia and polyuria, followed by polyphagia, panting, weight loss, hyperactivity, tachycardia and pyrexia (1-5).

If any signs suggestive of hyperthyroidism develop in dogs on L-T4 replacement, a post-pill T4 concentration should be measured to document thyrotoxicosis, and the daily L-T4 dose should be decreased as needed. If present, all clinical signs of hyperthyroidism should resolve within a few days after the daily L-T4 dosage has been lowered.

References:
  1. Peterson ME, Ferguson DC: Thyroid diseases, In: Ettinger SJ (ed): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat, Third Edition. Philadelphia, WB Saunders Co., 1989;1632-1675.
  2. Peterson ME: Hyperthyroidism and thyroid tumor in dogs. In: Melian C, Perez Alenza MD, Peterson ME, Diaz M, Kooistra H (eds): Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Multimedica, Barcelona, Spain, 2008;113-125.
  3. Mooney CT. Canine hyperthyroidism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology, Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:86-91.
  4. Refsal K, Nachreiner R. Monitoring thyroid hormone replacement therapy. In: Bonagura JD, Ed. Kirk’s Current Veterinary Therapy XII. Philadelphia: WB Saunders Co. 1995:364-368.
  5. Mooney CT, Shiel RE. Canine hypothyroidism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology, Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:63-85.
  6. Köhler B, C. Stengel C, Neiger R. Dietary hyperthyroidism in dogs. Journal of Small Animal Practice 2012; 53, 182–184.
  7. Fine DM, Tobias AH, Bonagura JD. Cardiovascular manifestations of iatrogenic hyperthyroidism in two dogs. Journal of Veterinary Cardiology 201012:141-146. 
  8. Dixon RM, Reid SW, Mooney CT. Treatment and therapeutic monitoring of canine hypothyroidism. Journal of Small Animal Practice 2002; 43, 334–340. 
  9. Le Traon G, Brennan SF, Burgaud S, et al. Clinical evaluation of a novel liquid formulation of L-thyroxine for once daily treatment of dogs with hypothyroidism. Journal of Veterinary Internal Medicine 2009;23:43-49. 

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