Abstract Case Report
A 14-year-old female American black bear housed at the Knoxville Zoological Gardens developed lethargy, obesity, and alopecia; hypothyroidism was included in the differential diagnosis. Blood was collected in October, 2001, and serum total thyroxine (T4), free T4 concentrations by equilibrium dialysis (fT4ED), and canine thyroid-stimulating hormone (TSH) concentrations determined (Animal Health Diagnostic Laboratory, Michigan State University) using assays validated for domestic dogs. Sera from eight (5.3) healthy adult conspecifics, obtained in the months of July–October, were also tested to establish reference intervals. All bears housed at the KZG are kept in heated indoor quarters through the winter months, thereby preventing winter sleep. The female bear with clinical signs of hypothyroidism had a total T4 level which was slightly low, and a fT4ED that was markedly lower than the reference bears’ levels.
Administration of levothyroxine sodium (Soloxine®, 0.8 mg tablets, Daniels Pharmaceuticals, St. Petersburg, Florida 33713) was started in late November at a standard initial canine dosage (0.022 mg/kg PO BID). Clinical improvement was noted within 30 days, with apparent weight loss, improved haircoat, and increased activity. At the 90-day recheck it was noted that appetite and activity had continued to improve. The bear’s body weight had decreased dramatically and the weight loss was visually apparent. Blood samples were obtained 6 hours after the morning levothyroxine dose, as recommended for evaluation of adequate dose level in hypothyroid dogs. The serum total T4 and fT4ED concentrations were well above the high end of the reference levels. The levothyroxine dose was decreased 20% to 0.018 mg/kg. One male conspecific had also been bled at that time, and T4 and fT4ED concentrations had decreased compared with its summer values.
Discussion
Thyroid physiology is complex in bears, and the interactions of the pituitary-hypothalamic-thyroid axis are not completely understood. There has been great interest in the effects of winter sleep (termed “hibernation” or “dormancy”) on ursine physiology and metabolism and, in particular, thyroid physiology. Results of several metabolic studies of American black (Ursus americanus), and brown (Ursus arctos arctos) bears have shown that from December through March, during winter sleep, there is a decrease in circulating total T4, total triiodothyronine (T3), free T4, and free T3 concentrations. There is a gradual increase to normal levels of these hormones several weeks after the end of this period, in April–May.1,3,5,8 This subnormal hormonal condition has been hypothesized to be a transient hypothalamic-hypothyroidism.1 No study was found that determined whether this “winter nadir” phenomenon occurs in captive bears prevented from denning.
Interestingly, these thyroid hormone patterns were inverted in a captive adult male polar bear, whose T3 and T4 concentrations peaked in January and reached a low point in summer; no data was available for female captive polar bears.4 Single blood samples obtained in October–December from free-ranging polar bears had higher T3 and T4 concentrations in the samples from females compared to those from males.4
These seasonal fluctuations may confound the clinical assessment of thyroid function in bears with suspected hypothyroidism. Despite the interest in ursid thyroid physiology, diagnostic reference intervals for thyroid hormone concentrations have not been determined.
There is one reported case of hypothyroidism and goiter in a grizzly bear (Ursus horribilis),7 diagnosed postmortem. There is also one report of congenital hyperplastic goiter, hypothyroidism, and cretinism in a 16-month-old male American black bear. This bear had low serum T3 and T4 concentrations in serum obtained before euthanasia, and the diagnosis was confirmed postmortem.2 Ante-mortem diagnosis and treatment of hypothyroidism in bears, however, has not been described.
In the dog, the current gold standard for the diagnosis of hypothyroidism is documentation of low circulating total T4 concentrations or low fT4ED with concurrent high TSH concentrations.6 A low total T4 or fT4ED value in concert with consistent clinical signs, however, is considered highly suspect and warrants a therapeutic trial.6 Total T4 measurements are affected by the level of serum thyroid hormone-carrying proteins, which vary between species, as well as nonthyroidal illness and concurrent drug therapy. The dialysis technique (fT4ED) for determination of thyroid status is expected to be the most valid test in novel species, since results are not influenced by plasma proteins, but there is no report of its use in bears. TSH assays are considered to be species-specific, with variable species cross-reactivity. Canine assays are available but are not expected to be valid for bears. Invalid TSH values in the hypothyroid bear and its conspecifics supported our prediction that this assay may not be useful in bears.
Conclusion
Total T4 concentration was low in this bear compared to a group of conspecific bears; the level determined may not be representative for all hypothyroid bears. In dogs, there is overlap between hypothyroidism and low normal thyroid concentrations. The canine fT4ED test was helpful in establishing a diagnosis, and response to levothyroxine treatment was confirmatory. Canine TSH assays do not appear to be valid for American black bears. The recommended initial canine dosage of levothyroxine proved to be too high in this hypothyroid bear.
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