Canine Hypothyroidism: Diagnosis and Treatment
Hypothyroidism is a common endocrine disease of dogs. It occurs when the thyroid glands fail to produce adequate amounts of the hormones thyroxine (T4) and triiodothyronine (T3). Primary hypothyroidism resulting from idiopathic thyroid gland atrophy or immune-mediated lymphocytic thyroiditis is the most common diagnosis. Uncommon causes of canine hypothyroidism include congenital disease resulting from dyshormonogenesis of thyroid hormone, abnormal thyroid-stimulating hormone (TSH) production, or abnormal thyroid gland development.1
Thyroid hormones are involved in a wide variety of metabolic processes, and low thyroid hormone levels result in a constellation of clinical signs and laboratory abnormalities that characterize hypothyroidism. Multiple hormone tests are required to make a diagnosis. The diagnosis should never be based on low T4 concentration as a sole finding.
Hypothyroidism typically affects middle-aged dogs, although it has been reported in younger and older dogs. Any breed can be affected. Clinical signs (BOX 1) may be nonspecific, which can result in overdiagnosis of this disorder; lethargy and weight gain are common.2,3 Clinical signs may have an insidious onset and may not be noticed by the owner. Hypothyroidism often causes hair coat changes, including bilaterally symmetric, nonpruritic alopecia over the trunk or areas of wear, post-clipping alopecia, and a dull, lusterless hair coat (FIGURE 1). Skin changes may include scaling, seborrhea, hyperpigmentation, and recurrent infections (pyoderma or otitis externa).2,3
Rare clinical signs and syndromes that have been associated with hypothyroidism include megaesophagus, vestibular dysfunction, facial nerve paralysis, and atherosclerosis.4,5,8
Dogs should be tested for hypothyroidism only when the disease is strongly suspected based on the patient’s history and physical examination findings (BOX 1). Complete blood count and serum biochemistry panel results may heighten clinical suspicion for hypothyroidism. Hypothyroidism can be misdiagnosed when testing is performed only because a dog is overweight or because a T4 concentration is included with a standard biochemistry panel.
A stepwise approach is helpful in accurately diagnosing canine hypothyroidism (FIGURE 2).
Step 1: Evaluate Minimum Database Results for Supportive Findings
Results from a complete blood count, serum biochemistry panel, and urinalysis are helpful to rule out concurrent disorders that could affect thyroid test results. However, none of the abnormal results that may be seen on these tests are specific for hypothyroidism.
Approximately 75% of hypothyroid dogs have elevated cholesterol levels.2,3 While mild hypercholesterolemia alone should not prompt testing for hypothyroidism, it supports a suspicion of hypothyroidism. Liver enzymes may be mildly elevated. A mild, nonregenerative anemia is present in about 30% to 40% of hypothyroid dogs.2,3 The urinalysis typically shows no abnormalities. Dilute urine, if present, should prompt investigation for concurrent illness or another cause of clinical signs.
Step 2: Screen With a T4 Concentration
Total T4 concentration is a useful screening test for hypothyroidism. The sensitivity of this test for the diagnosis of canine hypothyroidism is reported to be 89% to 100%.9-12 If the T4 concentration is well within reference range, it is very likely the dog is euthyroid and further thyroid testing is not required. Free T4 (fT4) and thyroid-stimulating hormone (TSH) are evaluated only if the T4 concentration is low (FIGURE 2). Combined T4, fT4, and TSH testing is not recommended at this stage and may add unnecessary expense since a normal T4 concentration effectively rules out hypothyroidism.
However, a T4 concentration below reference range is not diagnostic for hypothyroidism. In addition to normal daily fluctuations, several medications have been demonstrated to lower the serum T4 concentration of dogs (BOX 2), and some also affect fT4 and TSH concentrations. Certain drugs, such as trimethoprim–sulfamethoxazole, can have direct effects on the pituitary–thyroid axis and result in hypothyroidism.13 Furthermore, nonthyroidal illnesses can alter thyroid hormone metabolism and result in the euthyroid sick syndrome (BOX 3). Concentrations of fT4 are less likely to be affected by concurrent illness, but if the illness is severe enough, fT4 can also be low.21,22 Therefore, thyroid testing should not be performed in dogs that are systemically ill. If a dog with a concurrent illness is tested for hypothyroidism, test results should be interpreted with caution.
Because diagnosing hypothyroidism is not an emergency, sending samples out to a reference laboratory is advisable. Since additional confirmatory tests are required, it is helpful to collect and hold extra serum when collecting for the T4 test.
It is important to remember that “normal” reference ranges for T4 do not apply to sighthounds, as healthy dogs of these breeds have lower T4 concentrations than other breeds.23,24
Step 3: Confirm With an fT4 or TSH Concentration
When a dog suspected to have hypothyroidism has a low total T4 concentration, fT4 and/or TSH concentrations must be evaluated to help confirm or refute the diagnosis (TABLE 1). If the TSH concentration is high, hypothyroidism can be diagnosed. However, 13% to 38% of hypothyroid dogs have normal TSH concentrations,10-12,25 so a normal TSH concentration does not exclude the diagnosis. Because of this limitation, it is often helpful to evaluate fT4 and TSH simultaneously as confirmatory tests. If the fT4 is low, a diagnosis of hypothyroidism can be made.
If T4 is low and fT4 is within reference range, hypothyroidism cannot be diagnosed, and the clinician should consider other differentials for the dog’s clinical signs.
T3 concentrations vary widely and are not diagnostically useful.
Studies have shown that most dogs can be regulated with once-daily levothyroxine,26,27 usually initiated at 0.02 mg/kg PO q24h. Some clinicians begin with twice-daily administration of levothyroxine (0.02 mg/kg PO q12h) and attempt to reduce the dosing to once daily, once clinical signs are well controlled. Lethargy often improves after a few weeks. Most clinical signs improve within 4 to 6 weeks, although dermatologic changes take months to resolve.
Monitoring and Adjusting Therapy
After 4 weeks of therapy, blood is collected 4 to 6 hours post-pill for T4 measurement. (T4 can be measured as early as 2 weeks after starting or adjusting therapy,26 but waiting until 4 weeks allows for assessment of improvement in clinical signs at the same visit.) The post-pill T4 concentration should be at the upper end of the reference range or slightly above (<6 mcg/dL). Laboratory reference ranges for “initial” T4 concentrations and “post-pill” concentrations may be different, so careful sample labeling and interpretation are important.
If the post-pill T4 concentration is below the target concentration, the dose of levothyroxine should be increased by 25%. The T4 concentration is then rechecked in 2 to 4 weeks. The dose is gradually increased until the post-pill T4 concentration is within the target range. Similarly, if the post-pill T4 concentration is too high, the dose should be decreased by 25% and the concentration rechecked. Once an effective dose has been established, the interval between monitoring visits is increased to every 6 months.
Approximately 75% of hypothyroid dogs have elevated cholesterol levels.2,3 While mild hypercholesterolemia alone should not prompt testing for hypothyroidism, it supports a suspicion of hypothyroidism.
Treatment Failure and Adverse Effects
Treatment failure is uncommon. Possible reasons for failure to achieve the targeted T4 concentration include owner noncompliance in administering medication or patient refusal to swallow the pills. Variable gastrointestinal absorption of levothyroxine is also considered to be a possible cause.28 If a target post-pill T4 concentration has been achieved and clinical signs are not controlled, the dosing frequency should be increased to twice daily. Additionally, the diagnosis of hypothyroidism should be reconsidered. If the diagnosis of hypothyroidism is definitive and the dog’s T4 concentration is well controlled, consider whether a concurrent disorder could be causing clinical signs.
Dogs are generally resistant to the effects of excessive levothyroxine supplementation. However, clinical signs such as polyuria/polydipsia and hyperactivity may develop.26
Thyroid testing should be carried out only when patients are suspected of having thyroid disease. Measurement of T4 concentration is helpful to rule out hypothyroidism but should not be solely relied on to confirm the diagnosis. Combined testing that includes the serum T4 concentration along with fT4 and/or TSH levels is needed for definitive diagnosis and will help decrease the possibility for misdiagnosis of hypothyroidism. Since lifelong therapy is required, it is appropriate to achieve a definitive diagnosis before starting therapy.
- Graham PA, Refsal KR, Nachreiner RF. Etiopathologic findings in canine hypothyroidism. Vet Clin North Am Small Anim Pract 2007;37(4):617-631.
- Panciera DL. Hypothyroidism in dogs: 66 cases (1987-1992). JAVMA 1994;204(5):761-767.
- Dixon RM, Reid SW, Mooney CT. Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism. Vet Rec 1999;145(17):481-487.
- Jaggy A, Oliver JE, Ferguson DC, et al. Neurological manifestations of hypothyroidism: a retrospective study of 29 dogs. J Vet Intern Med 1994;8(5):328-336.
- Higgins MA, Rossmeisl JH, Panceria DL. Hypothyroid-associated central vestibular disease in 10 dogs: 1999-2005. J Vet Intern Med 2008;20(6):1363-1369.
- Panciera DL, Purswell BJ, Kolster KA, et al. Reproductive effects of prolonged experimentally induced hypothyroidism in bitches. J Vet Intern Med 2012;26(2):326-333.
- Finora K, Greco D. Hypothyroidism and myxedema coma. Comp Cont Educ Pract Vet 2007;29(1):19-32.
- Hess RS, Kass PH, Van Winkle TJ. Association between diabetes mellitus, hypothyroidism or hyperadrenocorticism, and atherosclerosis in dogs. J Vet Intern Med 2003;17(4):489-494.
- Nelson RW, Ihle SL, Feldman EC, et al. Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness. JAVMA 1991;198(8)1401-1407.
- Peterson ME, Melian C, Nichols R. Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentration for diagnosis of hypothyroidism in dogs. JAVMA 1997;211(11):1396-1402.
- Scott-Moncrieff JC, Nelson RW, Bruner JM, et al. Comparison of serum concentrations of thyroid-stimulating hormone in healthy dogs, hypothyroid dogs, and euthyroid dogs with concurrent illness. JAVMA 1998;212(3):387-391.
- Dixon RM, Mooney CT. Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism. J Small Anim Pract 1999;40(2):72-78.
- Hall IA, Campbell KL, Chambers MD, et al. Effect of trimethoprim/sulfamethoxazole on thyroid function in dogs with pyoderma. JAVMA 1993;202(12):1959-1962.
- Daminet S, Paradis M, Refsal KR, et al. Short-term influence of prednisone and phenobarbital on thyroid function in euthyroid dogs. Can Vet J 1999;40(6):411-415.
- Gaskill CL, Burton SA, Gelens HC, et al. Effects of phenobarbital treatment on serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs. JAVMA 1999;215(4):489-496.
- Muller PB, Wolfsheimer KJ, Taboada J, et al. Effects of long-term phenobarbital treatment on the thyroid and adrenal axis and adrenal function tests in dogs. J Vet Intern Med 2000;14(2):157-164.
- Williamson NL, Frank LA, Hnilica KA. Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs. JAVMA 2002;221(6):802-806.
- Frank LA, Hnilica KA, May ER, et al. Effects of sulfamethoxazole-trimethoprim on thyroid function in dogs. Am J Vet Res 2005;66(2):256-259.
- Daminet S, Courbels S, Duchateau L, et al. Influence of acetylsalicylic acid and ketoprofen on canine thyroid function tests. Vet J 2003;166(3):224-232.
- Gulikers KP, Panceria DL. Evaluation of the effects of clomipramine on canine thyroid function tests. J Vet Intern Med 2003;17(1):44-49.
- Kantrowitz LB, Peterson ME, Melian C, et al. Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease. JAVMA 2001;219(6):765-769.
- Torres SM, Feeney DA, Lekcharoensuk C, et al. Comparison of colloid, thyroid follicular endothelium, and thyroid hormone concentrations in healthy and severely sick dogs. JAVMA 2003;222(8):1079-1085.
- Shiel RE, Sist MD, Nachreiner RF, et al. Assessment of criteria used by veterinary practitioners to diagnose hypothyroidism in sighthounds and investigation of serum thyroid hormone concentrations in healthy Salukis. JAVMA 2010;236(3):302-308.
- Gaughan KR, Bruyette DS. Thyroid function testing in greyhounds. Am J Vet Res 2001;62(7):1130-1133.
- Ramsey IK, Evans H, Herrtage ME. Thyroid-stimulating hormone and total thyroxine concentrations in euthyroid, sick euthyroid, and hypothyroid dogs. J Small Anim Pract 1997;38(12):540-545.
- Dixon RM, Reid SWJ, Mooney CT. Treatment and therapeutic monitoring of canine hypothyroidism. J Small Anim Pract 2006;43(8):334-340.
- Lewis VA, Morrow CMK, Jacobsen JA, et al. A pivotal field study to support the registration of levothyroxine sodium tablets for canine hypothyroidism. JAAHA 2018;54(4):201-208.
- Nachreimer RF, Refsal KR. Radioimmunoassay monitoring of thyroid hormone concentrations in dogs on thyroid replacement therapy: 2,674 cases (1985-1987). JAVMA 1992;201(4):623-629.