Synthetic levothyroxine is the treatment of choice for hypothyroidism. Its administration orally should result in normal serum concentrations of T₄, T₃, and TSH, which attests to the fact that these products can be converted to the more metabolically active T₃ by peripheral tissues. A sodium levothyroxine product approved for use in dogs is recommended. Liquid and tablet formulations are effective. The initial dosage is 0.01 to 0.02 mg/kg body weight. Twice-daily administration is recommended initially unless the levothyroxine product has been specifically formulated for once-daily administration. Because of the variability in levothyroxine absorption and metabolism, the dose and frequency may have to be adjusted before a satisfactory clinical response is observed; this variability is one reason for monitoring therapy in dogs.

Thyroid hormone supplementation should be continued for a minimum of 4 weeks before critically evaluating the effectiveness of treatment. With appropriate therapy, all clinical signs and clinicopathologic abnormalities associated with hypothyroidism are reversible. Improvement in mental alertness and activity usually occurs within the first week of treatment; this is an important early indicator that the diagnosis of hypothyroidism was correct. Although some hair regrowth usually occurs within the first month in dogs with endocrine alopecia, it may take several months for complete regrowth and a marked reduction in hyperpigmentation of the skin to occur. Initially, the haircoat may worsen as large amounts of hair in the telogen stage of the hair cycle are shed. Improvement in neurologic manifestations is usually evident within days of initiating treatment; complete resolution of neurologic signs is unpredictable and may take 4 to 8 weeks or longer before it occurs.

Problems with levothyroxine therapy should be suspected if clinical improvement is not seen by 8 weeks after initiating therapy. An inappropriate diagnosis of hypothyroidism is the most obvious reason for a poor response. Hyperadrenocorticism can be mistaken for hypothyroidism, if other clinical signs (e.g., polyuria, polydipsia) commonly associated with hyperadrenocorticism are not present because of the suppressive effects of cortisol on serum thyroid hormone concentrations. Failure to recognize the impact of concurrent illness on thyroid hormone test results is another common reason for misdiagnosing hypothyroidism. Concurrent disease (e.g., allergic skin disease, flea hypersensitivity) is common in dogs with hypothyroidism and may affect the clinical impression of response to levothyroxine therapy if the concurrent disease is not recognized. Other possible reasons for a poor response to therapy include client compliance problems, problems with the dose, frequency of administration or tablet strength, and poor absorption from the gastrointestinal tract. Whenever a dog shows a poor response to levothyroxine therapy, the history, physical examination findings, and diagnostic test results that prompted the initiation of levothyroxine therapy should be critically re-evaluated and serum thyroid hormone and TSH concentrations measured.

Therapeutic monitoring includes evaluation of the clinical response to levothyroxine treatment, measurement of serum T₄ concentration before or after levothyroxine administration, or both, and measurement of serum TSH concentration. Serum T₄ and TSH concentrations should be measured 4 weeks after initiating therapy, whenever signs of thyrotoxicosis develop, or in the event that there has been minimal or no response to therapy. Concentrations should also be measured 2 to 4 weeks after an adjustment in levothyroxine therapy in dogs showing a poor response to treatment.

Serum T₄ and TSH concentrations are typically evaluated 4 to 6 hours after the administration of levothyroxine in dogs. Measuring serum T₄ concentration immediately before levothyroxine administration (i.e., trough level) is optional, but is recommended if levothyroxine is being given once a day. Measurement of serum free T₄ can be done in lieu of measuring T₄, but is more expensive and probably does not offer additional information except in dogs with T₄ autoantibodies. The presence of thyroid hormone autoantibodies does not interfere with the physiologic actions of levothyroxine.

Ideally, the serum T₄ concentration should be in the reference range when measured 4 to 6 hours after thyroid hormone administration and the TSH concentration should be in the reference range. Postdosing serum T₄ concentrations are frequently above the reference range. The finding of an increased postdosing serum T₄ concentration is not an absolute indication to reduce the dose of levothyroxine, especially if there are no clinical signs of thyrotoxicosis. However, a reduction in the dose is recommended whenever serum T₄ concentrations exceed 55 nmol/L. Postdosing serum T₄ concentrations may also be less than 20 nmol/L. In this situation, an increase in the dose or frequency of administration of levothyroxine is indicated if clinical manifestations of hypothyroidism persist, the serum TSH concentration remains increased, or both, but is not necessarily indicated if the clinical response to treatment is good and the serum TSH concentration is in the reference range. Resolution of clinical signs and a satisfied owner are the most important parameters when considering adjusting the levothyroxine dose, simply because the post-pill serum T₄ concentration is near the lower end of the reference interval.