ADDITIONAL TREATMENT CONSIDERATIONS
Overtreatment
The main complication of hypothyroidism treatment occurs when the patient receives more thyroid hormone than is required, which has been reported in 20% of cases.9 The primary risks of overtreatment are osteoporosis and atrial fibrillation. Care should be taken especially in vulnerable populations such as the elderly, who are particularly susceptible to atrial fibrillation, and postmenopausal women, who are prone to accelerated bone loss. Targeting a TSH level in the midnormal range (0.5-2.5 mIU/L) will help the clinician avoid overtreatment complications; if symptoms persist, other causes should be sought.
For persistent symptomatology in the presence of normal thyroid test results, clinicians should consider other potential causes.
Combination T4/T3 Treatment
Liothyronine is bioequivalent to T3 in the body. It is not recommended as a primary agent except in cases of thyroid suppression requiring quick reversal; its half-life is only approximately 18 hours. This short half-life makes it more difficult to monitor because T3 levels can vary substantially throughout the day.3
Recent media attention has focused on combination levothyroxine-liothyronine treatment for hypothyroidism, and patients may inquire about this treatment option. The healthy thyroid gland produces these hormones in a ratio of approximately 13:1; most of the active T3 in the body results from T4 to T3 conversion in the peripheral tissues.3
But is combination therapy an evidence-based treatment option for hypothyroidism? The ATA/AACE joint guidelines indicate that there is inadequate evidence to support the use of levothyroxine and liothyronine combinations to treat hypothyroidism. This recommendation was downgraded from Grade A to Grade B in the current guidelines.4 This is because a few studies suggest that some patients report feeling better on T4/T3 combinations, and it is possible that some patient subgroups may benefit from combination treatment.4 There are no data that clearly identify these subgroups, and it is unknown precisely why some patients report improvement; further research is required.4 Combination therapy is not recommended for pregnant women or those planning pregnancy because of the potential for harm to the fetus.4
Patients sometimes request a more “natural” treatment for hypothyroidism, and animal-derived desiccated thyroid is the one most often prescribed.4 The two commonly used forms of desiccated thyroid are porcine in origin. Each is a levothyroxine-liothyronine combination in a ratio of approximately 4:1. While a recent randomized, double-blind, crossover study compared desiccated thyroid extract (DTE) to levothyroxine treatment and found that 48.6% of study subjects preferred DTE therapy, the authors concluded that “DTE therapy may be relevant for some hypothyroid patients” without defining the characteristics of those patients.10
In addition, because desiccated thyroid is derived from a tissue product, there can be variability in dosing that may make it challenging to reach treatment goals consistently. Inquiring vegan and vegetarian patients would also need to be advised of the animal origin of desiccated thyroid.
Treatment When Tests are Normal
Clinicians commonly encounter patients who request treatment for hypothyroid symptoms in the absence of laboratory evidence of hypothyroidism. Although hypothyroid symptoms are common, vague, and nonspecific and pinpointing their precise etiology may be difficult, there is no benefit in treating patients for hypothyroidism when thyroid test results are normal. In fact, treatment may be harmful, as there is substantial risk for subclinical or overt hyperthyroidism.4
Generic vs Brand-Name Levothyroxine
Both generic and brand-name preparations of levothyroxine are available. Generic formulations are made by a variety of manufacturers, and formulations can vary in production; a brand name assures one manufacturer and consistency in production. It is difficult to accurately assess the bioequivalence and, therefore, the interchangeability, of the various manufacturers’ generic formulations.4 Differences in bioavailability of the drug may affect the dose the patient receives. Minor fluctuations may occur in thyroid function test results, which may or may not be clinically acceptable in an individual patient. Therefore, the current consensus encourages the use of a consistent levothyroxine preparation for individual patients to minimize variability from refill to refill.4 For patients for whom medication cost is a key factor, generic formulations can be considerably less expensive than their brand-name counterparts.
FOLLOW-UP TESTING
For primary hypothyroidism, the frequency of follow-up is dictated by symptoms and laboratory test values. Patients should be advised that symptoms will improve with treatment but that this improvement may not be noticeable for three to six months, even after TSH levels have reached the normal range.4
Thyroid function testing is typically repeated at four to eight weeks to assess initial dose titration; once an adequate replacement dose has been reached, testing may be repeated at six months and then annually thereafter unless symptoms arise.4 In pregnant women, TSH and FT4 levels should be measured every four weeks during the first half of pregnancy and at least once between 26 and 32 weeks’ gestation (levothyroxine dose requirements typically increase by 20% to 50% during pregnancy).4
Patients with secondary hypothyroidism should be referred for an endocrinology consultation for evaluation of their general pituitary or hypothalamic function.
Changes in Dose Requirements
Dose requirements may change over time in any given patient. Underlying thyroid function may wane, and any absorptive issues secondary to other diseases, such as celiac disease, may alter dose requirements. In pregnancy, dose requirements increase but generally revert back to baseline postpartum.4 Any addition or discontinuation of medications that affect plasma binding or metabolism will alter thyroid dosing.4 Increasing age or weight loss may require decreases in dosing. After any dose adjustment, thyroid function test results should be reevaluated in four to eight weeks, with the same follow-up schedule for repeat testing as after initiation of hypothyroidism treatment.
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