Levothyroxine Dose Adjustment to Optimise Therapy Throughout a Patients Lifetime

Due to its long half-life of about 7days, in patients in the clinically euthyroid state, levothyroxine is the preferred first-line treatment for primary hypothyroidism and has been the most commonly prescribed treatment since the 1980s 8. A multivariate analysis of the results revealed that physician characteristics may affect prescription patterns, with residents of North America, for example, being more inclined to prescribe therapies incorporating liothyronine than their colleagues in Europe 85, 86. However, the study was not designed to investigate whether this was due to physician-patient interaction, specific education following the meetings, the influence of pharmaceutical companies, or media exposure, or a combination of these.

As noted in the article, it is important to regularly monitor the TSH level until it is in the normal range, then make future adjustments based on symptoms or periodic testing. Several studies have shown that the levothyroxine dose requirement is decreased in older individuals 8, 48, 49. However, a recent study suggests that this decreased requirement may be mediated by the changes in weight that may accompany ageing 26.

Fig. 3.

• This means that it is necessary for clinicians to determine which patients are truly in need of dose adjustment.
• Currently, there is no clear, high-level guideline on how to best adjust the starting dosage in patients with a body mass index greater than 30 kg per m2.
• In the case of surgically athyreotic patients, the dose of levothyroxine required may be slightly higher than in those with autoimmune thyroid disease 8, presumably reflecting some retained thyroid hormone production in those with autoimmune thyroid disease.

Some of the studies cited include analyses, or studies with human participants, performed by the authors and completed prior to the initiation of this manuscript. Generally, hypothyroidism may be effectively treated via a constant daily dose of levothyroxine, and, for the majority of confirmed aetiologies, this needs to be lifelong. However, in this setting, there appear to be many cases of both levothyroxine over- and under-dosing and it may be that frequent adjustments of a dose are necessary. These adjustments need to be handled with caution and take into account the many contributing factors, as multiple levothyroxine dose adjustments evidently result in a greater burden on healthcare resources 24. This means that it is necessary for clinicians to determine which patients are truly in need of dose adjustment. Even more importantly, accumulating evidence suggests that many patients, for whom the indication for levothyroxine initiation is not adequately established and the diagnosis is not well documented, are remaining on levothyroxine therapy for longer than necessary.

When Levothyroxine Administration Is a Necessity

• However, in this setting, there appear to be many cases of both levothyroxine over- and under-dosing and it may be that frequent adjustments of a dose are necessary.
• Current guidelines recommend a levothyroxine dosage of 1.6 mcg per kg per day based on ideal body weight or lean body mass instead of actual body weight.3,4 Ideal body weight can be calculated as the weight for height that would generate a body mass index of 24 to 25 kg per m2.
• Some of the studies cited include analyses, or studies with human participants, performed by the authors and completed prior to the initiation of this manuscript.
• A multivariate analysis of the results revealed that physician characteristics may affect prescription patterns, with residents of North America, for example, being more inclined to prescribe therapies incorporating liothyronine than their colleagues in Europe 85, 86.

In keeping with this concept, the initial dose of levothyroxine in patients presenting to a clinic with primary hypothyroidism can be predicted by the patient’s TSH value prior to initiation of treatment 9. In the case of surgically athyreotic patients, the dose of levothyroxine required may be slightly higher than in those with autoimmune thyroid disease 8, presumably reflecting some retained thyroid hormone production in those with autoimmune thyroid disease. An example of the dose requirement in those with Hashimoto’s thyroiditis without residual function and post-surgical hypothyroidism is approximately 1.6μg/kg 8.

The dose of levothyroxine required by a patient following thyroidectomy can be predicted by either body weight or body mass index (BMI) 10–12. Body weight, BMI, ideal body weight, and lean body mass can all predict the initial dose requirement, with the latter three parameters providing the more accurate estimates 10, 13. These range from simple formulae based only on body weight or BMI to more complex formulae that also incorporate other factors such as patient sex 10, 14. Generally, both a TSH-based estimate and a body weight-based estimate yield similar initial estimates of dose requirement (Fig. 1). Currently, there is no clear, high-level guideline on how to best adjust the starting dosage in patients with a body mass index greater than 30 kg per m2. Monitoring TSH levels every six to eight weeks and adjusting levothyroxine dosages until the TSH reaches goal are critical to avoid iatrogenic hyperthyroidism or under-replacement.

If there is a suspicion for levothyroxine treatment having been prescribed unnecessarily, this can be investigated via a test period incorporating 6- to 8-week therapy discontinuation, followed by TSH testing. Email letter submissions to  Letters should be fewer than 400 words and limited to six ranitidine synthroid references, one table or figure, and three authors. Some of studies cited include analyses, or studies with human participants, performed by the authors and completed prior to the initiation of this manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Fig. 5.

As a person progresses through life, their dose may need to be adjusted because other diseases or medications can affect the dose needed for effective treatment. Pregnancy or weight gain can also affect the dose of levothyroxine needed by the patient, so patients and physicians need to work in partnership to ensure that the treatment is working as well as it can. The goal of this partnership is to maintain normal thyroid hormone levels without the patient experiencing any side effects or negative health consequences of taking too much or too little levothyroxine. Current guidelines recommend a levothyroxine dosage of 1.6 mcg per kg per day based on ideal body weight or lean body mass instead of actual body weight.3,4 Ideal body weight can be calculated as the weight for height that would generate a body mass index of 24 to 25 kg per m2. Lean body mass is a better predictor of the dosage requirement than actual body weight.5 Without this clarification, some patients may receive a dosage of levothyroxine that is too high. Thyroxine is actively transported to the various organs where it is converted to triiodothyronine by the activity of the deiodinases 6.

Levothyroxine is the standard therapy for patients with hypothyroidism, a condition that affects up to 5% of people worldwide. While levothyroxine therapy has substantially improved the lives of millions of hypothyroid patients since its introduction in 1949, the complexity of maintaining biochemical and clinical euthyroidism in patients undergoing treatment with levothyroxine cannot be underestimated. Initial dosing of levothyroxine can vary greatly and may be based on the amount of residual thyroid function retained by the patient, the body weight or lean body mass of the patient, and thyroid-stimulating hormone levels. As levothyroxine is usually administered over a patient’s lifetime, physiological changes throughout life will affect the dose of levothyroxine required to maintain euthyroidism.

The acidity of the thyroxine molecule, which caused diminished absorption resulting in low bioavailability, was an unresolved problem for more than 20 years following its discovery 3. The manufacture of sodium thyroxine (levothyroxine) thus resulted in a major pharmacological achievement in endocrinology, giving a more stable and effective thyroid hormone compound that, over the last few decades, has considerably improved the lives of millions of patients with various forms of hypothyroidism. In summary, it is necessary in all cases to periodically verify the need for dose adjustment and/or continuation of treatment.

Keywords relating to levothyroxine, hypothyroidism, treatment, levothyroxine dose adjustments, levothyroxine and concomitant conditions, levothyroxine and concomitant medications, and combined treatment with levothyroxine and liothyronine versus levothyroxine were searched. Potential articles of interest were identified by title and abstract, and citation lists of articles of interest were used to identify additional literature. This article is based on previously conducted studies and does not contain any studies with animals performed by any of the authors.