Weight-Based Levothyroxine Dosage Adjustment for Hypothyroidism

The acidity of the thyroxine molecule, which caused diminished absorption resulting in low bioavailability, was an unresolved problem for more than 20years 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.

Furthermore, dose adjustments may need to be made in patients with concomitant medical conditions, in patients taking certain medications, as well as in elderly patients. Patients who have undergone any weight or hormonal changes may require dose adjustments, and the majority of pregnant women require increased doses of levothyroxine. The physician is tasked with vigilant appraisal of the patient's status based on a thorough clinical and laboratory assessment and appropriate adjustment of their levothyroxine therapy. The patient in turn is tasked with medication adherence and reporting of symptomatology and any changes in their medical situation. The goal is consistent maintenance of euthyroidism, without the patient experiencing the adverse events and negative health consequences of under- or overtreatment.Funding Merck.Plain Language Summary Plain language summary available for this article.

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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.

Fig.1.

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 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.

Due to its long half-life of about 7 days, 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.

• A prospective clinical cohort follow-up study illustrated this by showing that, among 291 patients (84% females) on levothyroxine replacement therapy without a solid diagnosis of hypothyroidism and in whom the treatment was paused, 114 developed hypothyroidism, while 177 participants remained euthyroid.
• 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.
• 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.
• 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.

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.

Triiodothyronine, the active form of thyroid hormone, is secreted in small amounts by the thyroid but is mainly generated via extrathyroidal conversion of the prohormone thyroxine. Hypothyroidism is synthroid pap a common endocrine disease that requires timely and lifelong treatment since, if left untreated, it can contribute to hypertension, dyslipidaemia, and heart failure and induce reversible dementia and infertility, as well as neurosensory, musculoskeletal, and gastrointestinal symptoms 7. There is currently no other treatment for hypothyroidism, other than providing thyroid hormone replacement.

Controversies About Treatment Other Than Levothyroxine

Other important considerations regarding levothyroxine doses in older individuals include bearing age-adjusted TSH reference ranges in mind 50 and avoiding over-replacement that might potentially exacerbate other medical conditions 8. Both of these considerations would lead to targeting of higher TSH values in older individuals (Fig.3). Diligent monitoring of patients taking levothyroxine and regular dose adjustment to achieve optimised treatment and avoidance of adverse events are particularly emphasised.

• Furthermore, dose adjustments may need to be made in patients with concomitant medical conditions, in patients taking certain medications, as well as in elderly patients.
• 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.
• Patients who have undergone any weight or hormonal changes may require dose adjustments, and the majority of pregnant women require increased doses of levothyroxine.
• There is currently no other treatment for hypothyroidism, other than providing thyroid hormone replacement.
• 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.

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 1.6 μg/kg 8.

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Calcium supplements 74, 75 and iron 76, 77 also reduce absorption and thereby increase the levothyroxine dose requirement or increase serum TSH 52, 53. Vitamin C stands alone as an example of a supplement that may actually decrease the requirement for levothyroxine by enhancing its absorption, at least in patients with gastritis 78. Its chemical structure was determined in 1926 by Harington, and it was synthesised in 1927 by Harington and Barger 1, 2.