Levothyroxine Dose Adjustment to Optimise Therapy Throughout a Patient’s Lifetime

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 synthroid antacids 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.

Fig.5.

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.

Avoidance of Over- and Under-Dosing with 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.

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.

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 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.

• Hypothyroidism is 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.
• 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.
• 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.
• 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.

References

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 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 goal is consistent maintenance of euthyroidism, without the patient experiencing the adverse events and negative health consequences of under- or overtreatment. When commencing levothyroxine therapy, initial dose requirements can vary greatly from small doses such as 25–50 μg in an individual with mild or subclinical disease, where the therapy may be supplementing endogenous function, to larger doses of 88–175 μg in cases of patients with negligible endogenous thyroid function.

Initial Dosing and Dose Adjustment of Levothyroxine During Therapy

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. Hypothyroidism, a reduction in thyroid hormone levels, is one of the most common diseases worldwide. The medication most used to treat hypothyroidism is levothyroxine, a compound that acts as a replacement for a person’s thyroid hormone. People with hypothyroidism will often need to take levothyroxine for a long time, typically for the rest of their life, so it is important that their treatment is monitored closely and the dose is adjusted for the best effect as needed.

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.

Weight Changes and Hormonal Changes

• 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.
• Diligent monitoring of patients taking levothyroxine and regular dose adjustment to achieve optimised treatment and avoidance of adverse events are particularly emphasised.
• 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.
• 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.
• 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.

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.

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.