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Hypothyroid patients are not all the same: Part 1 – Issues in levothyroxine replacement

Hypothyroid patients are not all the same: Part 1 – Issues in levothyroxine replacement

Of all the different thyroid disorders, the management of hypothyroidism is the one that appears to be straightforward and without much controversy since all that is needed is to replace the insufficient hormone with a synthetic one. The American Thyroid Association guidelines for the treatment of hypothyroidism recommend levothyroxine as the preparation of choice for the treatment of hypothyroidism.1 Thus, in simple terms, all hypothyroid patients would just be treated similarly. But is this really the case?

The choice of preparation may be simple, but how it is initiated and titrated varies depending on several factors, such as the patient’s weight, lean body mass, age, sex, etiology of hypothyroidism, degree of thyroid stimulating hormone (TSH) elevation, presence of cardiac disease and, in women, pregnancy status.1 Thus, the management of hypothyroidism with levothyroxine should be personalized and individualized.

The initial dose of replacement therapy is usually computed using patient body weight. However, ideal body weight is the best parameter for daily levothyroxine dose calculation.2 Initial levothyroxine dose is titrated upward gradually, using serum TSH as a goal.

Age is a very important consideration in levothyroxine replacement. Young healthy adults may be given the full replacement dose, while the elderly (usually defined as those >65 years) may require 20 to 25% less. Adults with hypothyroidism require approximately 1.7 mg/kg of body weight/day of levothyroxine for full replacement. Children may require up to 4 mg/kg of body weight/day. Older patients may need <1 mg/kg of body weight/day because of a decrease in their rate of clearance of thyroxine3 and the fact that serum TSH normally tends to increase by 0.3 mIU/L for every 10 years above ages 30 to 39 years, especially in females.4 Thus, the dose needed to make the patient biochemically euthyroid would be less in the elderly compared with the young hypothyroid individual. Ironically, women usually have higher dose requirements, which may be related to the possible interaction of reproductive hormones in women.

Logically, patients who are athyreotic need higher doses of levothyroxine replacement compared with those with some residual thyroid function. However, in practice, patients with central (secondary) hypothyroidism require higher doses of daily levothyroxine. On the other hand, those who become hypothyroid because of Graves’ disease treatment usually require lower doses to achieve euthyroidism.2

The more severe the hypothyroidism, the greater the need for levothyroxine replacement. But the speed at which replacement is given must be tempered by the general clinical context and the possible presence of cardiac disease, especially in the elderly patient. The dictum in such cases is to ‘start low and go slow’. Patients older than 50–60 years, without evidence of coronary heart disease (CHD), may start with levothyroxine at 50 ug daily. However, in those with known CHD, the starting dose may be as low as 12.5–25 ug/day.2 This is then slowly up titrated to achieve target serum TSH levels.

Another very important population of patients with hypothyroidism are pregnant women. Pregnancy is associated with increased levothyroxine requirements, due to increased maternal renal iodine clearance, transfer of iodine to the fetus, coupled with the need for increased thyroid hormone production in the mother.5 Pregnant women, in general, need an increase of 25 to 30% in levothyroxine dose, and treatment should be adjusted as soon as possible when pregnancy is suspected.

Initially it may seem very simple to start patients on levothyroxine therapy. However, multiple factors and considerations must be made for precise and individualized treatment of patients with hypothyroidism.


References

  1. Jonklaas, J, et al. Guidelines for The Treatment of Hypothyroidism. Thyroid 2014;24(12):1670-1751.
  2. Garber JR, et al. for the AACE-ATA Taskforce on Hypothyroidism in Adults. Thyroid 2012;22(12):1200-1235.
  3. Singer PA, et al. JAMA 1995;273:808-812.
  4. Hollowell JG, et al. J Clin Endocrinol Metab 2002;87:489-499.
  5. Glinoer D. Best Pract Res Clin Endocrinol Metab 2004;18:133-52.
  6. De Groot L, et al. J Clin Endocrinol Metab 2012;97:2543-2565.

Nemencio Nicodemus Jr.

Professor
Department of Biochemistry & Molecular Biology
College of Medicine
University of the Philippines
Manila, Philippines
Clinical Associate Professor
Department of Medicine
Philippine General Hospital
Manila, Philippines
hypothyroidism
levothyroxine
patient age
pregnancy