The Starting Dose of Levothyroxine in Primary Hypothyroidism Treatment: A Prospective, Randomized, Double-blind Trial
Open accessAbstract
BACKGROUND: The treatment of hypothyroidism with levothyroxine is effective and simple; however, recommendations for the starting dose vary considerably. To our knowledge, the levothyroxine starting dose has never been studied prospectively. METHODS: We conducted a prospective, randomized, double-blind trial that compared a full starting levothyroxine dose of 1.6 mug/kg with a low starting dose of 25 mug (increased every 4 weeks) in patients with newly diagnosed cardiac asymptomatic hypothyroidism. Safety was studied by documenting cardiac symptoms and events, and efficacy was studied by monitoring thyrotropin and free thyroxine levels and by assessing improvement of signs and symptoms and quality of life. RESULTS: Seventy-five consecutive patients were enrolled, of whom 50 underwent randomization. At baseline, the severity of hypothyroidism and age were comparable in the full-dose (n = 25) vs the low-dose group (n = 25): thyrotropin, 61 vs 48 mIU/L; free thyroxine, 0.56 vs 0.64 ng/dL (7.2 vs 8.2 pmol/L); and age, 47 vs 47 years. No cardiac complaints or events were documented during treatment or at bicycle ergometry at baseline, 12 weeks, or 24 weeks. Euthyroidism was reached in the full-dose vs the low-dose group in 13 vs 1 (4 weeks), 19 vs 3 (8 weeks), 19 vs 9 (12 weeks), 20 vs 14 (16 weeks), 20 vs 18 (20 weeks), and 21 vs 20 (24 weeks) patients (P = .005). However, signs and symptoms of hypothyroidism and quality of life improved at a comparable rate. CONCLUSION: A full starting dose of levothyroxine in cardiac asymptomatic patients with primary hypothyroidism is safe and may be more convenient and cost-effective than a low starting dose regimen.
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Hypothyroid patients with minimal endogenous thyroid function require LT4 doses of 1.6-1.8 μg/kg actual body weight.
“Based on body weight, hypothyroid patients with minimal endogenous thyroid function require LT4 doses of 1.6-1.8 l g/kg of actual body weight (38,47,212,213,215-217,226,227), although some studies estimate higher doses of 2.0-2.1 l g/kg for some patient groups (212,213,226).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [227]
TH measurement is required to complement TSH measurement in pregnancy, intercurrent illness when TSH can be suppressed, and the initial treatment of hypo- or hyperthyroidism because the response of the pituitary-thyroid axis can be delayed after a change in thyroid status.
“TH measurement is also required to complement TSH measurement in a number of clinical situations (Table 2) such as pregnancy,60 intercurrent illness when TSH can be suppressed (the nonthyroidal illness syndrome61,62), and the initial treatment of hypo-63 or hyperthyroidism64 as the response of the pituitary-thyroid axis can be delayed after a change in thyroid status.57”
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- Authors
- Roos, A., Linn-Rasker, S. P., van Domburg, R. T., Tijssen, J. P., & Berghout, A.
- Affiliations
- Erasmus MC (NL)
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2005-08-08
- Volume
- 165
- Issue
- 15
- Pages
- 1714
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2126532627
- Cited by
- 150
- References
- 49
- Citations by year
- 2026: 1 · 2025: 12 · 2024: 5 · 2023: 12 · 2022: 12 · 2021: 9 · 2020: 4 · 2019: 10 · 2018: 2 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 13
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- levothyroxine, primary hypothyroidism, starting dose, euthyroidism, thyroid-stimulating hormone, free thyroxine, quality of life, hypothyroidism symptoms, treatment safety
- MeSH terms
- Adult, Aged, Double-Blind Method, Half-Life, Humans, Hypothyroidism, Male, Middle Aged, Prospective Studies, Quality of Life, Thyrotropin, Thyroxine
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