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Cited by 14Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

Recent evidence sets therapeutic targets for levothyroxine-treated patients with primary hypothyroidism based on risk of death

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Perros, Petros, Nirantharakumar, Krishnarajah, Hegedüs, Laszlo·2021·European Journal of Endocrinology
DOI 10.1530/eje-20-1229
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Abstract

Since the introduction of sensitive assays for serum thyroid-stimulating hormone (TSH) clinicians have advised hypothyroid patients to adjust the dose of levothyroxine (L-T4) in order to achieve a normal serum TSH. A minority of patients are dissatisfied with this treatment strategy and experience symptoms. Some indirect evidence suggests that a normal serum TSH may not necessarily reflect euthyroidism at the tissue level in patients treated with L-T4. Increasingly hypothyroid patients demand higher doses of L-T4 or liothyronine (L-T3) or animal thyroid extract, often purchased online, and titrate the dose against symptoms, although ample evidence suggests that combination treatment (L-T4 with L-T3) is no more effective than L-T4 alone. Community surveys show that up to 53% of treated hypothyroid patients at any time have a serum TSH outside the normal range. The recommendation by guidelines that the upper limit of the normal range for serum TSH should not be exceeded is supported by robust evidence and is generally accepted by clinicians and patients. However, until recently the lower limit of serum TSH for optimal L-T4 replacement has been controversial. New evidence obtained by two independent large population studies over the past two years has shown that mortality of hypothyroid patients treated with levothyroxine is increased when the serum TSH exceeds or is reduced outside the normal reference range. It is estimated that the implementation of a policy of normalising serum TSH in hypothyroid patients will reduce the risk of death of 28.3 million people in the USA and Europe alone.

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Authors
Perros, P., Nirantharakumar, K., & Hegedüs, L.
Affiliations
  • Royal Victoria Infirmary (GB)
  • University of Birmingham (GB)
  • 3Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
Corresponding author
Perros, Petros
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2021-02
Volume
184
Issue
2
Pages
C1-C3
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-20-1229
OpenAlex
W3110690492
Cited by
14
References
5
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 4
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
  • Newcastle University ePrints (Newcastle Univesity)
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
primary hypothyroidism, levothyroxine, thyroid-stimulating hormone, TSH reference range, mortality, thyroid hormone replacement, liothyronine, euthyroidism, treatment goals
MeSH terms
Implementation Science, Endocrinology, Humans, Hypothyroidism, Patient Care Planning, Prognosis, Surveys and Questionnaires, Reference Values, Risk Factors, Thyroid Hormones, Thyrotropin, Thyroxine, Practice Guidelines as Topic, Hormone Replacement Therapy, Evidence-Based Practice, Precision Medicine

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