2013 ETA Guideline: Management of Subclinical Hypothyroidism

Pearce, Simon H.S.; Brabant, Georg; Duntas, Leonidas H.; Monzani, Fabio; Peeters, Robin P.; Razvi, Salman; Wemeau, Jean-Louis

doi:10.1159/000356507

Cited by 877Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

2013 ETA Guideline: Management of Subclinical Hypothyroidism

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Pearce, Simon H.S., Brabant, Georg, Duntas, Leonidas H., Monzani, Fabio, Peeters, Robin P., Razvi, Salman, Wemeau, Jean-Louis·2013·European Thyroid Journal

DOI 10.1159/000356507PMC PMC3923601

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Abstract

Subclinical hypothyroidism (SCH) should be considered in two categories according to the elevation in serum thyroid-stimulating hormone (TSH) level: mildly increased TSH levels (4.0-10.0 mU/l) and more severely increased TSH value (>10 mU/l). An initially raised serum TSH, with FT4 within reference range, should be investigated with a repeat measurement of both serum TSH and FT4, along with thyroid peroxidase antibodies, preferably after a 2- to 3-month interval. Even in the absence of symptoms, replacement therapy with L-thyroxine is recommended for younger patients (<65-70 years) with serum TSH >10 mU/l. In younger SCH patients (serum TSH <10 mU/l) with symptoms suggestive of hypothyroidism, a trial of L-thyroxine replacement therapy should be considered. For such patients who have been started on L-thyroxine for symptoms attributed to SCH, response to treatment should be reviewed 3 or 4 months after a serum TSH within reference range is reached. If there is no improvement in symptoms, L-thyroxine therapy should generally be stopped. Age-specific local reference ranges for serum TSH should be considered in order to establish a diagnosis of SCH in older people. The oldest old subjects (>80-85 years) with elevated serum TSH ≤10 mU/l should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. If the decision is to treat SCH, then oral L-thyroxine, administered daily, is the treatment of choice. The serum TSH should be re-checked 2 months after starting L-thyroxine therapy, and dosage adjustments made accordingly. The aim for most adults should be to reach a stable serum TSH in the lower half of the reference range (0.4-2.5 mU/l). Once patients with SCH are commenced on L-thyroxine treatment, then serum TSH should be monitored at least annually thereafter.

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The optimal daily dose in overt hypothyroidism is 1.5-1.8 μg per kg of bodyweight, rounded to the nearest 25 μg.
“The optimal daily dose in overt hypothyroidism is 1•5-1•8 μg per kg of bodyweight, 107,142,144 rounded to the nearest 25 μg.”
From Hypothyroidism (2024) · cites this paper as [142]
The Recommendations (p. 10) advise approximately 1.5 μg/kg/day of L-thyroxine for patients without cardiac disease who are being treated for subclinical hypothyroidism. They do not give a 1.5–1.8 μg/kg/day range for overt hypothyroidism or instruct rounding to the nearest 25 μg. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Up to 10% of treated diagnosed hypothyroid individuals report impaired quality of life despite achieving serum free thyroxine and thyroid stimulating hormone (TSH) levels within the laboratory reference range.
“It is reported that up to 10% of treated diagnosed hypothyroid individuals report impaired quality of life, despite achieving serum free thyroxine and thyroid stimulating hormone (TSH) levels within the laboratory reference range”
From Natural desiccated thyroid for the treatment of hypothyroidism? (2024) · cites this paper as [5]
In “How to Treat?” (p. 10), the guideline says some treated patients with subclinical hypothyroidism have no improvement in symptoms and recommends adjusting treatment to bring TSH into the reference range. It does not report that up to 10% have impaired quality of life despite both free thyroxine and TSH being within laboratory reference ranges. (LLM, conf=0.79)
Experimental — accuracy not yet measured
L-T4 monotherapy is the standard treatment for primary hypothyroidism, central hypothyroidism, and subclinical hypothyroidism patients candidate for replacement.
“L-thyroxine (L-T4) monotherapy is the standard treatment for PH (4–6) and CH (4, 5, 7), and SCH patients candidate for replacement (4, 5, 8).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [8]
Current clinical guidelines propose that thyroid hormone replacement therapy should not be routinely offered for adults with subclinical hypothyroidism.
“which is supported by current clinical guidelines proposing that thyroid hormone replacement therapy should not be routinely offered for adults with subclinical hypothyroidism.12,13,14”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [13]
Current clinical guidelines from the American Thyroid Association and European Thyroid Association do not recommend treating subclinical hypothyroidism when TSH is 10 mIU/L or less (and without symptoms in younger individuals).
“Current clinical guidelines from the American Thyroid Association14 and European Thyroid Association13 do not recommend treating subclinical hypothyroidism when TSH is 10 mIU/L or less (and without symptoms in younger individuals).”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [13]

Larger elevations of TSH in younger patients require treatment with levothyroxine irrespective of the presence or absence of symptoms.
“Larger elevations of TSH in these younger patients require treatment with levothyroxine irrespective of the presence or absence of symptoms [22].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [22]
A strategy of watchful waiting is appropriate for very elderly patients, with use of levothyroxine where clearly necessary.
“A strategy of watchful waiting is appropriate for very elderly patients, with use of levothyroxine where clearly necessary [22].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [22]
Current European guidelines recommend a trial of levothyroxine treatment for younger patients (<65-70 y) with symptoms reminiscent of hypothyroidism and mildly elevated TSH (<10 mU/L).
“Current European guidelines recommend a trial of levothyroxine treatment for younger patients (<65–70 y) with symptoms reminiscent of hypothyroidism and mildly elevated TSH (<10 mU/L) [22].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [22]
An ETA guideline based on this meta-analysis recommended that a trial of LT4 should be considered in younger (<65 years) subjects with symptoms reminiscent of hypothyroidism with TSH that is elevated, but <10 mIU/L.
“A guideline from the European Thyroid Association (ETA) based on this meta-analysis recommended that a trial of LT4 should be considered in younger (<65 years) subjects with symptoms reminiscent of hypothyroidism with TSH that is elevated, but <10 mIU/L”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [130]
Younger subjects with thyrotropin >10 mIU/L should receive LT4 whether or not they have symptoms.
“Younger subjects with thyrotropin >10 mIU/L should receive LT4 whether or not they have symptoms”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [130]
LT4 can be withdrawn if symptoms have not resolved after normalisation of the thyrotropin level.
“LT4 can be withdrawn if symptoms have not resolved after normalisation of the thyrotropin level.”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [130]

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Global epidemiology of hyperthyroidism and hypothyroidism
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The prevalence of thyroid dysfunction and autoimmunity in women with history of miscarriage or subfertility.
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Overt and Subclinical Hypothyroidism in the Elderly: When to Treat
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The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis
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Levothyroxine therapy in elderly patients with hypothyroidism
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Thyroid function across the lifespan: do age-related changes matter?
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Quality of life following lobectomy versus total thyroidectomy is significantly related to hypothyroidism
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Mild Hypothyroidism in Childhood: Who, When, and How Should Be Treated?
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Association of Thyroid Hormone Therapy with Mortality in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis
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Relationship of thyroid dysfunction with cardiovascular diseases: updated review on heart failure progression
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Prevalence of gastrointestinal disorders having an impact on tablet levothyroxine absorption: should this formulation still be considered as the first-line therapy?
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Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement
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Defining optimal health range for thyroid function based on the risk of cardiovascular disease
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Thyroid dysfunction following radiofrequency ablation for benign thyroid nodules: more likely to occur within one-week and in high-risk population
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Different formulations of levothyroxine for treating hypothyroidism: a real-life study
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Does Subclinical Hypothyroidism Add Any Symptoms? Evidence from a Danish Population-Based Study
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Levothyroxine replacement in primary congenital hypothyroidism: the higher the initial dose the higher the rate of overtreatment
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Effect of Levothyroxine Supplementation on the Cardiac Morphology and Function in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis
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No evidence of increased risk of thyroid dysfunction in well treated people living with HIV
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Prevalence and factors associated with chronic use of levothyroxine: A cohort study
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Improvements in quality of life and thyroid parameters in hypothyroid patients on ethanol-free formula of liquid levothyroxine therapy in comparison to tablet LT4 form: an observational study
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Effect of Levothyroxine on Older Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis
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Authors: Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L.
Affiliations: Royal Victoria Infirmary (GB)
University Hospital Schleswig-Holstein (DE)
National and Kapodistrian University of Athens (GR)
University of Pisa (IT)
Erasmus MC (NL)
Queen Elizabeth Hospital (GB)
8 Clinique Endocrinologique Marc Linquette, CHU, Lille, France
ORCID: Pearce, Simon H.S.
Brabant, Georg
Duntas, Leonidas H.
Monzani, Fabio
Peeters, Robin P.
Razvi, Salman
Venue: European Thyroid Journal
Publisher: Bioscientifica
Published: 2013-11-26
Volume: 2
Issue: 4
Pages: 215-228
ISSN: 2235-0640 (ISSN-L)
2235-0802
DOI: 10.1159/000356507
PMC: PMC3923601
OpenAlex: W2149958970
Cited by: 877
References: 144
Citations by year: 2026: 75 · 2025: 61 · 2024: 79 · 2023: 71 · 2022: 86 · 2021: 94 · 2020: 93 · 2019: 81 · 2018: 77 · 2017: 64 · 2016: 36 · 2015: 39 · 2014: 20
FWCI: 24.91
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.karger.com/Services/SiteLicenses (vor, 4465 d)
Locations: European Thyroid Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
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 › Thyroid Cancer Diagnosis and Treatment
Keywords: subclinical hypothyroidism, thyroid-stimulating hormone, thyroid peroxidase antibodies, wait-and-see strategy, older adults, treatment response monitoring, dose adjustment

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2013 ETA Guideline: Management of Subclinical Hypothyroidism

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