Does Subclinical Hypothyroidism Add Any Symptoms? Evidence from a Danish Population-Based Study
Abstract
Background Few studies have scrutinized the spectrum of symptoms in subclinical hypothyroidism.Methods From 3 Danish Investigation on Iodine Intake and Thyroid Diseases (DanThyr) cross-sectional surveys performed in the period 1997 to 2005, a total of 8903 subjects participated in a comprehensive investigation including blood samples and questionnaires on previous diseases, smoking habits, alcohol intake, and education. From the 3 surveys we included patients with subclinical hypothyroidism (n = 376) and euthyroid controls (n = 7619). We explored to what extent patients with subclinical hypothyroidism reported 13 previously identified hypothyroidism-associated symptoms (tiredness, dry skin, mood lability, constipation, palpitations, restlessness, shortness of breath, wheezing, globus sensation, difficulty swallowing, hair loss, dizziness/vertigo, and anterior neck pain). In various uni- and multivariate regression models we searched for circumstances predicting why some patients have more complaints than others.Results Subclinically hypothyroid patients did not report higher hypothyroidism score [(median, interquartile range), 2 (0-4) vs 2 (0-4), P = .25] compared with euthyroid controls. Within the group of subclinical hypothyroid patients, comorbidity had the highest impact on symptoms (tiredness, shortness of breath, wheezing; all P < .001); TSH level had no impact on symptom score; and younger age was accompanied by higher mental burden (tiredness, P < .001; mood lability, P < .001; restlessness, P = .012), whereas shortness of breath was associated with high body mass index (P < .001) and smoking (P = .007).Conclusion Patients with a thyroid function test suggesting subclinical hypothyroidism do not experience thyroid disease-related symptoms more often than euthyroid subjects. In subclinical hypothyroidism, clinicians should focus on concomitant diseases rather than expecting symptomatic relief following levothyroxine substitution.
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Immune checkpoint inhibitors, especially combination therapy involving anti-PD-1, anti-PD-L1, and anti-CTLA-4 drugs, can cause hypophysitis that may result in panhypopituitarism.
“Immune checkpoint inhibitors, especially combination therapy involving anti-PD-1, anti-PD-L1, and anti-CTLA-4 drugs, cancausehypophysitis(inflammationofthepituitarygland)thatmay result in panhypopituitarism. 39”
From Hypothyroidism: A Review (2025) · cites this paper as [39]
Symptoms consistent with the presence of hypothyroidism are nonspecific and cannot be reliably used to differentiate those with hypothyroidism from euthyroid people.
“symptoms consistent with the presence of hypothyroidism are nonspecific and cannot be reliably used to differentiate those with hypothyroidism from euthyroid people. 39 -41”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [40]
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- Authors
- Carlé, A., Karmisholt, J. S., Knudsen, N., Perrild, H., Thuesen, B. H., Ovesen, L., Rasmussen, L. B., & Pedersen, I. B.
- Affiliations
- Aalborg University Hospital (DK)
- Bispebjerg Hospital (DK)
- Capital Region of Denmark (DK)
- Slagelse Hospital (DK)
- Corresponding author
- Carlé, Allan
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 134
- Issue
- 9
- Pages
- 1115-1126.e1
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W3153507445
- Cited by
- 25
- References
- 49
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 2 · 2021: 4
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- Funders
- Beckett Foundation
- 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, hypothyroidism symptoms, symptom burden, comorbidities, fatigue, emotional lability, dyspnea, wheezing, TSH levels, body mass index, smoking
- MeSH terms
- Adult, Age Factors, Alcohol Drinking, Denmark, Educational Status, Female, Humans, Hypothyroidism, Male, Mental Health, Middle Aged, Smoking, Thyrotropin, Thyroxine, Body Mass Index, Case-Control Studies, Asymptomatic Diseases, Symptom Assessment
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