• Allan Carlé, Jesper Scott Karmisholt, Nils Knudsen, Hans Perrild, Bettina Heinsbæk Thuesen, Lars Ovesen, Lone Banke Rasmussen, and Inge Bülow Pedersen.
• Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Institute, Aalborg University, Denmark. Electronic address: carle@dadlnet.dk.
• Am. J. Med. 2021 Sep 1; 134 (9): 1115-1126.e1.

BackgroundFew studies have scrutinized the spectrum of symptoms in subclinical hypothyroidism.MethodsFrom 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.ResultsSubclinically 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).ConclusionPatients 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.Copyright © 2021 Elsevier Inc. All rights reserved.

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