Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population- Based Case-Control Study Allan Carlé, MD, PhD, Inge Bülow Pedersen,

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Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population- Based Case-Control Study Allan Carlé, MD, PhD, Inge Bülow Pedersen, MDSci, PhD, Nils Knudsen, MDSci, PhD, Hans Perrild, MD, Lars Ovesen, MD, Stig Andersen, MDSci, PhD, Peter Laurberg, MDSci The American Journal of Medicine Volume 129, Issue 10, Pages 1082-1092 (October 2016) DOI: 10.1016/j.amjmed.2016.06.013 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Mean number of symptoms present at disease onset in autoimmune overt hypothyroidism and in age, gender-, and region-matched euthyroid controls by different age groups. Number of cases in the age groups 0 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, 60 to 69 years, and 70+ years were n = 8, 16, 32, 44, 31, and 9, respectively (corresponding numbers in controls were 4 times higher because of the individual matching). Mean numbers of symptoms presented at disease onset were 6.1, 5.6, 6.5, 5.0, 3.8, and 3.1. Mean (± standard error of the mean) duration of symptoms before hypothyroidism was diagnosed within the same age strata were 14.0 ± 3.3, 14.5 ± 4.2, 13.2 ± 3.4, 9.7 ± 1.2, 10.2 ± 2.0, and 10.4 ± 3.2. Asterisks depict statistically different number of symptoms between patients and healthy subjects (*P < .01, **P < .001). s.e.m. = standard error of the mean. The American Journal of Medicine 2016 129, 1082-1092DOI: (10.1016/j.amjmed.2016.06.013) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 ORs for autoimmune overt hypothyroidism in the presence of different number of symptoms. Calculations were performed in 2 groups (younger subjects aged <50 years [cases/controls], n = 56/224; older subjects aged ≥60 years, n = 40/160). ORs with 95% CIs for being hypothyroid in the presence of 0 to 1, 2 to 3, 4 to 6, 7 to 8, and 8+ symptoms were 0.04 (0.007-0.18), 0.34 (0.13-0.89), 3.18 (1.50-6.75), 2.78 (1.21-6.32), and 9.17 (3.75-22.8), respectively, at ages of 50 years or less. The corresponding figures were 0.34 (0.15-0.78), 1.49 (0.66-3.37), 1.57 (0.58-4.14), 2.11 (0.50-8.34), and 2.43 (0.56-9.94), respectively, among the older subjects aged 60 years or more. OR for ≥4 symptoms (16.4 [6.96-40.0] vs 2.22 [1.001-4.90]) also indicated a higher usefulness of symptoms in suspecting undiagnosed hypothyroidism in the young group. The intermediate group of patients aged 50 to 59 years was omitted from this analysis. The American Journal of Medicine 2016 129, 1082-1092DOI: (10.1016/j.amjmed.2016.06.013) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 3 Receiver operating characteristic curves for the hypothyroidism component score as a tool for suspecting overt autoimmune hypothyroidism. Four groups are depicted (men aged <50 years, women aged <50 years, men aged ≥60 years, and women aged ≥60 years). Hosmer-Lemeshow calibration chi-square goodness-of-fit test revealed statistically significant values in the 4 groups of 0.31 versus 0.28 versus 0.10 versus 0.16. ROC = receiver operating characteristic. The American Journal of Medicine 2016 129, 1082-1092DOI: (10.1016/j.amjmed.2016.06.013) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 4 Nautilus diagram depicting the prevalence of 13 hypothyroidism-associated symptoms in young patients (aged <50 years) and older patients (aged ≥60 years). Symptoms are ordered counterclockwise according to their DOR (see “Subjects and Methods”). Asterisks depict statistically different number of symptoms between patients and healthy subjects (*P < .05, **P < .01, ***P < .001). The American Journal of Medicine 2016 129, 1082-1092DOI: (10.1016/j.amjmed.2016.06.013) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 5 Nautilus diagram depicting the prevalence of 13 hypothyroidism-associated symptoms in young patients and euthyroid controls (A) among young subjects (aged <50 years) and (B) older subjects (age ≥60 years). Symptoms are ordered counterclockwise according to the their DOR (see “Subjects and Methods”). The size of the shaded areas between the 2 lines is proportionate to DOR and reflects the usefulness of asking for symptoms when evaluating whether the subjects may be hypothyroid or not. Asterisks depict statistically different number of symptoms between patients and healthy subjects (*P < .05, **P < .01, ***P < .001). The American Journal of Medicine 2016 129, 1082-1092DOI: (10.1016/j.amjmed.2016.06.013) Copyright © 2016 Elsevier Inc. Terms and Conditions