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We aimed to investigate the subjective well-being in patients with differentiated thyroid cancer after hormone withdrawal. Since this might be confounded by psycho-oncological processes unrelated to hypothyroidism we intended to minimize such factors by only including patients with a history of uneventful follow-up examinations for several years. We investigated 67 patients applying the General Health Questionnaire (GHQ-12) at 3 time points t1, t2, and t3. The time point t2 represented an intensified follow-up examination 5 years after thyroidectomy, which was performed either on hormone withdrawal (49 patients) or using rh-TSH (18 patients). The time points t1 and t3 took place during follow-up examinations 6 months before and after t2 in a euthyroid state. Additionally, we assessed the impact of age, gender, family status, and education on the GHQ-12 score at all 3 time points. Within the hormone withdrawal group the analyses demonstrated a significant difference between t1 and t2 as well as t3 and t2. Additionally, there was a significant negative correlation of age with GHQ-12 sum scores at t2, but not at t1 or t3. Subgroup analyses at t2 indicated that the subjective well-being in younger patients was more impaired compared to elderly patients. The between-group analysis showed no significant differences. However, concerning the age effect there was a significant difference between the subgroup of young hypothyroid patients and the total rh-TSH group at t2. We demonstrated preliminary evidence for an influence of age on the subjective well-being in hypothyroidism suggesting that younger subjects are subjectively more impaired by hypothyroidism than elderly ones.