Predictors of Long-Term Fatigue in Patients with Differentiated Thyroid Cancer: A Nationwide Prospective Study

Fatigue is a frequent and distressing symptom in patients with differentiated thyroid cancer (DTC) and may persist for years posttreatment, negatively impacting the quality of life. This study aimed to investigate predictors of long-term fatigue in DTC patients to identify patients who may benefit from early intervention to prevent fatigue and to examine whether thyrotropin (TSH) suppression is associated with fatigue.

This nationwide prospective study included 351 DTC patients treated with thyroidectomy and planned for radioiodine treatment during 2012-2017 in Sweden. Patients completed the Short Form-36 Health Survey (SF-36) and a study-specific questionnaire at inclusion and after 1, 3, and 5 years. Fatigue was assessed using the SF-36 vitality subscale. TSH values were retrieved from medical records. Fatigue 5 years after DTC treatment was predicted using linear regression with the following variables measured at 1 year: age, sex, education, number of comorbidities, body mass index (BMI), smoking, DTC risk, bodily pain, mental health, fatigue, sleep disturbance, change in view of life after diagnosis, and fear of cancer recurrence. The association between TSH and fatigue was studied using linear mixed models.

In univariable linear regression analyses, significant early predictors of 5-year fatigue were a higher number of comorbidities, higher BMI, more bodily pain, worse mental health, more early fatigue, more sleep disturbance, a negative view of life following DTC diagnosis, and greater fear of cancer recurrence. Fatigue and poor mental health 1 year after DTC treatment were highly correlated (r = 0.79) and therefore analyzed in separate multivariable models. In multivariable regression analyses, fatigue at year one remained a significant predictor of fatigue at year five (β = 0.66, p < 0.001). Worse mental health also remained a significant predictor of fatigue at year five (β = -0.41, p < 0.001). TSH was not a significant predictor of fatigue ( p = 0.161).

This study found several predictors of long-term fatigue in DTC patients. One year after treatment, fatigue and poor mental health are particularly important predictors of long-term fatigue. TSH suppression does not explain fatigue in DTC patients. Identifying early fatigue and mental health issues in the clinic posttreatment is important, as patients may benefit from intervention to prevent long-term fatigue.