Long-term treatment-related morbidity in differentiated thyroid cancer: a systematic review of the literature

Background: Differentiated thyroid cancer (DTC) occurs in relatively young patients and is associated with a good prognosis and long survival. The management of this disease involves thyroidectomy, radioiodine therapy, and long-term thyroid-stimulating hormone suppression therapy (THST). The long-term effects of the treatment and the interaction between subclinical hyperthyroidism and long-term hypoparathyroidism are poorly understood. This review sought to examine the available evidence. Methods: A PubMed search was carried out using the search terms “Thyroid Neoplasms” AND (“Thyroxine” OR “Hypocalcemia” OR “Thyrotropin”). Original English language articles published in the last 30 years studying the morbidity from thyroid-stimulating hormone (TSH) suppression and hypoparathyroidism following a surgery for DTC were retrieved and reviewed by 2 authors. Results: Of the 3,000 results, 66 papers including 4,517 patients were selected for the present study. Studies reported on a range of skeletal (included in 34 studies, 1,647 patients), cardiovascular (17 studies, 957 patients), psychological (10 studies, 663 patients), and other outcomes (10 studies, 1,348 patients). Nine of 26 studies on patients who underwent THST showed a reduction in bone density, and 13 of 23 studies showed an increase in bone turnover markers. Skeletal effects were more marked in postmenopausal women. There was no evidence of increased fracture risk, and only little data were available on hypoparathyroidism. Four of five studies showed an increased left ventricular mass index on echocardiography, and one study showed a higher prevalence of atrial fibrillation (AF). There was little difference in basic physiological parameters and limited literature regarding symptoms or significant events. Six studies showed associations between long-term TSH suppression and impaired quality of life. Impaired glucose metabolism and prothrombotic states were also found in DTC patients. Conclusion: There is limited literature regarding long-term DTC treatment-related morbidity, particularly regarding the effects of long-term hypocalcemia. Most studies have focused on surrogate markers and not on clinical outcomes. A large prospective study on defined clinical outcomes would help characterize the morbidity of treatment and stimulate research on tailoring treatment strategies.