This prospective longitudinal study investigated sleep quality before and after thyroid surgery among patients diagnosed with PTC, and explored the factors associated with persistent poor sleep quality in the target population. To the best of our knowledge, this is the first report to demonstrate the immediate and long-term impact of PTC and thyroid surgery on sleep quality among patients with PTC. Our results indicate that a considerable number of patients with PTC suffer from sleep disturbance before and after thyroid surgery, and that older age and higher preoperative PSQI scores are associated with persistent poor sleep quality.
Patients with thyroid cancer often complain of sleep disturbance after surgery. In fact, a cross-sectional study reported that poor sleep quality was more common among patients with thyroid cancer than in patients with benign thyroid disease, even after thyroid surgery 9. However, because of its cross-sectional design, the previous study could not evaluate the impact of surgery on sleep quality. A large-scale longitudinal study which investigated the natural course of insomnia among patients with various types of cancer over an 18-month period reported that the incidence of insomnia peaked before surgery and dwindled after surgery over the subsequent 18 months 23. Insomnia was observed in common among patients with many types of cancers including breast, prostate, gynecological, head and neck, and upper gastrointestinal tract cancers. The study showed that while the incidence of insomnia decreased over time after surgery, the incidence was still higher than that of the ‘non-cancer’ population. Likewise, in the current study, the mean PSQI score was highest before surgery and remained above 7 in the 10 months following surgery, although it tended to decrease after surgery.
In the current study, we found that sleep quality was significantly worse before thyroid surgery compared to after surgery. There are several factors which may be involved in the association between sleep disturbance and thyroid cancer. First, sleep disturbance itself may increase the risk of cancer. The prevalence of sleep disturbance is at least two times higher in patients with cancer than in the general population 5. Our results revealed the prevalence of poor sleep quality was much higher among patients with PTC (PSQI > 5, 89.1%; PSQI > 7,76.1%) than the general population (15.9–41.0%) 24,25. Another explanation for the high prevalence of sleep disturbance among patients with thyroid cancer is that sleep deprivation may cause thyroid stimulating hormone elevation 26 which may be associated with a greater likelihood of thyroid cancer 26–30. However, in the current study, preoperative serum thyroid stimulating hormone (TSH) levels were not different between good and poor sleepers. Impaired immune function caused by sleep disturbance has been proposed as another possible risk factor for thyroid cancer 31. Disrupted endocrine and physiologic circadian rhythms may lead to impaired circadian rhythm at the level of immune cells 32. A recent study demonstrated that patients with well-differentiated thyroid cancer exhibit altered expression of clock genes in comparison with healthy controls or subjects with benign thyroid nodules 33. Another study demonstrated alterations of clock genes, overexpression of BMAL1, and downregulation of CRY2, in patients with follicular thyroid carcinoma and PTC 34.
Fear is another important potential cause of sleep disturbance in patients with thyroid cancer. There are various relevant types of fear such as fear of cancer diagnosis and fear of general anesthesia or surgery, as well as fear of postsurgical treatment including life-long medication, surgical complications, or recurrence. A recent study reported that anxiety in patients with thyroid cancer significantly improved after surgery 35. PSQI scores decreased after surgery in that study. The authors believed that relief from fear of surgery or surgical complications was the key factor in the improvement in sleep quality after surgery. They suggested that because TSH levels are controlled after surgery with medication if needed, sleep disturbance may be caused by anxiety or fear, rather than the hormonal effects of the condition.
We hypothesized that when stratified by surgical type, sleep quality before and after surgery would be worse in the total thyroidectomy group compared to the lobectomy group. There are several reasons that patients undergoing total thyroidectomy may have more anxiety than those undergoing lobectomy prior to surgery. Total thyroidectomy is indicated for tumors larger than 4 cm, tumors with extensive lymph node involvement or distant metastasis, or for bilateral tumors, all of which are associated with unfavorable prognosis. In addition, there are complications which occur only after total thyroidectomy such as bilateral recurrent laryngeal nerve palsy, hypoparathyroidism, and life-long thyroid hormone replacement. During the preoperative period, concerns about poor prognosis and postoperative complications may aggravate the psychological fear of surgery among patients scheduled for total thyroidectomy. Contrary to our expectation, PSQI scores of total thyroidectomy group and lobectomy group had comparable during the pre- and postoperative period during the 10 months follow-up. This can be explained by the assumption that the number of the patients in the both groups were too small to show the difference and the concerns for thyroid surgery were alleviated after surgery.
The PSQI scores of the PTC patients 10 months after surgery remained higher than that of the normal population, which was reported to be 5.6 by a Korea Community Health Survey 25. This suggests that anxiety among patients with PTC may continue after surgery. On the other hand, the PSQI scores decreased to 5.4, which is comparable to that of the general population, by the PO 5-year timepoint 25. Furthermore, the PO 5-year PSQI scores indicate that the long-term sleep quality of the lobectomy group was significantly improved compared to the total thyroidectomy group. This suggests that sleep quality may improve as concern and anxiety is gradually alleviated over time, and the effect size may depend on the surgical extent.
Reports show that sleep disturbance may be associated with the initiation of radiotherapy or chemotherapy, and a high degree of sleep disturbance can be maintained over the treatment period with adjuvant therapies 9,36−38. Radioactive iodine treatment is the most common β radiation nuclear medicine therapy. A study reported that mean PSQI scores increased from 7.6 to 8.8 after radioactive iodine treatment 9. In the current study, among the six patients treated with total thyroidectomy followed by radioactive iodine therapy, the mean preoperative PSQI score was 9.8. At PO 1 month, the mean PSQI score reduced to 8.9, and further decreased to 7.8 at PO 4 months, before increasing again to 8.9 at PO 10 months. Our repeated measures of PSQI score data indicated that radioactive iodine treatment showed no harmful effect on sleep quality, although diet restriction and conditioning with severe hypothyroidism may have an unfavorable impact on sleep 39,40.
This study has several limitations. First, we did not evaluate mood disorders such as depression and anxiety, which are important factors associated with sleep disturbance among cancer patients (9). Although no patients were on medication for mood disorders during the study period, in-depth interview evaluations of mild mood disorders which do not require medication were not conducted. Second, we did not evaluate the sleep quality of study participants at regular intervals between PO 10 months and 5 years. Therefore, although we showed long-term sleep quality outcomes around 5 years after surgery, we were unable to ascertain the specific point at which the sleep quality of patients with PTC became comparable to that of the general population. Another limitation of this study is the lack of a control group. Comparing sleep quality of patients with PTC with that of patients with different cancers or patients without cancer may have further elucidated the impact of PTC on sleep disturbance in the target population. Last, we could not determine whether PTC had a causative role in sleep disturbance or sleep disturbance had a causative role in PTC occurrence. In this study, preoperative questionnaires were administered when cytologic tests result confirmed PTC and surgery was planned. Therefore, the results reflect only the patient’s sleep quality during a period when they were experiencing fear while waiting for surgery. The use of a measurement tool that reflects sleep quality before recognition of the thyroid nodule or diagnosis of thyroid cancer may be required to determine the causative role of sleep disturbance on thyroid cancer, or vice-versa.