Anxiety and depression status prior to radioactive iodine therapy among differentiated thyroid cancer patients during the COVID‑19 epidemic

Introduction

The poor psychological state of cancer patients will affect the quality of treatment, and even be related to the poor prognosis(1–4). At present, many studies on the psychological health status of cancer survivors have focused on who receives radiotherapy and chemotherapy(5–8). Anxiety and depression are the most common psychological problems in the treatment of cancer patients, which are related to the majority of medical diseases and physical symptoms. Moreover, anxiety and depression probably increase the risk of other diseases in cancer patients, such as acute radiation toxicities(9). Interestingly, studies have shown that anxiety and depression have more prevalent in head and neck tumor patients than in other tumors, notably, and also have a higher incidence before radiotherapy(5, 10).

In recent years, the incidence rate of thyroid cancer has increased worldwide(11, 12). Thyroid cancer is one of the most common head and neck cancers and one of the major endocrine cancers. Although the prognosis of thyroid cancer patients is generally good and the 10-year survival rate is over 90%, life-long follow-up and medication probably be required(13). Previous studies have indicated that anxiety is a common problem among thyroid cancer survivors(14). In addition, a study in North America has shown that the diagnosis and treatment of thyroid cancer can lead to a decline in quality of life(15). It has also been reported that the diagnosis of thyroid cancer could cause psychological distress in patients(16). These psychosocial studies suggested that there is a substantial unmet need for psychosocial support in patients with thyroid cancer. Fortunately, psychological nursing intervention can effectively alleviate the psychological pain of thyroid cancer patients and improve their quality of life(17).

Post-surgical radioactive iodine (RAI) therapy is one crucial and effective treatment for reducing the risk of recurrence and even the mortality of differentiated thyroid cancer (DTC) patients(18–20). Notably, DTC patients with RAI therapy probably experience physical symptoms (such as loss of appetite, fatigue, nausea, and neck pain)(21), in addition to might occurring various emotional symptoms in response (such as anxiety, depression, and uncertainty)(16). Moreover, there are other adverse effects of RAI therapy, such as salivary gland dysfunction and inducing secondary primary malignancies(22). For woman patients with DTC, RAI therapy possibly have an impact on ovarian function and fertility(23). Therefore, RAI therapy will inevitably increase the psychological burden of DTC patients. However, a few studies have focused on the relationship between psychological health conditions and RAI therapy. This may be related to the fact that RAI therapy is a specific treatment for thyroid cancer, rather than a common therapy for most cancers. Although previous a study has demonstrated radiation exposure is one significant influencing factor for thyroid cancer patients who had significant distress(16), only 9 patients was suffered the radiation exposure in study. Too few samples limited the research significance of radiation exposure in the psychosocial distress of thyroid cancer patients. Lee et al. has demonstrated that DTC patients showed insecurity and depression after RAI treatment(24). Additionally, many studies have shown that patients with tumors face more serious challenges of COVID-19 infection and psychological burdens than the general population(25–27). Numerous literatures have reported the psychological health status of different diverse cancer patients during the COVID-19 period(25–27). For example, the incidence of psychological symptoms in Chinese patients with thyroid cancer was remarkably higher than that before the COVID-19 epidemic(32).

However, there is a lack of research on anxiety and depression related factors in thyroid cancer patients before radioactive iodine therapy during the COVID-19 epidemic in China. We first aim to describe the psychological status of DTC patients before RAI therapy and then explore the influencing factors of anxiety and depression to obtain useful information for the development of such psychological nursing interventions. Therefore, nuclear medicine physicians can screen out the high-risk patients with poor psychological states through early intervention before RAI therapy, so as to timely correct the unfavorable psychological status of DTC patients and improve quality of life.

Methods

Study Participants

This is a cross-sectional study performed via an online survey run from March to June, 2021. In the nuclear medicine department of Shanghai Tenth People’s Hospital, an online anonymous questionnaire survey was conducted on hospitalized patients diagnosed with DTC according to postoperative pathological reports. Patients completed questionnaires before RAI therapy. We excluded patients with a history of psychological disorders or who cannot guarantee the authenticity of the information.

In online survey, the Generalized Anxiety Disorder Questionnaire (GAD-7)(33) and Patient Health Questionnaire (PHQ-9)(34) were used to assess anxiety and depression symptoms. Meanwhile, the patients’ basic information including age, gender, employment status, marital status, education level, alcohol drinking, smoking, the times of RAI therapy, and history of psychological disorder were collected.

Mental Health Assessment

The GAD-7, a seven-item anxiety scale reported by Spitzer et al, with a score of 0 to 3 for each item, was used to measure anxiety symptoms in patients. GAD-7 is one of the most concise and clinically proven methods to evaluate the symptoms of generalized anxiety disorder. The PHQ-9 scale, a nine-item questionnaire in each item scored 0–3, with good reliability and validity, was performed to reflect the severity of depression symptoms. The total scores of GAD-7 and PHQ-9 were categorized as follows: GAD-7, no anxiety (0–4), mild anxiety (5–9), moderate anxiety (10–14), and severe anxiety (15–21); and PHQ-9, no depression (0–4), mild depression (5–9), moderate depression (10–14), and severe depression (15–27).

Statistical Analysis

All data analysis was performed using SPSS version 22.0 (SPSS Inc.,Chicago, IL, USA). The internal consistency of PHQ-9 and GAD-7 scales was tested by Cronbach a coefficient, and the validity of the scales was analyzed by Barlett sphere test. For count data, frequencies and percentages were used, and the chi-square test was used to compare the data for different categorical variables. Univariate and multivariable logistic regression analysis with odd ratio (OR) and confidence interval (CI) were carried out to evaluate the association between psychological status and potential predictors. P-value < 0.05 was considered statistically significant.

Results

Basic Demographic Characteristics and Psychological Status

After excluding 8 patients who could not guarantee the effectiveness of information, a total of 112 DTC patients who completed the questionnaire were enrolled, and detail information was shown in Table 1. In all, the majority of patients were female (72.32%), employed (63.39%), married (80.36%), college degree or higher (52.68%), never smoked (87.50%), no drank (82.14%), and had no experience of radioactive iodine therapy (77.68%). Detailed basic demographic characteristics are shown in Table 1.

The questionnaire results showed that the mean GAD-7 scale score was 4.25 (0–21, IQR 0–7) and the mean PHQ-9 scale score was 4.19 (0–27, IQR 0–7). There were 46 patients (41.07%) reported anxiety symptoms, including 28 (25.00%) mild, 9 (8.04%) moderate, and 9 (8.04%) severe patients. The number of patients with depression symptoms was 38 (33.93%), including 24 (21.43%) mild, 8 (7.14%) moderate, and 6 (5.35%) severe patients.

Reliability and Validity Test of Scale

The Cronbach’s alpha coefficient for the GAD-7 was 0.927 and it still obtained good values (0.913–0.932) even if we delete an item (Table 2), indicating excellent internal consistency. Similarly, the Cronbach’s alpha coefficient of the PHQ-9 scale was 0.878, and the coefficient values were greater than 0.85 after deleting an item (Table 3). Also, the validity test showed that the KMO of GAD-7 and PHQ-9 was all above 0.85, and the Bartlett sphericity test was all P < 0.001 (Table 4), demonstrating that GAD-7 and PHQ-9 have excellent validity and reliability in this study.

Influencing factors related to anxiety and depression

Overall, there were similar associations of influencing factors with depression and with anxiety in DTC patients as shown in Tables 5. The chi-square test showed that among patients, gender and the times of RAI therapy were associated with anxiety and depression (Table 5, P < 0.05). The prevalence of anxiety among female patients was significantly higher than in males. Patients who had ever undergone RAI therapy were more likely to have anxiety symptoms than those who were the first time prepared for RAI therapy. Notably, being female and ever suffered RAI therapy patients also were associated with depression (Table 5, P < 0.05). The prevalence of anxiety and depression was not significantly different among patients of different ages, educational levels, marital statuses, and employment statuses (all P > 0.05).

In the univariate logistic regression analysis (Table 6), compared with male patients, being female was still an independent factor associated with anxiety (OR, 3.184; 95% CI, 1.234–8.216; P = 0.017) and depression (OR, 3.575; 95% CI, 1.245–10.265; P = 0.018), indicating female patients had a higher risk of anxiety and depression symptoms. Patients who had ever undergone RAI therapy were a significant risk factors of developing anxiety (OR, 2.710; 95% CI, 2.710; P = 0.032) and depression (OR, 2.687; 95% CI, 1.080–6.686; P = 0.034) symptoms. Notably, in multivariate analysis, only being female was significant associated with anxiety (OR, 3.625; 95% CI, 1.239–10.606; P = 0.019) and depression (OR, 4.348; 95% CI, 1.332–14.194; P = 0.015) in these patients.

Discussion

The study investigated the psychological status including anxiety and depression symptoms among 112 DTC patients before RAI therapy during the period of the COVID-19 epidemic. Overall, 41.08% had symptoms of anxiety and 33.93% had symptoms of depression. We also explored the influencing factors of demographic and clinical characteristics on psychological health status, showing that being female, having ever suffered RAI therapy were potential factors associated with poorer psychological health.

Cancer patients not only have physical symptoms due to the disease itself and treatment process, but also suffer from psychological distress caused by economic burden and social factors(34). Thus, cancer patients probable were in varying degree negative psychological states, such as anxiety and depression(39–42). Psychological symptoms including anxiety and depression could cause the declined of treatment adherence in cancer patients. Furthermore, anxiety and depression in cancer patients are associated with poorer quality of life(43, 44) and unfavorable prognosis(3, 45). Radiotherapy, chemotherapy and other treatments can further increase the psychological burden of cancer patients(46–48). Therefore, the psychological health of cancer patients before and during the treatment process must be valued.

Pre-COVID-19 studies have prompted that anxiety and depression are common in patients with thyroid cancer(14, 15, 17). During the COVID-19 period, the psychological burden of cancer patients further increased(27, 28). Data from a survey of Chinese thyroid cancer patients showed that during the COVID-19 crisis, thyroid cancer patients had higher levels of psychological symptoms, such as anxiety and depression, than Chinese cancer patients before the COVID-19 epidemic(32). This finding demonstrated that COVID-19 epidemic has significantly negative impact on the psychological health in thyroid cancer survivors. Currently, RAI therapy is one of the commonly used treatments for patients with high risk of thyroid cancer and can improve survival rate in advanced or metastatic patients(32), but whether some patients need RAI therapy and the dose of RAI are controversial(22). In addition, some side effects caused by radiation exposure caused due to RAI therapy cannot be ignored, such as radiation salivary gland damage(21). As a result, thyroid cancer patients who are preparing for RAI treatment may experience higher psychological distress due to the unknown course of treatment and the fear of adverse effects for radiation exposure. Although previous a few studies have investigated the association between mental health and RAI therapy in thyroid cancer patients, the results were contradictory. Wu, HX, etc(49) and Yoo, SH, etc(50) suggested that psychological and behavioral interventions for thyroid patients receiving RAI may improve their psychological status, while Seyedshahab, Banihashem, etc(51) thought that psychological interventions might be limited. After a comprehensive literature search, there were few studies on the psychological state of DTC patients before RAI therapy, especially during COVID-19 pandemic.

In the present study, our results clearly showed a higher incidence of these psychological symptoms including anxiety and depression, suggesting that DTC patients prior to RAI therapy may be more prone to psychological symptoms during the COVID-19 epidemic. We believed that this phenomenon is not only related to the increased psychological burden of DTC patients due to RAI therapy itself, but also to the fact that patients stop thyroid hormone supplementation before RAI therapy, and patients in the status of hypothyroidism might lead to psychological symptoms. However, some studies suggested that there is no significant relationship between hypothyroidism and depression or anxiety(52, 53). Therefore, anxiety and depression in these patients are more likely to be related to fear of RAI therapy.

The result in this study showed that gender was an independent factor associated with anxiety and depression, which was consistent with previous studies that female patients with DTC bear more psychological burden(54). Previous studies have shown that being female is an important risk factor for the decline of quality of life in the diagnosis and treatment of thyroid cancer(15). The thyroid is an endocrine organ, and both progesterone and estrogen may be involved in the occurrence and development of thyroid cancer(55, 56). Therefore, the levels of estrogen and progesterone may lead to female thyroid patients more prone to poor psychological state. In addition, many previous publications have indicated that female cancer patients seem to be more vulnerable(57). Thence, it may be universal that female cancer patients are more likely to develop psychological problems.

Interestingly, we found that ever-experienced RAI therapy was an independent factor of anxiety and depression in DTC patients, which was rarely reported in previous studies. Generally, multiple times RAI therapies mean higher risk in DTC patients with tumor progression, recurrence or distant metastasis, poor treatment effect, or even refractory to RAI therapy(18). Importantly, previous research suggested that anxiety in thyroid cancer patients may depend not only on the real threat of thyroid cancer itself, but also on subjective assumptions about the threat of cancer(14). We proposed that anxiety and depression in these patients are associated with fear of thyroid cancer progression, metastasis, and recurrence, leading to lower confidence in disease recovery, resulting in greater psychological pain. Moreover, financial burden, self-cognitive dissonance, and lack of social support may also be important factors that significantly negatively modulate the psychological state of patients receiving multiple times RAI therapy. Together, we found independent factors associated with symptoms of anxiety and depression, so that patients at higher risk for psychological distress could be identified earlier and more accurately in the future. It is necessary to screen and identify DTC patients with higher levels of mental health problems in the COVIN-19 epidemic. During the COVIN-19 crisis, in addition to current public health interventions, psychological nursing and intervention should be implemented to support people with thyroid cancer in coping with depression and anxiety.

This study has some limitations. First of all, although GAD-7 scale and PHQ-9 scale are common approaches to evaluate patients' anxiety and depression, these two scales have certain limitations, and it is also limited to evaluate anxiety and depression with only the single scale. The patient’s psychological symptoms and their severity can be more reliably reflected if multiple recognized and valid psychological scales are used simultaneously. Secondly, the long-term psychological health and associated influencing factors of DTC patients after RAI therapy should be further investigated in followed up studies. Finally, since this study was a single-institution study with a small patient sample size, a larger sample size and multi-center study may be required for a more representative prospective study.

Declarations

Acknowledgement

Ethics approval

The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital (ethics No.: shsy - IEC - ki - 4.0/16-18/01).

Consent to participate

All individual participants consented to participate in the study.

Consent for publication

All individual participants consented to having their data published.

Conflict of interest

All the authors state that they have no conflicts of interest.

Authors' contributions

All authors contributed to the study conception and design. Tingting Qiao, Dingwei Gao, Yun Shen, and Jiayue Ma conceived the study and participated in research design and data interpretation; Tingting Qiao and Dingwei Gao contributed significantly to analysis and manuscript preparation; Tingting Qiao and Junyu Tong performed the data analyses; Tingting Qiao and Dingwei Gao prepared figures and tables; and Tingting Qiao wrote the first draft of manuscript; Dan Li and Zhongwei Lv helped perform the analysis with constructive discussions; Dan Li and Zhongwei Lv helped revise the article. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This research was funded by National Natural Science Foundation of China (Grant No. 82071964), Shanghai Shenkang Three-year Action Project (Grant No. SHDC2020CR2054B), Key discipline construction project of the three-year action plan of Shanghai public health system (Grant No.GWV-10.1-XK9), Shanghai Leading Talent program sponsored by Shanghai Human Resources and Social Security Bureau (Grant No.2019).

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, LD, upon reasonable request.

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