Influence of COVID-19 Related Quarantine on Thyroid Function and Depression in ‎Egyptian Patients with Overt Hypothyroidism

INTRODUCTION

Currently, the corona virus disease-2019 (COVID-19) pandemic seriously threatens the health ‎of human being with increasing deaths. Unfortunately, the pandemic of COVID-19 adversely ‎affected mental and physical health of the general population [1]. High transmissibility, ‎mortality rate, diverse course, lack of approved treatment, limited tools of medical aids, ‎lockdown related restricted movement and social isolation resulted in detrimental effects on the ‎psychological health of the public [2].‎

In March 2020 the Egyptian government imposed a national lockdown to control the dramatic ‎transmission of COVID-19 and increased death rate. Commonly, restriction measures of the ‎lockdown are associated with an unpleasant sensation, and multiple adverse psychological ‎effects. Stress resulted from fear of infection, death, limitations of social activities, work and ‎restricted movement adversely affected the psychological health of the general population [3-‎‎5]. The endocrine system; particularly adrenal and thyroid provide physiological‎‎‎ changes to cope ‎with the stressful situations [6, 7]. Hypothyroidism is considered the most prevalent endocrine ‎disorder affecting more than 10% of humans globally [8]‎,

A peculiar interrelationship between depression and thyroid dysfunction has been identified. ‎Depression may develop in more than half of the patients with hypothyroidism. Moreover, ‎disrupted thyroid function is usually encountered in patients with depression [9]. Commonly, ‎thyroid disorders particularly autoimmune thyroiditis with elevated thyroid autoantibodies ‎coincide with depression. The risk of depression is increased more than 6 times in patients with ‎thyroid disorders than others  [10 - 13].

We aimed to detect the prevalence and grade of depression as well as alterations of thyroid ‎function among Egyptian patients with pre-existing hypothyroidism throughout the lockdown ‎period of COVID-19.‎

PATIENTS AND METHODS

An observational longitudinal follow-up study was conducted at the endocrine outpatient clinic of Mansoura University Hospital, Egypt during the period from March 2020 to August 2020. This study included 160 Egyptian patients with pre-existing hypothyroidism, aged 18-70 years, who attended their scheduled follow-up visits during the lockdown period of COVID-19. Primary hypothyroidism and Hashimoto’s thyroiditis were the main causes of hypothyroidism of the participants. Participants with proper adherence to levothyroxine replacement therapy and proper compensation were included. They were subjected to a comprehensive education for the proper dosage and time of levothyroxine administration on empty stomach; at least one hour before breakfast. During the Holy Ramadan (April/May 2020) the patients were instructed to administer levothyroxine one hour before Suhor (pre-dawn meal).  Recorded characteristics of the patients in December 2019 were considered as baseline data at the pre-quarantine visit. We excluded patients out of age limits, dropped-out patients, reluctant patients for thyroid function monitoring, poor adherence, prior history of thyroid surgery or radioactive iodine ablation therapy, pregnant, patients with previous or current; proven or suspected COVID-19 exposure and patients with prior depression symptoms as shown in figure [1]. Moreover, any patient who acquired COVID-19 infection during the study was excluded. We excluded patients with acute or chronic co-morbidities such as cardiac, renal, hepatic, pulmonary diseases, systemic infections, cancer, other endocrine disorders, other autoimmune diseases or administrating medications that my affect the study outcomes such as glucocorticoid, dopamine agonists, somatostatin analogues, amiodarone, metformin, lithium, tricyclic antidepressants, selective serotonin reuptake inhibitors, antiepileptic drugs, interferon-alpha, cytotoxic, antineoplastic, biological therapy, immune therapy or iodine-based contrast exposure.

Follow-up visits were scheduled at the beginning of COVID-19 lockdown (March 2020), after three months (June 2020), and after five months (August 2020). These visits were electronically arranged to avoid overcrowding as part of the national measures to minimize the risk of infection transmission. All cases were subjected to a detailed history taking, physical examination with anthropometric measures, and laboratory testing of thyroid stimulating hormone (TSH). In every follow-up visit, about 3 ml of venous blood was withdrawn for assessment of TSH using immune-luminescent method (Abbott i2000, Wiesbaden, Germany) with intra-assay coefficient of variation (CV) of 3.10% and an inter-assay CV of 3.50%. TSH for normal population range is 0.4–4.2 mIU/l.  Ultrasensitive TSH assessment represent a corner stone for evaluation of thyroid disorders. TSH is evident to predict slight disruption of thyroid function. It is more sensitive than serum based thyroid hormone in anticipation of thyroid dysfunction. [14, 15]. Unlike ultrasensitive TSH, total and free thyroxin levels were not available for the pre-quarantine visit; December 2019 for some participants, therefore were ruled out from statistical work. Following the onset of the quarantine, the prevalence and grade of depression was evaluated for all participants based on the Patient Health Questionnaire-9 (PHQ-9) scale by the psychiatrist co-investigator. It is a 9-item depression module quoted from the full PHQ. The questionnaire includes 9 questions, and the answer of each question ranges between 0 and 3. Thus, zero is the lower limit while 27 is the major limit for PHQ-9. Patients were diagnosed with minimal or no depression on having 0 – 4 points, mild depression 5 – 9 points, moderate depression 10 – 14 points, and higher scores for moderately severe and severe depression [16].

Statistical analysis

IBM’s SPSS v.23 was used for statistical analysis of the collected data. The Shapiro-Wilk test was used to check the normality of the data distribution. P-value < 0.05 was considered statistically significant. Quantitative variables were expressed as mean and standard deviation, median, inter-quartile range and minimum to maximum range while categorical variables were expressed as frequency and percentage. Values of the Follow-up visits were compared to their corresponding baseline values using paired-t test and Wilcoxon matched pairs signed ranks test. Pearson’s and Spearman’s correlation coefficient tests were applied.

RESULTS

This study included 160 patients with a mean age 42.34 year and female proportion 70.6%.The mean duration of hypothyroidism was 26.06 ± 10.095 months with a mean daily levothyroxine dose 89.06 ± 24.713 mcg. Regarding residence; 103(64.4%) cases were from rural areas and 57(35.6%) were urban residents as shown in table (1).

Table (2) shows the progress of TSH level in the sequential follow-up visits during COVID-19 lockdown. TSH showed slight changes, but with statistically significant differences in June and August 2020 compared to December 2019 with mean values of 2.54 ± 1.313 and 2.73 ± 1.425 mIU/L versus 2.38 ± 1.216, respectively (p < 0.001). However, non-significant difference was observed in March 2020; the onset of the lockdown (p = 0.287). (See table 2)

Table (3) shows the prevalence and grade of depression among the participants during the subsequent follow-up visits. With use of PHQ-9 scale, the prevalence of mild depression increased progressively from 3.8% (June 2020) to 14.4% in (August 2020)

TSH was positively correlated with PHQ-9 score at June and August 2020 (r = 0.699 and 0.940, respectively; p < 0.001). Also, a significant positive correlation was noticed between TSH and grade of depression in June and August 2020 (r = 0.441 and 0.781, respectively; p<0.001) as shown in table (4).

‎Table (1): Demographic baseline characteristics of the participants.