Content of this journal is licensed under a Abstract
Objective:
This study aimed to investigate the psychosocial impact of the pandemic in pediatric patients with congenital adrenal hyperplasia and their families and whether congenital adrenal hyperplasia imposes an additional burden compared to other endocrine disorders.
Materials and Methods:
Patients with congenital adrenal hyperplasia (n = 38) and congenital hypothyroidism (n = 41) and their families were enrolled in the prospective longitudinal survey study. Questionnaires that were completed remotely in June 2020 and in July 2021 included Depression Anxiety Stress Scale short form, The State-Trait Anxiety Inventory for Children, and purpose-built daily routine, parent, and child COVID information scores, factors affecting drug usage, and parents’ thoughts about the pandemic. At the end of 1 year, Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children were repeated in the congenital adrenal hyperplasia group and they were questioned about the incidence and severity of coronavirus infection.
Results:
Median Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children scores were similar between the congenital adrenal hyperplasia and congenital hypothyroidism groups. In the congenital adrenal hyperplasia group, median purpose-built daily routine was higher in those who had a State-Trait Anxiety Inventory for Children-State score above the threshold (P = .048), also Depression Anxiety Stress Scale short form-Depression, Depression Anxiety Stress Scale short form-Anxiety, Depression Anxiety Stress Scale short form-Stress, Parent COVID Information Score were higher among parents who followed news/data because of chronic diseases/medications of the child (P = .010, P = .034, P = .044, P = .045, respectively), and State-Trait Anxiety Inventory for Children-State was higher among parents who believed “having chronic diseases” and “using medications” increase the risk of COVID-19 infection (P = .011, P = .016, respectively). In the second survey, State-Trait Anxiety Inventory for Children-State, Depression Anxiety Stress Scale short form-Anxiety, and Depression Anxiety Stress Scale short form-Stress decreased significantly (P < .01, P = .009, P = .008, respectively). Three patients with congenital adrenal hyperplasia who reported positive nasopharyngeal swab tests revealed mild symptoms.
Conclusion
: The pandemic has negative consequences on the mental well-being of individuals with chronic diseases, albeit from different causes.
Keywords: COVID-19, congenital adrenal hyperplasia, hypothyroidism, children, anxiety, stress, depression
What is already known on this topic?
COVID-19 is a global health emergency leading to increased stress, anxiety, and depression levels. Patients with pre-existing medical conditions seem to have been more vulnerable.
What this study adds on this topic?
The pandemic has negative consequences on the mental well-being of individuals with chronic diseases, albeit from different causes.
Introduction
COVID-19 is a global health emergency with high mortality and morbidity rates. By the time of the declaration of the pandemic in March 2020, social isolation measures to prevent rapid spreading led to deterioration in social life, economics, and routine practices. Since then, many studies demonstrated an association between pandemic and increased stress, anxiety, and depression levels mostly due to the social isolation measures.1-7
Children with chronic diseases are a special group with already increased depression and anxiety levels and reduced quality of life due to the need for hospitalizations and medical care, decrease in social interactions, and limitation in physical activity.8-12 Recent studies demonstrated that patients with pre-existing medical conditions seem to have been more vulnerable to the pandemic.13-15
Congenital adrenal hyperplasia (CAH) is an endocrine disorder characterized by impaired cortisol synthesis with a worldwide incidence ranging from 1 : 14 000 to 1 : 18 000 live births.16 The incidence of classical 21-hydroxylase and 11β-hydroxylase in Turkey is 1 : 15 000 and 1 : 60000, respectively.17 Need for life-long steroid replacement therapy, risk of adrenal crisis, and hyperandrogenism result in psychiatric comorbidities, impaired cognitive function, and reduced quality of life.18-20 Also, a longitudinal survey of adult patients with adrenal insufficiency (AI), carried out to determine the impact of the pandemic, reported similar quality of life compared to pre-pandemic levels, however, stated that younger age, lower quality of life before the pandemic, and difficulties with AI management during the pandemic were associated with higher levels of anxiety and stress,14 addressing the importance of social support. Another report of adult patients with AI stated the need for glucocorticoid uptitrations due to the pandemic-related stress.21
Impairment of the immune system in the case of altered circadian rhythm of glucocorticoids22 has raised the question of whether people with AI are at higher risk for COVID-19 infection. Recent studies revealed the same incidence of COVID-19 and disease severity among adult patients with AI compared to controls or the population.14,21,23
As far as we know, there is no study investigating the impact of the pandemic on children with AI. In this study, we aimed to investigate the impact of the pandemic on the psychological characteristics of pediatric CAH patients and their families. As it is already known that patients with chronic diseases have been more vulnerable to the pandemic, we also aimed to investigate whether CAH causes an additional burden of mental illnesses compared to chronic and frequent endocrine disorder, namely congenital hypothyroidism (CH). Finally, we aimed to investigate COVID-19 prevalence and disease severity among CAH patients.
MATERIALS AND Methods
Patients with CAH and CH and their families were enrolled in a prospective longitudinal survey study at the outpatient clinic of a tertiary center. The study protocol was approved by Hacettepe University Faculty of Medicine Ethics Committee (GO20/625 2020/12-70).
Patients
All CAH (n = 55) and CH (n = 75) patients between 6 and 18 years of age followed at our clinic were evaluated. After excluding children with other autoimmune diseases, developmental disorders, and those who did not have an outpatient visit in the last 6 months before restrictions, the study population consisted of 50 children with CAH and 65 with CH. We contacted 115 families by phone call, and 12 patients with CAH and 21 with CH were excluded due to unavailability or unwilling to consent. Following the family’s consent to participate in the study by email, the first questionnaires were sent to 38 patients with CAH and 41 with CH via Google® forms in June 2020. In the CAH group, 3/38 patients had 11-hydroxylase and 35/38 had 21-hydroxylase deficiency (5/35 simple virilizing, 30/35 salt wasting).
The patients with CAH were classified into good- and poor-controlled according to their 6-monthly visits, 18 months prior to the pandemic. In each visit, we conducted assessments of growth velocity, weight, blood pressure, physical examinations, and obtained androgen levels (17-hydroxyprogesterone and androstenedione) in order to assess glucocorticoid dose.16 Visits were labeled as “good” if there was no need for glucocorticoid dose adjustments and as “poor” otherwise. After that, the patients were labeled as poorly controlled if ≥2 out of 3 visits were poor and as good-controlled otherwise. Congenital hypothyroidism was due to either dyshormonogenesis or dysgenesis. Puberty was staged according to Tanner24 based on the last outpatient visit before restrictions.
Survey
The web-based survey is composed of 3 main sections. The first section was prepared by the researchers and consisted of the sociodemographic characteristics including age, gender of the patient, residence, availability of garden/park for leisurely activities, and socioeconomic status of the parents. Socioeconomic data were obtained using The Hollingshead–Redlich scale. This scale determines the socioeconomic-sociocultural level of the family, and it is based on the educational and occupational status of the parents.25 There is no Turkish adaptation of the Hollingshead–Redlich scale. During the statistical analysis, the scale was reduced to 3 levels due to the limited number of cases.
The second section was also prepared by the researchers. To evaluate the severity of the changes in daily routines, as well as the need for information about COVID-19, daily routine score (DRS), parent (PCIS), and child COVID information (CCIS) scores were calculated (Supplementary Table 1). Daily routine score constituted 6 questions with 5 Likert scale (minimum 0, maximum 24 points, a higher score indicating higher deterioration of daily routines), similarly PCIS and CCIS each constituted 6 questions with 3 Likert scale (minimum 0, maximum 12 points, a higher score indicating higher demand of knowledge). Child COVID information was completed by patients over 12 years of age, and other scores were completed by the parents. Factors affecting compliance with medications were questioned as well (Supplementary Table 1). Also, the parents were asked “Do you follow the news/data about the pandemic to be informed about the agenda, or because of chronic diseases and/or medications of your child?,” and “Do you think that chronic diseases, and medications of your child may increase the risk of COVID-19?.”
Supplementary Table 1.
Questions and Scoring of Daily routines, parent and child COVID information scores and drug compliance changes
| Daily routines score (DUS) | Eating and dietary habits Relationship with sibling |
Much improved | 0 |
| Little improved | 1 | ||
| Not changed | 2 | ||
| Little worsened | 3 | ||
| Much worsened | 4 | ||
| Screen time | Much decreased | 0 | |
| Little decreased | 1 | ||
| Not changed | 2 | ||
| Little increased | 3 | ||
| Much increased | 4 | ||
| Time spent on reading Time spent on daily education Time spent on daily physical activity |
Much increased | 0 | |
| Little increased | 1 | ||
| Not changed | 2 | ||
| Little decreased | 3 | ||
| Much decreased | 4 | ||
| Parent and child COVID information score (PCIS and CCIS) | Need information about; Transmission of Sars-CoV-2 Prevention of Sars-CoV-2 infection Treatment of COVID-19 disease Risk of contracting virus or exhibiting worse prognosis associated with chronic disease Management of chronic diseases in the pandemic era |
No, I have enough information | 0 |
| Not sure having enough information | 1 | ||
| Yes, I need information | 2 | ||
| Drug compliance | My/my child’s drug compliance has…. due to; Child being at home due to restrictions Parent being at home due to restrictions Change in sleep timing and duration Mealtime changes Anxiety about pandemics Fear of having COVID-19 disease Fear of hospital admission Fear of drug side effects |
Improved | 0 |
| Not changed | 1 | ||
| Worsened | 2 | ||
The third section of the survey included Depression Anxiety Stress Scale short form (DASS) to be completed by the parents and The State-Trait Anxiety Inventory for Children (STAI-CH). The DASS is a short form of Lovibond and Lovibond’s (1995) 42-item self-report measure of depression, anxiety, and stress. The scale has a 4-point Likert-type rating, ranging from 0 "not at all convenient to me" to 3 "completely suitable to me." It consists of 3 sub-dimensions: anxiety (DASS-A), depression (DASS-D), and stress (DASS-S). The Turkish adaptation of the short form of the scale was published by Yılmaz et al.26 High scores show high-intensity symptoms, and subscale scores have cut-off points of 3.5 for DASS-A, 4.5 for DASS-D, and 7 for DASS-S. The State-Trait Anxiety Inventory for Children (Spielberger, 1973) is a 20-item self-reported measure indicative of current (STAI-CH-S) and long-lasting anxiety (STAI-CH-T), widely used in children and adolescents.27 The STAI-CH asks for ratings of agreement on a 3-point scale using the stem “I feel...” indicative of the presence of anxiety; 1 “not upset” to 3 “very upset” and reverse-worded; 1 “very calm” to 3 “not calm” items. Total scores for the STAI-CH are between 20 and 60, and the cut-off point is 40. The Turkish adaptation of the scale was published by Ozusta.28
Timing of Surveys
First round of survey was conducted in June 2020. At the time of the initial survey, patient visits were carried out remotely via telemedicine. Information regarding each child’s condition and complaints was obtained from the parents; necessary information and guidance were provided online. During the first round of the study, all participants in the CAH and CH groups were asked to fill out all parts of the survey.
Second round of survey was conducted in July 2021 and questionnaires were only sent to the CAH group. This time only the third section of the survey (DASS and STAI-CH questionnaires) was sent to participants, and also, they were asked for any past or present infection symptoms, necessity of nasopharyngeal swab testing for any reason and results of swab testing from March 2020 to July 2021. In July 2021, all patient visits were held on at the outpatient clinic and COVID-19 vaccinations were only available for people above 18 years of age in Turkey, so none of our patients had the opportunity to get vaccinated during the second round of the study.
Statistical Analysis
Statistical analyses were performed using the Statistical Package for Social Sciences, version 19.0 software (SPSS Inc.; Chicago,IL, USA). Variables were tested for normal distribution using the Shapiro–Wilk test. Normally distributed data were expressed as mean and standard deviation. Median and minimum-maximum were calculated for non-normally distributed variables. Mean values of continuous variables were compared using independent samples t tests and medians were compared using the Mann–Whitney U test or the Wilcoxon test, as appropriate. Chi-square test and Fisher’s exact test were used to compare between-group differences of categorical variables. Spearman’s correlation was used to determine the relationship between non-parametric variables. Paired samples’ Wilcoxon test and McNemar test were used to compare distributions in paired samples. A P-value <.05 was considered to be statistically significant.
Results
The study consisted of 38 patients (19 males, 50%) with CAH and 41 (22 males, 54%) with CH. The mean age was 12.2 ± 4.3 years in the CAH and 11.7 ± 3.1 years in the CH group (P = .82). Demographic characteristics were similar between the groups (Supplementary Table 2).
Supplementary Table 2.
Sociodemographic characteristics of children with congenital adrenal hyperplasia (CAH) and congenital hypothyroidism (CH)
| CAH, n (%) | Hypothyroidism, n (%) | p | ||
|---|---|---|---|---|
| Gender | Female | 19 (50) | 19 (46) | 0.745a |
| Male | 19 (50) | 22 (54) | ||
| Socioeconomic status (Hollinshead-Redditch Scale) | II | 21 (55.3) | 18 (43.9) | 0.585a |
| III | 12 (31.6) | 17 (41.5) | ||
| IV-V | 5 (13.2) | 6 (14.6) | ||
| Maternal education | Elementary school | 14 (36.8) | 19 (46.3) | 0.145a |
| High school | 15 (39.5) | 8 (19.5) | ||
| University | 9 (23.7) | 14 (34.2) | ||
| Paternal education | Elementary school | 9 (23.7) | 7 (17.1) | 0.280a |
| High school | 11 (28.9) | 19 (46.3) | ||
| University | 18 (47.4) | 15 (36.6) | ||
| Employment of mother | Employed | 9 (31) | 17 (41.4) | 0.093a |
| Not employed | 29 (69) | 24 (58.5) | ||
| Employment of father | Employed | 31 (81.5) | 38 (92.6) | 0.183a |
| Not employed | 7 (18.5) | 3 (7.4) | ||
| Residence | Urban | 35 (92.1) | 38 (92.6) | 1.0a |
| Rural | 3 (7.9) | 3 (7.4) | ||
| Garden/park use | Yes | 20 (52.6) | 15 (36.5) | 0.151a |
| No | 18 (47.4) | 26 (63.5) | ||
aPearson Chi-Square test.
Anxiety, Stress, and Depression Scores at the First Survey
Median DASS-D, DASS-A, DASS-S, STAI-CH-T, and STAI-CH-S were similar between the CAH and the CH groups (Table 1). When patients were stratified according to age (either under or above 12 years old) and gender, there was no difference in any score between the groups (Table 1).
Table 1.
Median DASS-D, DASS-A, DASS-S, STAI-CH-S, and STAI-CH-T Scores in the Congenital Adrenal Hyperplasia (CAH) and Congenital Hypothyroidism (CH) Groups with Respect to Diagnosis, Age, and Gender.
| n | DASS-Da | P b | DASS-Aa | P b | DASS-Sa | P b | STAI-CH-Sa | P b | STAI-CH-Ta | P b | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diagnosis | CAH | 38 | 2 (0-21) | .674 | 2 (0-21) | .631 | 4 (0-21) | .779 | 33 (20-60) | .533 | 14 (0-40) | .559 |
| CH | 41 | 4 (0-21) | 4 (0-18) | 5 (0-17) | 33 (22-46) | 13 (0-37) | ||||||
| ≤12 years old | CAH | 20 | 2 (0-10) | 1.0 | 2 (0-11) | .827 | 3 (0-13) | .713 | 32.5 (20-52) | .506 | 15 (0-31) | .081 |
| CH | 20 | 1.5 (0-14) | 2.5 (0-18) | 3.5 (0-15) | 31 (22-41) | 10 (0-37) | ||||||
| >12 years old | CAH | 18 | 4.5 (0-21) | .943 | 3.5 (0-21) | .921 | 9 (0-21) | .631 | 34.5 (24-60) | .778 | 12 (2-40) | .236 |
| CH | 21 | 5 (0-21) | 4 (0-18) | 7 (0-17) | 35 (24-46) | 16 (1-28) | ||||||
| Female | CAH | 19 | 1 (0-21) | .687 | 1 (0-21) | .869 | 2 (0-21) | .517 | 31 (20-60) | .884 | 10 (0-40) | .977 |
| CH | 19 | 2 (0-21) | 2.5 (0-8) | 3 (0-13) | 33 (23-42) | 12 (4-28) | ||||||
| Male | CAH | 19 | 4 (0-21) | .393 | 3 (0-13) | .478 | 7 (0-19) | .948 | 35 (24-52) | .249 | 14 (2-31) | .618 |
| CH | 22 | 6 (0-17) | 5.5 (0-18) | 7 (0-17) | 33.5 (22-46) | 15.5 (0-37) |
aMedian (minimum-maximum); bMann–Whitney U test.
DASS-D, Depression Anxiety Stress Scale-Depression; DASS-A, Depression Anxiety Stress Scale-Anxiety; DASS-S, Depression Anxiety Stress Scale-Stress; STAI-CH-S, The State-Trait Anxiety Inventory for Children-State; STAI-CH-T, The State-Trait Anxiety Inventory for Children-Trait.
Depression Anxiety Stress Scale-Depression, DASS-A, and DASS-S scores were above the threshold in 36%, 39%, and 31% of the parents in the CAH group and 46%, 53%, and 31% in the CH group, respectively (P = .392, P = .207, and P = .990, respectively). The State-Trait Anxiety Inventory for Children-State was above the threshold in 57% of children in the CAH group and 58% in the CH group (P = .954).
There was a moderate correlation between STAI-CH-S and STAI-CH-T (R = 0.523, P = .001), as well as between STAI-CH-S and DASS-A (R = 0.428, P = .007) in the CAH group. In subgroup analysis, there was a strong correlation between STAI-CH-S and STAI-CH-T (R = 0.873,P < .01), STA-CH-S and DASS-A (R = 0.687,P < .01), and a moderate correlation between STAI-CH-S and DASS-D (R = 0.504,P = .033), STAI-CH-S and DASS-S (R = 0.573,P = .013) in the CAH group among those above 12 years of age. In the CH group, there was only a moderate correlation between STAI-CH-S and STAI-CH-T (R = 0.422,P = .049) among those above 12 years of age.
Sociodemographic Characteristics and Anxiety, Stress, Depression Scores at the First Survey
A higher proportion of parents of female hypothyroid patients had a DASS-D score above the threshold (P = .017). Higher proportion of parents whose children above 12 years of age had a DASS-S score above the threshold compared to those below 12 years of age in the CAH group (P = .020). Higher proportion of children whose ages were above 12 years of age had a STAI-CH-S score above the threshold in the CH group compared to those below 12 years of age (P = .019) (Tables 2 and 3). Depression Anxiety Stress Scale-Depression, DASS-A, and DASS-S scores were above the threshold in a higher proportion of the high school-graduated mothers compared to the elementary and university-graduated mothers in the CAH group (P = .003, P = .014, and P = .005, respectively) (Table 2).
Table 2.
Sociodemographic Characteristics of the Congenital Adrenal Hyperplasia Group According to DASS-D, DASS-A, DASS-S, and STAI-CH-S Thresholds
|
|
DASS-D, n (%) | DASS-A, n (%) | DASS-S, n (%) | STAI-CH-S, n (%) | |||||
|---|---|---|---|---|---|---|---|---|---|
| ≤4.5 | >4.5 | ≤3.5 | >3.5 | ≤7 | >7 | ≤40 | >40 | ||
| Gender, n (%) | Female | 13 (68.5) | 6 (31.5) | 13 (68.5) | 6 (31.5) | 14 (73.5) | 5 (26.5) | 10 (52.6) | 9 (47.4) |
| Male | 11 (58) | 8 (42) | 10 (52.6) | 9 (47.4) | 12 (63.1) | 7 (36.9) | 6 (31.5) | 13 (68.5) | |
| P | .737a | .319a | .485a | .189a | |||||
| Regulation of disease, n (%) | Good | 16 (66.6) | 8 (33.3) | 14 (58.3) | 10 (41.7) | 15 (62.5) | 9 (37.5) | 10 (41.7) | 14 (58.3) |
| Poor | 8 (57.1) | 6 (42.9) | 9 (64.3) | 5 (35.7) | 11 (78.6) | 3 (21.4) | 6 (42.9) | 8 (57.1) | |
| P | .557a | .717a | .472b | .943a | |||||
| Age, n (%) | ≤12 years | 15 (75) | 5 (25) | 14 (70) | 6 (30) | 17 (85) | 3 (15) | 9 (45) | 11 (55) |
| >12 years | 9 (50) | 9 (50) | 9 (50) | 9 (50) | 9 (50) | 9 (50) | 7 (39) | 11 (61) | |
| P | .111a | .208a | .020 a | .703a | |||||
| Change in household income, n (%) | No change | 16 (64) | 9 (36) | 15 (60) | 10 (40) | 18 (72) | 7 (28) | 13 (52) | 12 (48) |
| Decreased | 8 (61.5) | 5 (38.5) | 8 (61.5) | 5 (38.5) | 8 (61.5) | 5 (38.5) | 3 (23) | 10 (77) | |
| P | 1.0b | .927a | .714b | .087a | |||||
| Maternal education, n (%) | Elementary school | 10 (71.4) | 4 (28.6) | 8 (64.2) | 6 (35.8) | 11 (78.5) | 3 (21.5) | 8 (57.1) | 6 (42.8) |
| High school | 5 (33.3) | 10 (66.7) | 6 (40) | 9 (60) | 6 (40) | 9 (60) | 4 (27) | 11 (63) | |
| University | 9 (100) | 0 (0) | 9 (100) | 0 (0) | 9 (100) | 0 (0) | 4 (44) | 5 (56) | |
| P | .003 a | .014 a | .005 b | .248a | |||||
| Paternal education, n (%) | Elementary school | 5 (56) | 4 (44) | 6 (66) | 3 (33) | 6 (66) | 3 (33) | 5 (56) | 4 (44) |
| High school | 8 (72.7) | 3 (27.3) | 7 (63.6) | 4 (36.4) | 8 (72.7) | 3 (27.3) | 4 (36.3) | 7 (63.7) | |
| University | 11 (61) | 7 (39) | 10 (55) | 8 (45) | 12 (66) | 6 (33) | 7 (39) | 11 (61) | |
| P | .754b | .835b | 1.0b | .698b | |||||
| Employment of mother, n (%) | Employed | 6 (66) | 3 (33) | 7 (77) | 2 (23) | 7 (77) | 2 (23) | 3 (33) | 6 (66) |
| Not employed | 18 (62) | 11 (38) | 16 (55) | 13 (45) | 19 (65.5) | 10 (34.5) | 13 (44.8) | 16 (55.2) | |
| P | 1.0b | .273b | .689b | .706b | |||||
| Employment of father, n (%) | Employed | 21 (67.7) | 10 (32.3) | 19 (61.2) | 12 (38.8) | 23 (74) | 8 (26) | 14 (45) | 17 (55) |
| Not employed | 3 (43) | 4 (57) | 4 (57) | 3 (43) | 3 (43) | 4 (57) | 2 (28) | 5 (72) | |
| P | .387b | 1.0b | .176b | .675b | |||||
| Residence, n (%) | Urban | 21 (60) | 14 (40) | 20 (57) | 15 (43) | 24 (68.5) | 11(31.5) | 14 (40) | 21 (60) |
| Rural | 3 (100) | 0 | 3 (100) | 0 | 2 (66) | 1 (33) | 2 (66) | 1 (33) | |
| P | .283b | .264b | 1.0b | .562b | |||||
| Garden/park use, n (%) | Yes | 14 (70) | 6 (30) | 13 (65) | 7 (35) | 14 (70) | 6 (30) | 9 (45) | 11 (55) |
| No | 10 (55.5) | 8 (44.5) | 10 (55.5) | 8 (44.5) | 12 (66.6) | 6 (33.4) | 7 (38.8) | 11 (61.2) | |
| P | .357a | .552a | .825a | .703a | |||||
aPearson chi-square; bFisher’s exact test. A P <.05 was considered to be statistically significant.
DASS-D, Depression Anxiety Stress Scale-Depression; DASS-A, Depression Anxiety Stress Scale-Anxiety; DASS-S, Depression Anxiety Stress Scale-Stress; STAI-CH-S, The State-Trait Anxiety Inventory for Children-State.
Table 3.
Sociodemographic Characteristics of the Congenital Hypothyroidism Group According to DASS-D, DASS-A, DASS-S, and STAI-CH-S Thresholds.
|
|
DASS-D, n (%) | DASS-A, n (%) | DASS-S, n (%) | STAI-CH-S, n (%) | |||||
|---|---|---|---|---|---|---|---|---|---|
| ≤4.5 | >4.5 | ≤3.5 | >3.5 | ≤7 | >7 | ≤40 | >40 | ||
| Gender, n (%) | Female | 14 (73.6) | 5 (26.4) | 11 (57.8) | 8 (42.2) | 15 (78.9) | 4 (21.1) | 9 (47.3) | 10 (52.7) |
| Male | 8 (36.7) | 14 (63.7) | 8 (36.4) | 14 (63.6) | 13 (59) | 9 (41) | 8 (36.4) | 14 (63.6) | |
| P | .017a | .168a | .173a | .476a | |||||
| Age, n (%) | ≤12 years | 13 (65) | 7 (35) | 11 (55) | 9 (45) | 16 (85) | 4 (15) | 12 (60) | 8 (40) |
| >12 years | 9 (42.8) | 12 (57.2) | 8 (38) | 13 (62) | 12 (57.2) | 9 (42.8) | 5 (23.8) | 16 (76.2) | |
| P | .155a | .278a | .116a | .019a | |||||
| Change in household income, n (%) | No change | 13 (52) | 12 (48) | 13 (52) | 12 (48) | 17 (68) | 8 (32) | 12 (48) | 13 (52) |
| Decreased | 9 (56.2) | 7 (43.8) | 6 (37.5) | 10 (62.5) | 11 (68.7) | 5 (31.3) | 5 (31.3) | 11 (68.7) | |
| P | .790a | .364a | .960a | .288a | |||||
| Maternal education, n (%) | Elementary school | 10 (52.6) | 9 (47.4) | 9 (47.4) | 10 (52.6) | 13 (68.4) | 6 (31.6) | 6 (31.6) | 13 (68.4) |
| High school | 5 (62.5) | 3 (37.5) | 4 (50) | 4 (50) | 6 (75) | 2 (25) | 5 (62.5) | 3 (37.5) | |
| University | 7 (50) | 7 (50) | 6 (42.8) | 8 (57.2) | 9 (64.3) | 5 (35.7) | 6 (42.8) | 8 (57.2) | |
| P | .846b | 1.0b | 1.0b | .354b | |||||
| Paternal education, n (%) | Elementary school | 5 (71.4) | 2 (28.6) | 3 (42.8) | 4 (57.2) | 5 (71.4) | 2 (28.6) | 1 (14.3) | 6 (85.7) |
| High school | 10 (52.6) | 9 (47.4) | 10 (52.6) | 9 (47.4) | 14 (73.7) | 5 (26.3) | 10 (52.6) | 9 (47.4) | |
| University | 7 (46.6) | 8 (53.4) | 6 (40) | 9 (60) | 9 (60) | 6 (40) | 6 (40) | 9 (60) | |
| P | .644b | .776b | .747b | .260b | |||||
| Employment of mother, n (%) | Employed | 8 (47) | 9 (43) | 6 (35.3) | 11 (64.7) | 10 (58.8) | 7 (41.2) | 7 (41.2) | 10 (58.8) |
| Not employed | 14 (58.3) | 10 (41.7) | 13 (54.2) | 11 (45.8) | 18 (75) | 6 (25) | 10 (41.7) | 14 (58.3) | |
| P | .476a | .233a | .273a | .975a | |||||
| Employment of father, n (%) | Employed | 20 (52.6) | 18 (47.4) | 18 (47.4) | 20 (52.6) | 26 (68.4) | 12 (31.6) | 17 (44.7) | 21 (55.3) |
| Not employed | 2 (66.6) | 1 (33.4) | 1 (33.4) | 2 (66.6) | 2 (66.6) | 1 (33.4) | 0 (0) | 3 (100) | |
| P | 1.0b | 1.0b | 1.0b | .254b | |||||
| Residence, n (%) | Urban | 20 (52.6) | 18 (47.4) | 17 (44.7) | 21 (55.3) | 26 (68.4) | 12 (31.6) | 16 (42.1) | 22 (37.9) |
| Rural | 2 (66.6) | 1 (33.4) | 2 (66.6) | 1 (33.4) | 2 (66.6) | 1 (33.4) | 1 (33.4) | 2 (66.6) | |
| P | 1.0b | .588b | 1.0b | 1.0b | |||||
| Garden/park use, n (%) | Yes | 7 (46.6) | 8 (53.4) | 7 (46.7) | 8 (53.3) | 12 (80) | 3 (20) | 7 (46.7) | 8 (53.3) |
| No | 15 (57.6) | 11 (42.4) | 12 (46.1) | 14 (53.8) | 16 (61.5) | 10 (38.5) | 10 (38.5) | 16 (61.5) | |
| P | .495a | .975a | .305b | .607a | |||||
aPearson chi-square; bFisher’s exact test. A P-value <.05 was considered to be statistically significant.
DASS-D, Depression Anxiety Stress Scale-Depression; DASS-A, Depression Anxiety Stress Scale-Anxiety; DASS-S, Depression Anxiety Stress Scale-Stress; STAI-CH-S, The State-Trait Anxiety Inventory for Children-State.
Daily Routines Score, COVID-19 Information Score, and Drug Compliance Change
In the CAH group, the median DRS was 15 (range, 11-22), the median PCIS was 4 (range, 0-12), and the median CCIS was 5 (range, 0-12). In the CH group, the median DRS was 14 (range, 7-22), the median PCIS was 4 (range, 0-12), and the median CCIS was 3 (range, 0-12). Daily routine score, PCIS, and CCIS were similar between the CAH and the CH groups (P = .269, P = .835, and P = .980, respectively). “Time spent on daily education” in the CAH group (R = 0.750, P < .01) and “relationship with sibling” in the CH group (R = 0.653, P < .01) were the factors that affected DRS most. While PCIS and CCIS were most affected by “risk of contracting virus or exhibiting worse prognosis associated with chronic disease” in the CAH group (R = 0.827, P < .01 and R = 0.860, P < .01, respectively), in the CH, PCIS was most affected by “transmission of Sars-CoV-2” (R = 0.926, P < .01), and CCIS was most affected by “prevention of Sars-CoV-2 infection” (R = 0.904, P < .01). The most frequently stated factor adversely affecting drug compliance was “change in sleep timing and duration” in the CAH and CH groups. On the other hand, “parent being at home due to restrictions” was the most frequently stated factor contributing to the improvement of drug compliance in both groups (Table 4).
Table 4.
Factors Affecting Drug Compliance in the Congenital Adrenal Hyperplasia (CAH) and Congenital Hypothyroidism (CH) Groups
| CAH (n = 38), n (%) | CH (n = 41), n (%) | P | |||||
|---|---|---|---|---|---|---|---|
| Improved | Not Changed | Worsened | Improved | Not Changed | Worsened | ||
| Child being at home due to restrictions | 12 (31.5) | 24 (63) | 2 (5.5) | 8 (20) | 28 (68) | 5 (12) | .314a |
| Parent being at home due to restrictions | 14 (37) | 23 (60.5) | 1 (2.5) | 9 (22) | 30 (73) | 2 (5) | .403a |
| Change in sleep timing and duration | 7 (18.5) | 18 (47.5) | 13 (34) | 3 (7) | 23 (56) | 15 (37) | .326b |
| Mealtime changes | 12 (31.5) | 15 (39.5) | 11 (29) | 7 (17) | 21 (51) | 13 (32) | .305b |
| Anxiety about pandemics | 6 (16) | 20 (52.5) | 12 (31.5) | 4 (10) | 26 (63) | 11 (27) | .573b |
| Fear of having COVID-19 disease | 6 (16) | 23 (60.5) | 9 (23.5) | 5 (12) | 27 (66) | 9 (22) | .862b |
| Fear of hospital admission | 5 (13) | 23 (60.5) | 10 (26.5) | 4 (10) | 29 (70) | 8 (20) | .662a |
| Fear of drug side effects | 5 (13) | 27 (71) | 6 (16) | 4 (10) | 35 (85) | 2 (5) | .250a |
aFisher’s exact test; bPearson chi-square test.
Daily Routine Score, COVID-19 Information Score, Drug Compliance Change, and Anxiety, Stress, Depression Scores at the First Survey
Daily routine score was higher in those who had a STAI-CH-S above the threshold in the CAH group (P = .048) and in those who had a DASS-D above the threshold in the CH group (P = .040). Parent COVID Information Score was higher in those who had a DASS-D and DASS-A above the threshold in the CH group (P = .023, P = .001) (Table 5).
Table 5.
Results of DRS, PCIS, and CCIS Scores According to DASS-D, DASS-A, DASS-S, and STAI-CH-S Thresholds in Congenital Adrenal Hyperplasia (CAH) and Congenital Hypothyroidism (CH) Groups.
| n | DRSa | P b | PCISa | P b | n | CCISa | P b | |||
|---|---|---|---|---|---|---|---|---|---|---|
| CAH | DASS-D | ≤4.5 | 24 | 14 (11-20) | .361 | 3.5 (0-12) | .878 | 9 | 6 (0-12) | .509 |
| >4.5 | 14 | 16.5 (11-22) | 5 (0-10) | 10 | 4 (0-8) | |||||
| DASS-A | ≤3.5 | 23 | 14 (11-20) | .344 | 3 (0-12) | .555 | 9 | 6 (0-12) | .509 | |
| >3.5 | 15 | 17 (11-22) | 5 (0-12) | 10 | 4 (0-8) | |||||
| DASS-S | ≤7 | 26 | 15 (11-20) | .899 | 4.5 (0-12) | .294 | 10 | 6.5 (0-12) | .342 | |
| >7 | 12 | 15 (11-22) | 2 (0-10) | 9 | 4 (0-8) | |||||
| STAI-CH-S | ≤40 | 16 | 13 (11-20) | .048 | 3.5 (0-12) | .988 | 7 | 3 (0-12) | .393 | |
| >40 | 22 | 16.5 (11-22) | 5 (0-12) | 12 | 6 (0-12) | |||||
| CH | DASS-D | ≤4.5 | 22 | 13 (7-19) | .040 | 2.5 (0-12) | .023 | 10 | 1.5 (0-12) | .302 |
| >4.5 | 19 | 15 (12-22) | 7 (0-12) | 13 | 5 (0-12) | |||||
| DASS-A | ≤3.5 | 19 | 15 (8-20) | .486 | 2 (0-10) | .001 | 9 | 1 (0-12) | .061 | |
| >3.5 | 22 | 14 (7-22) | 6.5 (0-12) | 14 | 5.5 (0-12) | |||||
| DASS-S | ≤7 | 28 | 13 (8-19) | .210 | 4 (0-12) | .397 | 14 | 4 (0-12) | .309 | |
| >7 | 13 | 15 (7-22) | 4 (0-12) | 9 | 2 (0-10) | |||||
| STAI-CH-S | ≤40 | 17 | 15 (8-18) | .394 | 4 (0-12) | .883 | 6 | 3.5 (0-12) | .972 | |
| >40 | 24 | 14 (7-22) | 4 (0-12) | 17 | 3 (0-12) |
aMedian (minimum-maximum); b Mann–Whitney U test. A P-value <.05 was considered to be statistically significant.
CCIS, Child COVID information score; DASS-D, Depression Anxiety Stress Scale-Depression; DASS-A, Depression Anxiety Stress Scale-Anxiety; DASS-S, Depression Anxiety Stress Scale-Stress; DRS, drug usage score; PCIS, parent COVID information score; STAI-CH-S, The State-Trait Anxiety Inventory for Children-State.
Thoughts About the Chronic Disease and Medications of the Child in the Congenital Adrenal Hyperplasia Group
In the CAH group, 58% of the parents followed news/data about the pandemic because of chronic diseases and/or medications of the child, while in the hypothyroidism, 68% of them just wanted to have information about the agenda (P = .024). In the CAH group, 76% and 37% of parents thought that chronic diseases and using medications increase the risk of COVID-19 infection, respectively. On the other hand, in hypothyroidism, only 32% and 15% of them thought chronic diseases and using medications increase the risk and these were significantly lower than the CAH group (P = .0001, P = .027, respectively). In the CAH group, parents who were following news/data due to the chronic diseases and/or medications of the child had higher DASS-D, DASS-A, DASS-S, and PCIS compared to those who wanted to have information about the agenda (P = .010, P = .034, P = .044, and P = .045, respectively) (Supplementary Table 3). The State-Trait Anxiety Inventory for Children-State was higher in those stating “having chronic diseases increase the risk of COVID-19 infection” (P = .011) and “using medications increase the risk of COVID-19 infection” in the CAH group (P = .016) (Supplementary Table 3).
Supplementary Table 3.
Thoughts About the Chronic Disease and Medications of the Child in the Congenital Adrenal Hyperplasia Group
| Reason for following news/data about the pandemic | Do you think that chronic diseases of your child may increase the risk of COVID-19? | Do you think that medications of your child may increase the risk of COVID-19? | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Chronic diseases and/or medications of the childd (n = 22a) | In order to have information about the agendad (n = 16a) | pe | Yesd (n = 29b) | Nod (n = 9b) | pe | Yesd (n = 14c) | Nod (n = 24c) | pe | |
| DASS-D | 4.5 (0-21) | 1 (0-21) | 0.010 | 2 (0-21) | 1 (0-21) | 0.521 | 3.5 (0-11) | 2 (0-21) | 0.530 |
| DASS-A | 3.5 (0-13) | 1.5 (0-21) | 0.034 | 2 (0-21) | 2 (0-13) | 0.729 | 3.5 (0-12) | 2 (0-21) | 0.531 |
| DASS-S | 6 (0-19) | 1 (0-21) | 0.044 | 6 (0-21) | 1 (0-19) | 0.342 | 5.5 (0-14) | 3.5 (0-21) | 0.446 |
| STAI-CH-S | 35.5 (20-56) | 30.5 (20-60) | 0.280 | 35 (20-60) | 27 (20-56) | 0.011 | 42 (20-52) | 30.5 (20-60) | 0.016 |
| DRS | 16 (11-22) | 13 (11-20) | 0.181 | 16 (11-22) | 13 (11-20) | 0.247 | 16.5 (11-20) | 13.5 (11-22) | 0.117 |
| PCIS | 6 (0-12) | 1.5 (0-12) | 0.045 | 4 (0-12) | 5 (0-12) | 0.509 | 6 (0-11) | 2.5 (0-12) | 0.592 |
| CCIS | 5 (0-12) | 3 (0-12) | 0.428 | 5.5 (0-12) | 3 (0-12) | 0.888 | 6.5 (1-8) | 4 (0-12) | 0.451 |
CCIS: Child COVID information score, DASS-D: Depression Anxiety Stress Scale-Depression, DASS-A: Depression Anxiety Stress Scale-Anxiety, DASS-S: Depression Anxiety Stress Scale-Stress, DRS: drug usage score, PCIS: Parent COVID information score, STAI-CH-S: The State-Trait Anxiety Inventory for Children-State. aFor CCIS, n is 11 and 9, respectively. bFor CCIS, n is 14 and 5, respectively. cFor CCIS n is 6 and 13, respectively. dmedian (minimum-maximum). eMann-Whitney-U test
Anxiety, Stress, and Depression Scores at the Second Survey of Congenital Adrenal Hyperplasia
Thirty-five participants fulfilled the second survey in the CAH group. Depression Anxiety Stress Scale-Depression, DASS-A, and DASS-S were above the threshold in 48%, 28%, and 14% of the parents, respectively. Compared to the first survey, the proportion of those above the DASS-D and DASS-A thresholds was similar (P = .581, P = .180, respectively), while the DASS-S decreased significantly (P = .016). The State-Trait Anxiety Inventory for Children-State was below the threshold in all patients and decreased significantly (P < .01). Depression Anxiety Stress Scale-Depression (median 4, range 4-18) did not change significantly (P = .662), while DASS-A (median 2, range 0-10) and DASS-S (median, 4; range, 0-17) decreased significantly (P = .009, P = .008) (Figure 1).
Figure 1.
DASS-D, DASS-A, DASS-S, and STAI-CH-S scores of the congenital adrenal hyperplasia group at the first and the second survey. *P < .05, paired-samples t test. DASS-D, Depression Anxiety Stress Scale-Depression; DASS-A, Depression Anxiety Stress Scale-Anxiety; DASS-S, Depression Anxiety Stress Scale-Stress.
COVID-19 Infection
Eight patients with CAH (21%) took a nasopharyngeal swab test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two of them were tested for medical procedures, 4 of them for symptoms suggestive of COVID-19 infection, and 2 for exposure to infected persons. Three patients tested for symptoms or exposure to infected persons had a positive test and all showed mild symptoms.
Family members of 3 patients tested positive; Although these 3 patients were not tested for COVID-19, they did not show any symptoms. Six patients had mild symptoms suggestive of upper respiratory tract infection; however, they were not tested for the SARS-CoV-2 since family members did not have any symptoms. Glucocorticoid doses were increased appropriately.
Discussion
This longitudinal study revealed increased anxiety and stress levels in patients with CAH and their families, associated with the pandemic, and addressed the importance of negative illness perceptions which contribute to the psychological comorbidities. We also found a similar frequency of anxiety, depression, and stress symptoms between the CAH and hypothyroidism groups at the first phase of the pandemic, suggesting the pandemic has similar consequences for people with chronic diseases, albeit from different causes.
Patients with hypothyroidism need life-long medication, medical visits, and laboratory testing, and despite being on appropriate drug therapy, some reports demonstrated increased anxiety and depression levels.29,30 Despite the lack of a risk of adrenal crisis and no need for drug dosage adjustments in the case of infection in hypothyroidism, the frequency of depression, anxiety, and stress symptoms was similar to CAH in the first survey. This could be explained with the pandemic itself which caused increased anxiety and stress levels, independent of the type of chronic disease, which may be due to reasons such as the necessity to postpone medical visits and laboratory tests, and concerns about accessing medication. On the other hand, according to the PCIS and CCIS scores, the need for information about the transmission and prevention of the virus in the CH group was at the forefront, while concerns about chronic diseases were at the forefront in the CAH group suggesting that patients with different chronic diseases may have different concerns about the pandemic.
We found a positive correlation between the stress, anxiety, and depression levels of parents and children, especially over 12 years of age in the CAH group. Dyadic coping involves 2 people supporting each other in a relationship and coping with a common stressor.31 Although several forms of dyadic coping may mitigate the negative effects of stress, they can also increase negative stress.31,32 Nap-van der Vlist et al31 reported a negative dyadic coping of chronically diseased children and their parents associated with lower pediatric quality of life, and a parents’ emotion-oriented dyadic coping was related to the higher pediatric quality of life. Developing coping strategies and concomitantly disease adaptation has a positive effect on the Health Related Quality of Life (HRQoL) and well-being.33,34 The first survey was made within the third month of the pandemic, and this unexpected acute event generated anxiety and stress in parents and children. This anxiety and stress could be related to the negative dyadic coping between parents and children and it was an expected situation since parents and children could not have been able to develop a coping strategy at this time yet. So, helping children and their parents to jointly deal with stressful situations is important to improve mental well-being.
We found higher levels of anxiety, depression, and stress symptoms in high school-graduated mothers. Education seems as a predictor of an individual’s demand for health35 and some reports showed lower educational status as a risk factor for anxiety, depression, and stress symptoms in normal circumstances.3,36 Awareness of health problems and seeking medical advice could relieve the anxiety and stress symptoms of highly educated persons. However, pandemic, an acute health threat, makes this period more complicated. In the acute era of the pandemic, awareness of health threat could increase anxiety levels in highly educated mothers. On the other hand, university-graduated mothers had lower levels of anxiety, stress, and depression symptoms compared to high school-graduated mothers. This could be related to the better skills of obtaining information, such as prevention and treatment of Sars-CoV-2, and developing adequate coping strategies in university-graduated mothers compared to high school-graduated ones.
Social isolation due to COVID-19 caused significant disruption of daily routines in many domains such as school, physical activity, sleep, and nutrition for the global community, as well as for children. Change in daily routines is a risk factor for emotional well-being37 and maintaining a daily routine is important, especially for individuals with chronic diseases, in terms of providing coherence and predictability.38 In our study, children and parents with higher levels of anxiety and depression scores had more disruption in daily routines. Also, changes in daily structures such as sleep timing and sleep duration seem to lead to disruption of drug compliance both in patients with CAH and CH. During the first phase of the pandemic, the schools had to be locked down in Turkey as in many countries. Loss of daily structure, education time, restricted access to peers, increase in screen time, and concomitantly decrease in physical activity can affect mental health adversely. Planning the day efficiently, spending quality time at home, and also increasing physical activity should be encouraged. These measures could help to improve mental well-being.
Negative illness perceptions have been found to correlate with increased depression and anxiety levels and reduced HRQoL.39-41 In the CAH group, 58% of the parents followed news/data about the pandemic because of chronic diseases and/or medications of the child, and 76% and 37% of them thought having chronic diseases and using medications increased the risk of COVID-19 infection respectively. Also, these parents had higher levels of depression, anxiety, and stress symptoms and sought more information about the pandemic. Several studies showed increased infection risk in patients with AI.42,43 Decreased natural killer cell cytotoxicity44 and altered circadian rhythm of glucocorticoid22 are the suggested mechanisms. European Society of Endocrinology stated the presence of a higher risk of medical complications and increased mortality risk and proposed a steroid regimen in the case of COVID-19 infection in patients with AI.45 However, recent studies have not supported this notion yet.14,21,23 In our cohort, none of the patients reported severe symptoms associated with COVID-19. The children with CAH could even remain asymptomatic in a COVID-19-infected household. Thus, witnessing that no severe infection occurred in their children during the first year of pandemic may be a factor in the lower scores of anxiety and stress in the parents at the end of the first year of the pandemic. The most striking findings of the surveys were “need of information about risk of contracting virus or exhibiting worse prognosis associated with chronic disease,” and they showed the need for accurate information about chronic diseases during acute events.
This study has several limitations. The main limitation is a relatively small number of participants from a single center. The characteristics of the population refusing to participate in the study are unknown, which may be a bias. Data were collected through parents’ self-reports, which may impact the reporting. Therefore, it may not be appropriate to generalize the results to all children with CAH. We do not have anxiety and stress levels of the patients and parents before the pandemic; however, we thought that the survey conducted 1 year after the first one could provide information about the pre-pandemic levels. Also, we could not take a healthy control group, due to the lockdown process in the first phase of the pandemic. The DRS, PCIS, and CCIS scores that we built to evaluate the severity of the changes in daily routines and the need for information about COVID-19 are not validated scores. However, we thought that these scores were useful for evaluating the effects of the pandemic because we found that participants with higher anxiety, depression, or stress scores also had higher purpose-built scores.
In conclusion, the pandemic has negative consequences on the mental well-being of individuals with chronic diseases, albeit from different causes. Helping children and their parents to jointly deal with stressful situations, providing and updating correct information for the management of the diseases in the pandemic era, and establishing new daily routines for stressful situations are important.
Footnotes
Ethics Committee Approval: This study was approved by Ethics committee of Hacettepe University Faculty of Medicine (Approval No: GO20/625 2020/12-70).
Informed Consent: All participants provided informed consent in the format required by the relevant authorities and/or boards.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept and Design – N.B.C., Y.U., A.M.Y., B.S., D.C.E, N.G., A.O., E.N.O., A.A.; Supervision – N.G., A.O., E.N.O.; Resources – N.B.C., D.C.E; Data Collection and/or Processing – N.B.C., D.C.E; Analysis and/or Interpretation – N.B.C., D.C.E, A.Y.M., B.S., N.G., A.O., E.N.O., A.A.; Literature Search – N.B.C.; Writing Manuscript – N.B.C., D.C.E, N.G., A.O., E.N.O., A.A.; Critical Review – N.B.C., D.C.E, N.G., A.O., E.N.O.
Declaration of Interests: The authors have no conflict of interest to declare.
Funding: The authors declared that this study has received no financial support.
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