European Journal of Molecular & Clinical Medicine

ISSN 2515-8260 Volume 10, Issue 1, Winter 2023

ORIGINAL RESEARCH

Managing pediatric diabetes and other endocrine disorders in the midst of

the COVID-19 pandemic presents a number of difficult challenges
1
Dr. Zalak Upadhyay, 2Dr. Mitulkumar B Kalathia
1
Assistant Professor, 2Associate Professor, Department of Pediatrics, Shantaba Medical
College, Amreli, Gujarat, India

Correspondence:
Dr. Zalak Upadhyay
Assistant Professor, Department of Pediatrics, Shantaba Medical College, Amreli, Gujarat,
India
Email: [email protected]

Received: 22 November, 2022 Accepted: 26 December, 2022

ABSTRACT
Background: It determined the frequency, dimensions, treatment, and results of the COVID-
19 pandemic in children who had endocrine problems and diabetes.
Methods: A worldwide network of endocrine societies was sent an internet survey in the form
of a cross-sectional questionnaire. The professional and practice characteristics of respondents,
the size of their clinics, the nation in which they practiced medicine, and the influence that
COVID-19 had on endocrine illnesses were explored.
Results: The study was completed by respondents from 134 pediatric endocrine institutions
located in 51 different countries and across all seven continents. The majority of pediatric
endocrinology clinics have made adjustments to their standard checkups as well as their
educational programming. More than twenty percent of clinics reported experiencing a lack of
availability of crucial supplies or drugs. Patients diagnosed with diabetes and COVID-19
needed therapy in an intensive care unit. It has been clearly stated that pediatric patients with
endocrine abnormalities have alterations in their biopsychosocial functioning as well as their
behaviors.
Conclusions: This extensive worldwide study was carried out during the COVID-19 pandemic,
and its findings underscore the fact that diabetes is more difficult to control than any other
juvenile endocrine illness, and it also carries a higher risk of morbidity. It is necessary to
acknowledge and treat the psychological anguish that has been caused by COVID-19. Every
patient ought to have easy access to medical supplies, and it is essential that they maintain
frequent interaction with the medical staff who are responsible for their treatment.
Keywords: COVID-19, children, diabetes, obesity and metabolic syndrome, adrenal, thyroid,
growth, puberty.

INTRODUCTION
Still having a significant influence on a worldwide scale is the COVID-19 pandemic, which
was brought on by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (1).
Even if there has been progress made in immunization, there is a good chance that there will
be repeated "waves" of infection over the course of many years before the vast majority of
the population either becomes immune via infection or through vaccination (1–4).
There have been isolated cases of a disease similar to Kawasaki disease that has been linked
to SARS-CoV-2 infection. This disease is now recognized as a complication of COVID-19

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[multisystem inflammatory syndrome (MIS) in children (MIS-C)]. Children in general have a

milder form of the disease than adults (5–8). On the other hand, very little is known regarding
the effects of COVID-19 on patients who have ongoing disorders such as endocrine diseases,
particularly youngsters (9). The majority of contemporary research has focused on endocrine
problems that affect adult populations (10–13). Despite the fact that healthcare professionals
(HCPs) and families need guidance on the clinical management of children with endocrine
disorders during the challenging circumstances of the COVID-19 pandemic, this is not the
case. This is especially true for children who have suspected or confirmed cases of COVID-
19.
The results of a worldwide survey of healthcare professionals who specialize in pediatric
endocrinology and are registered in the database maintained by the International Consortium
for Pediatric Endocrinology (ICPE) are shown here. We discuss the clinical features of
patients who were handled throughout the pandemic, and we emphasize the knowledge and
practice of healthcare professionals working in pediatric endocrinology, as well as the
particular problems they have experienced during the epidemic. In addition, we discuss the
gaps that were identified between a previous survey on diabetes that was conducted early on
in the pandemic (9) and the current survey that was conducted to evaluate and explain the
frequency, dimensions, management, viewpoints, and outcomes of the COVID-19 pandemic
in children, adolescents, and young people who are living with chronic endocrine disease.

METHODS
This was a digital cross-sectional survey that was carried out over the course of eight weeks,
beginning on December 3, 2020 and ending on February 5, 2021. The survey was carried out
with the assistance of Google Forms (Google LLC, Mountain View, California, United
States), which enables results to be stored and then evaluated using a spreadsheet-based
format. In a recent publication of ours, the methodology behind the data gathering and survey
is broken out in detail (9).
The target population was determined with the help of a worldwide network of endocrine
societies that operate under the auspices of the International Council for Pediatric
Endocrinology (ICPE). This network includes the International Society for Pediatric and
Adolescent Diabetes (ISPAD), the European Society for Pediatric Endocrinology (ESPE), the
Global Pediatric Endocrinology and Diabetes (GPED), the Latin American Society of
Pediatric Endocrinology (SLEP), the Australasian Pediatric Endocrine (RAE). Previous
attendees of the conferences, training schools, or postgraduate courses hosted by the societies
were also considered for inclusion.
Six pediatric endocrinologists were responsible for developing the survey questions, and
ICPE members were provided with a direct online connection as well as the opportunity to
provide their approval to take part in the poll by email and other social media platforms
(Facebook, Twitter, and LinkedIn).
The questionnaire was broken up into fourteen different sections, each of which asked a
different set of questions about the respondents' professional and practice profiles, the sizes
of their clinics, the countries in which they practiced medicine, and how they managed the
most common endocrine diseases.
The questions covered the practice and perceptions of HCPs in relation to the number of
patients that were cared for, the organization of education sessions, the impact of the COVID-
19 pandemic on daily routine, the availability of medications, the frequency of acute
complications, delays to diagnoses, deterioration of disease control, and the psychological
impact on patients and their families. We asked a few more detailed questions in order to
define the profile of patients who tested positive for SARS-CoV-2 infection. These questions

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focused on the patients' features, clinical presentation, diagnosis, and treatment options.
Completing the survey required around thirty minutes of time.
STATA 14.0 for Windows was used to do the analysis on the data (College Station, TX,
USA). One center served as the point of correspondence for the analytic unit. During the
COVID-19 pandemic, descriptive statistics were used in order to display demographic data as
well as analyze the level of knowledge, attitudes, and perspectives held by HCPs. Means and
standard deviations (SD) were used to describe the quantitative variables, whereas numbers
and percentages were used to describe the qualitative variables. Because participants may
choose more than one answer to a question, the total number of replies was more than the
sum of some of the findings. Some of the questions were open-ended, and their responses
were examined using a coding method. In this method, answers that are quite close to one
another are condensed and approximated into information that is very similar semantically
(14).

RESULTS
There were a total of 136 replies that were analyzed; during the course of the research
project, a total of 134pediatric endocrine centers from 51 different countries and across all
continents took part in the gathering of data that was subsequently analyzed. Table 1 displays
the respondent's countries of origin as well as their professional backgrounds, center settings,
and sizes.
Table 1: Endocrine clinical center characteristics and staff profiles.
Characteristics (n respondents) Respondent
Centers by country
United Sates of America 12
Spain 10
Philippines 8
Germany 8
Egypt, Italy 6 each
Argentina, Brazil, United Kingdom 6 each
Canada, Greece 5 each
India, Japan, Netherlands, Portugal 3 each
Belgium, Bulgaria, Congo, Denmark, Indonesia, Iran, Malaysia, Mexico, New 2 each
Zealand, Peru, Serbia and Montenegro, Sweden, Turkey
Australia, Austria, Bangladesh, Chile, Cyprus, Finland, Georgia, Hong Kong, 1each
Hungary, Iceland, Iraq, Ireland, Israel, Lebanon, Luxembourg, Malta,
Netherlands Antilles, Poland, Romania, Slovenia, Sudan Taiwan, Ukraine
Current clinical role (134)
Pediatric endocrinologist/diabetologist 110
Pediatrician with interest in endocrinology 16
Resident or fellow or trainee in pediatrics/pediatric endocrinology or 5
diabetology or diabetes researcher
Adult physician looking after pediatric or adolescent patients 2
Nurse practitioner/registered nurse 1
Clinical setting (134)
University/academic hospital or clinic 66
Public/governmental hospital or clinic 42
Private hospital or clinic 25
Primary care center 1
Estimate case-mix, patients by endocrine disorders

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Type 1 diabetes
<100 50
100-250 40
251-500 15
>500 12
Type 2 diabetes
≤50 47
51-100 2
>100 5
Other forms of diabetes
≤50 40
51-100 1
>100 3
Obesity and metabolic syndrome
≤50 39
51-100 9
>100 20
Hyperinsulinemichypoglycemia
≤50 40
>50 2
Thyroid
≤50 50
51-100 14
>100 25
Adrenal
≤50 52
50-100 10
>100 4
Bone metabolism
≤50 25
>50 5
Pituitary and other CNS disorder
≤50 57
>50 5
Growth
≤50 45
51-100 50
>100 15
Pubertal
≤50 50
51-100 15
>100 5
Others: Gender dysphoria
≤50 1
>50 1
During the COVID-19 pandemic, routine follow-up visits and education were modified in the
majority of pediatric endocrine centers. Care and disease literacy were most commonly
delivered face-to-face (F2F) while wearing appropriate personal protective equipment (PPE),

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while telephone and video consultations were used in a less significant capacity. When it
came to diabetic care, only one caregiver was allowed to provide F2F care. On the other
hand, for hyperinsulinemichypoglycemia (HH) and bone metabolism disorders, more than
one fifth of centers continued to provide treatment in the same manner as before. It should
come as no surprise that the families' own anxiety about COVID-19 prevented them from
having much interaction with the diabetes or endocrine specialists in the majority of the
centers.
Table 2: Assessment of pediatric diabetes care during the COVID-19 pandemic by
clinical centers.
Type 1 Type 2 Other forms
diabetes diabetes of diabetes
Estimate proportion of delayed diagnose due to 47% 18% 18%
COVID-19
Estimate perception of worsening disease 30% 68% 30%
management
Use of technologies among patients
• Insulin pump N/A N/A
○ Less than 10 40
○ 10-25 15
○ 26-50 25
○ 51-75 24
○ 76-100 10
• CGMS N/A N/A
○ Less than 10 35
○ 10-25 27
○ 26-50 20
○ 51-75 24
○ 76-100 5
• Flash GMS N/A N/A
○ Less than 10 35
○ 10-25 30
○ 26-50 20
○ 51-75 21
○ 76-100 10
Testing
• COVID-19 tests for newly diagnosed. 75 N/A N/A
• Positivity
○ No positives with standardized tests 55 N/A N/A
○ Less than 25% 55
○ 26-50% 1
○ More than 75% 2
• COVID-19 tests in DKA cases 80 N/A N/A
• Positivity with standardized tests
○ Less than 10%
Testing
• COVID-19 tests for newly diagnosed. 70 N/A N/A
• Positivity
○ No positives with standardized tests 50 N/A N/A
○ Less than 25% 55

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○ 26-50% 1
○ More than 75% 2
• COVID-19 tests in DKA cases 80 N/A N/A
• Positivity with standardized tests
○ Less than 10% 75 N/A N/A
○ 10-25% 5
○ 26-50% 2
○ More than 75% 2
Diabetic ketoacidosis episodes
• Increase of newly-onset cases 55 N/A N/A
• Increase in stablished cases 35 N/A N/A
• Proportion of DKA episodes
○ 0-25% 65 N/A N/A
○ 26-50% 15
○ 51-75% 20
○ 76-100% 13
• Proportion of mild DKA N/A N/A
○ 0-25% 65
○ 26-50% 35
○ 51-75% 15
○ 76-100% 5
• Proportion of moderate DKA N/A N/A
○ 0-25% 70
○ 26-50% 33
○ 51-75% 10
○ 76-100% 5
• Proportion of severe DKA N/A N/A
○ 0-25% 85
○ 26-50% 15
○ 51-75% 15
○ 76-100% 3
• Perception of worsening episodes 50 N/A N/A
Severe Hypoglycemia episodes
• Increase of SH episodes 11 N/A N/A
Routine check-up
• As usual, no changes 20 10 9
• Sent SMS and emails for consultation. 35 10 14
• Apps 19 5 12
• Telephone consultations 75 25 25
• Video consultations 50 23 15
• Face to face consultation with appropriate 76 N/A N/A
personal protective equipment restricted to just one
parent/caregiver
• Face to face consultation with appropriate 14 35 30
personal protective equipment where all caregivers
are allowed to attend
• No consultation during complete lockdown or 3 1 0
postponing it to annual visits

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• Limited contact with diabetes team because of 84 39 35

COVID-19 fear
Daily routine
• Maintenance of physical activity
○ Less than 10% 25 N/A N/A
○ 10-25% 45
○ 26-50% 20
○ 51-75% 15
○ 76-100% 10
• Worsening of dietary choices
○ Less than 10% 25 N/A
○ 10-25% 30
○ 26-50% 38
○ 51-75% 10
○ 76-100% 10 N/A
• Increase of body weight
○ Less than 10% 25 N/A
○ 10-25% 30
○ 26-50% 35
○ 51-75% 19
○ 76-100% 10
• Extra dose of insulin
○ Yes 1
○ No N/A
○ Not on insulin therapy N/A N/A
• Average glycemic control during pandemic
○ Mostly improved 24
○ Mostly maintained same level 58 34
○ Mostly worsened 36 N/A
• Regular use of anti-hypertensive
○ ACE inhibitor N/A
○ B-blocker
○ Ca channel blocker 4 20 N/A
○ Control with salt-free diet 21
○ None 15
N/A
School activities
• Parental concerns to return to school activities 75 15 N/A
• Specific school guidelines during pandemic 80
Patient and family education
• As usual, no changes 5 6 3
• By telephone 50 25 30
• Video consultations 50 21 20
• Apps/digital platforms 20 15 15
• Face to face education wearing appropriate 95 40 40
personal protective equipment
Supplies
• Refill prescription N/A N/A

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○ Refill prescription every month 15

○ Refill prescription every 3 months or less 50
○ Refill prescription every 6 months or less 15
○ Refill prescription every year or less 11
○ As required by patient 15
○ Automatic refill prescription from pharmacy 5
○ I am not directly involved with prescription 5
• Shortage of supplies
○ Yes 24 7 5
○ No, everything was secured 75 33 35
○ I am not aware of situation 10 11 6
• Item under shortage
○ Basal insulin 14 2 1
○ Bolus insulin 11 0 1
○ Glucose test strips 15 5 4
○ Blood glucose sensors 14 1 3
○ Insulin pump supplies 6 0 0
○ Ketone test strips 10 0 0
○ Oral medication 1 1 1
○ Genetic tests 0 1 2
Characteristics of COVID-19 cases
• Estimate mean age, years 10.5 12.7 N/A
• Estimate % boys 50.1 52.1
• Estimate % girls 52.1 40.1
• Estimate mean duration of disease, years 4.0 1.5
• Estimate mean HbA1c value, % 8.5 7.5
• BMI, Kg/m² N/A
• Presence of comorbidities
○ Asthma 30 15 5
○ Cancer 4 2 5
○ Obesity 45 50 10
○ Hypertension 20 25 1
○ Heart disease 3 0 2
○ Kidney disease 15 3 8
○ Neurological disease 2 0 2
○ Celiac disease 10 1 0
○ Hypothyroidism 7 0 0
○ Cystic fibrosis or bronchial dysplasia 10 2 11
○ Other: Allergy, other autoimmune disease, 4 2 2
dyslipidemia, Polycystic ovary syndrome, Lupus,
Anemia
○ No 35 5 20
Psychological concerns
• Anxiety 70 35 25
• Parenting stress 65 25 15
• Depression 45 25 13
• Insomnia/hypersomnia or other sleep disruption 35 15 5
• Eating disorder 25 15 5

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• Panic attacks 15 10 5
• Suicide attempt 5 2 1
• Patient or caregivers have improved the mood 4 0 1
• None have had psychological problems so far 31 17 20
Open in a separate window N/A, not applicable.
Table 3: Assessment of pediatric endocrine care other than diabetes during COVID-19
pandemic by clinical centers.
Obesity and Hyperinsulin Thyr Adre Bone Pituita Gro Pube
Metabolic emichypogly oid nal metab ry and wth rtal
Syndrome cemia disor disor olism other disor disor
ders ders disord CNS ders ders
ers disorde
rs
Estimated 40.1 9.5 21.1 14.5 18.5 21.5 35.3 37.6
proportion of
delayed
diagnoses due
to COVID-19
Estimated N/A 7.5 N/A 4.6% N/A N/A N/A N/A
proportion of
increase in
severity
Estimate 85.2 23.1 20.3 33.1 32.1 27.4 35.5 34.5
perception of
worsening
disease
management
Patient and
family
education
• As usual, no 5 3 7 5 2 2 5 4
changes
• By telephone 30 27 53 35 23 35 40 37
• Video 20 10 28 25 11 25 25 15
consultations
• Apps/digital 11 10 12 14 5 10 12 11
platforms
• Face to face 45 35 68 55 15 50 55 59
education
wearing
appropriate
personal
protective
equipment
Supplies
• Shortage of
supplies
○ Yes 10 9 10 15 8 15 16 15
○ No, 50 31 75 45 21 45 55 48

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everything was
secured
• Item under
shortage
○ Oral/nasal 5 8 7 15 5 10 1 1
medications
(e.g.,
metformin,
diazoxide,
levothyroxine,
methimazole,
hydrocortisone,
fludrocortisone,
calcitriol,
desmopressin,
estrogen)
○ Injectable 4 2 1 2 2 2 10 2
medications
(e.g., insulin,
octreotide,
glucagon,
bisphosphonate,
GnRHa, rhGHa)
○ Topic 0 0 1 0 0 1 0 0
medications
(e.g., estrogen)
○ Test strips N/A 1 N/A 1 N/A N/A N/A N/A
○ Syringe 0 2 0 0 0 0 1 0
○ Genetic 1 1 1 1 2 2 4 2
testing /imaging
• Presence of
comorbidities
○ Asthma 25 3 17 5 1 4 20 4
○ Cancer 2 0 5 2 3 12 3 2
○ Obesity 1 5 25 5 10 24 20 21
○ 35 1 3 3 0 2 3 1
Hypertension
○ Heart 2 1 5 2 1 3 11 2
disease
○ Kidney 4 2 3 1 12 3 1 2
disease
○ 0 2 1 0 1 0 0 2
Neurological
disease
○ No 10 25 44 38 40 25 32 30
Use of
medications
• Anti- N/A N/A N/A N/A N/A N/A N/A
hypertensive

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○ ACE 22
inhibitors I/II
○ Beta- 2
blocker
○ Ca channel 2
blocker
○ Salt-free 2
diet
○ No 21
treatment
○ 47
Continuation of
anti-
hypertensive
○ No 45
complication
with anti-
hypertensive use
○ N/A N/A N/A N/A N/A N/A N/A N/A
Maintenance of
treatment during
COVID19
• Management N/A N/A N/A N/A N/A N/A N/A
of adrenal crisis
○ Fluid and
electrolyte
resuscitation
○ Ample 3 45
doses of
glucocorticoids
○ Chronic 5 4
glucocorticoid
and
mineralocorticoi
d replacement
○ Treatment 1
of the
precipitating
illness
Table 2 shows the proportion of centers that had patients impacted by COVID-19 for all
types of diabetes. Table 3 shows the percentage of centers that had patients affected by
COVID-19 for other endocrine illnesses. Patients with diabetes were the most impacted by
COVID-19, with more severe symptoms, perhaps owing to a larger proportion of
comorbidities (Table 2) than patients with other endocrine disorders. Patients with diabetes
also had a higher mortality rate than patients with other endocrine diseases (Table 3). It is
important to highlight that individuals with bone metabolism problems seemed to have a
greater susceptibility to COVID-19 infection owing to the fact that they had concomitant
renal illness.
The majority of individuals diagnosed with COVID-19 either had no symptoms or had
symptoms ranging from mild to severe (Tables 4). However, symptoms seemed to be more

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common and severe in centers where patients with type 1 diabetes had a positive COVID-19
test than in centers where patients with other endocrine problems were treated (Tables 4).
There were no documented fatalities associated with any endocrine disorder.
Table 4: Symptoms, complications, and outcomes of pediatric diabetes cases during the
COVID-19 pandemic by clinical center.
Type 1 Type 2 Other forms
diabetes diabetes of diabetes
Symptoms and/or complications among
COVID-19 cases
• Asymptomatic
○ None 70 32 31
○ 1-25% 20 5 2
○ 26-50% 10 2 3
○ 51-75% 5 4 5
○ 76-100% 11 5 5
• Fever
○ None 25 35 31
○ 1-25% 21 6 8
○ 26-50% 15 5 5
○ 51-75% 10 5 5
○ 76-100% 15 0 1
• Cough
○ None 31 33 21
○ 1-25% 30 4 7
○ 26-50% 25 12 5
○ 51-75% 15 4 2
○ 76-100% 10 5 2
• Pharyngeal erythema
○ None 78 36 41
○ 1-25% 25 10 10
○ 26-50% 5 3 5
○ 51-75% 10 10 8
○ 76-100% 5 2 1
• Rhinorrhea
○ None 55 35 40
○ 1-25% 21 10 10
○ 26-50% 21 5 5
○ 51-75% 15 6 6
○ 76-100% 10 1 3
• Shortness of breath
○ None 80 45 42
○ 1-25% 31 6 4
○ 26-50% 5 3 1
○ 51-75% 2 3 0
○ 76-100% 2 1 2
• Headache
○ None 55 40 40
○ 1-25% 34 10 5
○ 26-50% 6 5 3
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○ 51-75% 10 7 4
○ 76-100% 6 0 0
• Myalgia
○ None 55 35 40
○ 1-25% 43 12 7
○ 26-50% 15 5 6
○ 51-75% 8 8 1
○ 76-100% 9 0 4
• Hyperglycemia
○ None 60 35 40
○ 1-25% 21 4 5
○ 26-50% 15 9 6
○ 51-75% 15 4 2
○ 76-100% 8 2 0
• Hypoglycemia
○ None 110 45 45
○ 1-25% 15 6 4
○ 26-50% 0 1 0
○ 51-75% 3 0 0
○ 76-100% 0 0 1
• Diabetic ketoacidosis
○ None 80 51 51
○ 1-25% 25 7 2
○ 26-50% 5 4 1
○ 51-75% 5 0 0
○ 76-100% 1 1 0
Outcomes for COVID-19 cases
• Admission
○ None 65 56 40
○ 1-25% 35 10 4
○ 26-50% 5 1 4
○ 51-75% 4 1 1
○ 76-100% 7 2 1
• Admission to intensive care unit
○ None 70 51 45
○ 1-25% 20 5 2
○ 26-50% 2 0 3
○ 51-75% 5 3 3
○ 76-100% 5 0 0
• Need for bronchodilators and
glucocorticoids
○ None 87 45 48
○ 1-25% 25 8 2
○ 26-50% 5 0 2
○ 51-75% 0 4 0
○ 76-100% 0 0 0
• Need for oxygen
○ None 55 43 45

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○ 1-25% 20 7 6
○ 26-50% 10 5 1
○ 51-75% 1 0 1
○ 76-100% 3 1 0
• Need for intubation and ventilation
○ None 110 50 41
○ 1-25% 15 6 1
○ 26-50% 1 0 1
○ 51-75% 0 2 0
○ 76-100% 0 0 0
• No need for specific treatments
○ None 60 35 40
○ 1-25% 10 5 3
○ 26-50% 10 3 5
○ 51-75% 15 5 4
○ 76-100% 25 7 5
• Increased insulin dosage/other treatment
adjustment
○ None 45 35 40
○ 1-25% 20 8 9
○ 26-50% 24 5 5
○ 51-75% 5 1 4
○ 76-100% 20 2 5
• Need for antivirals
○ None 115 55 45
○ 1-25% 7 5 4
○ 26-50% 0 0 0
○ 51-75% 0 0 0
○ 76-100% 0 0 0
• Need for anti-IL6 therapy
○ None 115 55 45
○ 1-25% 2 0 0
○ 26-50% 0 2 0
○ 51-75% 0 0 0
○ 76-100% 0 0 0
• Need for hydroxychloroquine
○ None 112 50 45
○ 1-25% 3 1 0
○ 26-50% 2 0 1
○ 51-75% 0 0 0
○ 76-100% 0 0 0
• Need for azithromycin
○ None 85 45 45
○ 1-25% 7 3 1
○ 26-50% 11 1 1
○ 51-75% 5 3 1
○ 76-100% 5 0 1
• Average glycemic control during the

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pandemic
○ Mostly improved 21 5 N/A
○ Mostly maintained same level 65
○ Mostly worsened 43
In most cases, it was not essential to treat COVID-19 with general treatment procedures.
Patients did not need to be admitted to the hospital in the majority of centers, and the vast
majority of them did not need beds in an intensive care unit (ICU), with the exception of
patients who had diabetes. (Tables 4). In patients with type 1 diabetes, type 2 diabetes and
obesity, the percentage of patients who required bronchodilators and glucocorticoids more
often was greater than in individuals with other endocrine diseases who tested positive for
COVID-19. They also required oxygen at a higher rate, non-invasive ventilation at a higher
rate, intubation and ventilation at a lower rate, and other treatments (such as antibiotics and
antiviral medicines more often than patients with other endocrine problems (Tables 4).
Although patients with COVID-19 only rarely required specific therapeutic measures for
endocrine management, adjustments to the background treatment dose were common.
The proportion of centers reporting an increase in newly diagnosed cases of moderate to
severe diabetic ketoacidosis (DKA) and new episodes in already established patients showed
in (Table 2).
The majority of HCPs carried out COVID-19 testing on newly diagnosed patients (55%), as
well as on existing patients (35%) for DKA episodes; (Table 2).
There was a delay in new diagnosis as well as a deterioration of the therapy for the vast
majority of the endocrine illnesses that were evaluated. The majority of individuals who were
diagnosed with COVID-19 either did not exhibit any symptoms or had symptoms ranging
from mild to severe (Tables 3,4).
Surprisingly, individuals with obesity or metabolic syndrome were able to continue using
ACE inhibitors, the antihypertensive medicine that was used the most, without interruption
and without experiencing any consequences to this day. It is important to highlight that less
than 10% of patients with HH reported having at least one episode of severe hypoglycemia.
There were two pediatric endocrine facilities that specialized in treating children and
adolescents who struggled with gender dysphoria. The majority of patients received follow-
up and education either via a telephone appointment or face-to-face interaction while wearing
proper PPE. Because of the worry that the pandemic might spread, communication with the
endocrine team was severely restricted at both locations. As a result, the diagnosis was
sometimes delayed, but this did not seem to make the treatment any less effective. Patients
diagnosed with gender dysphoria did not have an increased risk of suffering from COVID-19,
contrary to what was seen for the majority of other endocrine diseases.
Lack of physical activity and inferior food choices were found, leading to a rise in body
weight (25%) in these patients. Seventy-five percent of those who participated in the survey
showed significant levels of parental worry on the return to school activities (Table 2). In
spite of this troubling finding, it was heartening to see that the majority of schools, In
addition, children diagnosed with pediatric endocrine disorders, which may include any and
all types of diabetes, often report abnormalities in their overall psychosocial and behavioral
functioning. Anxiety, sadness, the stress of parenthood, sleep disruptions, and eating
disorders were indicated as being the most frequent types of difficulties. In point of fact,
attempts at suicide were found in all conditions, with the exception of puberty problems
(Tables 2,3).
DISCUSSION
According to the results of this study, the percentage of children with endocrine abnormalities
who tested positive for COVID-19 is sufficiently low that pediatric endocrine diseases should
not be considered a risk associated with a poor prognosis for COVID-19. As was previously

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documented, children and adolescents with any kind of endocrine disease did not have an
elevated risk of contracting COVID-19 compared to children who did not have any type of
endocrine condition (14,15). Comparing the proportion of patients with diabetes and COVID-
19 in our previous survey with those reported here [only diabetes was assessed previously
(9)], there was a significant increase in the number of children and adolescents with type 1
diabetes or other forms of diabetes who tested positive for COVID-19. This was the case
despite the fact that only diabetes was evaluated in the previous survey (9). This is most
likely attributable to the fact that much more COVID-19 testing was carried out as the
epidemic proceeded as opposed to during the early stages of the pandemic (January-
September 2020) and the reopening of schools in several nations.
Patients with type 1 or type 2 diabetes were not only more likely to suffer from COVID-19
but also experience moderate to severe symptoms, especially when other comorbidities were
present. While the majority of pediatric patients with endocrine disorders affected by
COVID-19 have asymptomatic or mild symptoms (16), it is important to note that patients
with type 1 or type 2 diabetes were not only more likely to suffer from COVID-19 but also
experience moderate to severe symptoms (17, 18). As a consequence of this, the number of
diabetic patients admitted to the intensive care unit (ICU) also increased when compared to
our previous survey (9), reaching a higher proportion of centers that reported intubation and
ventilation in comparison to other endocrine conditions that were included in our survey.
Diabetes and obesity are also risk factors for increased morbidity and mortality in adult
patients with COVID-19 (19–21), although it is heartening that in individuals less than 25
years old, the mortality rate approaches zero even when diabetic or obese. So far, no fatalities
have been documented.
Although there are some data on adult patients (10–13), very little is known regarding the
influence of COVID-19 on other endocrine illnesses in the pediatric population. To the best
of our knowledge, this is the first real-world and worldwide research that has been conducted
on this subject. The present experiences of healthcare professionals who specialize in
pediatric endocrinology imply that the treatment of diabetes is much more time-consuming
and difficult than the management of other endocrine diseases. COVID-19 and diabetes
mellitus are linked to one another in both directions. Diabetes that is not under control is
associated with a more severe form of COVID-19 in adults. In addition, serious metabolic
consequences, such as diabetic ketoacidosis (DKA), have been documented in individuals
who had COVID-19, either at the outset (22, 23) of their diabetes or in patients who already
had diabetes (24). Although it does not seem that pediatric patients with diabetes have an
increased risk of SARS-CoV-2 infection, it is nonetheless important to avoid being infected
and to take all preventative measures feasible (25). In addition to this, it has been postulated
that SARS-CoV-2 could cause diabetes in and of itself, much as SARS-coronavirus 1
pneumonia does in its victims (26). On the other hand, this link has not yet been shown to
exist, and further research in both adults and children is required.
According to the results of the current study, the COVID-19 pandemic was responsible for a
delay in hospital admissions for diabetes and other endocrine illnesses, which led to a larger
number of severe DKA patients, among other things, as has been documented elsewhere (22,
23, 27). It is essential to have a safe route that does not involve COVID-19 through pediatric
emergency departments in order to assist and reassure parents who wish to bring their
children to the hospital as quickly as possible in order to avoid needless complications in
diabetes and other endocrine disorders (22).
Once endocrine illness has been diagnosed, it is essential to have an open line of
communication with healthcare providers (HCPs), as is advocated by a multitude of
endocrine organizations (9, 28, 29), particularly via the use of telemedicine so as to avoid
congested waiting rooms. However, in the current survey, we found that despite the need to

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reduce the number of unnecessary hospital visits during the pandemic by using dedicated
platforms or video calls, text messaging, and emails, routine face-to-face visits remained the
most common method of consultation. This was the case despite the fact that these methods
were available. It is possible that an increase in awareness about telemedicine may assist
patients and their families acquire confidence in this method of providing medical treatment.
Complications in these patients may be avoided by giving priority to counseling on care
management and accelerating innovation in telehealth. This is particularly important in
situations where there are limited resources. Video platforms have been adopted at several
institutions, particularly for educational purposes; however, not all of these institutions allow
telehealth for inpatient care, and the usefulness of telemedicine for educational purposes is
still up for debate [30-32].
During the COVID-19 pandemic, some parents were worried about the safety of returning
their children who suffered from endocrine problems, most notably diabetes, back to school
because they believed that these children had a larger probability of being infected with
coronavirus. On the other hand, and this is reassuring, the vast majority of them were aware
with the school's requirements and made sure that a disease care plan was in place (25, 30,
31).
It is of the utmost significance to have quick access to endocrine and diabetic care drugs and
supplies, which was already a problem in a huge portion of the globe prior to the epidemic.
Even though daily self-management, sick day management, and survival are all dependent on
the availability of medical supplies, access issues have been exacerbated as a result of the
pandemic. Important infrastructure, such as outpatient clinics and public transport, has been
severely limited as a result of the pandemic. Fortunately, the current study found that a lack
of supplies was reported by only a small percentage of centers (ranging from 6-22%
depending on the kind of endocrine condition).
We made the observation that COVID-19 was associated with endocrine illness and
comorbidities, with obesity and hypertension being the comorbidities that were reported the
most often in relation to all endocrine disorders. Comorbidities were common among the
children and adolescents who required acute medical care. As a result, it is of the utmost
importance to have an understanding of which modifiable risk factors have the potential to
play a part in enhancing the severity of COVID-19 (32–36). Comorbidities are less common
in young patients than in adults, which may explain why children are less prone to COVID-
19 but why some children still become critically sick. The reasons for why some children
suffered from more severe COVID-19 are yet unknown. Because of the recent spike in the
prevalence of type 2 diabetes and obesity in children and adolescents, it is possible that a
considerable number of youngsters are at an increased risk.
Comorbidities in mental health have been made worse across the board as a result of the
COVID-19 epidemic, particularly in people who suffer from diabetes and other endocrine
illnesses (37,38). Children are at a greater risk of developing adverse health effects than
adults because their neurological systems, endocrine systems, and hypothalamic-pituitary-
adrenal axis are not fully matured. Children who are experiencing mental health issues often
experience emotions of abandonment, hopelessness, incompetence, and tiredness, which may
even increase the likelihood of their taking their own lives. Notably, the results of our study
showed that children suffering from a broad variety of endocrine disorders had a much higher
risk of attempting suicide during the pandemic. The provision of psychosocial support for
children and their families is an essential component of both the health response to a
catastrophe and the recovery from it. This is particularly true for families with children who
suffer from chronic health disorders. Protective measures that are timely and adequate are
required in order to forestall psychological and behavioral issues. It is possible that emerging
digital applications and health services, such as telemedicine, social media, mobile health,

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and remote interactive online education, can assist bridge the social distance and support the
mental and behavioral health of children (39).
The SARS-CoV-2 virus has several pathophysiologic linkages with endocrine systems, and
these interconnections have the potential to produce changes in pituitary, adrenal, and thyroid
function, as well as mineral metabolism. The majority of the research done on the dangers of
SARS-CoV-2 infection in people with underlying endocrine abnormalities has been done on
adults (40). However, the limited data that are currently available are generally favorable in
terms of the endocrine complications of COVID-19 in the pediatric population (41), as
confirmed in our survey, where children with well-managed endocrine conditions did not
seem to be at increased risk of getting infected with COVID-19 or becoming severely ill from
the virus.
Previous research shown that the use of telemedicine for the treatment of juvenile obesity was
effective; however, adapting this methodology to the use of telemedicine for the treatment of
other endocrine diseases may be difficult (42).
At this time, there is no evidence to suggest that children and adolescents who have
underlying thyroid abnormalities have an increased chance of getting SARS-CoV-2 infection
or an altered illness course. It is essential to bear in mind, however, that individuals
diagnosed with Graves' disease who are undergoing treatment with anti-thyroid medication
run a significantly increased risk of developing agranulocytosis as well as secondary
infections (43). This is of particular significance in light of the findings of a single research
which indicated that one-half of those who did not survive COVID-19 also developed a
subsequent infection (44). In addition, similar to other infections, COVID-19 has the
potential to bring on a thyroid storm in individuals whose hyperthyroidism is not under
adequate management (41). In individuals affected with COVID-19, an underlying thyroid
condition, particularly hypothyroidism, does seem to be a risk factor for a more severe
disease course (45–47). Children who suffer from metabolic bone disease or skeletal
dysplasia, both of which may lead to respiratory insufficiency as a consequence of an altered
chest wall structure, may have a higher risk of COVID-19 problems (48).
Due to the impaired natural immunity function that is characterized by a defective action of
neutrophils and natural killer cells, which is known to be associated with primary adrenal
insufficiency, patients with primary adrenal insufficiency (such as congenital adrenal
hyperplasia) are slightly more susceptible to infections in general. This is because primary
adrenal insufficiency is known to be associated with primary adrenal insufficiency (49).
Additionally, susceptibility to infections may also be explained by an inadequate increase in
the dose of hydrocortisone at the start of an illness. This may be the case if the dosage was
not increased enough. According to the guidelines, therefore, children who are not
experiencing any symptoms should continue to take their normal replacement doses of
hydrocortisone rather than receiving higher dosages of the medication. If you have symptoms
that might point to COVID-19, it is suggested that you immediately increase the dosages of
hydrocortisone you are taking until the fever subsides, and then add an additional dose that is
doubled.
Children who have been given a clinical diagnosis of hypopituitarism do not have an elevated
risk for COVID-19. Due to the fact that a sizeable proportion of these individuals are
suffering from secondary adrenal insufficiency, the same guidelines that are given to children
who have adrenal insufficiency should be followed (50). In the case of COVID-19, the
hyperinsulinemichypoglycemia side effects of the medications that are used to treat
hyperinsulinemichypoglycemia (for example, diazoxide side effects include water retention
and pulmonary hypertension; somatostatin analogues side effects include cardiac arrhythmias
and cardiac conduction disorders) should be taken into consideration. The care of
hypoglycemia in children should be followed throughout this pandemic. This includes close

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monitoring of glucose levels, proper hydration, guaranteeing the availability of drugs, and an
emergency protocol. However, it is comforting to know that survey statistics reveal that all of
these endocrine problems did not create any significant discomfort to patients, and the only
severe concern that patients will have to deal with is the possibility of a lack of medications
and/or supplies.
The vast majority of endocrine data comes from guidelines for the treatment of juvenile
endocrine problems that have been provided by a variety of health organizations and
endocrine groups. These recommendations were produced throughout the pandemic. The
majority of children with endocrine abnormalities do not constitute a high-risk group for
contamination or severe manifestation of COVID-19; thus, according to the specified "sick
day management standards" and seeking medical treatment without delay are only required in
the majority of situations (51).
Although it is difficult to analyze the effects of COVID-19 on endocrine disorders in children
due to a lack of studies and relatively less severe cases as compared to adults (52–54), it
appears, looking at the data collected with the present survey, that diabetes is still more
difficult to manage than any other pediatric endocrine disorder with an increased risk of
morbidity. This is the case despite the fact that it is difficult to analyze the effects of COVID-
19 on endocrine disorders in children.
There are a few problems with this research. In general, we obtained a lower response rate
than we did in the last survey, which was centered on diabetes. We have a working
hypothesis that health care professionals see COVID-19 as having a greater impact on
diabetes, both directly and indirectly. Directly, diabetes is a risk factor for mortality and
morbidity related to COVID-19. Indirectly, the pandemic can influence the management of
diabetes and the availability of supplies. Other factors that may have contributed to the lack
of responses include the pressures brought on by COVID-19, survey weariness brought on by
the pandemic, an inadequate reach of potential participants by email, perceived stress, and
burnout connected to job. Despite this, this is the first research ever conducted on a
worldwide scale to investigate the effects of COVID-19 in any and all pediatric
endocrinology problems. The majority of pediatric endocrinologists who participated in the
study were located in nations that were badly damaged by COVID-19, and they were
employed at academic or university facilities. This contributed to the reliability of the data as
well as its worldwide reach.

Conclusion:
In conclusion, the findings presented here demonstrate that diabetes posed a unique treatment
burden during the COVID-19 pandemic and is associated with an elevated risk of
morbidities, including diabetic ketoacidosis (DKA). It is vital to establish specific techniques
in order to educate and reassure parents about the need of keeping in regular touch with their
HCPs and promptly attending the emergency department in the event that their children
develop symptoms that are unrelated to COVID-19. It is imperative that important
medications continue to be available across the world. The use of telemedicine has to be
improved and should become standard practice at all facilities. It is necessary to attend to the
requirements of children and adolescents suffering from endocrine diseases in terms of their
mental health. In order to lessen the severity of the effects that COVID-19 has on pediatric
patients suffering from diabetes and other endocrine problems, guidelines at the international
level must be developed with a particular focus on the psychological effects of the virus.
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