Þórbergur Atli Þórsson¹
Ragnar Bjarnason^1,2
Soffía Guðrún Jónasdóttir³
Berglind Jónsdóttir²

¹Faculty of Medicine, Department of Health Sciences, University of Iceland, Reykjavík, ²Childrens Hospital Hringurinn, National University Hospital of Iceland, Reykjavík, ³Domus Medica, Reykjavík.

Correspondence: Berglind Jónsdóttir, bergljon@landspitali.is

Key words: Graves‘ disease‘, pediatric, treatment, Iceland.

INTRODUCTION: Graves‘ disease is an autoimmune disease in which autoantibodies cause an increase in the production of thyroid hormones, and is the most common cause of thyrotoxicosis in children. Symptoms in children are often more obscure than in adults. The aim of the study is to assess the incidence of Graves' disease in children and adolescents in Iceland over the span of two decades (2001-2021), and furthermore to investigate if the incidence rate has increased, as well as to describe treatment options and disease recurrence.

MATERIAL/METHODS: This retrospective descriptive study included all children diagnosed with Graves‘ disease in the years 2001-2021 in Iceland. Information was obtained from the Directorate of Health‘s drug database and from ICD-10 diagnoses at Landspítali – The National University Hospital.

RESULTS: In total, 57 children and adolescents were diagnosed with Graves', the overall incidence rate was 3.5/100,000 person-years. Gender ratio was 1:2.7 (male : female) and the mean age at diagnosis was 13.6 for boys and 13.9 years for girls. Of those 12 individuals currently receiving drug therapy (21.8%), four patients have had disease relapse. Thirteen patients reached an euthyroid state with medication (23.7%), 25 received treatment with radioactive iodine (45.5%) and 5 underwent surgery (9.1%). Boys were more likely to relapse. Disease recurrence was 31.8%.

CONCLUSION: The incidence of Graves‘ disease did not increase during the study period. The disease was more common in girls, although the gender ratio was lower than expected. Antithyroid drugs were the first choice in treatment and radioactive iodine was the most common permanent treatment option. Disease recurrence was common. A possible relationship between the duration of the original drug therapy and disease recurrence should be investigated.

Table I: The female:male ratio, mean- and median age of individuals diagnosed in different decades of the study period.

	First decade (n = 28)	Second decade (n = 29)
Sex
Boys	6 (21.4 %)	10 (34.5 %)
Girls	22 (78.6 %)	19 (65.5 %)
Age (years)
Mean	14.2	13.4
Median [Min; Max]	14.3 [6.8; 17.9]	14.6 [5.5; 17.6]

Table II: The number of individuals with a medical- or a family history of different diseases.

	Medical history No Proportion		Family history No Proportion
Autoimmune diseases
Thyroid disease (Hypo- or hyperthyroidism)	-	-	30	54.5 %
Coeliac disease	3	5.5 %	1	1.8 %
Diabetes mellitus type 1	2	3.6 %	1	1.8 %
Rheumatoid arthritis	1	1.8 %	1	1.8 %
Crohn‘s disease	0	0.0 %	1	1.8 %
Vitiligo	0	0.0 %	1	1.8 %
Allergic diseases
Allergy	5	9.1 %	2	3.6 %
Asthma	4	7.3 %	0	0.0 %
Eosinophilic eosophagitis	0	0.0 %	1	1.8 %
Other
Down‘s syndrome	2	3.6 %	0	0.0 %
Asperger syndrome	1	1.8 %	0	0.0 %
Thyroid nodules	0	0.0 %	1	1.8 %

Table III: Signs or symptoms experienced by individuals at disease diagnosis.

Signs or symptoms	No (n = 55)	Proportion
Tremor	31	56.4 %
Weight loss	27	49.1 %
Heat sensitivity and sweating	22	40.0 %
Fatigueness	21	38.2 %
Mood swings	20	36.4 %
Tachycardia	20	36.4 %
Learning difficulties	14	25.5 %
Graves‘ ophthalmopathy	13	23.6 %
Difficulity breathing/ Obstruction of airway	13	23.6 %
Insomnia	10	18.2 %
Diarrhoea	8	14.5 %
Tongue fasciculation	6	10.9 %
Dizziness	4	7.3 %
Abnormal menstruation	4	7.3 %
Hypertension	3	5.5 %
Nausea	3	5.5 %
Elevated liver enzymes (ASAT og ALAT)	2	3.6 %
Dysphonia	1	1.8 %
Syncope	1	1.8 %
Epiphora	1	1.8 %
Hair loss	1	1.8 %
Thyroid bruit	1	1.8 %

Figure 1: Distribution of individuals in the total study cohort regarding exclusion or disease diagnosis.

Figure 2: Age distribution at date of diagnosis. Incidence rate increases in both sexes after the age of 10. Figure 3: All patients in the research cohort started off with drug therapy. Of those 12 individuals currently receiving drug therapy, four have had disease relapse. An euthyroid state was reached with drug therapy in 27 patients of those 14 had disease relapse later on. Drug therapy did not suffice in the case of 20 patients.