Short summary

Grave's Disease (GD) is a relatively rare condition in children and adolescents. However, recent Danish data showed an increased incidence during the last decades. Currently, there is no knowledge about long-term consequences of Juvenile GD (JGD). In this study we investigate whether JGD has a long-term impact on health and education and whether it has socio-economic implications to be a parent to a child with JGD. The results for JGD are compared with findings in age- and sex-matched healthy controls and controls with type 1 diabetes. The knowledge gained through the study can be used to inform and counsel children with JGD and their parents.

Rationale

In this study we investigate whether Juvenile Graves' Disease (JGD) has a long-term impact on health and education. The study will also reveal whether it has socio-economic implications to be a parent of a child with JGD.

In 95% of the cases juvenile thyrotoxicosis is caused by Graves' Disease. This is an autoimmune disease in which circulating TSH-receptor antibodies (TRaB) stimulate the thyroid gland to increase thyroid hormone production. As a consequence the person will develop thyrotoxicosis.

The aetiology of JGD is not known in detail, but it is thought to be caused by a complex interaction of environmental and genetic factors. The clinical symptoms and signs of JGD are nonspecific, and the onset of disease can be insidious which often delays the diagnosis. Juvenile GD is most frequently diagnosed in adolescence and has a female preponderance.

Previous Danish registry studies in the adult population have demonstrated that having or have had thyrotoxicosis has long-term consequences for the person's health. Thus, thyrotoxicosis is associated with increased morbidity, somatic as well as psychiatric. Adults with thyrotoxicosis have an increased mortality, regardless of prior comorbidities but related to the duration of hyperthyroidism. Moreover, in adults thyrotoxicosis is associated with reduced capacity to work, reduced labor income and increased risk of receiving disability pension.

Hyperthyroidism (thyrotoxicosis) is a relatively rare condition in children and adolescents. However, recent data from Denmark showed an increased incidence of thyrotoxicosis during the last decades. Thus, in Denmark approximately 20 children and young people are annually diagnosed with thyrotoxicosis. Despite therapy, only one third of these children will obtain clinical remission, while approximately two third of the patients will need medical treatment  for several years. Currently, there is no knowledge about long-term consequences of having or have had JGD. In this project, we use a national patient population, whereby the possible long-term consequences of having or have had JGD can be evaluated with great power.

Description of the cohort

This study is a register-based cohort study based on all children and adolescents (1-17,9 years) in Denmark diagnosed with JGD in the period 1977-2017. All the included patients must be registered with the diagnosis of GD in the Danish National Patient Register (DNPR), classified by International Classification of Diseases 8 and 10 (ICD 8 and 10, E242.00 in the period 1977-1993 and E05.0 in the period 1994-2017). Furthermore, parents to the abovementioned patients are included in the cohort.

Data and biological material

This study is based on the following Danish registers:

The CPR register:

Relevant socioeconomic factors on the cohort and control group such as average results on graduating exams from elementary school and in a subgroup of patients > 30 years the level of education will be registered. Furthermore, in this subgroup earned income, social class and marital status (married, children, cohabiting, divorced) will be evaluated. For the parents to the cohort and control group relevant socio-economic consequences such as divorce rate, household income, labour market and social class will be registered.

The Danish National Patient Register (DNPR):

Relevant diagnoses on Grave's Disease, autoimmune disorders and psychiatric diseases classified by ICD-8 and ICD-10

The Prescription Database:

Relevant ATC-codes for antithyroid medicine, antidepressant drugs and drugs used to treat ADHD Attention-Deficit-Hyperactivity-Disorder (ADHD)

Collaborating researchers and departments

H. C. Andersen Children's Hospital, Odense University Hospital

• Specialist registrar Rikke Havgaard Kjær, MD
• Consultant Dorte Hansen, MD, PhD

Department of Endocrinology, Odense University Hospital

• Thomas Brix, MD, PhD

• Chief physician Hans Perrild