Summary

A large number of children and adolescents suffering from type 1 diabetes have organ-specific autoantibodies, islet autoantibodies and hence diagnosed with an autoimmune condition, the most common being thyroid disorders- hypo- and hyperthyroidism. Screening of common subclinical and asymptomatic comorbid conditions can help in timely identification and treatment.

This guideline, based on the ISPAD Clinical Practice Consensus Guidelines 2018 Compendium, elaborates on autoimmune thyroid disorders that arise in children and adolescents with type 1 diabetes (T1D).

Hypothyroidism

As per observations mentioned in the ISPAD Clinical Practice Consensus Guidelines 2018 Compendium, children and adolescent patients of T1D are more prone to thyroid disease than non-patients.

The presence of islet autoantibodies to GAD (Glutamic Acid Decarboxylase) and ZnT8 (Zinc Transporter-8) are said to be associated with thyroid autoimmunity. Hypoglycaemia is said to be related to hypothyroidism, even though glycaemic control may not show any impact.

Typical clinical symptoms of hypothyroidism include (a painless) goitre, reduced linear growth, fatigue, cold intolerance, bradycardia and weight gain.

Diagnosis

• Children testing positive for anti-thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) should be observed for the development of hypothyroidism
• Hypothyroidism is detected by checking for a low, free T4 level and a raised thyroid stimulating hormone (TSH) concentration. However, thyroid function tests can be misleading if a patient’s metabolic state is not stable (e.g. diabetic ketoacidosis or the patient has suboptimal blood glucose control)
• In patients testing positive with thyroid autoantibodies, asymptomatic individuals, compensated hypothyroidism may also reflect a normal free T4 level and a mildly increased TSH

Treatment: It is the same for T1D patients as is in general population. It is based on replacement with oral-levothyroxine (synthetic T4) to normalise TSH levels. If goitre is present in such patients, it may allow for its regression.

Management

• Routine monitoring of TSH levels is essential
• Measurement of thyroid function tests after changing levothyroxine dosage and after blood pressure or lipid lowering medications should be initiated
• It is important that hypothyroidism be treated at the earliest, else it can worsen total cholesterol, LDL cholesterol and triglyceride levels
• In children, the thyroid gland should be examined by touching annually to check for any nodules or cysts. If they are found to be present, further evaluation is advised

Hyperthyroidism

As per the updated ISPAD Compendium, hyperthyroidism is less common in T1D patients as compared to hypothyroidism but more common when such patients are compared to the general population. Hyperthyroidism in T1D patients may also be because of the presence of Graves’ disease or the hyperthyroid phase of Hashimoto’s thyroiditis.

1. Symptoms of hyperthyroidism are weight loss, increase in appetite, palpitations, tachycardia, tremors, hyperactivity with difficulty in concentrating, heat intolerance and thyroid enlargement. Mild characteristic eye findings such as exophthalmos and lid lag can be seen in children as compared to adult T1D patients.
2. Symptoms of Graves’ disease are weight loss, increased appetite, palpitations, heat intolerance, goiter, proptosis and poor glycemic control.
3. Symptoms of Hashimoto’s thyroiditis are decreased linear growth, a painless goiter, fatigue, cold intolerance, bradycardia, weight gain and occurrence of hypoglycemia.

Diagnosis

1. Hyperthyroidism can be diagnosed by checking for suppression of TSH levels and elevation of one or more measures of the thyroid hormone (Free T4 and/or Free T3).
2. Graves’ disease can be confirmed positive if the test shows the presence of TSH receptor antibodies (Thyroid stimulating immunoglobulin, TSH, T4 or free T4 and T3).
3. It is recommended to test for thyroid function (using measurements of TSH and anti-thyroid peroxidase antibodies) once the patient is diagnosed with T1D and then every second year in asymptomatic individuals without goiter or if thyroid autoantibodies are absent. More frequent assessment is indicated otherwise.
4. Hashimoto’s Thyroiditis is confirmed with the presence of Antithyroid peroxidase antibodies, antithyroglobulin antibodies, TSH, T4 or free T4. Screening for Hashimoto’s Thyroiditis should be done by measuring anti-thyroid peroxidase and anti-thyroglobulin antibodies and TSH and at the time of diagnosis (after glucose control is established).
5. The screening is recommended every 2 years, for TSH (and sooner if positive thyroid antibodies are found at the time of diagnosis or owing to symptoms).

Treatment: Hyperthyroidism is treated with carbimazole or methimizolehe, which is recommended especially for children due to the increased risk of liver failure as observed in those treated with propylthiouracil.

Management

• Beta-adrenergic blocking drugs are recommended during the acute phase of thyrotoxicosis to control tachycardia and agitation
• If a patient does not go into remission or cannot be controlled on anti-thyroid medications, definitive treatment options including thyroidectomy or ablation with radioactive iodine can be considered