Introduction

When the body produces too much thyroid hormone, one may develop thyrotoxicosis. The hormone that regulates the body's metabolism, or how it converts the food you ingest into energy, is the thyroid hormone. The metabolism grows rapidly when you have thyrotoxicosis, which can lead to symptoms that impact your entire body. You can feel as though you have no control over your body, or that it is operating in overdrive. The most frequent cause of thyrotoxicosis is hyperthyroidism, or an overactive thyroid gland. However, the body might produce too much thyroid hormone in different ways.¹ Thyrotoxicosis is an uncommon yet dangerous condition that affects kids and teenagers. The most frequent cause is Graves' disease, an autoimmune condition brought on by autoantibodies stimulating the thyrotropin receptor. Achieving and maintaining a euthyroid condition requires early detection and precise interpretation of tests. This would prevent the potentially serious and fatal effects of acute thyrotoxicosis while also optimising growth, development, and development from child to young adulthood.²

Although thyrotoxicosis can happen at any age, its frequency rises with age and peaks in adolescence. In children under the age of sixteen, the incidence of Graves' illness has been reported to be 1 in 100,000. Subacute thyroiditis, early Hashimoto's thyroiditis, chronic lymphocytic thyroiditis, autonomous functional nodules, amiodarone-induced thyrotoxicosis, and activating TSH receptor mutations are less frequent causes of thyrotoxicosis. With association studies showing a higher incidence of thyrotoxicosis, which is probably due to cytokine fluxes, as described in adult populations, COVID-19 infections have been suggested as triggers in more recent times.² In order to raise awareness and improve care for this susceptible group, this article attempts to give a thorough overview of thyrotoxicosis in paediatric patients, including its aetiology, clinical symptoms, diagnostic techniques, treatment options, and long-term prognosis.

Etiology and pathophysiology

Various autoimmune diseases such diabetes mellitus, coeliac disease, primary adrenal insufficiency, vitiligo, systemic lupus erythematosus, rheumatoid arthritis, and pernicious anaemia are more common in children with Graves' disease. Graves' illness has a subtype called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, which has a higher death rate. Given the broader treatment implications, it is imperative to detect polyglandular autoimmune endocrinopathy, in which Graves' disease is linked to Addison's disease and diabetes. In situations like trisomy and Turner's syndrome, where the underlying risk is higher, the risk of related autoimmune disorders must also be taken into account.²

Neonatal thyrotoxicosis is a danger for infants whose mothers have a history of hyperthyroidism. Measurements of thyroid receptor antibodies (TRAbs) during pregnancy and the mother's medical history should be used to identify these babies. Even if the mother is euthyroid or hypothyroid, she may still have thyroid receptor antibodies in her blood, which could make her current thyroid function deceptive. Antibodies against thyroid peroxidase (TPO) do not need to be investigated in neonates because they are not an indicator for hyperthyroidism in this age group.⁴

Results from laboratory testing for TRAbs are reported as either positive or negative; high-risk mothers have a track record of thyrotoxicosis on antithyroid medication, a history of thyrotoxicosis managed by radioactive iodine or thyroid surgery, or any mother with positive TRAbs; low-risk mothers have a history of thyrotoxicosis treated only with antithyroid medication, are currently euthyroid, and are not receiving antithyroid treatment; and, finally, have negative TRAbs.⁴

Antibody titres should be assessed at booking for all moms with a history of thyrotoxicosis. These should be revisited later in pregnancy if the results are positive. 'High Risk' should be the baby's management status if thyroid antibodies are found. If thyroid antibodies are not found at booking, no more steps are needed for the low-risk or negligible risk groups.⁴

Clinical presentation

Weight loss, an enlarged thyroid gland, elevated blood pressure, and irregular heartbeat are the hallmarks of hyperthyroidism in children. Tremors, low heat tolerance, anxiety, hyperactivity, trouble focussing, difficulty sleeping, loose or increased bowel motions, exhaustion, and mild menstruation are some of the symptoms. Girls may have lighter, less frequent periods and a greater hunger. Redness, soreness, or eye bulging are additional symptoms of Graves' eye disease, sometimes referred to as Graves' ophthalmopathy or thyroid eye disease. There are remedies for these symptoms. Untreated or inadequately managed hyperthyroidism can result in a rare but potentially fatal illness known as a thyroid storm, or thyrotoxic crisis, which necessitates immediate medical attention.⁵

Diagnostic evaluation

Elevated serum free T4 and T3 levels differentiate between visible and subclinical hyperthyroidism, while low serum TSH levels are very sensitive and specific for thyroid diseases. Free alpha-subunit concentrations, elevated T4 and T3 levels, and normal or elevated TSH levels are all possible symptoms of pituitary-dependent causes of hyperthyroidism. Antibodies to the TSH receptor found in serum have a 98% sensitivity and a 99% specificity in diagnosing Graves disease.⁶

Thyroid scans or radioactive iodine uptake studies can be used to distinguish between thyrotoxicosis sources other than Graves disease. Unless there are nodules or fibrosis, radioactive iodine uptake in Graves disease is usually diffuse. Patients with subacute, postpartum, or painless thyroiditis, as well as those who have recently consumed excessive amounts of iodine or used thyroid hormones, should undergo thyroid scintigraphy and ultrasound.⁶

Due to higher serum hCG levels, gestational transitory thyrotoxicosis is characterised by suppressed TSH and raised T4 levels in the early stages of pregnancy. Positive thyroid receptor antibodies, increased fT4 and fT3, or low or undetectable TSH values are indicators of thyroid storm. Increased T3/T4 levels, low TSH, decreased absorption, and low thyroglobulin levels are common symptoms of factitious thyrotoxicosis, which is brought on by purposeful thyroid supplement consumption.⁶

Management

Neonatal thyrotoxicosis is treated with medication, such as carbimazole monotherapy, concomitant propranolol and/or iodine therapy, and consultation with a paediatric endocrinology consultant. Carbimazole inhibits the production of thyroid hormones and decreases the thyroid's absorption of iodine. Propranolol reduces the conversion of T4 to T3 and helps manage symptoms brought on by adrenergic stimulation. When an infant has haemodynamic instability, Lugol's iodine solution is used to quickly stop thyroid hormone production, stop thyroid hormone release, and lower amounts of free thyroid hormone.⁴

Treatment options for paediatric hyperthyroidism include thyroidectomy, beta-blockers, methimazole, and radioactive iodine therapy. Methimazole can be used for at least two years and lowers thyroid hormone levels. While continued treatment is required, remission happens when symptoms go away. Low white blood cell count, liver issues, joint pain, and skin rash are some of the side effects. Hyperthyroidism can be permanently treated using radioactive iodine, which shrinks the thyroid gland and lowers hormone output. Thyroidectomy surgery involves removing all or part of the thyroid gland, and hormone replacement medicine may be necessary. Regular office visits to track symptoms, thyroid hormone levels, and growth are part of follow-up care.⁵

With titration depending on clinical response, the treatment seeks to eradicate hyperthyroidism without resulting in hypothyroidism. Given that TSH levels may be suppressed for two to three weeks, routine TFTs and TSH assessments are essential. In 0.03% of patients, carbimazole may result in agranulocytosis.⁴

Complications

One extremely uncommon and severe type of thyrotoxicosis is a thyroid storm. Untreated thyrotoxicosis, severe trauma, stress, infection, surgery, radioiodine, and drugs can all cause it. It has the potential to be fatal. Tachycardia, heart failure, fever, severe anxiety, disturbed mental state, and upset stomach are among the symptoms. Although they can be useful, scoring systems that were created for adults to help with diagnosis have not been proven to work for kids.³

Summary

Despite being relatively uncommon, thyrotoxicosis in paediatric children is a disorder that must be promptly recognised and carefully managed because of its significant effects on growth, development, and general health. The most frequent cause is still Graves' disease, although other causes include thyroiditis, exposure to exogenous hormones, and uncommon hereditary disorders also need to be taken into account. Early identification is difficult but essential since the clinical presentation can vary greatly, ranging from traditional symptoms like weight loss, tachycardia, and heat sensitivity to more subdued indicators like behavioural abnormalities or poor academic performance.

Accurate diagnosis and separation from other illnesses depend on diagnostic examination, which includes imaging studies, thyroid function testing, and antibody evaluations. A variety of treatments are included in management techniques, each with potential adverse effects and a unique set of considerations. These options include thyroidectomy, radioactive iodine therapy, and antithyroid medicines. To keep an eye out for issues including thyroid storm, heart problems, and effects on bone and growth health, long-term monitoring is essential.

It is impossible to exaggerate the value of a multidisciplinary strategy that includes paediatric endocrinologists, primary care physicians, and occasionally surgeons to guarantee thorough care. Education of patients and their families is essential for maintaining treatment compliance and identifying warning indications of problems. New treatments and enhanced diagnostic techniques could lead to better results as research progresses.

In conclusion, early diagnosis, appropriate therapy, and careful follow-up can greatly enhance quality of life and long-term prognosis, even though thyrotoxicosis in paediatric patients poses special obstacles. Optimising care for this vulnerable population requires increasing knowledge and awareness of this condition among carers and healthcare professionals.