Chapter 78: Thyroid Disorders

• The most common disorder causing thyrotoxicosis in children is Graves' disease.

• Thyroid hormones upregulate β-adrenergic receptors causing symptoms of sympathetic nervous system overactivity.

• Signs of sympathetic hyperactivity include tremor, brisk deep tendon reflexes, tachycardia, supraventricular tachycardia, flow murmur, overactive precordium, and a widened pulse pressure. Other cardiac disturbances such as atrial fibrillation and congestive heart failure (CHF) may also occur.

• Precipitating factors for thyroid storm in a patient with hyperthyroidism are thyroid surgery, withdrawal of antithyroid medications, radioiodine therapy, palpation of a goiter, iodinated contrast dyes, and stress.

• Thyroid storm is suggested by severe hyperpyrexia, atrial dysrhythmia, CHF, delirium or psychosis, severe gastrointestinal hyperactivity, and hepatic dysfunction with jaundice.

• Treatment consists of antithyroid drug propylthiouracil (PTU) at a dosage of 175 mg/m²/day or 4 to 6 mg/kg/day at 6- or 8-hour intervals, iodine therapy started 1 hour after antithyroid medication is initiated, β-adrenergic blockade with propranolol, 10 to 20 mg every 8 to 12 hours, and supportive management.

Hyperthyroidism is a state of increased production and secretion of thyroid hormones resulting in the hypermetabolic clinical syndrome of thyrotoxicosis. The term thyroid storm refers to an extreme state of decompensated thyrotoxicosis and is a thyroid emergency that can be potentially fatal.

The most common cause of hyperthyroidism in children is Graves' disease. This disease occurs in 1 in 5000 children with a peak incidence between 11 and 15 years of age. The male to female ratio is 1:5.¹ Although the true incidence of childhood thyrotoxicosis is unknown, 5% of all thyrotoxicosis occurs in childhood² and 0.6% to 10% of neonates born to mothers with Graves' disease will show signs of thyrotoxicosis.³ The reported mortality in neonatal thyrotoxicosis is as high as 20%.⁴ Because childhood hyperthyroidism occurs mostly in adolescents, thyroid storm also occurs more frequently in this group (Fig. 78-1).²

Thyrotoxicosis results from thyroid hormone excess either caused by overproduction of thyroid hormone by the thyroid gland or by administration of synthetic hormone. Increased concentration of serum-free thyroid hormone is almost always found in thyrotoxicosis. In Graves' disease, activated B-lymphocytes produce antibodies against antigen shared by the thyroid gland and eye muscle.^1,5 Thyrotropin receptor-stimulating antibodies (TRSAb) bind to TSH receptors to increase thyroid hormone production. In congenital hyperthyroidism, transplacental transfer of TRSAb from the mother with Graves' disease stimulates the thyroid gland to cause hyperthyroidism or thyrotoxicosis.^1,3,4

The actions of thyroid hormone at the cellular level include calorigenesis, acceleration of substrate turnover, amino acid, and lipid metabolism and stimulation of water and ion transport. Thyroid hormones also activate the adrenergic system by upregulation of β-adrenergic receptors causing symptoms of sympathetic nervous system overactivity, including hyperthermia. Why some individuals with hyperthyroidism have few symptoms and others develop the extreme clinical manifestation of thyroid hormone excess, thyroid storm, is still poorly understood. In thyroid storm, the clinical manifestations of thyroid hormone excess are thought to be because of an uncoupling of oxidative phosphorylation secondary to the illness, resulting in an enhanced rate of lipolysis, with fatty acid oxidation, increased oxygen consumption, calorigenesis, and hyperthermia. Specific conditions such as thyroid surgery, withdrawal of antithyroid medications, radioiodine therapy, palpation of a large goiter, and iodinated contrast dyes are known to precipitate thyroid storm in a patient with hyperthyroidism.

The causes of thyrotoxicosis may be divided into conditions in which the source of excess thyroid hormone is endogenous or exogenous (Table 78-1). The most common disorder causing thyrotoxicosis in children, as in adults, is the autoimmune disorder, Graves' disease.^2,6,7 In 5% to 10% of thyrotoxicosis, the cause is autoimmune thyroiditis or Hashitoxicosis. In an even smaller percentage of patients, subacute thyroiditis can cause thyrotoxicosis because of destruction of thyroid tissue. This process is usually because of viral or granulomatous diseases, classically presents with a painful thyroid gland and is self-limiting. Autonomously functioning thyroid nodules (toxic adenoma) are sometimes encountered in children.¹ Multinodular goiters with thyrotoxicosis are unusual in childhood. Rarely, hyperthyroidism is secondary to TSH over-secretion from a pituitary tumor or because of congenital isolated pituitary resistance to negative feedback control by thyroid hormones. The possibility of a molar pregnancy, which produces a thyroid stimulating hormone, must be considered in adolescent females with thyrotoxicosis.⁸ Administration of iodine-containing medications, such as radiocontrast, to patients with a nodular goiter may rarely induce hyperthyroidism in Hashimoto's thyroiditis, endemic goiter, multinodular goiter, and nontoxic diffuse goiter. Finally, thyrotoxicosis can occur as the result of intentional or iatrogenic excess thyroxine or triiodothyronine intake.

Children who present with thyrotoxicosis have symptoms of nervousness, palpitations, weight loss, muscle weakness, and fatigue. A history of developmental delay and declining school performance may be found.⁹ Other symptoms include tremulousness, anxiety, excessive sweating, temperature intolerance, and emotional lability. Gastrointestinal overactivity with symptoms of frequent stools is common. An increased appetite is classically present. However, an apathetic state, including decreased appetite, occasionally occurs.

The signs of Graves' disease are similar to those seen in adults but the ophthalmologic signs are usually milder in children.^10,11 Signs of sympathetic and cardiac overactivity are common. These include tremor, brisk deep tendon reflexes, tachycardia, supraventricular tachycardia, flow murmur, overactive precordium, and a widened pulse pressure. Other cardiac atrioventricular conduction disturbances may occur, such as atrial fibrillation, atrioventricular block, or sinoatrial block. CHF may develop because of the inability of cardiac function to meet metabolic demands and papillary muscle dysfunction, causing mitral valve prolapse, may occur.^12,13 Except in neonates and children with underlying cardiac disease, CHF is uncommon in childhood thyrotoxicosis. In thyroid storm, severe hyperpyrexia, atrial dysrhythmia and CHF, delirium or psychosis, severe gastrointestinal hyperactivity, and hepatic dysfunction with jaundice are present.¹⁴ A history of a precipitating event, illness, or major stress, should be identified.

Conditions that cause tachydysrhythmias (atrial flutter, atrial fibrillation, and ventricular tachycardia) must be differentiated from hyperthyroidism.¹⁵ These include electrolyte disturbances and cardiac disease. The murmur of mitral valve prolapse in association with tachycardia may lead to a mistaken diagnosis of CHF and cardiac valvular disease. The patient who is febrile and appears “toxic” may have sepsis alone or as a precipitating factor in thyroid storm. Intoxication with adrenergic and anticholinergic drugs may also mimic the hypermetabolic state seen in thyrotoxicosis. Gastrointestinal hyperactivity may imitate an acute abdomen in thyroid storm (Table 78-2).

Treatment of severe thyrotoxicosis or thyroid storm is directed at preventing further thyroid hormone synthesis and secretion, alleviating the acute peripheral effects of excess thyroid hormone, and supportive measures.^{2–4,6,7,14,16}

Initial laboratory tests should include the measurement of total and free T₄, T₃, and TSH levels, along with a complete metabolic profile.

Initiate and continue blockade of thyroid hormone synthesis until the crisis resolves:

• PTU at a dosage of 175 mg/m²/day or 4 to 6 mg/kg/day divided and given at 6- or 8-hour intervals or 200 mg every 4 hours.

• Methimazole 30 mg every 6 hours.

Blockade of release of thyroid hormone

• Start 1 to 3 hours after antithyroid medication is initiated.

• Sodium Iodide 0.05 mg IV every 12 hours.

• Lugol's solution (5% iodine) three to five drops orally every 8 hours.

• Lithium 600-mg oral loading dose followed by 300 mg every 6 hours (do not use with CHF, renal failure, arrhythmia).

Inhibition of peripheral T₄ and T₃ conversion:

• Dexamethasone 2 mg IV followed by 2 mg orally every 6 hours.

β-adrenergic antagonists:

• Propranolol 10 to 20 mg orally every 8 hours in children and adolescents.

Hyperthermia

• Acetaminophen.

• Cooling blankets, ice packs.

• Salicylates must be avoided because they can displace thyroid hormone from binding sites, potentially worsening the hypermetabolic state.

Fluid Resuscitation

• Administer normal saline, 20 mL/kg; then calculate the fluid deficit and replace in the form of half-normal saline with 5% dextrose over the next 24 to 48 hours.

Cardiovascular Complications

• Arrhythmias and CHF are treated with antiarrhythmics, digoxin, and diuretics.

• In all cases, the precipitating event causing severe thyrotoxicosis must be sought and treated.

Neonatal hyperthyroidism, characterized by growth failure, microcephaly, wide-eyed stare and symptoms of tachycardia, and irritability is usually seen a few days after birth; occasionally, the onset can be delayed by weeks. Neonatal thyrotoxicosis is usually seen in newborns whose mothers are on antithyroid drugs.¹

Antithyroid Treatment

• PTU 5 to 10 mg every 8 hours.

• Iodide drops (sodium or potassium salt) one drop every 8 hours orally.

• β-adrenergic blockade.

• Propranolol 2 mg/kg/day every 12 hours.

Supportive Measures

• Treatment of CHF, arrhythmia, airway management, fluid, and caloric replacement.

Treatment and disposition of children with thyrotoxicosis should always be undertaken with the consultation of a pediatric endocrinologist. Children with severe thyrotoxicosis, thyroid storm, and those with cardiovascular complications, such as arrhythmia, CHF, and shock, should be admitted to a pediatric intensive care unit for further management.