Definition (Pediatr Rev 2006;27:155)
• Overactivity of the thyroid gland 2/2 overstimulation, inflammation, or abnormal thyroid axis function (overproduction or failure of feedback inhibition)
Etiology (JCEM 2007;92:797)
• Graves dz (increase in thyroid-stimulating immunoglobulin [TSI]) most common childhood etiology. Incidence peaks in late childhood; 
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• Other etiologies; early Hashimoto (autoimmune thyroiditis), subacute thyroiditis hyperfunctioning thyroid nodule, pituitary adenoma–secreting TSH, activating mutation of TSH receptor, pituitary resistance to T4, or exogenous thyroxine intake (ingestion or factitious)
Clinical Manifestations (JCEM 2007;92:797; Pediatr Rev 2006;27:155)
• Classically w/ tachycardia, palpitations, widened pulse pressure, tremor, brisk DTRs, fatigue, proximal muscle weakness, heat intolerance, ↑ perspiration, ↑ appetite but often w/ weight loss, diarrhea
• May present w/ behavioral disturbance; hyperactivity, emotional lability, ↓ concentration (worsening school performance), insomnia, anxiety
• Thyroid storm: Hyperthyroidism w/ acute onset, hyperthermia, tachycardia, jaundice, liver failure. Can progress to delirium, coma, and death
• W/ Graves dz may find ophthalmopathy (less common in children) w/ proptosis and or lid lag. Pretibial myxedema is a rare finding
Diagnostic Studies (JCEM 2007;92:797)
• Labs: TSH, free T4, total T3, TSH-R titers (TSI), thyroid autoantibodies (antithyroid peroxidase, antithyroglobulin); TBI-Ab (neonates)
• Radioactive thyroid uptake (Tc or 123I) can help distinguish btw transient hyperthyroidism (e.g., Hashimoto thyroiditis, viral thyroiditis) and persistent (e.g., Graves disease, McCune–Albright [activating mutation of TSH receptor])
Therapy (J Clin Endocrinol Metab 2007;92:797; Clin Endocrinol 2009; Feb 25 epub ahead of print; Thyroid 2011;21(6):593)
• Thyroid storm:
• Propylthiouracil (PTU) and potassium iodide for short-term control (suppress release of thyroid hormone and peripheral conversion of T4 to T3)
• IV β-blocker for HTN, other sx. Glucocorticoids for metabolic support if Al
• Graves disease:
• Medical management w/ methimazole (MMI), surgery, or radioactive iodine (RAI). Risk of liver failure: PTU should be avoided in children (J Clin Endocrinol Metab 2010;953260–7)
• 0.5% w/ serious complications: MMI → agranulocytosis; up to 25% develop rash, arthralgias, pruritus, transaminitis, or leukopenia
• Titrate MMI until euthyroid; d/c when thyroid small & pt euthyroid (high recurrence rate)
• Surgery well tolerated; Rare complications: Recurrent laryngeal nerve injury, hypoparathyroidism. Surgery preferred for: Large goiters, significant ophthalmopathy
• RAI: Hypothyroidism usually follows w/i few months. (2nd dose required in 10% pts) → lifetime thyroid replacement becomes necessary (J Clin Endocrinol Metab 2011 Mar;96(3):580–588)