Hyperthyroidism

 

Introduction

Hyperthyroidism is defined as the excessive production and secretion of thyroid hormone by the thyroid gland. In the pediatric population, this is most commonly secondary to Graves disease. The clinical manifestations of hyperthyroidism in children are similar to those in adults, although they have added importance due to their effects on growth, development and behavior. It is important to differentiate "hyperthyroidism" from "thyrotoxicosis"; while hyperthyroidism refers to overproduction of thyroid hormone, thyrotoxicosis is the accurate term for describing the clinical and biochemical manifestations of excess thyroid hormone.

 

Clinical presentation of thyrotoxicosis

 

Thyrotoxicosis has many systemic findings; the clinical picture can vary by patient but often presents as behavioral symptoms, such as decereasing school performance. Children being evaluated for ADHD should also be evaluated for hyper- or hypothyroidism.

 

  • Behavioral: Decreased attention span, difficulty concentrating, emotional lability, hyperactivity, difficulty sleeping, nervousness
  • Systemic: Weight loss, increased appetite, increased perspiration, warmth and heat intolerance (late findings), upper percentiles for height
  • HEENT: Proptosis, exopthamos, lag of upper eyelid on downward gaze, conspicuous stare (Graves)
  • Cardiovascular: Tachycardia, palpitations, widened pulse pressure, overactive precordium, increased risk for mitral valve prolapse
  • Neuromuscular: Tremors, shortened deep tendon reflex relaxation phase, fatigue, proximal muscle weakeness
  • GI: Diarrhea, increased gut motility, malabsorption
  • Reproductive: Menstrual irregularities in postpubertal girls

 

Evaluation of hyperthyroidism

 

If hyperthyroidism is suspected, it should be confirmed with serum thyroid function tests:

  • Serum TSH: best initial test, suppressed in primary hyperthyroidism (<0.05mU/L)
  • Serum free T4: bound to thyroxine binding globulin (TBG), thransthyretin (TBPA) or albumin, acts as storage
  • Serum total T4, T3: available for uptake into cells
  • Thyrotropin receptor-stimulating antibody (TSHR-Ab): If elevated, confirmatory for Graves, either measuring TSI or TBII

 

Radioiodine uptake:

  • Oral administration of iodine-123, assess uptake at 6 and 24 hours
  • See below for differentiation of uptake patterns and diagnoses

 

Differential diagnosis

 

Because 96% of pediatric patients with hyperthyroidism are due to Graves disease, additional information on Graves is provided below.

 

Graves Disease

  • Occurs in 0.02% of children, peak ages 11-15 years
  • Females are affected more than males (5:1 ratio), particularly among older children
  • 80% association with genetic factors; many have a family history of autoimmune disease
  • Increased risk in children with Turner syndrome and Down syndrome
  • Graves ophthalmopathy in children is less common and milder than in adults, but still occurs in 50-75% and strongly suggests the diagnosis of Graves
  • Antibodies can cross the placenta and cause Graves disease of the newborn

Graves disease.JPG

Photo of a young woman with untreated Graves' disease demonstrating the classic Graves' ophthalmopathy and goiter.

 

Other causes of hyperthyroidism

 

 

Pathogenesis

Presentation

Labs

Treatment

Graves

Autoantibodies against thyroid TSH receptors stimulate excessive production and release of T4

Diffusely enlarged thyroid, soft texture with well-delineated border

Elevated free or total T4, decreased TSH, elevated TSHR-Ab in 60 to 90% of children, diffuse increased RAI uptake

Anti-thyroid medication, radioiodine ablation, surgical removal

Hashimoto’s thyroiditis (early phase)

Shorter duration of illness, autonomous release of preformed TH 2/2 inflammation

 

Tg-Ab and TPO-Ab positive, RAI uptake low or absent

B-adrenergic antagonists during thyrotoxic phase

Subacute granulomatous thyroiditis (de Quervain’s)

 

Autonomous release of preformed TH, most likely caused by viral infection

Painful swelling of thyroid gland

Ab negative, low RAI uptake

B-adrenergic antagonists during thyrotoxic phase

Solitary thyroid nodule (toxic adenoma)

 

TSH receptor-activating mutations (often)

Single nodule

Increased T3, Ab negative, RAI uptake in nodule only

Anti-thyroid medication, often surgical removal

McCune Albright

 

Activating mutation of the alpha subunit of the stimulatory G protein

 

Diffuse enlargement of thyroid gland evolve into multinodular goiter; associated with polyostotic fibrous dysplasia, café-au-lait spots, endocrinopathies, precocious puberty

Ab negative, RAI uptake in multiple nodules

Anti-thyroid medication; consider radioactive iodine ablation or surgery

Iodine or radiation induced

Iodine exposure from radiocontrast materials and medications (amiodarone, clioquinol) or radiation from ALL treatment

Typically have preexisting multinodular goiter

Increased RAI uptake

B-adrenergic antagonists during thyrotoxic phase

Exogenous TH

Often teenagers trying to lose weight

Absent goiter

Low thyroglobulin, low RAI uptake

Cessation of intake

Pituitary adenoma

TSH secreted from a pituitary adenoma

Diffusely enlarged thyroid

Elevated free T4, high TSH alpha subunit, confimed on MRI

Surgical resection

 

Therapy

 

Thioamide drugs - inhibit thyroid hormone production

  • Propylthiouricil (PTU) also blocks peripheral conversion of T4 to T3, is preferred during pregnancy (crosses the placenta less), has more severe side effects
  • Methimazole (MMI) has a longer half life
                    
    • Side effects: pruritic popular or urtricarial rash, joint pain, stiffness, hair loss, nausea, headache, transient granulocytopenia
    • Severe side effects: agranulocytosis, drug fever, nephritis, hepatitis, lupus like reaction

 

Radioiodine therapy

  • Oral administration of iodine-131, causes cell death in thyroid gland
  • Cure rate of 90% or greater in Graves disease
  • Potential risks include hypothyroidism (40-80%), increased risk of thyroid cancer (highest risk in children <5 years old), increased risk of leukemia

 

Surgical resection

  • Indicated in patients who fail medical therapy, relapse after cessation of medication, significant drug reactions, large goiters, severe ophthalmopathy
  • Cure rate of 90% in Graves disease
  • Potential risks include hypoparathyroidism and recurrent laryngeal nerve damage, hypothyroidism

 

References:

 

  1. Sills, IN. Hyperthyroidism. Ped in Rev 1994; 15; 417.
  2. Kokotos, F. Hyperthyroidism. Ped in Rev 2005; 27:155-157
  3. LaFranchi, S. Clinical manifestations and diagnosis of hyperthyroidism in children and adolescents. In: UpToDate, Geffner, M (Ed), UpToDate, Waltham, MA, 2013.