Hyperthyroidism in children
Houssam Fayad, MD
Hyperthyroidism in Children
Graves’ disease
Chronic lymphocytic thyroiditis with thyrotoxic phase
Subacute granulomatous thyroiditis
Solitary thyroid nodule and hyperthyroidism
Toxic multinodular goiter
Factitious hyperthyroidism
Iodine-induced hyperthyroidism
Neck trauma-induced thyrotoxicosis
TSH-producing adenoma
Graves’ Disease in Children
The most common cause of
hyperthyroidism in children and
adolescents
0.02 % (1:5000) of children
11- to 15-year age group
Female/male is 5 : 1
Graves’ Disease : Association
with Autoimmune Diseases
High incidence within families
Increased incidence with IDDM,
Addison’s disease
More common in patients with Trisomy
21
Associated with non-endocrine
autoimmune disorders: SLE, RA, ITP,
myasthenia gravis, pernicious anemia
Graves’ Disease: Genetics
High correlation of Graves’ disease and
other autoimmune thyroiditis in
families
36% of children of patients with GD
have positive anti-thyroid antibodies;
50% of siblings have anti-thyroid Ab
Linkage with MHC Class II: > 50% of
GD patients are HLA-DR3 positive
PATHOGENESIS
Thyrotropin (TSH) receptor-stimulating
antibodies (TRS-Ab),
Graves' ophthalmopathy: antibodies
against a TSH receptor-like protein in
retro orbital connective tissue
Graves’ Disease: Clinical Presentation
Growth: Acceleration of growth is accompanied by
advancement of epiphyseal maturation
Puberty: Delayed
Eyes: Stare and lid lag, exophthalmos
Goiter: Diffuse goiter, smooth surface, fleshy in
consistency, without palpable nodules
Cardiovascular: Increase in cardiac output and HR.
Serum lipids: low (HDL)
Graves’ Disease: Clinical Presentation
Gastrointestinal: Failure to gain weight or weight
loss, despite an increase in appetite
Musculoskeletal: Proximal muscle weakness, and
osteoporosis
Neuropsychologic: Tremor, hyperactive deep
tendon reflexes, ataxia, chorea, mood swing, and
decreased attention span.
Skin: Warm and smooth.
Onycholysis
Graves’ Disease: Diagnosis
Elevated T4, T3, free T4, free T3
LOW TSH
TSI or TSAb (Thyroid-stimulating
immunoglobulin/ antibody) and/or
TBII (TSH-receptor binding inhibitory
immunoglobulin) present in 90%
Graves’ Disease: Diagnosis
TRH stimulation test seldom necessary;
will be depressed in Graves’ disease
Thyroid scan may be necessary to
distinguish from subacute thyroiditis or
factitious thyrotoxicosis. Iodine uptake
is increased in Graves’ disease,
decreased in the other two.
Presence of nodule: scan indicated
Graves’ Disease: Treatment
Antithyroid Drugs (ATD)
Radioactive Iodine Therapy (RI)
Surgery: Thyroidectomy
Antithyroid Drug Therapy
Medications: Propylthiouracil (PTU)
and Methimazole (MMI)
Mechanism: Inhibition of thyroid
peroxidase. PTU also inhibits
conversion of T4 to T3 by inhibiting
5’ deiodinase activity
Antithyroid Drug Therapy
PTU and MMI may have
immunosuppressive properties
New T4 / T3 synthesis blocked, but
preformed hormone is released for
several weeks, depending on goiter size
Antithyroid Drug Therapy:
Strategies
1. Titration: Give enough ATD to
maintain normal T4 and TSH
2. Combination: Totally suppress T4
production with ATD, give synthroid to
replace T4
Antithyroid Drug Therapy
Remission rate: 25-65%
Relapse rate: 3-47%
– Within one year, but later relapses do occur
– The risk of relapse is higher in non-Caucasians
and in patients with higher initial free T4
– The risk decreases with increasing age and
with longer duration of antithyroid drug
therapy
Antithyroid Drug Therapy
Compliance, compliance, compliance
Higher TSI titres, larger goiter, higher
T4 or T3 at diagnosis all associated with
poor response to ATD
Antithyroid Drug Therapy
Side effects of ADT: Agranulocytosis
Lupus-like syndrome
Arthralgia
Hepatitis
Aplastic anemia
Nephrosis
Rashes
Nausea/vomiting
Radioiodine therapy
Use as first-line of therapy is increasing
in the pediatric population, especially
among adolescents, due to concerns
about compliance with ATD; also
increased patient preference.
Possible long term effects of radioiodine
therapy on oncogenesis, effect on
offspring still a concern
Radioiodine therapy: Indications
Patient preference
Failed ATD therapy (compliance, drug
intolerance, maximal dosing)
Surgery: To Cut is to Cure
Lowest incidence of recurrence
Procedure: subtotal thyroidectomy
Patient should be euthyroid prior to
surgery (ADT, iodine, propranalol)
Complications uncommon, but
incidence increases with decreasing age
of patient
Thyroidectomy: Complications
Transient or permanent hypocalcemia
due to parathyroid gland damage
Recurrent laryngeal nerve damage:
stridor, poor vocalization due to vocal
cord paralysis
Hemorrhage: temporary tracheostomy
Increased risk with repeat procedure
Thyroid Storm
Infrequent but very dangerous
complication of Graves’ disease
Uncompensated thyrotoxicosis with
tachyarrhythmias, fever, altered mental
status, ultimately high-output shock
Triggers include infection, trauma,
surgery in poorly controlled patients
Thyroid Storm: Treatment
Propranalol
Glucocorticoids
Cooling, sedation, fluids, respiratory
support, antibiotics
ATD: PTU, MMI
Neonatal Graves’ Disease
Accounts for only 1% of thyrotoxicosis
in children
Usually positive hx of GD in the mother
In children of mothers with GD, 1 of 70
will develop neonatal Graves’ ds.
Mother might NOT be thyrotoxic
Neonatal Graves’ Disease
TSI pass transplacentally to cause
stimulation of fetal thyroid gland (TSH
receptors)
Prediction of neonatal GD:
TSI titre of >5 times normal has high
association with development of
symptoms
Neonatal Graves’ Disease:
Complications
Fetal tachycardia
Airway compromise due to goiter
Microcephaly/craniosynostosis
Irritability
Poor weight gain
High output CHF
Exophthalmos
Neonatal Graves’ Disease:
Clinical Course
Presentation variable, dependent on
maternal status: on ATD, no Rx.
Symptoms may be congenital, usually
onset at 10-14 days, lasts 3-12 weeks.
Rx: ATD, Propranalol, Iodide
Long-term: no increased risk of GD, but
higher risk of hypothyroidism due to
suppressive effect on HPT axis
Chronic lymphocytic thyroiditis with thyrotoxic
phase
Hashitoxicosis
Few months rather than years
Ophthalmopathy is absent
Anti-thyroglobulin antibodies (Tg Ab) and
thyroid peroxidase antibodies (TPO Ab):
Positive
TRS-Ab (TSI): Negative
RAI uptake is typically low or absent
Subacute granulomatous thyroiditis
De Quervain's disease
painful thyroiditis
Rare in childhood
thyrotoxic phase euthyroidism
hypothyroidism euthyroidism
Viral infection
Thyroid antibodies: Negative
RAI uptake: Low or absent
Solitary thyroid nodule and
hyperthyroidism
Toxic adenomas
Uncommon cause of hyperthyroidism in childhood
Hyperthyroidism and palpation of a nodule on neck
examination
Typically produce T3
Elevated T3 and suppressed TSH
Normal or elevated FT4
TSI: Negative
RAI uptake and scan: Uptake only in the functioning
nodule, with the rest of the gland suppressed
Toxic multinodular goiter
Uncommon cause of hyperthyroidism in children
Ultrasound: Sensitive
Antithyroid antibodies, including TSI: Negative
RAI uptake and scan: The uptake will be elevated
and seen in the multiple nodules
Other causes
Neck trauma-induced thyrotoxicosis:
– RAI uptake is decreased in the area of
injury
– Thyroid function tests gradually normalize
over three to six weeks.
Pituitary tsh-secreting adenoma:
– rare at any age,
– Elevated FT4 with a normal (not
suppressed) TSH level
Other causes
Resistance to thyroid hormone:
– Autosomal dominant
– Goiter and elevated serum FT4 and, to a lesser extent, T3
levels, while TSH is normal or slightly elevated
Factitious thyrotoxicosis:
– Hyperthyroidism but absent goiter
– Adolescent
– Measurement of serum thyroglobulin is useful, as it is
elevated in all the endogenous forms of hyperthyroidism,
but low in factitious thyrotoxicosis
– RAI uptake will also be low or absent
