This document provides information on hyperthyroidism in children, including definitions, epidemiology, causes, clinical features, diagnosis, and management. The most common causes of hyperthyroidism in children are Graves' disease, toxic multinodular goiter, and subacute thyroiditis. Symptoms can include excessive sweating, heat intolerance, rapid heart rate, tremors, and weight loss. Diagnosis involves testing thyroid hormone levels, TSH, and thyroid antibodies. Treatment options include beta-blockers for symptom relief, antithyroid medications, radioactive iodine, and surgery. The goals of treatment are to normalize thyroid hormone levels and resolve symptoms of hyperthyroidism.

1. HYPERTHYROIDISM
IN
CHILDREN
• Dr.C.S.N.Vittal

2. Concept map
■ What are hyperthyroidism & thyrotoxicosis
■ Epidemiology
■ Causes
■ Clinical features
■ Diagnosis
■ Management

3. Definitions
■ Thyrotoxicosis - clinical state that results from
inappropriately high thyroid hormone action in
tissues generally due to inappropriately high
tissue thyroid hormone levels
■ Hyperthyroidism – a form of thyrotoxicosis due
to inappropriately high synthesis and secretion
of thyroid hormone(s) by the thyroid
• Bahn et al. Hyperthyroidism andOtherCauses ofThyrotoxicosis: ManagementGuidelines of the AmericanThyroid Association and American
Association of Clinical Endocrinologists.Thyroid, 2011Jun;21(6):593-646 & Endocr Pract, 2011 May-Jun;17(3):456-520

4. Epidemiology
■ Estimated prevalence of hyperthyroidism in children is around 1 in 10,000 in
the United States’ pediatric population.
■ Prevalence : 1.2 % (0.5% - overt, 0.75% subclinical)
■ Hyperthyroidism is much more common in women and in older people.
■ 5 % of all cases of Graves’ disease occurs in children.
■ Age
– Graves disease 20 to 40
– Toxic MNG > 50 yrs
– Toxic Single Adenoma 35 to 50
– Sub AcuteThyroiditis Any age
■ Sex M : F ratio
– Graves Disease 1: 5 to 1:1
– Toxic MNG 1: 2 to 1: 4

5. Possible Etiology of Hyperthyroidism
■ Primary
– Graves’ Disease (DiffuseToxic Goiter)
■ Secondary
– Toxic NodularGoiter (Multinodular Goiter)
– Thyroiditis
– Functioning adenoma of thyroid
– Rare Causes
■ Excessive intake of thyroid hormones
■ Abnormal secretion ofTSH
■ Excessive intake of iodine
■ Pituitary tumors leading to excessTSH
■ Thyrotoxicosis factitial: INF, amiodarone, SSRI
■ Struma ovarii (dermoid and ovarian tumors)

6. Graves’ Disease
■ Most common cause of thyrotoxicosis (50-60%)
■ Organ specific autoimmune disease
■ Most imp autoantibody:
– Thyroid stimulating immunoglobulin (TSI orTSA) which acts as a proxy for
TSH and stimulatesT4 andT3 via the adenyl cyclase cAMP system
I123 or TC99m Normal v/s Graves
• Onset may be insidious
• Poor school performance may be
marked, but usually from poor
concentration, tiredness and
behavior disturbances with temper
tantrums and emotional lability

7. Toxic Multinodular Goiter (TMG)
■ 2nd most common cause of hyperthyroidism (20%)
■ More in elderly individuals
■ Lumpy bumpy thyroid
■ Milder manifestations (apathetic hyperthyroidism)
■ Mild elevation of FT4 and FT3
■ Slow progression
■ Multiple firm nodules on palpation (Plummer’s
disease)
■ Scintigraphy: hot and normal areas

8. Sub AcuteThyroiditis (SAT)
■ Second common hyperthyroidism – 15%
■ T4 andT3 are extremely elevated in this condition
■ Immune destruction of thyroid due to viral infection
■ Destructive release of preformed thyroid hormone
■ Thyroid gland is painful and tender on palpation
■ Nuclear Scintigraphy scan - no RIU in the gland
■ Treatment is NSAIDs and Corticosteroids

9. Toxic Single Adenoma (TSA)
■ Single hyper functioning follicular thyroid adenoma.
■ Benign monoclonal tumor that usually is larger than
2.5 cm
■ It is the cause in 5% of patients who are thyrotoxic
■ Nuclear Scintigraphy scan shows only a single hot
nodule
■ TSH is suppressed by excess of thyroxines. So the
rest of the thyroid gland is suppressed

10. MedullaryThyroid Carcinoma (MTC)
■ <10% of thyroid carcinomas arises from parafollicular (C) cells and
nearly always secretes calcitonin and sometimes other hormones
■ Associated with syndromes involving tumors of neuroectodermal
origin (multiple endocrine neoplasia – MEN) inherited autosomal
dominantly MEN type 2 (MEN 2)

11. Common Symptoms
■ Excessive Sweating
■ Heat Intolerance
■ Increased Bowel Movements
■ Tremor (Usually Fine Shaking)
■ Nervousness /Agitation
■ Rapid Heart Rate / Palpitations
■ Insomnia
■ Breathlessness
■ Irregular or Scant Menstrual Periods
■ Fatigue
■ Weight Loss (despite increased
appetite)
■ MuscleWeakness
■ Hair Loss
■ irregular heart rhythms and heart
failure / palpitations
■ Psychiatric Symptoms in Graves'
disease:
■ Anxiety, nervousness, fluctuating
moods and irritability

12. Common Signs
■ Hyperactivity / Hyperkinesis
■ Sinus tachycardia or atrial arrhythmia, AF, CHF
■ Systolic hypertension, wide pulse pressure
■ Warm, moist, soft and smooth skin, warm hands
■ Excessive perspiration, palmar erythema, onycholysis
■ Lid lag and stare (sympathetic overactivity
■ Fine tremor
■ Large muscle weakness
■ Gynaecomastia

13. Specific to Graves’ Diseases
■ Diffuse painless and firm enlargement of thyroid gland
■ Thyroid bruit is audible with bell of stethoscpe
■ Ophthalmopathy in 50% cases
– Sand in eyes, periodic edema, conjunctival edema (chemsis),
– Von Graefe's sign (lid lag sign)
– Möbius sign (poor convergence)
– Joffroy sign (absent creases in the forehead on superior gaze)
– Stellwag sign (incomplete and infrequent blinking)
– Extra ocular muscle dysfunction, diplopia, pain on eye movements and proptosis
■ Dermo-acropathy in 20% cases
– Deposition of glycosaminoglycans in dermis of lower leg – non pitting edema, thickening of
skin without pain or pruritus (pre tibial myxedema)

14. MNG and Graves
Huge Toxic MNG Diffuse Graves Thyroid

15. Proptosis
Lid lag
(Von Graefe's sign)
Thyroid Ophthalmopathy

16. Ophthalmopathy in Graves
■ Thyroid associated orbitopathy is thought to be due to antibody reaction against
thyroid stimulating hormone receptor (TSHR) with orbital fibroblast modulation
ofT-Cell lymphocytes
Periorbital edema and chemosis

17. (incomplete and infrequent blinking) (absent creases in the
forehead on superior gaze)

18. Ophthalmopathy in Graves
Ocular muscle palsy Laka Laka Laka

19. Thyroid Dermopathy
Pink and skin coloured papules, plaques on the shin
Pretibial
myxoedema
• Stimulation of fibroblasts by anti-TSHR antibodies
and production of glucosamnoglycans

20. Clubbing and
Osteoarthropathy
Thyroid Acropathy

21. Onycholysis

22. Non specific changes
■ Hyperglycemia,Glycosuria
■ Osteoporosis and hypercalcemia
■ ↓ LDL andTotal Cholesterols
■ Atrial fibrillation, LVH, ↑ LV EF
■ Hyperdynamic circulatory state
■ High output heart failure

23. Diagnosis – Clinical Clues
■ Hyperthyroidism can be suspected in patients with:
– tremors,
– excessive sweating,
– smooth velvety skin,
– fine hair,
– a rapid heart rate, and
– an enlarged thyroid gland.

24. Diagnosis
1. Typical clinical presentation
2. Markedly suppressedTSH (<0.05 µIU/mL)
3. Elevated FT4 and FT3 (Markedly in Graves)
4. Thyroid antibodies – by Elisa – anti-TPO,TSI
5. ECG to demonstrate cardiac manifestations
6. Nuclear Scintigraphy to differentiate the causes

25. Diagnosis - Labs
■ Blood levels of thyroid hormones can be measured directly and usually
are elevated with hyperthyroidism.
■ Measurement of the bloodTSH levels – which is low
(In secondary hyperthyroidism –TSH levels elevated)
■ Antibody screening (forGraves' disease) and
■ Thyroid scan using radioactively-labelled iodine

26. Diagnosis - Labs
■ LowTSH, High RAIU
– Graves; disease
– Toxic MNG
– Toxic Adenoma
– Chronic gonadotrophin induced
– Inherited non-immune
hyperthyroidism (TSH receptor of
G protein mutation)
• Normal or elevatedTSH
• TSH-secreting pituitary tumors
• Thyroid hormone resistance
higher ratio of FT3 to FT4 suggests that the patient may have
Graves' disease,

27. Diagnosis - Labs
LowTSH, Low RAIU
• Iodine induced hyperthyroidism
• Amiodarone associated hyperthyroidism (due to excess iodine release)
• Thyroiditis
• Autoimmune (Hashimato’s, Lymphocytic thyroiditis)
• Viral or post viral (subacute granulomastous thyroiditis)
• Drug induced
• Amiodarone, lithium, interferon, IL -2, GM-CSF
• Infectious – acute
• Post partum
• Iatrogenic: Over replacement
• Thyrotoxic factitia
• Ingestion of natural products containing thyroid hormone
• Hamburger thyroiditis
• Thyromimetic compounds (Tiracol)
• Stroma ovarii
• Metastatic functioning thyroid carcinoma

28. Issues in Biochemical Evaluation
■ TSH has highest sensitivity and specificity
■ Diagnostic accuracy improves with measurement of freeT4
■ FreeT4 gives baseline measurement of degree of thyrotoxicosis
– Important for monitoring success of initial treatment
– Though not always related to severity of symptoms
■ T3 toxicosis
– Can be sign of early disease

29. 9 Square Interpretation ofThyroid Hormones
High
Normal
Low
Low Normal High
fT4
TSH
PRIMARY
HYPERTHYROIDISM
EUTHYROID
SECONDARY
HYPERTHYROIDISM
PRIMARY
HYPOTHYROIDISM
SECONDARY
HYPOTHYROIDISM
SUBCLINICAL
HYPERTHYROIDISM
SUBCLINICAL
HYPOTHYROIDISM
NONTHYROID
ILLNESS
Or
Pt is onThyroid
Hormones
NONTHYROID
ILLNESS

30. Role of Imaging in Hyperthyroidism
■ Thyroid Ultrasound
– Color Doppler Flow helpful in AIT 1 vs. AIT 2.
– May reveal nodular disease or increased vascularity (seen in Grave’s)
■ Thyroid Uptake & Scan
– High uptake:
■ Graves’, toxic MNG, toxic adenoma
– Low uptake:
■ Thyroiditis, iodine-induced hyperthyroidism

31. Toxic adenoma
Nucleotide Scintigraphy

33. DestructiveThyroiditis
Ultrasonography
Doppler US
Graves Disease
Toxic Adenoma
Thyrotoxicosis Suspected
Thyrotoxicosis Confirmed
Detailed history, PE,TSH, FT4,TSH receptor Abs, if needed
Diffuse
hypoechogenicity
or
normoechogenicit
y
(no nodules)
h vascularity Absent or minimal vascularity
Nodular
RAIU and Scan
Toxic MNG Cold Nodule
RAI therapy OR Surgery FNAB

34. Treatment
■ Goals:
– Normalize serumTSH levels
– Reversecorrect clinical signs & symptoms and metabolic derangements.
■ Steps:
– Rest
– Sedation
– Beta-blockers
– Antithyroid medication
– NSAIDs and Corticosteroids – for SAT
– I -131
– Surgery
■ Thyroidectomy – Subtotal orTotal

35. Symptom Relief
■ Rehydration is the first step
■ β – blockers to decrease the sympathetic excess
 Propranalol, Atenelol, Metoprolol
 valuable during the first 2–3 weeks of treatment in providing
symptomatic relief of tachycardia, nervousness and tremor and can
then be discontinued as the specific antithyroid drug becomes
clinically effective
 Rate limiting CCBs if β – blockers contraindicated

36. Symptom Relief
■ Iodinated contrast (Idopate 0.001 μg/kg/day) and
■ Lugol iodine (5% iodine and 10% potassium iodide; 126 mg/mL
iodine, 1 drop 8 hourly) are effective in reversing of features of
hyperthyroidism.
■ Prednisolone (1- 2 mg/kg/day) inhibits peripheral conversion of
T4 toT3 and is useful in treatment of hyperthyroid storm.
■ Treatment of CHF, Arrhythmias

37. Treatment - Medical
■ Methimazole (MMI) – 5-30 mg daily
– Inhibit thyroid hormone synthesis by interfering with the thyroid peroxidase-
mediated iodination of tyrosine residues in thyroglobulin
– Effects seen 1-2 weeks after initiation of therapy.
■ Propylthiouracil (PTU) – 100-300 mg per day divided BID/TID
– PTU can also block the conversion of thyroxine (T4) to triiodothyronine (T3)
■ Side effects:
– Rash, arthralgias, nausea
– Vasculitis
– Liver function tests abnormalities (liver failure with PTU)
– Agranulocytosis
– Embryopathy
Check baseline CBC/diff and LFT’s

38. AntiThyroid Drugs (ATD)
Imp. considerations Methimazole Propylthiouracil
Efficacy Very potent Potent
Duration of action Long acting BID/OD Short acting QID/TID
In pregnancy Contraindicated Safely can be given
Mechanism of action Iodination, Coupling Iodination, Coupling
Conversion ofT4 toT3 No action Inhibits conversion
Adverse reactions Rashes, Neutropenia Rashes, ↑Neutropenia
Dosage 20 to 40 mg/ OD PO 100 to 150mg qid PO

39. How long to give ATD ?
■ Reduction of thyroid hormones takes 2-8 weeks
■ CheckTSH and FT4 every 4 to 6 weeks
■ In Graves, many go into remission after 12-18 months
■ In such pts ATD may be discontinued and followed up
■ 40% experience recurrence in 1 yr. Re treat for 3 yrs.
■ Treatment is not life long. Graves seldom needs surgery
■ MNG andToxic Adenoma will not get cured by ATD.
■ For them ATD is not the best.Treat with RAI.

40. Radio Active Iodine (RAI Rx.)
■ In women who are not pregnant
■ In cases ofToxic MNG andTSA
■ Graves disease not remitting with ATD
■ RAI Rx is the best treatment of hyperthyroidism in adults
■ The effect is less rapid than ATD orThyroidectomy
■ It is effective, safe, and does not require hospitalization.
■ Given orally as a single dose in a capsule or liquid form.
■ Very few adverse effects as no other tissue absorbs RAI

41. Radio Active Iodine (RAI Rx.)
■ I123 is used for Nuclear Scintigraphy (Dx.)
■ I131 is given for RAI Rx. (6 to 8 milliCuries)
■ Goal is to make the patient hypothyroid
■ No effects such asThyroid Ca or other malignancies
■ Never given for children and pregnant / lactating women
■ Not recommended with patients of severe Ophthalmopathy
■ Not advisable in chronic smokers

42. SurgicalTreatment
■ SubtotalThyroidectomy,TotalThyroidectomy
■ HemiThyroidectomy with contra-lateral subtotal
■ ATD and RAI Rx are very efficacious and easy – so Surgical
treatment is reserved for MNG with
1. Severe hyperthyroidism in children
2. Pregnant women who can’t tolerate ATD
3. Large goiters with severe Ophthalmopathy
4. Large MNGs with pressure symptoms
5. Who require quick normalization of thyroid function

43. Treatment – Medical – Beta-blockers
■ Pregnancy- absolute contraindication
■ Graves’ disease – goal is hypothyroidism after treatment
– Fixed dose or calculation (weight [g] x 150 µCi/g x 1/24 hour uptake %)
■ Toxic MNG andToxic Adenoma – can be euthyroid following treatment
■ May repeat in 6 months if initial dose not effective

44. Graves’ Ophthalmopathy
■ Up to 50% may have eye involvement
■ Can be euthyroid or hypothyroid in small minority (< 10 %)
■ High dose steroids
■ Radiation
■ Surgery – orbital decompression
■ Selenium
■ Supportive therapies (lubricants, prisms, etc.)
■ Alternative therapies (e.g. rituximab, botox)

45. Thyroid Storm
■ Life threatening condition associated with untreated hyperthyroidism
■ Dangerously high blood pressure, fever, and heart failure, mental changes, such
as confusion and delirium
■ Precipitating factors may be any major stress such as trauma, infection, etc.
Treatment: 5 Bs
1. Block hormone synthesis: Anti-thyroid drugs
2. Block release: Iodine
3. BlockT4 intoT3 conversion: High dose PTU, steroids
4. Beta-blockers: propranolol
5. Block enterohepatic circulation:Cholestyramine

46. Neonatal Hyperthyroidism
■ Caused by the passage across the placenta of maternal stimulating
antibodies directed against theTRAbs
■ Generally transient, occurring in only about 2% of the offspring of mothers
with GD.
■ Tachycardia, hyperexcitability, poor weight gain contrasting with a normal or
large appetite, small anterior fontanel, advanced bone age,
hepatosplenomegaly
■ Craniostenosis, microcephaly, and psychomotor disabilities may occur in
severely affected infants
■ MMI is preferred (1 mg/kg/day, in three doses). Propranolol (2 mg/kg/day, in
two divided doses) can also be needed to control tachycardia during the first
one to two weeks of treatment.

47. Summary
■ Thyrotoxicosis is a common condition encountered in practice
■ Subclinical disease is more common than overt thyrotoxicosis
■ TSH best for screening and freeT4 for confirmation and monitoring
treatment
■ Radioiodine uptake and scan preferred imaging modality
■ Treatment with methimazole or I-131 usually preferred

48. ■ Dr.C.S.N.Vittal