lecture

1. Thyroid disorders in children
Abdulmoein EidAl-Agha, MBBS, DCH, CABP, FRCPCH
Professor of Pediatric Endocrinology,
KingAbdulaziz University Hospital,
Website: http://aagha.kau.edu.sa

2. Objectives
Hypothyroidism
At the end of the lecture, medical student will
be able to:
-Recognize the anatomy, physiology of the thyroid
gland and thyroid hormone biosynthesis
-Description of the hypothalamic-pituitary regulation
of Thyroid Gland
- Discuss various cause of primary, secondary &
tertiary hypothyroidism including congenital
and acquired hypothyroidism
- Description of the clinical features of congenital &
acquired hypothyroidism
- Knowledge on how to investigate and expected
laboratoryfindingsand management of
hypothyroidism

3. Hyperthyroidism
 At the end of the lecture, medical student will
be able to:
Enumerate various causes of thyrotoxicosis
includingneonatal form
Description of clinical presentation of thyrotoxicosis
Enumerate various causes of thyrotoxicosis.
Knowledge on different laboratory & radiogical
Investigations and management of thyrotoxicosis

4. Thyroid gland
Thyroid gland derives from the floor of
embryonic pharynx
Begins to develop around 4 weeks of gestation
Moves down the neck while forming its
characteristic bilobular structure
Thyroid development is largely completed
between 10-20 weeks of gestation
Thyroid gland size increase gradually by 1g/year
until age of 15 years were it achieves adult size (15-
25 g)

5. Sites of normal & ectopic thyroid tissue

6. Thyroid gland
 Thyroid gland is composed over a million cluster
of follicles
 Follicles are spherical & consists of
epithelial cells surrounding a central mass
(colloid)
Thyroglobulin is storage room
Two main hormones:
Tetraiodothyronine (Thyroxin)
Triiodothyronine

7. FUNCTIONAL
UNIT IS THE
FOLLICLE

8. Thyroid gland
Thyroid gland normally secretes mainly T4
 70 % of T3 derived from T4 in peripheral
tissues
T4 is converted to T3 by 5-deiodinase enzyme
Both T4 and T3 are in bound form (TBG, pre
albumin & albumin)
Only 0.025% of T4 and 0.35% of T3 are free
Free hormone concentration best correlates
with thyroid status
T4 production is 5-6 µg/kg/day in infancy with
gradual decrement to 1.5 µg/kg/day in adult

9. Thyroid Regulation
Somatostatin,
Glucocorticoid
Dopamine

10. Thyroid hormone synthesis
1) Iodide pump
• Rate -limiting step in thyroid hormone synthesis which
needs energy
• Follicleshave in their basement membrane an iodide
trapping mechanism which pumps dietary I - into the cell
• Normal thyroid: serum iodine is 30-40:1
- Iodide uptake enhancers:
• TSH
• Iodine deficiency
• TSH receptors antibody
- Iodide uptake inhibitors
• Iodide ion
• Drugs
- Digoxin
- Thiocynate
- perchlorate

11. Thyroid hormone synthesis
2) Iodide oxidation to iodine and Organification
 Inside the cells, iodide is oxidized by peroxidase system
to more reactive iodine
 Iodine immediately reacts with tyrosine residue
on a thyroid glycoprotein called “thyroglobulin”
to form :
T1= mono-iodotyrosyl thyroglobulin
T2= di-iodotyrosyl thyroglobulin
 Both processes are catalyzed by thyroid peroxidase
enzyme

12. Thyroid hormone synthesis
3) Coupling
T1& T2 couple together to form T3&T4
 MIT +DIT = T3 (Tri-iodothyronine)
 DIT + DIT = T4 (Thyroxin)
All attached to thyroglobulin and stored in the
colloid Thyroglobulin molecule
This process is stimulated by TSH

13. Production of Thyroid Hormones
NIS (Na+/I- Sympoter)
TPO

14. Effects of thyroid hormones
 Fetal brain & neuronal development up to age of 5 years
 Skeletal maturation from intrauterine life into closure of
epiphysis after puberty
 Increase in basal metabolic rate
 Inotropic & chronotropic effects on heart
 Increases sensitivity to catecholamine
 Stimulates gut motility
 Increase bone turnover
 Increase in serum glucose, decrease in serum cholesterol
 Conversion of carotene to vitaminA
 Play role in thermal regulation

15. Causes , Clinical Features &
Consequences of Hypothyroidism
Congenital Hypothyroidism
Acquired Hypothyroidism

16. Etiology
 Congenital
Acquired
Primary
Secondary
Tertiary

17. Congenital Hypothyroidism
Etiology of primary hypothyroidism
Thyroid dysgenesis
Commonest cause in 95% of cases
Athyreosis (40%)
Hypoplasia (40%)
Ectopia (base of tongue, midline) (20%)
 Thyroid dyshormonogenesis (A.R) (10%)
Etiology of secondary/ tertiary hypothyroidism
 Hypothalamic-pituitary hypothyroidism
Anencephaly, Holoprosencephaly, septo-optic
dysplasia
idiopathic

18. Congenital hypothyroidism

19. Lingual ectopic thyroid gland

20. Neonate with Holoprosencephaly & midline facial
defect associated with Hypopituitarism

21. Neonate with cleft lip & palate,
associated with hypopituiterism

22. Presentations of congenital hypothyroidism
 Macroglosia
 Prolonged hyperbilirubinemia
 Poor feeding
 Hoarse cry
 Decreased activity
 Constipation
 Umbilical hernia
 Dry yellow skin
 large fontanel
 Delayed skeletal maturation

23. Neonatal screening for congenital
hypothyroidism
 Routine in most countries worldwide as well in Saudi Arabia
 Filterpaper blood spot measuringTSH
 Why??
 Clinicalmanifestationsat birth, usually are subtle or even
absent (passive transplacental maternal thyroxin)
 At birth, surge of TSH (stress of delivery) up to 30 -40 µu/ml
 Early detection will prevent mental retardationor
decreasing IQ of affected neonates
 Thyroxin is important for CNS development from birth till 3
years of life
 Screening program will miss 2ry/ tertiary cases
 The program is hampered by a high rate of false positive results

24. Causes of acquired Hypothyroidism
 More common than hyperthyroidism
 99% is primary (< 1% due to TSH deficiency)
 Hashimoto’s thyroiditis:
most common cause
most common cause in iodine-replete areas
chronic lymphocytic thyroiditis
Associated with TPO (thyroid peroxidase) antibodies
(90%), less commonly Tg (thyroglobulin) antibodies
 Iatrogenic Hypothyroidism from radioactive iodine
therapy
 Iodine deficiency (Not in Saudi Arabia, as iodine is added
to table salt)
 Medication related (Amidarone)

25. Transient causes of acquired Hypothyroidism
 Subacute thyroiditis
Painful, often radiates to the ear
c/o malaise, pharyngitis, fatigue, fever, neck pain/swelling
Viral etiology (URI/ pharyngitis)
self-limited.
 Can tx inflammation w/ ASA, NSAID’s or steroids
 Suppurative/Acute Infectious thyroiditis
Infections of the thyroid are rare
normally protected from infection by its thick capsule
Bacterial >> fungal, mycobacterial or parasitic
Pt’s are acutely ill w/ a painful thyroid gland
assoc w/ fever/chills, anterior neck pain/swelling,
dysphagia
and dysphonia

26. Acquired Hypothyroidism
• Symptoms
-General slowing down
-Lethargy/somnolence
-Depression
-Modest weight gain
-Cold intolerance
-Hoarseness
-Dry skin
-Constipation (↓ peristaltic
activity)
-Generalaches/pains
• Arthralgia or myalgia
-Brittle & dry hair
-Menstrual irregularities
•Excessive bleeding
•Failure of ovulation

27. Acquired Hypothyroidism
Examination
Dry, pale, course skin with yellowish tinge
Periorbital edema
Puffy face & extremities
Sinus bradycardia
 Hypothermia
Delayed relaxation of reflexes (ankle)
Megacolon (↓ peristaltic activity)
Pericardial/ pleural effusions
Congestive heart failure
Non-pitting edema (myxedema)
Hoarse voice
Proximalmyopathy

28. Goiter
Aswollen thyroid gland
Could be associated with
hypo/hyperthyroidism or
even physiological goiter
especially during puberty
 Assessment;
-how big, how quickly
has it developed, is it
smooth or nodular, is it
painful, any associated
lymph nodes, any
sudden changes, is it
big enough to cause
local symptoms (e.g.
breathingproblems)

29. Hypothyroidism with short stature

30. Diagnosis
Congenital hypothyroidism
Thyroid hormone level (fT4& fT3)
TSH
Thyroid scan
Acquired Hypothyroidism
TSH
fT4 (not total)
Thyroid antibodies (anti-TPO/ TG)
Thyroid ultrasound

31. Treatment
 L-thyroxin replacement should be started
as soon as possible
 If treatment is delayed > 2 months of life,
 > 75% risk of hypothyroidism
 On the other hand, delayed treatment of
hyperthyroidism will lead to advanced
skeletal maturation, craniosynostosis and
intellectual deficits
 L-Thyroxin is the main drug for treatment
of hypothyroidism, whatever is the cause

32. Causes , Clinical Features &
Consequences of Hyperthyroidism

33. Thyrotoxicosis in children
 Graves' disease is by far the most common cause
of hyperthyroidism accounting for more than 95 %
of cases
Rarely, conditions other than Graves' disease
may cause hyperthyroidism in children include:
Subacute granulomatous thyroiditis (de
Quervain's disease)
Solitary hyper functioning thyroid nodule
Toxic multinodular goiter
Pituitary thyroid-stimulating hormone (TSH)-
secreting adenoma
Hyperthyroidism induced by iodine, neck
trauma, radiation or Amidarone medication

34. Thyrotoxicosis
Persistent
 Graves’disease
 Toxic multinodular goiter
 Toxic solitary adenoma
 Central TSH producing adenoma
(TSH oma)

35. Neonatal thyrotoxicosis due to passive
transfer of Autoantibodies from the mother
to her fetus (transient)
AColorAtlas of Endocrinologyp51

36. Grave’s disease
Pathogenesis
 T-cell dependent autoimmune disease
 60% have HLAassociation withA1, B8,
DR3,DR4,DR5
 Autoimmune disorder that results in production
of antibodies directed against thyroid antigens:
TSH receptors antibody (TRAB, TSI)
Thyroglobulin autoantibody
Thyroid peroxidase autoantibody

37. Hyperthyroidism
May result in significant morbidity,,
mortality & even death
 Symptoms
Jittery, shaky, nervous
Difficulty concentrating
Emotional lability
Insomnia
Rapid HR, palpitations
Feeling Hot
Weight Loss
Diarrhea
Fatigue
Menses : lighter flow, shorter
duration

38. Hyperthyroidism
 Sign
- Eye findings (20%)
- Goiter
- Thyroid bruit or thrill
Sinus tachycardia, Atrial Fibrillation
- Flow murmur
- Systolic hypertension
- Hyperreflexia
- Tremors
- Proximal muscle weakness
- Clubbing
- Onycholysis (<1%)
• separation of nail from the
nailbed
- Dermopathy (1%)

40. Hyperthyroid Eye Disease

41. Graves’Dermopathy
Thickening & redness of
the dermis due to
lymphocytic infiltration

42. Clubbing
Thyroid acropachy
This is most marked in the index fingers and thumbs

43. Tremor of the hand
AColorAtlas of Endocrinologyp49

44. Diagnosis
TSH level usually < 0.05 µu / ml
 95 % of cases, high fT4 & fT3
 In 5% high fT3 with normal T4 (T3
Thyrotoxicosis)
Thyroid receptor (TRAB) are usually
elevated at diagnosis
 Antibodies against thyroglobulin,
peroxidase or both are present in the
majority of patients

45. Toxic adenoma

46. Treatment Modalities
Three modalities for more than last 50 years
Radioactive iodine ,antithyroid drugs &surgery
None is optimal
None interrupts the autoimmune process
Each has a drawbacks

47. Treatment
 Most pediatric endocrinologists recommend
antithyroid therapy as initial treatment
RAI also may be used as initial treatment for children
older than 10 years
Surgical near-total thyroidectomy is an effective and
safe treatment, but is the last option

48. Medical therapy
Most children & adolescents respond well to
antithyroid drug
Methimazole (MMI, 0.25 to 1.0 mg/kg per day)
Propylthiouracil (PTU, 5 to 10 mg/kg per day) is
effective, but has more frequent and severe side
effects, including risk of severe hepatotoxicity
Because of these safety concerns, the Endocrine
Society
and the American Thyroid Association (ATA)
recommend against the use of PTU as first-line
treatment for Graves' disease in children, and the
US (FDA) has issued a boxed warning

49. Medical therapy
Anti-thyroid drugs inhibit the synthesis of
thyroid hormones
Interfere with iodination of tyrosine
residues
Effects seen 1-2 weeks after initiation of
therapy
Side effects
Rash, arthralgia, nausea
Vacuities
Liver function tests abnormalities (liver
failure with PTU)
Agranulocytosis
Embryopathy

50. Patients who develop prominent symptoms of
adrenergic over activity (palpitations & tremor),
can be treated with β blockers until thyroid
hormone levels decline in response to the
antithyroid drug therapy
Atenolol: cardio-selective, and therefore has
reduced risk of bronchospasm as compared
with other beta blockers is first choice. In
addition, it is administered once daily,
resulting in better compliance, dose of
Atenolol for children & adolescents (1 - 2 )
mg/kg daily
Propranolol has the potential benefit of
decreasing T4 to T3 conversion, is preferred by
some clinicians
β blockers

51. RAI (131-I)
 RAI (131-I) therapy is an effective alternative treatment
for children & adolescents with hyperthyroidism
Recommend as secondary therapy for patients who have:
recurrent hyperthyroidism after long-term treatment
with an antithyroid drug who request definitive
treatment
for those who have a major side effect while receiving
an antithyroid drug
Some pediatric endocrinologists consider it the initial
treatment of choice in older children & adolescent
RAI usually should be restricted to children older than 10
years of age, consistent with guidelines from the ATA and
American Association of Clinical Endocrinologists (AACE)

52. Surgery (sub-total thyroidectomy)
Although thyroidectomy is not often recommended as initial therapy for
children or adolescents with Graves' hyperthyroidism, it is an effective
therapy for the disorder
Is the preferred treatment for Graves' disease in children younger than five
years of age when definitive therapy is required because RAI is not
recommended for this young age group
 Surgery also may be particularly appropriate for those with very large
goiter, as studies in adults suggest that individuals with large thyroid
glands (greater than 80 grams) are unlikely to respond to RAI treatment
 Risks
 Permanenthypoparathyroidism
 Recurrent laryngeal nerve problems
 bleeding as thyroid is highly vascular gland

53. ‫بأذن‬ ‫موفقين‬
‫هللا‬