health

1. .
Common Thyroid Disorders in
Children
Dr Sarar Mohamed
FRCPCH (UK), MRCP (UK), CCST (Ire), CPT (Ire),
DCH (Ire), MD
Consultant Paediatric Endocrinologist & Metabolist
Assistant Professor of Pediatrics
King Saud University

2. Endocrine Glands

3. .
Agenda
• Thyroid Anatomy and physiology
• Thyroid Function Test
• Congenital Hypothyroidism
• Newborn screening for congenital
hypothyroidism
• Acquired hypothyroidism
• Hyperthyroidism
• Causes of goitre

4. Newborn Screening

5. THYROID GLAND
Location: Located close to thyroid cartilage. Has two lateral
lobes connected by thyroid isthmus medially.
Development: first endocrine gland to appear during
development. Develops from endodermal floor of early
pharynx

6. THYROID GLAND
Innervation: Vagus Nerve (X)
Arterial Supply: superior thyroid artery (branch of external carotid
artery).
Functions:
THYROXIN – regulate rate of metabolism
CALCITONIN – decreases levels of calcium and phosphate in the blood
(partially antagonistic to parathyroid hormone).

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

10. t1/2 = 5-7d
t1/2 = < 24 hrs

11. T4
T3
85% (peripheral conversion)
15%
Protein binding + 0.03% free T4
Protein binding + 0.3% free T3
(10-20x less than T4)
Normal Daily Thyroid Secretion Rate:
T4 = 100 ug/day
T3 = 6 ug/day
( ratio T4:T3 = 14:1 )

12. T4 T3
Potency 1 10
Protein Bound 10-20 1
Half-Life 5-7d < 24h
Secreted by
thyroid
100 ug/d 6 ug/d

14. Thyroid Function: blood tests
TSH 0.4 –5.0
mU/L
Free T4 (thyroxine) 9.1 – 23.8
pM
Free T3 (triiodothyronine) 2.23-5.3 pM

15. Effects of thyroid hormones
• Fetal brain & skeletal maturation
• Increase in basal metabolic rate
• Inotropic & chronotropic effects on heart
• Stimulates gut motility
• Increase bone turnover
• Increase in serum glucose, decrease in
serum cholesterol
• Play role in thermal regulation

16. Dysfunction Thyroid Gland
1. Too little thyroxin – hypothyroidism
a. short stature (aquiered), developmental delay (congenital)
2. Too much thyroxin – hyperthyroidism
a. Agitation, irritability, & weight loss

17. Hypothyroidism
• Decreased thyroid hormone levels
• Low T4
• Possibly Low T3 too.
• Raised TSH (unless pituitary problem!)

18. Causes of hypothyroidism
• Congenital
• Autoimmune (Hashimoto)
• Iodine deficiency
• Subacute thyroiditis
• Drugs (amiodarone)
• Irradiation
• Thyroid surgery
• Central hypothyroidism (radiotherapy, surgery, tumor)
.

19. Clinical features of Acquired hypothyroidism
• Weight gain
• Goitre
• Short sature
• Fatigue
• Constipation
• Dry skin
• Cold Intolerance
• Hoarseness
• Sinus Bradycardia
.

20. Hypothyroidism with short stature

21. Diagnosis
• High TSH, low T4
• Thyroid antibodies
.

22. Hashimoto’s Disease
• Most common cause of hypothyroidism
• Autoimmune lymphocytic thyroiditis
• Antithyroid antibodies:
• Thyroglobulin Ab
• Microsomal Ab
• TSH-R Ab (block)
• Females > Males
• Runs in Families!

24. Subacute (de Quervain’s) Thyroiditis
• Preceding viral infection
• Infiltration of the gland with granulomas
• Painful goitre
• Hyperthyroid phase  Hypothyroid phase

26. Treatment of Hypothyroidism
• Replacement thyroid hormone medication: Thyroxine

27. Congenital Hypothyroidism: Causes
• Agenesis or dysgenesis of thyroid gland
• Dyshormonogenesis
• Ectopic gland
• Maternal hypothyroidism
.

28. Newborn Screening
Facts
Mother Fetus
Mid-Gestation
Immature
Hypothalamic
Pituitary
Thyroid Axis
Pregnancy
Mother
supplies T4
to fetus via
placenta T4
T4
Mature
Hypothalamic
Pituitary
Thyroid Axis
Normal Newborn
Euthyroid
Mother

29. Newborn Screening
Clinical Features of Congenital Hypothyroidism
Finding %
Lethargy 96%
Constipation 92%
Feeding problems 83%
Respiratory problems 76%
Dry skin 76%
Thick tongue 67%
Hoarse cry 67%
Umbilical hernia 67%
Prolonged jaundice 12%
Goiter 8%

30. Newborn Screening

31. Newborn Screening
suspect Clinical
Confirm
Rx & FU
Biochemical (screening)
Lab ( TSH & FT4 )
T scan
B age
Optional
Thyroxine
Congenital Hypothyroidism
X
Growth & D
TSH & FT4

32. Newborn Screening
High TSH & Low T4
Management
Primary Congenital Hypothyroidism
Thyroxine
10 -15 ug/kg/day
12 -17 ug/kg/day
37.5 – 50 ug/day
Higher dose in
Severe cases
T4< 5ug/dl
Tablets
25-50-75 ug
Crush it, add to
5-10 cc water
Or milk
Normal T4
In 2 wks
(upper ½ of N)
Normal TSH
In one month
(lower ½ of N)
Dose Form Goals

33. Newborn Screening
Definitions
Screening: search for a disease in a large unselected populatio
PKU
Congenital hypothyroidism

34. Newborn Screening
Principal of newborn screening
• Aim is to identify affected infants before
development of clinical signs

35. Newborn Screening
Success Stories in Pediatric Medicine
 Immunization programs
 Newborn Screening program
 Oral Rehydration Therapy
Pencillin

36. Newborn Screening
Guthrie Test
1962, Robert Guthrie
Phenylketonuria

37. Newborn Screening
Possible screening tests
• Glucose-6-phosphate dehydrogenase deficiency (G6PD)
• Sickle cell anemia (Hb SS) > 1 in 5,000; among African-Americans 1 in 400
• Sickle-cell disease (Hb S/C) > 1 in 25,000
• Hb S/Beta-Thalassemia (Hb S/Th) > 1 in 50,000
• Tyrosinemia I (TYR I) < 1 in 100,000
• Tyrosinemia II
• Argininemia
• Argininosuccinic aciduria (ASA) < 1 in 100,000
• Citrullinemia (CIT) < 1 in 100,000
• Phenylketonuria (PKU) > 1 in 25,000
• Maple syrup urine disease (MSUD) < 1 in 100,000
• Homocystinuria (HCY) < 1 in 100,000
• Glutaric acidemia type I (GA I) > 1 in 75,000
• Glutaric acidemia type II
• HHH syndrome (Hyperammonemia, hyperornithinemia, homocitrullinuria
syndrome)
• Hydroxymethylglutaryl lyase deficiency (HMG) < 1 in 100,000
• Isovaleric acidemia (IVA) < 1 in 100,000
• Isobutyryl-CoA dehydrogenase deficiency
• 2-Methylbutyryl-CoA dehydrogenase deficiency
• 3-Methylcrotonyl-CoA carboxylase deficiency > 1 in 75,000
• Beta-methyl crotonyl carboxylase deficiency
• 3-Methylglutaconyl-CoA hydratase deficiency
• Methylmalonyl-CoA mutase deficiency (MUT) > 1 in 75,000
• Methylmalonic aciduria, < 1 in 100,000
• Beta-ketothiolase deficiency (BKT) < 1 in 100,000
• Propionic acidemia (PROP) > 1 in 75,000
• Adenosylcobalamin synthesis defects
• Multiple-CoA carboxylase deficiency (MCD) < 1 in 100,000
• Carnitine palmityl transferase deficiency type 2 (CPT)
• Long-chain acyl-CoA dehydrogenase deficiency (LCAD)
• Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) > 1 in 75,000
• Short-chain acyl-CoA dehydrogenase deficiency (SCAD)
• Short-chain hydroxy Acyl-CoA dehydrogenase deficiency (SCHAD)
• Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) > 1 in 25,000
• Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) > 1 in 75,000
• Carnitine/acylcarnitine Translocase Deficiency (Translocase)
• Multiple acyl-CoA dehydrogenase deficiency (MADD)
• Trifunctional protein deficiency (TFP) < 1 in 100,000
• Carnitine uptake defect (CUD) < 1 in 100,000
• Congenital toxoplasmosis
• HIV
• Cystic fibrosis (CF) > 1 in 5,000
• Maternal vitamin B12 deficiency
• Congenital
hypothyroidism (CH) >
1 in 4,000
• Biotinidase deficiency (BIOT) > 1 in 75,000
• Congenital adrenal hyperplasia (CAH) > 1 in 25,000
• Classical galactosemia (GALT) > 1 in 50,000

38. Newborn Screening
Congenital Hypothyroid
Screening started 1974 in Quebec & Pittsburgh
Objective : Eradication of MR secondary to CH
Incidence 1:3000 – 4000 ( more than PKU )
Female : Male is 2 : 1

39. Newborn Screening
Congenital Hypothyroidism
 One of the most common Treatable causes of MR
 CH Screening is the most cost effective program
Almost all affected NB have no S/S at birth
Congenital Anomalies increased by 10%(cardiac)
 In more than 90% of the cases it is permanent
 The earlier dx the better IQ

40. Newborn Screening
Newborn Screening Criteria
Wilson Criteria
 Incidence >1/100,000
 Significant morbidity/mortality
 Successful treatment
 Reasonable cost
 Test: specific/sensitive/acceptable
Congenital hypothyroidism
 1/3,000 to 1/4,000
 Mental retardation
 Thyroxine
 $3.00
 immunoassay

41. Newborn Screening
Screening Technique
• Specimen is a blood spot in a filter paper
• Obtained by heel brick
• Or cord blood

42. Newborn Screening

43. Newborn Screening

44. Newborn Screening
Good Specimen

45. .
Congenital Hypothyroidism
Every Newborn is considered
Hypothyroid
Until Proven Otherwise
Objective from screening:
Eradication of MR secondary to CH

46. Newborn Screening
Method & Timing of Thyroid Screening
Primary-TSH
Backup-T4
Both
TSH&T4
Primary-T4
Backup-TSH
Cord
Blood
Venous
Blood
Age
At Birth
Age
2-5 days

47. Newborn Screening
Clinical Outcome
• Pre-screening data:
– Mean IQ = 76
Age of Diagnosis % with IQ > 85
3 months 78%
6 months 19%
> 7 months 0%

48. Newborn Screening
Clinical Outcome
• Post-screening data:
– Children screened & treated by age 25 days
• Mean IQ = 104

49. Newborn Screening
> screening < screening

50. Newborn Screening
Congenital Hypothyroidism

51. Hyperthyroidism
• Increased thyroid hormone levels
• High T4 +/- High T3
• Low (suppressed) TSH

52. Causes of hyperthroidism
• Graves Disease
• Overtreatment with thyroxine
• Thyroid adenoma (rare)
• Transient neonatal thyrotoxicosis
.

53. Graves’ Disease
• Most common cause of hyperthyroidism
• Goitre, proptosis
• TSH-R antibody (stimulating)
• 40-70% relapse after 2 years of treatment

54. Hyperthyroidism S&S
• Heat intolerance
• Hyperactivity, irritability
• Weight loss (normal to increased appetite)
• diarrhea
• Tremor, Palpitations
• Diaphoresis (sweating)
• Lid retraction & Lid Lag (thyroid stare)
• proptosis
• menstrual irregularity
• Goitre
• Tachcardia

55. Tremor of the hand
A Color Atlas of Endocrinology p49

57. Neonatal hyperthyroidism born to mother
with Graves’ disease
A Color Atlas of Endocrinology p51

58. “Exophthalmos”

59. Grave’s ophthalmopathy

60. Hyperthyroid Eye Disease

61. investigations
• TSH, free T3&T4
• Thyroid antibodies (TSH receptors antibodies)
• Radionucleotide thyroid scan (incease uptake)
.

63. Hyperthyroidism
• Treatment
– Beta-blockers
– Carbimazole
– PTU (propylthiouracil)
– Radioactive iodine (in adults)
– surgery

64. Causes of goitre
• Congenital (maternal antithyroid drugs, maternal
hyperthyroidism, dyshormonogenesis)
• Physiological (puberty)
• Iodine deficiency
• Graves disease
• Hashimoto thyroiditis
• Tumor
.

65. Goiter
• A swollen thyroid
gland

66. Newborn Screening
Thank You!