1. Common Thyroid Disorders in Children.
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.
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 Functions: 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. Normal Daily Thyroid Secretion Rate:
T4 = 100 ug/day
T3 = 6 ug/day
( ratio T4:T3 = 14:1 ) T4
Protein binding % free T4
85% (peripheral conversion) T3
Protein binding % free T3
15%
(10-20x less than T4)

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

14. Thyroid Function: blood tests
TSH –5.0 mU/L
Free T4 (thyroxine) – 23.8 pM
Free T3 (triiodothyronine) 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.
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.
Congenital Hypothyroidism: Causes
Agenesis or dysgenesis of thyroid gland
Dyshormonogenesis
Ectopic gland
Maternal hypothyroidism

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

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

30. Newborn Screening

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

32. Management Primary Congenital Hypothyroidism Thyroxine Dose Form Goals
Newborn Screening
Management
Primary Congenital Hypothyroidism
High TSH & Low T4
Thyroxine
Dose
Form
Goals
ug/kg/day
ug/kg/day
37.5 – 50 ug/day
Higher dose in
Severe cases
T4< 5ug/dl
Tablets 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)

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

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

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

36. Newborn Screening
Phenylketonuria
Guthrie Test
1962, Robert Guthrie

37. Possible screening tests
Newborn Screening
Possible screening tests
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
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

38. Congenital Hypothyroid
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. Congenital Hypothyroidism
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 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
This slide illustrates the diseases in relation to the newborn screening criteria – as we must consider this criteria prior to adding on new disease screening. As you can see here, the combination of these conditions are estimated to affect approximately 1 in 5,000 to 1 in ten thousand livebirths. The conditions can cause severe medical complications or death - FAOD alone are thought to account for 5% of sudden infant death. Treatment in the form of dietary management and avoidance of fasting, is effective at preventing mortality and improving quality of life. The initial cost of performing the analysis by tandem mass spec for these disorders is less than $10.00.
Although effective treatments do not exist yet for all of the metabolic disorders identifiable by tandem mass spectrometry,it is thought that some advantage can be achieved for the family and healthcare professionals through early diagnosis. This benefit is clearly seen when even though a child may die in the neonatal period before results are available information is now available for future reproductive use.

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

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

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

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

49. Newborn Screening
> screening
< screening

50. Congenital Hypothyroidism
Newborn Screening X
Congenital Hypothyroidism

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

52. Causes of hyperthroidism.
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. Thank You!
Newborn Screening