. Common Thyroid Disorders in Children Dr Sarar Mohamed FRCPCH (UK), MRCP (UK), CCST (Ire), CPT...
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Transcript of . Common Thyroid Disorders in Children Dr Sarar Mohamed FRCPCH (UK), MRCP (UK), CCST (Ire), CPT...
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Common Thyroid Disorders in Children
Dr Sarar Mohamed FRCPCH (UK), MRCP (UK), CCST (Ire), CPT (Ire),
DCH (Ire), MDConsultant Paediatric Endocrinologist & Metabolist
Assistant Professor of PediatricsKing Saud University
Endocrine Glands
.Agenda
• Thyroid Anatomy and physiology• Thyroid Function Test• Congenital Hypothyroidism• Newborn screening for congenital
hypothyroidism• Acquired hypothyroidism• Hyperthyroidism• Causes of goitre
Newborn Screening
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
THYROID GLAND
Innervation: Vagus Nerve (X)
Arterial Supply: superior thyroid artery (branch of external carotid artery).
Functions: THYROXIN – regulate rate of metabolismCALCITONIN – decreases levels of calcium and phosphate in the blood (partially antagonistic to parathyroid hormone).
Production of Thyroid Hormones
NIS (Na+/I- Sympoter)
TPO
t1/2 = 5-7d
t1/2 = < 24 hrs
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/dayT3 = 6 ug/day
( ratio T4:T3 = 14:1 )
T4 T3
Potency 1 10
Protein Bound 10-20 1
Half-Life 5-7d < 24h
Secreted by thyroid
100 ug/d 6 ug/d
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
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
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
Hypothyroidism
• Decreased thyroid hormone levels• Low T4• Possibly Low T3 too.• Raised TSH (unless pituitary problem!)
Causes of hypothyroidism
• Congenital• Autoimmune (Hashimoto)• Iodine deficiency• Subacute thyroiditis• Drugs (amiodarone)• Irradiation• Thyroid surgery• Central hypothyroidism (radiotherapy, surgery, tumor)
.
Clinical features of Acquired hypothyroidism
• Weight gain• Goitre• Short sature• Fatigue• Constipation• Dry skin• Cold Intolerance• Hoarseness• Sinus Bradycardia
.
Hypothyroidism with short stature
Diagnosis
• High TSH, low T4• Thyroid antibodies
.
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!
Subacute (de Quervain’s) Thyroiditis
• Preceding viral infection• Infiltration of the gland with granulomas• Painful goitre• Hyperthyroid phase Hypothyroid phase
Treatment of Hypothyroidism
• Replacement thyroid hormone medication: Thyroxine
Congenital Hypothyroidism: Causes
• Agenesis or dysgenesis of thyroid gland• Dyshormonogenesis• Ectopic gland• Maternal hypothyroidism
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Newborn Screening
Facts
Mother Fetus
Mid-Gestation
ImmatureHypothalamic
PituitaryThyroid Axis
Pregnancy
Mother supplies T4 to fetus via
placenta T4
T4Mature
HypothalamicPituitary
Thyroid Axis
Normal Newborn
EuthyroidMother
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%
Newborn Screening
Newborn Screening
suspect Clinical
Confirm
Rx & FU
Biochemical (screening)
Lab ( TSH & FT4 )
T scanB age
Optional
Thyroxine
Congenital HypothyroidismX
Growth & D
TSH & FT4
Newborn Screening
High TSH & Low T4
Management Primary Congenital Hypothyroidism
Thyroxine
10 -15 ug/kg/day12 -17 ug/kg/day37.5 – 50 ug/day
Higher dose inSevere cases
T4< 5ug/dl
Tablets25-50-75 ug
Crush it, add to5-10 cc water
Or milk
Normal T4 In 2 wks
(upper ½ of N)
Normal TSHIn one month(lower ½ of N)
Dose Form Goals
Newborn Screening
Definitions
Screening: search for a disease in a large unselected populationPKUCongenital hypothyroidism
Newborn Screening
Principal of newborn screening• Aim is to identify affected infants before
development of clinical signs
Newborn Screening
Success Stories in Pediatric Medicine
Immunization programs
Newborn Screening program
Oral Rehydration Therapy
Pencillin
Newborn Screening
Guthrie Test1962, Robert Guthrie
PhenylketonuriaPhenylketonuria
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
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
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
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
Newborn Screening
Screening Technique
• Specimen is a blood spot in a filter paper
• Obtained by heel brick
• Or cord blood
Newborn Screening
Newborn Screening
Newborn Screening
Good Specimen
.
Congenital Hypothyroidism
Every Newborn is considered Hypothyroid
Until Proven Otherwise
Objective from screening:
Eradication of MR secondary to CH
Newborn Screening
Method & Timing of Thyroid Screening
Primary-TSHBackup-T4
BothTSH&T4
Primary-T4Backup-TSH
Cord Blood
Venous Blood
AgeAt Birth
Age2-5 days
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%
Newborn Screening
Clinical Outcome• Post-screening data:
– Children screened & treated by age 25 days
• Mean IQ = 104
Newborn Screening
> screening < screening
Newborn Screening
Congenital Hypothyroidism
X
Hyperthyroidism
• Increased thyroid hormone levels• High T4 +/- High T3• Low (suppressed) TSH
Causes of hyperthroidism
• Graves Disease• Overtreatment with thyroxine• Thyroid adenoma (rare)• Transient neonatal thyrotoxicosis
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Graves’ Disease
• Most common cause of hyperthyroidism• Goitre, proptosis• TSH-R antibody (stimulating)• 40-70% relapse after 2 years of treatment
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
Tremor of the hand
A Color Atlas of Endocrinology p49
Neonatal hyperthyroidism born to mother with Graves’ disease
A Color Atlas of Endocrinology p51
“Exophthalmos”
Grave’s ophthalmopathy
Hyperthyroid Eye Disease
investigations
• TSH, free T3&T4• Thyroid antibodies (TSH receptors antibodies)• Radionucleotide thyroid scan (incease uptake)
.
Hyperthyroidism
• Treatment– Beta-blockers– Carbimazole– PTU (propylthiouracil)– Radioactive iodine (in adults)– surgery
Causes of goitre
• Congenital (maternal antithyroid drugs, maternal hyperthyroidism, dyshormonogenesis)
• Physiological (puberty)• Iodine deficiency• Graves disease• Hashimoto thyroiditis• Tumor
.
Goiter
• A swollen thyroid gland
Newborn ScreeningThank You!Thank You!