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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)

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Clinical features of Acquired hypothyroidism

• Weight gain• Goitre• Short sature• Fatigue• Constipation• Dry skin• Cold Intolerance• Hoarseness• Sinus Bradycardia

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Hypothyroidism with short stature

Diagnosis

• High TSH, low T4• Thyroid antibodies

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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

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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)

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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

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Goiter

• A swollen thyroid gland

Newborn ScreeningThank You!Thank You!