Download THYROID DISEASES FOR STUDENTS king saud

.
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
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 metabolism
CALCITONIN – 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
Normal Daily Thyroid Secretion Rate:
T4 = 100 ug/day
T3 = 6 ug/day
( ratio T4:T3 = 14:1 )
T4
Protein binding
+ 0.03% free T4
Protein binding
+ 0.3% free T3
85% (peripheral conversion)
15%
T3
(10-20x less than T4)
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
mU/L
Free T4 (thyroxine)
pM
Free T3 (triiodothyronine)
0.4 –5.0
9.1 – 23.8
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
Newborn Screening
Facts
Mother
supplies T4
to fetus via
placenta
Normal Newborn
Mother
Fetus
Immature
Hypothalamic
Pituitary
Thyroid Axis
T4
Mid-Gestation
T4
Euthyroid
Mother
Mature
Hypothalamic
Pituitary
Thyroid Axis
Pregnancy
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
Congenital Hypothyroidism
Clinical
X
suspect
Biochemical (screening)
Optional
Confirm
Lab ( TSH & FT4 )
T scan
B age
Rx & FU
Thyroxine
Growth & D
TSH & FT4
Newborn Screening
Management
Primary Congenital Hypothyroidism
High TSH & Low T4
Thyroxine
Dose
10 -15 ug/kg/day
12 -17 ug/kg/day
37.5 – 50 ug/day
Higher dose in
Severe cases
T4< 5ug/dl
Form
Goals
Tablets
Normal T4
In 2 wks
(upper ½ of N)
25-50-75 ug
Crush it, add to
5-10 cc water
Or milk
Normal TSH
In one month
(lower ½ of N)
Newborn Screening
Definitions
Screening: search for a disease in a large unselected populatio
PKU
Congenital 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
Phenylketonuria
Guthrie Test
1962, Robert Guthrie
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
Congenital hypothyroidism










Incidence >1/100,000
Significant morbidity/mortality
Successful treatment
Reasonable cost
Test: specific/sensitive/acceptable
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
Objective from screening:
Eradication of MR secondary to CH
Every Newborn is considered
Hypothyroid
Until Proven Otherwise
Newborn Screening
Method & Timing of Thyroid Screening
Primary-TSH
Backup-T4
Cord
Blood
Age
At Birth
Both
TSH&T4
Primary-T4
Backup-TSH
Venous
Blood
Age
2-5 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
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
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
Thank You!
Newborn Screening