Thyroid gland secretes :

1) Thyroid hormones : Thyroxine (T4) & Triiodothyronine (T3) 2) Calcitonin (which deposit calcium salts in bone)

1. 2. 3.

Normal maturation of the growing brain in the first year of life. Normal skeletal growth. Oxidative metabolism & heat production in all cells.

1. 2. 3. 4.

Iodide transport (trapping) Iodide is oxidized to iodine by thyroid peroxidase enzyme (organification) Iodination of tyrosine to form mono & di iodotyrosine Coupling of :

5.

6.

T3 & T4 are stored in thyroid gland as colloid (thyroglobulin) Only 20% if circulating T3 is produced by thyroid while 80% is produced by peripheral conversion of T4 by deiodinase.

2 Diiodotyrosine T4 Monoiodotyrosine & diiodotyrosine

T3

1.

2.

Thyroid is regulated by pituitary thyroid stimulating hormone (TSH) in a feedback mechanism. TSH synthesis & release is controlled by hypothalamic TSH releasing hormone (TRH).

A) Primary hypothyroidism
1. Thyroid dysgenesis
2. Dyshormogenesis

The commonest cause (90%) Aplasia, hypoplasia or ectopic gland The second common All are autosomal reseccive disorders. Associated with goitre Types :
Iodide transport defect Organification defect Thyroglobulin synthesis defect Iodotyrosine defect.

3. Transient hypothyroidism
1. 2.
1. 2.

Transplacental passage of maternal : Neonatal iodine containing antiseptics.

TSH receptor blocking antibodies Drugs (eg : antithyroid drugs, excessive iodine)

4. Maternal iodine deficiency : endemic goitre. 5. End organ responsiveness

B) Secondary hypothyroidism
Due to TSH deficiency either :
Isolated With multiple pituitary deficiencies

C) Tertiary hypothyroidism
Due to TSH releasing hormone deficiency.

In neonatal period

Prolonged physiologic jaundice Lethargy; cry little, sleep much Poor feeding; lack interest, chocking spells during feeding Wide posterior fontanel Noisy breathing due to large tongue Distended abdomen, constipation with umbilical hernia Heavy at birth Subnormal temperature * baby may be asymptomatic, so neonatal screening is mandatory

Full picture (by age 3-6 months)

Delayed growth proportionate short stature Delayed mental milestones. Delayed motor milestones. Physical features may include :
Head :

Hair is course, brittle with low anterior hair line

Delayed closure of anterior fontanel Eyes are puffy, narrow palpebral fissure Broad nose & depressed bridge Delayed teething Thick large protruding tongue Hoarse cry

 Neck

Short neck with supraclavicular pad of fat Thyroid is enlarged in :

Endemic goitre Dyshormonogynesis Pseudohypothyroidism

Cardiac

Bradycardia Pericardial effusion Cardiomegaly

Abdomen Protruding with umbilical hernia

Constipation

 Genitalia
Delayed sexual maturation Rarely precocious puberty

Limbs
Short broad hands Generalized hypotonia Occasional reversible generalized pseudohypertrophy most prominent in calf (Kocher Debre Semelaigne Syndrome)

Skin
Cold Dry (increased myxoedematous tissue) Pale (resistant anemia) May be yellow ( increased carotene)

1.

Confirm diagnosis of hypothyroidism

Low serum T4; (normal level = 4-9 g/dl)

In hypothyroidism theres compensatory increase in peripheral conversion of T4 to T3; so measuring of T3 may be misleading

Serum TSH; ( normal level <10 unit/ml post neonatal)

High in primary hypothyroidism (>100 unit/ml) Low in 2ry & 3ry hypothyroidism

* In pseudohypothyroidism, all T3, T4, TSH are high

2.

A. X-ray findings
A. B. C. D.

For effect

Delayed bone age : Epiphyseal dysgenesis : multiple foci of ossification in heads of femur & humerus. Beaking of anterior part of T12 & L1 vertebrae Skull : intrasutural (wormian) bones, large fontanels, delayed teething. Chest : may show cardiomegaly ECG show bradycardia and low voltage Echo may show cardiac enlargement and effusion High serum cholesterol Macrocytic anemia
At birth : absent distal femoral epiphysis (knee) Later : delayed appearance of ossific centers (wrist)

B.

E.

Cardiac

C. Other

3.

For the cause

a) Thyroid scintigraphy (using radioactive I123) :
Absent uptake in aplasia or iodide trapping defect Increased uptake in dyshormonogenesis Can localize ectopic thyroid

b) TRH stimulation test : ( perform only with TSH)

differentiate between hypothalamic & pituitary defects i.v bolus TRH If T4 increase : hypothalamic defect ( tertiary hypothyroidism) If T4 does increase : pituitary defect ( secondary hypothyroidism)

c) Skull x-ray, CT, & MRI for pituitary tumors.

Replacement therapy with sodium L-thyroxin (Eltroxin 50 mcg tablet) for life Dose :
10 mcg/kg/d in neonate 6 mcg/kg/d in infant 4 mcg/kg/d in child Overdose Lowdose

Dose is adjusted according to clinical response : Follow up

diarrhea, fever, tachycardia, appetite constipation, hypothermia, bradycardia

Clinical : monitor activity, milestone & growth Laboratory : monitor T4 and TSH (should be in normal range) Radiologic : monitor bone age

Diagnosis & treatment before 3 months : good mentality. Diagnosis & treatment at 3-6 months : variable response. Diagnosis & treatment after 6 months : permanent mental retardation. As diagnosis of hypothyroidism is difficult in the first 3 months, screening for thyroid function for all neonates is done in the first week of life.