Hypothyroidism in Infants and Children/Congenital hypothyroidism/Acquired juvenile hypothyroidism/features/blood test/treatment/Thyroxine dose

 Hypothyroidism in Infants and Children

Hypothyroidism results from decreased

production of thyroid hormone, either due to a defect in the gland itself (primary

hypothyroidism) or because of reduced thyroid-stimulating hormone (TSH) stimulation (central or hypopítuitary hypothyroidism). The disorder

may be manifested from birth (congenital) or acquired.

Epidemiology

• Prevalence of congenital hypothyroidism

in infants is about 1:3000-1:4000.

• Acquired hypothyroidism is most

commonly due to chronic lymphocytic

thyroiditis; 6% of children age 12-19

years have evidence of autoimmune

thyroid disease, which occurs with a 2:1

female: male predominance.

Etiology/causes

1. Congenital hypothyroidism

               1. Hypoplasia, aplasia, or

               maldescent of thyroid -

               Embryonic defect of thyroid

              development

            2. Inborn errors of thyroid hormone

             synthesis, secretion, or recycling

            (resulting from autosomal

            recessive mutations)

                        I. lodide transport detect

                        ii. Organification defect

                              => Mutation in iodine

                               peroxidase

                             =>Mutation in

                              pendrin: Pendred

                             syndrome,associated with                                 congenital sensorineural

                            deafness

                   ii. Coupling defect

                   iv. lodotyrosine deiodinase defect

                    V. Inability to convert T4 toT3

                    vi. Abnormal iodinated                                      polypeptide

       3. TSH receptor defect

       4. Maternal antibody-mediated

       (inhibit TSH binding to receptor)

       5. Thyroid hormone receptor defect

      6. Intrauterine exposures

                i. Radioiodine

                ii. lodine excess

                iii. Goitrogens:(propylthiouracil,

                  methimazole)

      7. lodide deficiency (endemic cretinism)

2. Acquired juvenile hypothyroidism)

1. Autoimmune (ymphocytic)

thyroiditis

2. Thyroidectomy or radioiodine

therapy for

     i. Thyrotoxicosis

     ii. Thyroid cancer

3. Irradiation to the thyroid

4. TRH deficiency due to

     hypothalamic disease or injury

5. Thyrotropin deficiency

       i. Isolated

       ii. Associated with other

        anterior pituitary

         hormone deficiencies

6. Large hemangiomas

7. Medications

       i. lodides

                  1. Deficiency

                  2. Excess (eg,

                  amiodarone)

     ii. Lithium

     iii. Cobalt

8. Idiopathic.

Clinical features

1. Congenital hypothyroidism:

• Most newborns are normal at

birth and gain weight normally 

Hypothyroidism in Infants and Children

for the first few months of life

without any treatment

• Jaundice related to an

unconjugated hyperbilirubinemia

may be present in newborns

• Obvious findings of thick tongue,

hypotonia, large fontanelles,

constipation, umbilical hernia,

hoarse cry, and dry skin may be

present in some infants.

2. Acquired hypothyroidism:

=>Frequently presents with short

stature and abnormal weight

gain.

=>Skin may be dry, thick, scaly, pale

or yellowish, coarse, cool, or mottled

=>Late epiphyseal development

causing delayed closure of

fontanels, and retarted dental

eruption

=>Hair can be dry, coarse, or brittle.

Lateral thinning of the eyebrows

may occur

=>Muscular hypotonia and a slow

relaxation component of deep

tendon reflexes

=>Patient may have physical and

mental slowness, nonpitting

myxedema, hoarse voice or cry,

constipation, large tongue,

hypothermia, bradycardia,

Hypothyroidism in Infants and Childrer

umbilical hernia, and transient

deafness

=>Delayed puberty,

metromenorrhagia,

pseudopuberty, galactorrhea can

also occur

=>The thyroid gland may be

enlarged in hypothyroidism due

to enzymatic defects, ingestion

of goitrogens, or chronic

lymphocytic thyroiditis

=>In children, thyroid enlargement

is usually symmetrical, and the

gland is moderately firm and not

nodular

=>The thyroid often has a

cobblestone surface in chronic

lymphocytic thyroiditis.

Investigations

1. Laboratory Findings

=>Total T4 and FT4 levels are

decreased

=> T3 resin uptake (T3RU) is low

=> The serum TSH level is increased

in primary hypothyroidism, and

may be low or inappropriately

normal in central hypothyroidism

=> Autoantibodies to thyroid

peroxidase and thyroglobulin

may be present in blood

=>Serum prolactin may be elevated 

typothyroidism in Infants and Childrer

=> Serum GH may be decreased in

severe primary hypothyroidism

=> Low IGF-1 and/or IGF-binding

protein 3 levels.

2. Imaging

=>Thyroid imaging is useful in

detecting the cause of

congenital hypothyroidism

=> Bone age x-rays show that bone

age is late; centers of

ossification, particularly of the

hip, may show multiple small

centers or a single stippled,

=> Thyrotrophic hyperplasia

characterized by an enlarged

sella or pituitary gland is related

to long-standing primary

porous, or fragmented center

=>Cardiomegaly is typically present

3. Screening Programs for Neonatal

Hypothyroidism

=> Neonates should be screened for

congenital hypothyroidism

shortly after birth.

=> T4 and TSH levels should be

checked if newborn screening

results are abnormal.

D/D 

Primary hypothyroidism should be differentiated from central hypothyroidism by testing serum TSH, T4 and other related tests.

Management

For acquired hypothyroidism,

Thyroxine/Levothyroxine Sodium is

the drug of choice.

For children age 1-3 yr, the average dosage

is 4-6 wg/kg/day;

For age 3-10 yr, 3-5 pg /kg/day; and

For age 10-16 yr, 2-4 ug /kg/day.

Treatment must be monitored by measuring

serum free T4 and TSH every 4-6 months as

well as 6 weeks after any change in dosage.

In children with central hypothyroidism,

serum free T4 level should be maintained in the upper half of the normal reference range for age.

• For neonates with congenital

hypothyroidism, levothyroxine is used

where the initial dose is 10-15

mcg/kg/day (totaling 37.5-50.0 Hg/day

for most term infants).

Prognosis 

1. Congenital:

=>The prognosis for infants with

congenital hypothyroidism has

improved significantly with the

introduction of neonatal screening programs for detection of congenital hypothyroidism

=>Early diagnosis and sufficient

treatment from the 1st weeks of

hypothyroidism

life cause normal linear growth

and development

=> Delayed diagnosis, inadequate

treatment, failure to correct early

hypothyroxinemia quickly, and

poor compliance in the 1 st 2-3

years of life result in brain

damage

=>Intense intellectual impairment

and retarded growth are seen in

affected infants having no

treatment.

2. Acquired:

=>Worsening of schoolwork,

restlessness, short attention

span, and behavioral problems

might result during the 1st yr of

treatment

=> In older children, after catch-up

growth is complete, the growth

rate gives a good index of the 

sufficiency of treatment.