THYROID DISEASEBy: Dr Ismah

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Contents

1. Physiology and development

2. Epidemiology

3. Hyperthyroidism

4. Hypothyroidism

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1. Physiology and development

Thyroid glands descend to ant lower neck by the end of 1st trimester

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Hypothalamic-pituitary-thyroid axis becomes functional in 2nd trimester

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Peripheral metabolism of thyroid hormones matures in 3rd trimester

T3, T4, TSH do not cross placenta in significant amount

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Functions of thyroid hormones

Target tissue Mechanism

Nervous system Promote normal brain development

Heart • Increase number, affinity of beta adrenergic receptors• Enhance responses to circulating catecholamine

Muscle Increase protein breakdown

Bone Promote normal growth and skeletal development

Gut Associated with carbohydrate absorption

Adipose tissue Stimulate lipolysis

Lipoprotein Stimulate formation of LDL receptors

Other • Stimulate oxygen consumption by metabolically active tissues

• Increase metabolic rates• Promote development of reproductive system • Maturation of fetal lungs

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Normal level of thyroid hormones

Age TSH (mIU/L) Free T4 (pmol/L)

Birth-D3 OL <21 26-65

D4-D30 0.51-10.8 12-30

D31-1yr 0.39-7 9-16.1

≥ 1 yr 0.4-6 13.2-22.2

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2. Epidemiology

Hypothyroidism:

Incidence of congenital hypothyroidism worldwide is 1:2500 - 4000 live births

In Malaysia, it is reported as 1:3666

It is the commonest preventable cause of mental retardation in children

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Hyperthyroidism:

Study in US (2008) concluded that the incidence among individuals aged 0-11 years was 0.44 cases per 1000 population

The incidence among individuals aged 12-17 years was 0.59 cases per 1000 population.

Thus, the incidence increases throughout childhood, with a peak incidence in children aged 10-15 years

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3. Hypothyroidism

Decreased free T4, increased TSH

Primary, secondary or tertiary

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A. Congenital hypothyroidism

Causes

Maldescent thyroid, athyrosis

Dyshormonogenesis

Iodine deficiency

TSH deficiency

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Clinical features

FTT

Feeding problem

Prolonged jaundice

Constipation

Pale, cold, mottled skin

Quiet baby

Coarse face

Large tongue

Hoarse cry

Goiter

Umbilical hernia

Delayed development

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MOSTLY , ASYMPTOMATIC AT BIRTH

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CORD TSH

Treatment

Timing Should begin immediately after diagnosis is

established

If features of hypothyroidism are present, treatment is started urgently.

Duration Treatment is life long

Except in children suspected of having transient hypothyroidism where re-evaluation is done at 3 years of age.

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Preparation

L-thyroxine tablets

The L-thyroxine tablet should be crushed, mixed with breast milk, formula, or water and fed to the infant.

Tablets should not be mixed with soy formulas or any preparation containing iron (formulas or vitamins), both of which reduce the absorption of T4.

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19Pediatric Protocol 3rd ed

Goal of therapy

To restore the euthyroid state

Serum FT4 level usually normalise within 1-2 weeks, and then TSH usually become normal after 1 month of treatment.

Some infants continue to have high serum TSH concentration (10 - 20 mU/L) despite normal serum FT4 values due to resetting of the pituitary-thyroid feedback threshold.

Compliance to medication has to be reassessed and emphasised.

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21Pediatric Protocol 3rd ed

Follow up

Monitor growth parameters and developmental assessment.

Imaging studies

If the FT4 is low and the TSH value is elevated, permanent hypothyroidism is confirmed and life-long L-thyroxine therapy is needed.

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Measurement schedule (FT4, TSH)

The recommended by American Academy of Pediatrics

At 2 and 4 weeks after initiation of T4 treatment.

Every 1 to 2 months during the first 6 months of life.

Every 3 to 4 months between 6 months and 3 years of age.

Every 6 to 12 months thereafter until growth is completed.

After 4 weeks if medication is adjusted.

At more frequent interval when compliance is questioned or abnormal values are obtained.

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Re-evaluation of patients likely having transient hypothyroidism

Can be due to factors primarily affecting the thyroid-like iodine deficiency or excess, maternal TSHR antibodies, maternal use of anti thyroid drugs

This is best done at age 3 years when thyroid dependent brain growth is completed at this age.

Stop L-thyroxine for 4 weeks then repeat thyroid function test: FT4, TSH.

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B. Acquired hypothyroidism

The commonest cause autoimmune thyroiditis i.e. Hashimoto thyroiditis

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Clinical features

Short stature

Cold intolerance

Dry skin

Cold peripheries

Bradycardia

Thin, dry hair

Goiter

Slow relaxing reflexes

Constipation

Delayed puberty

Obesity

Slipped upper femoral epiphysis

Learning difficulties

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Hashimoto thyroiditis

In older children, adolescence

+ve family h/o thyroid disease in 25-35% of patient

Autoimmune process targeted the thyroid gland thus resulting in fibrosis and atrophy of thyroid glands

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Firm, non tender, diffuse goiter

Onset after 6 years old

Associated with DM type 1, adrenal insufficiency and hypoparathyroidism, down syndrome, turner syndrome

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Diagnosis

Clinically

Confirmed by serum antithyroid peroxidase and antithyroid globulin antibodies

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Treatment

L thyroxine

Monitor TSH, FT4 6-12 monthly

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4. Hyperthyroidism

Increased T4, T3 & decreased TSH

Clinical features

Systemic

Anxiety

Restlessness

Sweating

Diarrhea

Weight loss

Rapid growth in ht

Tremor

Tachycardia

Warm peripheries

Learning difficulty

Behavior problems

Psychosis

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Eye signs (not common in children)

Exophthalmos

Ophthalmoplegia

Lid retraction

Lid lag

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Lid retraction

Exophthalmos

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Opthalmoplegia

Lid lag means delay in moving the eyelid as the eye moves downwards

A. Graves’ disease

Autonomous functioning of thyroid caused by thyroid stimulating immunoglobulins (TSIs)

Increased thyroid hormones production and peripheral conversion

Firm, diffuse goiter

Common in girls, in adolescence

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TREATMENT

1.

Drugs

2.

Surgery

3.

Radioactive iodine

Drugs

Block thyroid hormones synthesis

Carbimazole

PTU

- Side effect: rash, fever, arthralgia, agranulocytosis, liver damage, lupus like syndrome

Beta blockers e.g. propranolol

- To control cardiac manifestation

- Contraindicated in asthmatic pt

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Surgery

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Thyroidectomy

Indications:

- Failed medical treatment

- Large goiters, especially with pressure effects

- Severe progressive ophthalmopathy

B. Thyroid storm

Medical emergency. The mortality is 20 - 30 %.

Exacerbation of the hyperthyroid state with evidence of decompensation in one or more organ systems

Precipitated by stress including concurrent infections, surgery

Clinical diagnosis with features of severe thyrotoxicosis, hyperpyrexia and neuro-psychiatric manifestations such as delirium

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Management

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Rehydration

Treat hyperpyrexia (use fans, tepid sponging and oral paracetamol)

Do NOT use aspirin or NSAIDs

Beta sympathetic blocking agentsOral propanolol 40 mg qid, or I/V 1-2 mg 4-6hourly

Iodide

Oral saturated solution of potassium iodide (SSKI) 5 drops 6-hourly

or I/V Sodium Iodide 500 mg 8 hourly

or oral Lugol's iodine 5-10 drops, 6-hourly

Antithyroid Drugs

Carbimazole 15-20 mg 6-hourly

or propylthiouracil 150-200 mg 6-hourly

Corticosteroids

I/V dexamethasone 2 mg 6-hourly

or I/V hydrocortisone 200 mg 6-hourly

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C. Other causes (rare)

McCune-Albright syndrome

Thyroid neoplasm

TSH hypersecretion

Subacute thyroiditis

Excessive iodine or thyroid hormone ingestion

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D. Neonatal hyperthyroidism

Associated with infant of mother with Graves’ disease

Transient placenta transfers of thyroid stimulating immunoglobulins (TSIs)

Potentially fatal

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Clinical features

Irritability

Tachycardia

Polycythemia

Craniosynthesis

Poor feeding

FTT

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Treatment

Minimally affected: observation

Severe:

Oral propranolol

PTU

Spontaneous resolution because of TSIs usually in 2-3 months of age

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Take home message

Important to understood the physiology of thyroid hormone

Congenital hypothyroidism – screening, treat to prevent MR

Patient education and compliance to treatment/follow up

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50American Association of Clinical Endocrinologists (AACE)

References:

1. Nelson Essential of Pediatrics 6th ed

2. Illustrated Textbook of Pediatrics 3rd ed

3. Pediatric Protocol 3rd ed

4. Practice Guidelines for Thyroid Disorders The Malaysian Consensus 2000

Thank You

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