Thyroid disease in a child

Question 1

Define congenital hypothyroidism.

Answer 1

Deficiency of thyroid hormone present at birth which leads to severe neurodevelopmental delay.

Question 2

Explain the aetiology of congenital hypothyroidism.

Answer 2

Thyroid gland dysgenesis (85%)- usually sporadic; resulting in thyroid aplasia/hypoplasia, ectopic thyroid (lingual/sublingual).

Thyroid hormone biosynthetic defect (15%); hereditary, e.g. Pendred’s syndrome.

Iodine deficiency.

Congenital TSH deficiency (rare).

Question 3

Summarise the epidemiology of congenital hypothyroidism.

Answer 3

Relative common, incidence 1/3500 live births.

M:F = 1:2.

Question 4

What are the symptoms of congenital hypothyroidism in neonates?

Answer 4

Majority asymptomatic secondary to transplacental passage of moderate amounts of maternal T4 (can produce fetal level 25- 50% of normal). May present with poor feeding, constipation, jaundice, thickened skin, hypothermia with poor perfusion, peripheral cyanosis, bradycardias.

Question 5

What are the symptoms of congenital hypothyroidism in infants?

Answer 5

First sign is often prolonged neonatal jaundice. Subsequently may develop other symptoms of hypothyroidism including lethargy, slow feeding, respiratory distress with feeds, excessive sleeping, little vocalization and constipation.

Question 6

What are signs of congenital hypothyroidism?

Answer 6

Physical sings: Coarse dry hair, flat nasal bridge, protruding tongue secondary to macroglossia, hypotonia, slowly relaxing reflexes, umbilical hernia, slow pulse and cardiomegaly.

Developmental delay (untreated): Later global developmental delay, learning disabilities, delayed puberty and dentition, short stature, slow relaxation of tendon reflexes, sensorineural hearing loss.

Question 7

What are investigations for congenital hypothyroidism?

Answer 7

Universal neonatal screening: Heel prick blood spot at 5-7/7 (Guthrie test) for TSH level (> 50 microunit/l is diagnostic). Infants with TSH deficiency are not detected so clinical vigilance is still required.

Blood: Decreased T4 (not in thyroid-binding globulin deficiency), decrease or increase TSH (depending on cause), decrease Hb, unconjugated hyperbilirubinaemia.

Wrist and hand XR: Bone age < chronological age. Rough ‘bone age’ is calculated by analyzing the number of ossification centres present.

Radio-active technetium scan: Detects functional thyroid tissue and therefore dysgenesis or ectopia.

Echocardiogram: Cardiomegaly +/- pericardial effusions detection

Question 8

What is the management for congenital hypothyroidism?

Answer 8

Universal neonatal screening, confirmation and early treatment avoid serious sequelae.

Thyroxine replacement: PO sodium L-thyroxine (10-15micro gram/kg/d).

Regular follow up: Monitor TSH, T4 levels, development and growth, bone age (ensure adequate osseous development, delayed with undertreatment).

Lifelong follow-uo to monitor for adequate levels of thyroid hormone.

Question 9

What are complications associated with congenital hypothyroidism?

Answer 9

Excessive treatment with thyroxine leads to advancement of bone age and later to adult height as the epiphyses fuse prematurely; inadequate treatment leads to severe mental neurological delay.

Question 10

What is the prognosis of congenital hypothyroidism?

Answer 10

Prognosis is good with early detection. Some studies suggest mildly lower IQ scores, subtle neurodevelopmental delays and motor deficits in children adequately treated.

Question 11

Define acquired hypothyroidism.

Answer 11

Acquired hypothyroidism may be due to a primary thyroid problem or indirectly to a central disorder of hypothalamicpituitary function.

Question 12

Explain the aetiology/risk factors of acquired hypothyroidism.

Answer 12

Primary hypothyroidism (raised TSH; Low T4/T3): Autoimmune (hashimoto’s or chronic lymphocytic thyroiditis), iodine deficiency- most common worldwide, subacute thyroiditis, drugs (amiodranone, lithium), post-irradiation (e.g bone marrow transplant- total body irradiation), postablative (radioiodine therapy or surgery).

Central hypothyroidism (low serum TSH and low T4) hypothyroidism due to either pituitary or hypothalamic dysfunction: intracranial tumours/masses, postcranial radiotherapy/surgery, developmental pituitary defects (genetic, e.g. PROP1 Pit-1 genes): isolated TSH deficiency; multiple pituitary hormone deficiencies.

Question 13

Summarise the epidemiology of acquired hypothyroidism.

Answer 13

Relatively uncommon condition with an estimated prevalence of 0.1-0.2% in the population. The incidence in girls is 5-10 times greater than boys.

Question 14

What are symptoms of acquired hypothyroidism?

Answer 14

Symptoms are usually insidious and can be extremely difficult to diagnose clinically. Goitre (primary hypothyroidism).

Increased weight gain/obesity, fatigue, constipation.

Question 15

What are signs of acquired hypothyroidism?

Answer 15

Decreased growth velocity/delayed puberty, delayed skeletal maturation (bone age).

Fatigue: Mental slowness, deteriorating school performance, dry skin, pseudo-puberty: girls= isolated breast development; boys= isolated testicular enlargement, slipped upper (capital) femoral epiphysis: hip pain/limp

Question 16

What are investigations for acquired hypothyroidism?

Answer 16

TFTs: High TSH Low T4

Thyroid antibody screen: Raised antibody titres: antithyroid peroxidase, antithyroglobulin, TSH receptor (blocking type).

Question 17

What is the management of acquired hypothyroidism?

Answer 17

Oral levothyroxine

Monitor thyroid function tests every 4-6 months during childhood, monitor growth and neurodevelopment.

Question 18

What are complications associated with acquired hypothyroidism?

Answer 18

Anaemia

Heart failure

Question 19

What is the prognosis of acquired hypothyroidism?

Answer 19

Thyroid hormone treatment reverses the signs and symptoms of hypothyroidism. With treatment, other secondarily affected laboratory values (eg, circulating lipid levels and elevated prolactin levels) should improve.

Question 20

Define Grave’s Disease.

Answer 20

Autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid.

Question 21

Explain the aetiology/risk factors for Grave’s Disease.

Answer 21

Graves’s disease is an autoimmune disorder with genetic and environmental factors contributing to susceptibility.

Several HLA-DR gene loci (DR3; DQA1*0501) have been identified as susceptibility loci and there is often a family history of autoimmune thyroid disease (girls > boys). Graves’s disease occurs due to a predominance of stimulating type autoantibodies to the TSH receptor.

Question 22

Summarise the epidemiology of Grave’s Disease.

Answer 22

The female preponderance has been estimated to be 4-7 girls for every boy affected. Thyrotoxicosis of 0.79 cases per 100,000 person-years in children aged 0-14 years.

Question 23

What are symptoms of Grave’s Disease?

Answer 23

Dysphagia, irritability/emotional lability, sleeplessness, inability to concentrate, diarrhea, palpitations, pruritus, weight loss, increased appetite, nocturia, infrequent or light menses, weakness and tiredness, exercise intolerance, heat intolerance.

Question 24

What are the signs of Grave’s Disease?

Answer 24

Diffuse goiter (majority) Grave’s ophtalmopathy: exothalmos/proptosis

Eyelid lag or retraction

Periorbital oedema/chemosis

Ophthalmoplegia/extraocular muscle dysfunction

Question 25

What are appropriate investigations for Grave’s Disease?

Answer 25

TFTs: high T4/high T3, low TSH

Thyroid antibody screen: Antithyroid peroxidase antithyroglobulin +ve; TSH receptor antibody (stimulatory type) +ve; radionucleotide thyroid scan-increased uptake.

Question 26

What is the management of Grave’s Disease?

Answer 26

The aims of therapy are to induce remission of Graves’s disease with antithyroid drugs (carbimazole or propylthiouracil) and, if necessary, to bring the symptoms of thyrotoxicosis (anxiety, tremor, tachycardia) under control using a B-blocking agent (propranolol).

Two alternative regimens are practised.

Dose titration regimen: Antithyroid treatment titrated to achieve normal thyroid function.

Block and replace regimen: Antithyroid treatment maintained at the lowest dose necessary to induce complete thyroid suppression and therapeutic hypothyroidism. In this situation replacement thyroxine therapy is also necessary to achieve euthyroidism. Antithyroid therapy is usually given for 12–24mths in children, before considering a trial off treatment. Thyroid function (serum-free T4; TSH levels) should be monitored at regular intervals (1–3mths).

Question 27

What are complications associated with Grave’s Disease?

Answer 27

Pregnancy issues later in life

Heart disorders

Thyroid storm

Weak bones

Question 28

What is the prognosis of Grave’s Disease?

Answer 28

Following completion of treatment 40–75% of children will relapse over the next 2yrs. Relapses may be treated with a further course of antithyroid drugs, although definitive therapy with radioiodine is being offered as the first-line treatment.

Thyroid surgery is another approach for management of relapses. Following ablative treatment (either radioiodine or surgery), lifelong thyroxine replacement therapy will be required.

Question 29

Define thyroiditis.

Answer 29

Inflammation of the thyroid gland that may result in goitres. Initial thyrotoxicosis is usually followed by hypothyroidism.

Recognized causes include:

• Autoimmune thyroiditis (Hashimoto’s)
• Acute suppurative (pyogenic) thyroiditis
• Subacute (de Quervain) thyroiditis.

Question 30

Summarise the epidemiology of thyroiditis.

Answer 30

Prevalence of thyroid antibodies as high as 12.5% in some areas. Acute thyroiditis is more common in geographic areas where antibiotic use is less prevalent. Male to Female = 1.2-1.6

Question 31

What are the symptoms of thyroiditis?

Answer 31

Clinical presentation is usually insidious with a diffusely enlarged, nontender, firm goitre. Most children are asymptomatic and biochemically euthyroid. Some children may present with hypothyroidism.

A few children may have symptoms suggestive of hyperthyroidism, i.e. ‘Hashitoxicosis’. The clinical course is variable. Goitres may become smaller and disappear or may persist. Many children who are initially euthroid eventually develop hypothyroidism within a few months or years of presentation. Periodic follow-up is therefore necessary.

Question 32

What are the signs of thyroiditis?

Answer 32

Fever

Neck tenderness

Gotire

Signs of both hyper- and hypothyroidism

Question 33

What are appropriate investigations for thyroiditis?

Answer 33

Diagnosis can be established by thyroid biopsy (but not indicated).

• Thyroid biochemistry may be normal or abnormal.
• Anti-microsomal thyroid antibody titres are usually raised, whereas anti-thyroglobulin titres are increased in only approximately 50%.

Question 34

What are the complications associated with thyroiditis?

Answer 34

Symptomatic thyroid dysfunction

Question 35

What is the prognosis of thyroiditis?

Answer 35

Acute thyroiditis: Recovery is usually complete, and thyroid function returns to normal.

Subacute thyroiditis: This is self-limiting disease and may last 2-7 months.

Chronic autoimmune thyroiditis: Permanent hypothyroidism is the main complication. Approximately 20% of children with subclinical hypothyroidism enter remission and become euthyroidism.

Question 36

Define neonatal thyrotoxicosis.

Answer 36

In 710% of women with Graves’s disease, thyroid-stimulating hormone (TSH) receptor-stimulator antibodies cross the placenta causing neonatal thyrotoxicosis. Foetus most likely to be affected if high maternal IgG serum level develops, or mother requires treatment during pregnancy.

Question 37

What are investigations for neonatal thyrotoxicosis?

Answer 37

Take cord blood for TSH, fT4, and TSH receptor antibody (TRAB).

Question 38

What are the signs and symptoms of neonatal thyrotoxicosis? What is the treatment and prognosis of neonatal thyrotoxicosis?

Answer 38

Affected neonates are irritable, flushed, and tachycardic. Weight gain is poor and cardiac failure may be present.

The condition is self-limiting.

Supportive treatment, e.g. beta blocker therapy is required.