THYROID DISORDERSTHYROID DISORDERS

Bereket Fantahun

Pediatrics Endocrinology Fellow

December ,2010

Fetal Development of the Fetal Development of the ThyroidThyroidThe thyroid is capable of hormone

synthesis in the fourteenth week of gestation, when TSH is detected in the fetal serum and pituitary gland.

TSH does not normally cross the placenta, but T4 and T3 cross in limited amounts.

The fetal pituitary-thyroid axis functions largely independently of the maternal pituitary-thyroid axis.

Antithyroid drugs, including propylthiouracil (PTU) and methimazole, freely cross the placenta, and goitrous hypothyroid newborns may be born to hyperthyroid mothers who undergo treatment during pregnancy.

THYROID PHYSIOLOGYTHYROID PHYSIOLOGYThe main function of the thyroid gland

is to synthesize T4 and T3. The only known physiologic role of

iodine is in the synthesis of these hormones

The recommended dietary allowance of iodine is

30 μ g /kg/24 hr for infants, 90–120 μ g/24 hr for children, and 150 μ g/24 hr for adolescents and

adults.

THYROID PHYSIOLOGYTHYROID PHYSIOLOGY

Whatever the chemical form ingested, iodine eventually reaches the thyroid gland as iodide.

Thyroid tissue has an affinity for iodine and is able to trap, transport, and concentrate it in the follicular lumen for synthesis of thyroid hormone.

THYROID PHYSIOLOGYTHYROID PHYSIOLOGYPituitary TSH stimulates the thyroid

gland to take up iodine and synthesize active thyroid hormones ( I. e, T3 and T4).

Active hormone produced in excess of physiologic needs is stored within the thyroid follicles as thyroglobulin.

The release of active thyroid hormones into the circulation is regulated by a negative feedback mechanism involving pituitary TSH and free thyroid hormone.

THYROID PHYSIOLOGYTHYROID PHYSIOLOGY

+

+

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- Synthesize TRH by 6-8th week

Secrete TSH by 12th week

Feedback mechanism starts by 3rd month

THYROID PHYSIOLOGYTHYROID PHYSIOLOGYBefore trapped iodide can react with

tyrosine, it must be oxidized; this reaction is catalyzed by thyroidal peroxidase.

The thyroid cells also elaborate a specific thyroprotein, (thyroglobulin).

Iodination of tyrosine forms monoiodotyrosine and diiodotyrosine; 2 molecules of diiodotyrosine then coupled to form 1 molecule of T4, or 1 molecule of diiodotyrosine and 1 of monoiodotyrosine to form T3.

Once formed, hormones are stored as thyroglobulin in the lumen of the follicle (colloid) until ready to be delivered to the body cells.

THYROID PHYSIOLOGYTHYROID PHYSIOLOGY

THYROID PHYSIOLOGYTHYROID PHYSIOLOGYThe metabolic potency of T3 is 3

to 4 times that of T4. In adults, the thyroid produces

approximately 100 μ g of T4 and 20 μ g of T3 daily.

Only 20% of circulating T3 is secreted by the thyroid; the remainder is produced by deiodination of T4 in the liver, kidney, and other peripheral tissues by type I 5′-deiodinase.

THYROID PHYSIOLOGYTHYROID PHYSIOLOGYIn the pituitary and brain, approximately

80% of required T3 is produced locally from T4 by a different enzyme, type II 5′-deiodinase.

The level of T3 in blood is 1/50th that of T4,but T3 is the physiologically active thyroid hormone.

Thyroid hormones -increase oxygen consumption, -stimulate protein synthesis, -influence growth and

differentiation, -and affect carbohydrate, lipid, and

vitamin metabolism.

THYROID PHYSIOLOGYTHYROID PHYSIOLOGYAbout 70% of the circulating T4 is firmly

bound to thyroxine-binding globulin (TBG). Less important carriers are thyroxine-binding prealbumin, called transthyretin, and albumin.

Only 0.03% of T4 in serum is not bound and comprises free T4.

Approximately 50% of circulating T3 is bound to TBG, and 50% is bound to albumin; 0.30% of T3 is unbound, or free, T3.

Because the concentration of TBG is altered in many clinical circumstances, its status must be considered when interpreting T4 or T3 levels.

THYROID REGULATIONTHYROID REGULATIONThe thyroid is regulated by TSH, a

glycoprotein produced and secreted by the anterior pituitary.

This hormone activates adenylate cyclase in the thyroid gland and is important in all steps of thyroid hormone biosynthesis, from trapping of iodine to release of thyroid hormones.

TSH synthesis and release are stimulated by TSH-releasing hormone (TRH), which is synthesized in the hypothalamus and secreted into the pituitary.

THYROID REGULATIONTHYROID REGULATIONIn states of decreased production

of thyroid hormone, TSH and TRH are increased.

Exogenous thyroid hormone or increased thyroid hormone synthesis inhibits TSH and TRH production.

Except in the neonate, levels of TRH in serum are very low.

THYROID REGULATIONTHYROID REGULATIONIn many nonthyroidal illnesses,

extrathyroidal production of T3 decreases; factors that inhibit -type I 5′-deiodinase include fasting, chronic malnutrition, acute illness, and certain drugs. Levels of T3 may be significantly decreased, whereas levels of free T4 and TSH remain normal.

Presumably, the decreased levels of T3 result in decreased rates of oxygen production, of substrate use, and of other catabolic processes.

Thyroid Hormone Studies Thyroid Hormone Studies

SERUM THYROID HORMONES. -T4, free T4, T3, and free T3.• Age must be considered in

interpreting results, particularly in the neonate.

TSH and T4 at birthTSH and T4 at birth

Thyroid Hormone StudiesThyroid Hormone StudiesTSH levels in serum are an

extremely sensitive indicator of primary hypothyroidism.

After the neonatal period, normal levels of TSH are less than 6 μ U/ml .

These sensitive TSH assays decrease the need for TRH stimulation in the diagnosis of most patients with thyroid disorders.

Thyroid Hormone StudiesThyroid Hormone StudiesTBG the degree of saturation is

affected by Pregnancy , newborn , heroin and estrogen.

Thyroid scanning- to detect ectopic thyroid tissue. Technetium is preferred.

HypothyroidismHypothyroidismHypothyroidism results from deficient

production of thyroid hormone or a defect in thyroid hormone receptor activity .

It might be congenital or acquired . When symptoms appear after a period

of apparently normal thyroid function, the disorder may be truly “acquired” or may only appear so as a result of one of a variety of congenital defects in which the manifestation of the deficiency is delayed.

CONGENITALHYPOTHYROIDISMCONGENITALHYPOTHYROIDISMMost cases of congenital

hypothyroidism are not hereditary and result from thyroid dysgenesis.

Some cases may be familial, usually caused by one of the inborn errors of thyroid hormone synthesis, and may be associated with a goiter.

In many cases, the deficiency of thyroid hormone is severe, and symptoms develop in the early weeks of life.

In others, lesser degrees of deficiency occur, and manifestations may be delayed for months.

EPIDEMIOLOGYEPIDEMIOLOGY• The prevalence of congenital

hypothyroidism based on nationwide programs for neonatal screening is 1/4,000 infants worldwide;

• Prevalence is lower in black Americans (1/32,000) and higher in Hispanics and Native Americans (1/2,000).

• Twice as many girls as boys are affected.

CONGENITALHYPOTHYROIDISMCONGENITALHYPOTHYROIDISM

1.THYROID DYSGENESIS It can be hypoplasia , aplasia or an

ectopic gland and it is the most common cause of congenital hypothyroidsim and 98 % of the cases are sporadic.

2.DYSHORMONOGENESIS -The problem is in TH synthesis,

when the defect is incomplete compensation occurs and the manifestation of hypothyroidism is delayed.

-Goiter is almost always present.

CONGENITALHYPOTHYROIDISMCONGENITALHYPOTHYROIDISM

3.Ingestion of goiterogenous substance by the mother during pregnancy

4.Iodine deficency- in endemic goiter hypothyroidism with congenital goiter.

5.Hypothalamus and pituitary defect6.TH unresponsiveness- resistant to

endogeneous and exogeneous T4 and T3 most patients have goiter and levels of T4 , T3 and free T4 and T3 is high and TSH moderately elevated or normal

Clinical ManifestationClinical Manifestation• Asymptomatic at birth even in case

of agenesis• They have low serum T4 and

elevated TSH and this will be detected during newborn screening.

• F:M 2:1, birth wt and length normal but head size may be slightly increased

• Prolonged physiologic jaundice, delayed passage of stool

Clinical ManifestationClinical Manifestation Feeding difficulties, especially

sluggishness, lack of interest, somnolence, and choking spells during nursing, are often present during the 1st mo of life.

Respiratory difficulties, due in part to the large tongue, include apneic episodes, noisy respirations, and nasal obstruction. Typical respiratory distress syndrome may also occur.

Affected infants cry little, sleep much, have poor appetites, and are generally sluggish.

Clinical ManifestationClinical ManifestationThere may be constipation that does

not usually respond to treatment. The abdomen is large, and an

umbilical hernia is usually present. The temperature is subnormal, often

less than 35°C (95°F), and the skin, particularly that of the extremities, may be cold and mottled.

Edema of the genitals and extremities may be present.

Clinical ManifestationClinical Manifestation

Signs and Symptoms• Include:

– Coarse facial features

– Macroglossia

– Large fontanelles (anterior and posterior)

– Umbilical hernia

– Mottled, rough or dry skin

– Developmental delay

– Pallor, hypothermia

– Myxedema

– Chocking during feeding.

Clinical ManifestationClinical ManifestationThe pulse is slow, and heart

murmurs, cardiomegaly, and asymptomatic pericardial effusion are common.

Macrocytic anemia is often present and is refractory to treatment.

Because symptoms appear gradually, the clinical diagnosis is often delayed.

Clinical ManifestationClinical ManifestationApproximately 10% of infants with

congenital hypothyroidism have associated congenital anomalies.

Cardiac anomalies are most common, but anomalies of the nervous system and eye have also been reported.

If congenital hypothyroidism goes undetected and untreated, these manifestations progress.

Retardation of physical and mental development becomes greater during the following months, and by 3–6 mo of age the clinical picture is fully developed .

Clinical ManifestationClinical ManifestationWhen there is only partial deficiency

of thyroid hormone, the symptoms may be milder, the syndrome incomplete, and the onset delayed.

Although breast milk contains significant amounts of thyroid hormones, particularly T3, it is inadequate to protect the breast-fed infant with congenital hypothyroidism, and it has no effect on neonatal thyroid screening tests.

Clinical ManifestationClinical ManifestationThe child's growth will be stunted, the

extremities are short, and the head size is normal or even increased.

The anterior and posterior fontanels are open widely; observation of this sign at birth may serve as an initial clue to the early recognition of congenital hypothyroidism.

Only 3% of normal newborn infants have a posterior fontanel larger than 0.5 cm.

Clinical ManifestationClinical ManifestationThe eyes appear far apart, and the bridge

of the broad nose is depressed. The palpebral fissures are narrow and the eyelids swollen.

The mouth is kept open, and the thick, broad tongue protrudes.

Dentition will be delayed. The neck is short and thick, and there may

be deposits of fat above the clavicles and between the neck and shoulders.

The hands are broad and the fingers short. The skin is dry and scaly, and there is little

perspiration.

Clinical ManifestationClinical ManifestationMyxedema is manifested,

particularly in the skin of the eyelids, the back of the hands, and the external genitals. The skin shows general pallor.

The scalp is thickened, and the hair is coarse, brittle, and scanty. The hairline reaches far down on the forehead, which usually appears wrinkled.

Clinical ManifestationClinical ManifestationDevelopment is usually retarded. Hypothyroid infants appear lethargic

and are late in learning to sit and stand.

The voice is hoarse, and they do not learn to talk.

The degree of physical and mental retardation increases with age.

Sexual maturation may be delayed or may not take place at all.

Clinical ManifestationClinical ManifestationThe muscles are usually

hypotonic, but in rare instances generalized muscular pseudohypertrophy occurs

Affected patients have hypothyroidism of longer duration and severity.

LaboratoryLaboratory -T4 when T4 is low do TSH -Retarded osseous development in

about 60% of the cases there will be a discrepancy b/n chronological age and bone age.

-Scintigraphy can help to pinpoint the underlying causes in infants with congenital hypothyroidism

-ECG – low voltage P and T waves with diminished QRS complex due to poor LV function and pericardial effusion.

Primary/Central Primary/Central HypothyroidismHypothyroidismHallmark of primary

hypothyroidism *Serum T4 is LOW and TSH is

elevated• Hall mark of central Hypothyroidism (Hypothalamus/pitutary) *Serum T4 and TSH levels are lowTertiary versus Secondary

Hypothyroidism

TREATMENTTREATMENTSodium L-thyroxine given Po is the

Rx of choice and the dose is 10-15 microgram/kg for neonates and 4 microgram/kg for children

Prognosis Early diagnosis and treatment

from the first week of life good prognosis ,otherwise delay in diagnosis ,inadequate treatment and poor compliance will result in variable brain damage

PrognosisPrognosisAround 20 % of children will have

a neuro sensorial hearing loss and without treatment affected infants become profoundly mentally deficit dwarfs.

ACQUIRD HYPOTHYROIDISM ACQUIRD HYPOTHYROIDISM Epidimiology• It is most commonly a result of

chronic lymphocytic thyroditis• 1.3 % have evidence of AI

thyroidal disease and occurs with 2:1 F:M ratio.

EtiologyEtiologyAutoimmune -Hashimoto thyroditisIatrogenic-

drugs ,irradiation , thyroidectomy

Systemic disease- histiocytosis -xHypopitutarismTransient after discontinuation of

long term treatment

Clinical manifestationsClinical manifestations

Symptoms & Signs- Slow growth rate -Bradicardia , low

PP- Constipation - short stature- Cold intolerance - mild over weight- Lethargy -Delayed

dentation - Over sleep -Goiter- Delayed oss.maturation - Dull ,flaccid expression

ACQUIRD HYPOTHYROIDISMACQUIRD HYPOTHYROIDISM

• All of these features may return to normal if there is early and appropriate treatment

• Diagnosis and treatment are the same as congenital hypothyroidism.

LYMPHOCYTIC THYROIDITIS LYMPHOCYTIC THYROIDITIS (HASHIMOTO THYROIDITIS, (HASHIMOTO THYROIDITIS,

AUTOIMMUNE THYROIDITISAUTOIMMUNE THYROIDITIS))Lymphocytic thyroiditis is the most common cause of thyroid disease in children and adolescents .

It is also the most common cause of acquired hypothyroidism, with or without goiter.

1 - 2% of younger school-aged children and 4–6% of adolescents have positive antithyroid antibodies as evidence of autoimmune thyroid disease

ETIOLOGYETIOLOGY• This typical organ-specific

autoimmune disease is characterized histologically by lymphocytic infiltration of the thyroid and subsequent atrophy of the follicles with varying degree of fibrosis

HASHIMOTO THYROIDITISHASHIMOTO THYROIDITISA variety of different thyroid antigen

auto antibodies are also involved. Thyroid antiperoxidase antibodies

(TPOAbs) and antithyroglobulin antibodies are demonstrable in the sera of 90% of children with lymphocytic thyroiditis and in many patients with Graves disease.

TPO Abs inhibit enzyme activity and stimulate natural killer cell cytotoxicity.

There will be dysimmune regulation

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONS The disorder is 2–4 times more

frequent in girls than in boys. It may occur <3 yr of age more common after the age of 6 yr peak incidence is during

adolescence. The most common clinical

manifestations are goiter and growth retardation.

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONSThe goiter may appear insidiously and

may be small or large. In most patients, the thyroid is

diffusely enlarged, firm, and non tender.

In about 30% of patients, the gland is lobular and may seem to be nodular.

Most of the affected children are clinically euthyroid and asymptomatic; some may have symptoms of pressure in the neck. Some children have clinical signs of hypothyroidism, but others who appear clinically euthyroid have laboratory evidence of hypothyroidism.

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONS

The clinical course is variable.Familial clusters of lymphocytic thyroiditis

are common; the incidence in siblings or parents of affected children may be as high as 25%.

AD pattern of inheritanceIt is associated with other AID -Addison’s -IDDM Schmidit

syndrome -HASHIMOTO

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

pernicious anemia, vitiligo, or alopecia. Associated with congenital

rubella,Turner syndrom and Down syndrom

LaboratoryTH are usually normalTSH may be slightly or moderatly

elevated Antibodies TPO,anti TGB testDefinative diagnosis is by FNAC.

TreatmentTreatmentIf there is evidence of

hypothyroidism, replacement treatment with levothyroxine (50–150 μg daily) is indicated.

The goiter usually shows some decrease in size but may persist for years.

A large goiter in a euthyroid patient will also regress with suppressive doses of levothyroxine.

GoiterGoiterA goiter is an enlargement of the

thyroid gland. Persons with enlarged thyroids may

have normal function of the gland (euthyroidism), thyroid deficiency (hypothyroidism), or overproduction of the hormones (hyperthyroidism).

Goiter may be congenital or acquired, endemic, or sporadic.

GoiterGoiterThe goiter often results from

increased pituitary secretion of thyroid-TSH in response to decreased circulating levels of thyroid hormones.

Thyroid enlargement may also result from infiltrative processes that may be inflammatory or neoplastic.

Goiter in patients with Graves disease and thyrotoxicosis is caused by thyrotropin receptor–stimulating antibodies (TRSAbs).

Congenital GoiterCongenital Goiter Etiology1.Antithyroidal drugs or iodides during

pregnancy- PTU and amidarone interfere with TH production

2.Congenital hyperthyroidismInfants born to mother’s with Graves

disease3.Iodine deficiency4.Dyshormonogenesis5.Teratoma

Clinical ManifestationClinical Manifestation

• Respiratory distress, hyperextended neck

• When there is severe respiratory obstruction partial thyroidectomy rather than tracheostomy is indicated

Endemic goiterEndemic goiter

EtiologyIodine deficiency- there will be

compensatory hypertrophy and hyperplasia which result in goiter and there is euthyroid , but if there is decompesation it will result in Hypothyroidism.

Clinical ManifestationClinical Manifestation

• It depends on the degree of iodine deficiency

• Mild- goiter is not noticeable• Moderate- goiter observed in

school age and may disappear with maturation and may reappear when there is increased demand

• Severe- nearly ½ of the population will have large goiter and endemic cretinism will occur.

Endemic CretinitsmEndemic Cretinitsm

There are two types1.Neurologic type- fetal & maternal

hypothyroxemia

2.Myxedematous type - ? Thyroid auto immunity

Neurologic type-MR, deaf-mutism, gait disturbance and affected individuals have goiter but euthyroid and have normal pubertal development and adult stature.

Endemic CretinitsmEndemic Cretinitsm• Myxedematous- MR,deaf and

have neurologic sxs and delayed sexual developmet and growth , myxedema and absence of goiter.

• serum T4 is low and TSH is markedly elevated delayed skeletal maturation and thyroid atrophy

RxAdministration of a single IM injection

of poppy seed oil to woman prevents iodine deficiency in future pregnancy

HYPERTHYROIDISMHYPERTHYROIDISM

• Hyperthyroidism results from excessive secretion of thyroid hormone and, during childhood, with few exceptions, is due to Graves disease.

• Graves disease is an autoimmune disorder; production of thyroid-stimulating immunoglobulin (TSI) results in diffuse toxic goiter.

EPIDEMIOLOGY.EPIDEMIOLOGY.• Graves disease occurs in approximately

0.02% of children (1 : 5,000).• It has a peak incidence in the 11- to 15-

yr old; there is a 5 : 1 female to male ratio.

• Most children with Graves disease have a positive family history of some form of autoimmune thyroid disease.

• There will be autonomous production of T3 and T4 by thyroid gland (no more under TSH control)

MANIFESTATIONS OF MANIFESTATIONS OF HYPERTHYROIDISMHYPERTHYROIDISMSymptoms  

Hyperactivity, irritability, altered mood, insomnia, anxiety  

Heat intolerance, increased sweating  Palpitations  Fatigue, weakness  Dyspnea  Weight loss with increased appetite (weight

gain in 10% of patients)  Pruritus  Increased stool frequency  Thirst and polyuria  Oligomenorrhea or amenorrhea, loss of

libido

MANIFESTATIONS OF HYPERTHYROIDISMMANIFESTATIONS OF HYPERTHYROIDISM

Signs Sinus tachycardia, atrial fibrillation (rare in

children), supraventricular tachycardia   Fine tremor, hyperkinesis, hyperreflexia   Warm, moist skin   Palmar erythema, onycholysis   Hair loss   Osteoporosis   Hypercalcemia   Muscle weakness and wasting   High-output heart failure   Chorea   Periodic (hypokalemic) paralysis (primarily in

Asian men)   Psychosis (rare)

MANIFESTATIONS OF GRAVES DISEASEMANIFESTATIONS OF GRAVES DISEASEDiffuse goiterOphthalmopathy A feeling of discomfort in the eye Retrobulbar pressure or pain Eyelid lag or retraction Periorbital edema, chemosis, scleral

injection Exophthalmos (proptosis) Extraocular muscle dysfunction Exposure keratitis Optic neuropathyLocalized dermopathy (rare in children)Lymphoid hyperplasia

CONDITIONS ASSOCIATED WITH GRAVES CONDITIONS ASSOCIATED WITH GRAVES DISEASEDISEASE

Type 1 diabetes mellitusAddison disease VitiligoPernicious anemiaAlopecia areata  Celiac disease

LABORATORY FINDINGSLABORATORY FINDINGS Serum levels of thyroxine (T4),

triiodothyronine (T3), free T4, and free T3 are elevated.

In some patients, levels of T3 may be more elevated than those of T4.

Levels of TSH are suppressed to less than normal levels.

Antithyroid antibodies, including thyroid peroxidase antibodies, are often present.

LABORATORY FINDINGSLABORATORY FINDINGS Most patients with newly

diagnosed Graves disease have measurable TRSAb; its disappearance predicts remission of the disease.

Measurement of TRSAb is useful in confirming the diagnosis of Graves disease.

Advanced skeletal maturation

TreatmentTreatment

Medical treatment is recommended than radioiodine or subtotal thyroidectomy

Medical- antithyroid drugs like PTU and metimazol

Congenital Hyperthyroidism Congenital Hyperthyroidism ETIOLOGY AND PATHOGENESISNeonatal Graves disease is caused

by transplacental passage of TRSAb, But the clinical onset, severity, and

course may be modified by the concurrent presence of TRBAb and by the transplacental passage of antithyroid drugs taken by the mother.

Congenital Congenital HyperthyroidismHyperthyroidismVery high levels of TRSAb

usually result in classic neonatal hyperthyroidism,

But if the infant has been exposed to the anti thyroid drugs, onset of symptoms is delayed by 3–4 days to allow degradation of the maternally derived anti thyroid drug.

Congenital Congenital HyperthyroidismHyperthyroidismIf TRBAb is also present, onset of

hyperthyroid symptoms may be delayed for several weeks.

The mothers of these infants have active Graves disease, Graves disease in remission, or rarely hypothyroidism and a history of lymphocytic thyroiditis.

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS• premature and IUGR . Most have goiter. extremely restless, irritable, and

hyperactive, and appears anxious and unusually alert.

Microcephaly and ventricular enlargement may be present.

The eyes are opened widely and appear exophthalmic .

extreme increased in PR,RR and Temp.weight loss occurs despite a voracious

appetite

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONSSevere hypertension and cardiac

decompensation may occur. The infant may die if therapy is not

instituted promptly. The serum level of T4 is markedly

elevated, and TSH is suppressed. Advanced bone age, frontal bossing

with triangular facies, and cranial synostosis are common, especially in infants with persistent clinical manifestations of hyperthyroidism.

TREATMENTTREATMENT

Treatment of the neonate consists of oral administration of

propranolol 1–2 mg/kg/24 hr, orally in 3 divided doses and

PTU 5–10 mg/kg/24 hr given every 8 hrs or

Methimazole (0.25–1.0 mg/kg/24 hr given every 12 hr);

Lugol solution (1 drop every 8 hr) may be added.

Carcinoma of the ThyroidCarcinoma of the Thyroid

EPIDEMIOLOGY.Carcinoma of the thyroid is rare in

childhood; the annual incidence in children younger than 15 yr of age is approximately 2/100,000 cases, compared with an annual incidence at all ages around the world ranging from 4–10/100,000 cases.

Unlike other malignancies in childhood, thyroid cancer usually has an indolent course, even after pulmonary metastases have developed.

PATHOGENESISPATHOGENESISGenetic factors and radiation

exposure are important factors in the pathogenesis of thyroid cancer.

The thyroid gland of children is unusually sensitive to exposure to external radiation.

Carcinoma of the ThyroidCarcinoma of the ThyroidHistologically, the carcinomas are * Papillary (80%), * Follicular (17%), * Medullary (2%), or mixed

differentiated tumors. These are usually slow-growing

tumors and may remain dormant for years.

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONSGirls are affected twice as often as boys. The average age at diagnosis is 9 yr, but

the onset may be as early as the 1st yr of life.

A painless nodule in the thyroid or in the neck is the usual initial evidence of disease.

Large nodule size, firmness, fixation to adjacent tissues, and vocal cord paralysis are risk factors for thyroid cancer.

CLINICAL CLINICAL MANIFESTATIONSMANIFESTATIONSCervical lymph node

involvement is often present at the time of initial diagnosis.

The lungs are the most common site of metastases beyond the neck.

DIAGNOSISThe most helpful diagnostic test in

the case of a solitary nodule is fine-needle aspiration (FNA).

DIAGNOSISDIAGNOSISA thyroid scan, preferably using

99mTc-pertechnetate, can provide information on trapping function and whether the nodule is “cold,” “warm,” or “hot.

Rxsubtotal thyroidectomy and

suppressive doses of thyroid hormone