Lecture 02 Disorders of the thyroid and parathyroid glands
Disorders of the thyroid gland
Hypothyroidism
Hypothyroidism results from deficient production of thyroid hormone, either from a defect in the gland itself (primary hypothyroidism) or a result of reduced thyroid-stimulating hormone (TSH) stimulation (central or hypopituitary hypothyroidism). The disorder may be manifested from birth (congenital) or acquired. When symptoms appear after a period of apparently normal thyroid function, the disorder may be truly acquired or might only appear so as a result of one of a variety of congenital defects in which the manifestation of the deficiency is delayed.
Most cases of congenital hypothyroidism are not hereditary and result from thyroid dysgenesis. Some cases are familial; these are usually caused by one of the inborn errors of thyroid hormone synthesis and may be associated with a goiter. Most infants with congenital hypothyroidism are detected by newborn screening programs in the first few weeks after birth, before obvious clinical symptoms and signs develop. In infants born in areas with no screening program, severe cases manifest features in the first few weeks of life, but in cases of lesser deficiency, manifestations may be delayed for months.
Etiology of congenital hypothyroidism
Thyroid Dysgenesis. Some form of thyroid dysgenesis (aplasia, hypoplasia, or an ectopic gland) is the most common cause of congenital hypothyroidism, accounting for 80-85% of cases; 15% are caused by an inborn error of thyroxine synthesis (dyshormonogeneses), and 2% are the result of transplacental maternal thyrotropin-receptor blocking antibody (TRBAb). In about 33% of cases of dysgenesis, even sensitive radionuclide scans can find no remnants of thyroid tissue (aplasia). In the other 66% of infants, rudiments of thyroid tissue are found in an ectopic location, anywhere from the base of the tongue (lingual thyroid) to the normal position in the neck (hypoplasia).
The cause of thyroid dysgenesis is unknown in most cases. Thyroid dysgenesis occurs sporadically, but familial cases occasionally have been reported. The finding that thyroid developmental anomalies, such as thyroglossal duct cysts and hemiagenesis, are present in 8-10% of 1st-degree relatives of infants with thyroid dysgenesis supports an underlying genetic component.
Defective Synthesis of Thyroxine (Dyshormonogenesis). A variety of defects in the biosynthesis of thyroid hormone can result in congenital hypothyroidism; these account for 15% of cases detected by neonatal screening programs (1/30,000-1/50,000 live births). These defects are transmitted in an autosomal recessive manner. A goiter is almost always present. When the defect is incomplete, compensation occurs, and onset of hypothyroidism may be delayed for years.
Defect of Iodide Transport. Defect of iodide transport is rare and involves mutations in the sodium-iodide symporter. In the past, clinical hypothyroidism, with or without a goiter, often developed in the first few months of life; the condition has been detected in neonatal screening programs.
Thyroid Peroxidase Defects of Organification and Coupling. Thyroid peroxidase defects of organification and coupling are the most common of the T4 synthetic defects. After iodide is trapped by the thyroid, it is rapidly oxidized to reactive iodine, which is then incorporated into tyrosine units on thyroglobulin. This process requires generation of H2O2, thyroid peroxidase, and hematin (an enzyme cofactor); defects can involve each of these components, and there is considerable clinical and biochemical heterogeneity. In the Dutch neonatal screening program, 23 infants were found with a complete organification defect (1/60,000), but its prevalence in other areas is unknown.
Defects of Thyroglobulin Synthesis. Defects of thyroglobulin synthesis is a heterogeneous group of disorders characterized by goiter, elevated TSH, low T4 levels, and absent or low levels of thyroglobulin (TG). It has been reported in approximately 100 patients. Molecular defects, primarily point mutations, have been described in several patients.
Defects in Thyroid Hormone Transport. Passage of thyroid hormone into the cell is facilitated by plasma membrane transporters. The defective transporter appears to impair passage of T3 into neurons; this syndrome is characterized by elevated serum T3 levels, low T4 levels, normal or mildly elevated TSH levels, and psychomotor retardation.
Thyrotropin Receptor-Blocking Antibody. Maternal thyrotropin receptor-blocking antibody (often measured as thyrotropin-binding inhibitor immunoglobulin), is an unusual cause of transitory congenital hypothyroidism. Transplacental passage of maternal TRBAb inhibits binding of TSH to its receptor in the neonate. The incidence is approximately 1/50,000-100,000 infants. It should be suspected whenever there is a history of maternal autoimmune thyroid disease, including Hashimoto thyroiditis or Graves disease, maternal hypothyroidism on replacement therapy, or recurrent congenital hypothyroidism of a transient nature in subsequent siblings. In these situations, maternal levels of TRBAb should be measured during pregnancy.
Radioiodine Administration. Hypothyroidism can occur as a result of inadvertent administration of radioiodine during pregnancy for treatment of Graves disease or cancer of the thyroid. The fetal thyroid is capable of trapping iodide by 70-75 days of gestation. Whenever radioiodine is administered to a woman of childbearing age, a pregnancy test must be performed before a therapeutic dose of 131I is given. Administration of radioactive iodine to lactating women also is contraindicated because it is readily excreted in milk.
Thyrotropin and Thyrotropin-Releasing Hormone Deficiency. Deficiency of TSH and hypothyroidism can occur in any of the conditions associated with developmental defects of the pituitary or hypothalamus. More often in these conditions, the deficiency of TSH is secondary to a deficiency of thyrotropin-releasing hormone (TRH). TSH-deficient hypothyroidism is found in 1/30,000-50,000 infants; most screening programs are designed to detect primary hypothyroidism, so most of these cases are not detected by neonatal thyroid screening. The majority of affected infants have multiple pituitary deficiencies and present with hypoglycemia, persistent jaundice, and micropenis in association with septo-optic dysplasia, midline cleft lip, midface hypoplasia, and other midline facial anomalies.
Iodine-Deficiency Endemic Goiter. Iodine deficiency or endemic goiter is the most common cause of congenital hypothyroidism worldwide. Despite efforts at universal iodizination of salt in many countries, economic, political, and practical obstacles make achieving this objective difficult. Borderline iodine deficiency is more likely to cause problems in preterm infants who depend on a maternal source of iodine for normal thyroid hormone production.
Thyroid Function in Preterm Babies
Postnatal thyroid function in preterm babies is qualitatively similar but quantitatively reduced compared with that of term infants. The cord serum T4 is decreased in proportion to gestational age and birthweight. The postnatal TSH surge is reduced, and infants with complications of prematurity, such as respiratory distress syndrome, actually experience a decrease in serum T4 in the 1st wk of life. As these complications resolve, the serum T4 gradually increases so that generally by 6 wk of life it enters the T4 range seen in term infants. Serum free T4 concentrations seem less affected, and when measured by equilibrium dialysis, these levels are often normal. Preterm babies also have a higher incidence of transient TSH elevations and apparent transient primary hypothyroidism. Premature infants <28 wk of gestation might have problems resulting from a combination of immaturity of the hypothalamic-pituitary-thyroid axis and loss of the maternal contribution of thyroid hormone and so may be candidates for temporary thyroid hormone replacement; further studies are needed.
Most infants with congenital hypothyroidism are asymptomatic at birth, even if there is complete agenesis of the thyroid gland. This situation is attributed to the transplacental passage of moderate amounts of maternal T4, which provides fetal levels that are approximately 33% of normal at birth. Despite this maternal contribution of thyroxine, hypothyroid infants still have a low serum T4 and elevated TSH level and so will be identified by newborn screening programs.
The clinician depends on neonatal screening tests for the diagnosis of congenital hypothyroidism. Congenital hypothyroidism is twice as common in girls as in boys.
It can be suspected and the diagnosis established during the early weeks of life if the initial but less characteristic manifestations are recognized. Birthweight and length are normal, but head size may be slightly increased because of myxedema of the brain. Prolongation of physiologic jaundice, caused by delayed maturation of glucuronide conjugation, may be the earliest sign. 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. Affected infants cry little, sleep much, have poor appetites, and are generally sluggish.
There 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 lower, and the skin, particularly that of the extremities, may be cold and mottled. Edema of the genitals and extremities may be present. The pulse is slow, and heart murmurs, cardiomegaly, and asymptomatic pericardial effusion are common.
Macrocytic anemia is often present and is refractory to treatment with hematinics. Because symptoms appear gradually, the clinical diagnosis is often delayed.
Approximately 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. Infants with congenital hypothyroidism may have associated hearing loss.
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.
When 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 who has congenital hypothyroidism, and it has no effect on neonatal thyroid screening tests.
The 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 can 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. The eyes appear far apart, and the bridge of the broad nose is depressed. The palpebral fissures are narrow and the eyelids are 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 are short. The skin is dry and scaly, and there is little perspiration. Myxedema is manifested, particularly in the skin of the eyelids, the back of the hands, and the external genitals. The skin shows general pallor with a sallow complexion. Carotenemia can cause a yellow discoloration of the skin, but the sclerae remain white. The scalp is thickened, and the hair is coarse, brittle, and scanty. The hairline reaches far down on the forehead, which usually appears wrinkled, especially when the infant cries.
Development is usually delayed. 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 might not take place at all. The muscles are usually hypotonic, but in rare instances generalized muscular pseudohypertrophy occurs.
Some infants with mild congenital hypothyroidism have normal thyroid function at birth and so are not identified by newborn screening programs. In particular, some children with ectopic thyroid tissue (lingual, sublingual, subhyoid) produce adequate amounts of thyroid hormone for many years, or it eventually fails in early childhood.
Manifestation of the light forms of congenital hypothyroidism can be observed in any age of children, but mostly in the period of the first growth jump (4-6 years).
In many countries, infants with congenital hypothyroidism are identified by newborn screening programs. Blood obtained by heel-prick between 2 and 5 days of life is placed on a filter paper card and sent to a central screening laboratory. Many newborn screening programs in North America and Europe measure levels of T4, followed by measurement of TSH when T4 is low. This approach identifies infants with primary hypothyroidism, some with hypothalamic or pituitary hypothyroidism, and infants with a delayed increase in TSH levels. Other neonatal screening programs in North America, Europe, Japan, Australia, and New Zealand are based on a primary measurement of TSH. This approach detects infants with primary hypothyroidism and can detect infants with subclinical hypothyroidism (normal T4, elevated TSH), but it misses infants with delayed TSH elevation and with hypothalamic or pituitary hypothyroidism.
Serum levels of T4 or free T4 are low; serum levels of T3 may be normal and are not helpful in the diagnosis. If the defect is primarily in the thyroid, levels of TSH are elevated, often to >100 mU/L. Serum levels of thyroglobulin are usually low in infants with thyroid agenesis or defects of thyroglobulin synthesis or secretion, whereas they are elevated with ectopic glands and other inborn errors of thyroxine synthesis, but there is a wide overlap of ranges.
Retardation of osseous development can be shown radiographically at birth in about 60% of congenitally hypothyroid infants and indicates some deprivation of thyroid hormone during intrauterine life. The distal femoral epiphysis, normally present at birth, is often absent.
X-ray of the skull show large fontanels and wide sutures; intersutural bones are common. The sella turcica is often enlarged and round; in rare instances, there may be erosion and thinning. Formation and eruption of teeth can be delayed. Cardiac enlargement or pericardial effusion may be present.
Scintigraphy can help to pinpoint the underlying cause in infants with congenital hypothyroidism, but treatment should not be unduly delayed for this study.
Ultrasonographic examination of the thyroid is helpful, but studies show it can miss some ectopic glands shown by scintigraphy. The electrocardiogram may show low-voltage P and T waves with diminished amplitude of QRS complexes and suggest poor left ventricular function and pericardial effusion. Echocardiography can confirm a pericardial effusion. The electroencephalogram often shows low voltage. In children >2 yr of age, the serum cholesterol level is usually elevated. Brain MRI before treatment is reportedly normal, although proton magnetic resonance spectroscopy shows high levels of choline-containing compounds, which can reflect blocks in myelin maturation.
Treatment
Levothyroxine L-thyroxine is considered to be the best drug. Initial dose of it – 10-14 mkg/kg/day provides normalization of level Т4 for newborns during 1 week. Total dose of levothyroxine with age is gradually increased, and dose per kilogram of body mass is reduced.
Table. Levothyroxine doses for treatment of congenital hypothyroidism
|
Age |
Levothyroxine, mkg/kg/day |
|
0-3 months |
10-14 |
|
3-6 months |
8-12 |
|
6-12 months |
6-8 |
|
1-5 years |
4-6 |
|
6-12 years |
3-5 |
|
More then 12 years |
2-4 |
Evaluation of the treatment efficiency and correction of levothyroxine dose is conducted approximately monthly in the first 6 mo of life, and then every 2-3 mo between 6 mo and 2 yr. The dose of levothyroxine on a weight basis gradually decreases with age. ain criteria are speed of growth of a child, levels Т4 and TSH, detection of bone age (every 1-2 years).
Treatment is being added by neuro– and cardiotrophic drugs, vitamins, massage, therapeutic physical training.
ACQUIRED HYPOTHYROIDISM
Epidemiology
Studies of school-aged children report that hypothyroidism occurs in approximately 0.3% (1/333). Subclinical hypothyroidism (TSH >4.5 mU/L, normal T4 or free T4) is more common, occurring in approximately 2% of adolescents. Acquired hypothyroidism is most commonly a result of chronic lymphocytic thyroiditis; 6% of children aged 12-19 yr have evidence of autoimmune thyroid disease, which occurs with a 2 : 1 female : male preponderance.
ETIOLOGIC CLASSIFICATION OF ACQUIRED HYPOTHYROIDISM
Autoimmune (acquired hypothyroidism)
· Hashimoto thyroiditis
· Polyglandular autoimmune syndrome, types I and II
Iatrogenic
· Propylthiouracil, methimazole, iodides, lithium, amiodarone
· Irradiation
· Radioiodine
· Thyroidectomy
Systemic disease
· Cystinosis
· Langerhans cell histiocytosis
Hemangiomas (large) of the liver
Hypothalamic-pituitary disease
The most common cause of acquired hypothyroidism is chronic lymphocytic thyroiditis. Autoimmune thyroid disease may be part of polyglandular syndromes; children with Down, Turner, and Klinefelter syndromes and celiac disease or diabetes are at higher risk for associated autoimmune thyroid disease. In children with Down syndrome, anti-thyroid antibodies develop in approximately 30%, and subclinical or overt hypothyroidism occurs in approximately 15-20%. In girls with Turner syndrome, anti-thyroid antibodies develop in approximately 40%, and subclinical or overt hypothyroidism occurs in approximately 15-30%, rising with increasing age. In children with type 1 diabetes mellitus, approximately 20% develop anti-thyroid antibodies and 5% become hypothyroid. Williams syndrome is associated with subclinical hypothyroidism; this does not appear to be autoimmune, as anti-thyroid antibodies are negative.
Irradiation of the area of thyroid that is incidental to the treatment of Hodgkin disease or other head and neck malignancies or that is administered before bone marrow transplantation often results in thyroid damage. About 30% of such children acquire elevated TSH levels within a yr after therapy, and another 15-20% progress to hypothyroidism within 5-7 yr. Some clinicians recommend periodic TSH measurements, but others recommend treatment of all exposed patients with doses of T4 to suppress TSH.
Protracted ingestion of medications containing iodides—for example, expectorants—can cause hypothyroidism, usually accompanied by goiter. Amiodarone, a drug used for cardiac arrhythmias and consisting of 37% iodine by weight, causes hypothyroidism in about 20% of treated children. It affects thyroid function directly by its high iodine content. Children treated with this drug should have serial measurements of T4, T3, and TSH. Children with Graves’ disease treated with anti-thyroid drugs (methimazole or propylthiouracil) can develop hypothyroidism. Additional drugs that can produce hypothyroidism include lithium carbonate, interferon alpha, stavudine, thalidomide, valproate (subclinical), and aminoglutethimide.
Children with nephropathic cystinosis, a disorder characterized by intralysosomal storage of cystine in body tissues, acquire impaired thyroid function. Hypothyroidism may be overt, but subclinical forms are more common, and periodic assessment of TSH levels is indicated. By 13 yr of age, two thirds of these patients require T4 replacement.
Histiocytic infiltration of the thyroid in children with Langerhans cell histiocytosis can result in hypothyroidism.
Hypothyroidism can occur in children with large hemangiomas of the liver, because of increased type 3 deiodinase activity, which catalyzes conversion of T4 to rT3 and T3 to T2. Thyroid secretion is increased, but it is not sufficient to compensate for the large increase in degradation of T4 to rT3.
Any hypothalamic or pituitary disease can cause acquired central hypothyroidism. TSH deficiency may be the result of a hypothalamic-pituitary tumor (craniopharyngioma most common in children) or a result of treatment for the tumor. Other causes include cranial radiation, head trauma, or diseases infiltrating the pituitary gland, such as Langerhans cell histiocytosis.
Clinical Manifestations
Deceleration of growth is usually the first clinical manifestation, but this sign often goes unrecognized. Goiter, which may be a presenting feature, typically is nontender and firm, with a rubbery consistency and a pebbly surface. Weight gain is mostly fluid retention (myxedema), not true obesity. Myxedematous changes of the skin, constipation, cold intolerance, decreased energy, and an increased need for sleep develop insidiously.
Additional features include bradycardia, muscle weakness or cramps, nerve entrapment, and ataxia. Osseous maturation is delayed, often strikingly, which is an indication of the duration of the hypothyroidism. Adolescents typically have delayed puberty; older adolescent girls manifest menometrorhhagia. Younger children might present with galactorrhea or pseudoprecocious puberty. Galactorrhea is a result of increased TRH stimulating prolactin secretion. The precocious puberty, characterized by breast development in girls and macro-orchidism in boys, is thought to be the result of abnormally high TSH concentrations binding to the FSH, receptor with subsequent stimulation.
Children with suspected hypothyroidism should undergo measurement of serum free T4 and TSH. Because the normal range for thyroid tests is slightly higher in children than adults, it is important to compare results to age-specific reference ranges. Measurement of antithyroglobulin and antiperoxidase (formerly, antimicrosomal) antibodies can pinpoint autoimmune thyroiditis as the cause. Generally, there is no indication for thyroid imaging. In cases with a goiter resulting from autoimmune thyroid disease, an ultrasound examination typically shows diffuse enlargement with scattered hypoechogenicity.
There are hyponatremia, macrocytic anemia, hypercholesterolemia. All these changes return to normal with adequate replacement of T4.
Ultrasound examination is the most accurate method to follow nodule size and solid vs. cystic nature.
In children with a nodule and suppressed TSH, a radioactive iodine uptake and scan is indicated to determine if this is a “hot” or hyperfunctioning nodule.
A bone age X-ray at diagnosis is useful, in that the degree of delay approximates duration and severity of hypothyroidism.
Levothyroxine is the treatment of choice in children with hypothyroidism. The dose on a weight basis gradually decreases with age. For children 1-3 yr, the average l-T4 dosage is 4-6 mkg/kg/day; for 3-10 y4, 3-5 mk/kg/day; and for 10-16 yr, 2-4 mk/kg/day. Treatment should be monitored by measuring serum free T4 and TSH every 4-6 mo as well as 6 wk after any change in dosage. In children with central hypothyroidism, where TSH levels are not helpful in monitoring treatment, the goal should be to maintain serum free T4 in the upper half of the normal reference range for age.
HYPERTHYROIDISM
Hyperthyroidism results from excessive secretion of thyroid hormone; during childhood, with few exceptions, it is due to Graves disease. Graves disease is an autoimmune disorder; production of thyroid-stimulating immunoglobulin (TSI) results in diffuse toxic goiter.
In the thyroid gland, T helper cells (CD4+) predominate in dense lymphoid aggregates; in areas of lower cell density, cytotoxic T cells (CD8+) predominate. The percentage of activated B lymphocytes infiltrating the thyroid is higher than in peripheral blood. A postulated failure of T suppressor cells allows expression of T helper cells, sensitized to the TSH antigen, which interact with B cells. These cells differentiate into plasma cells, which produce thyrotropin receptor–stimulating antibody (TRSAb). TRSAb binds to the receptor for TSH and stimulates cyclic adenosine monophosphate, resulting in thyroid hyperplasia and unregulated overproduction of thyroid hormone.
The ophthalmopathy occurring in Graves disease appears to be caused by antibodies against antigens shared by the thyroid and eye muscle. TSH receptors have been identified in retro-orbital adipocytes and might represent a target for antibodies. The antibodies that bind to the extraocular muscles and orbital fibroblasts stimulate the synthesis of glycosaminoglycans by orbital fibroblasts and produce cytotoxic effects on muscle cells.
Clinical Manifestations
About 5% of all patients with hyperthyroidism are <15 yr of age; the peak incidence in these children occurs during adolescence.
The clinical course in children is highly variable. Symptoms develop gradually; the usual interval between onset and diagnosis is 6-12 mo and may be longer in prepubertal children compared with adolescents. The earliest signs in children may be emotional disturbances accompanied by motor hyperactivity. The children become irritable and excitable, and they cry easily because of emotional lability. They are restless sleepers and tend to kick their covers off. Their schoolwork suffers as a result of a short attention span and poor sleep. Tremor of the fingers can be noticed if the arm is extended. There may be a voracious appetite combined with loss of or no increase in weight. Recent height measurements might show an acceleration in growth velocity.
The size of the thyroid is variable. It may be so minimally enlarged that it initially escapes detection, but with careful examination, a diffuse goiter, soft with a smooth surface, is found in almost all patients.
Exophthalmos is noticeable in most patients but is usually mild. Lagging of the upper eyelid as the eye looks downward, impairment of convergence, and retraction of the upper eyelid and infrequent blinking may be present. Ocular manifestations can produce pain, lid erythema, chemosis, decreased extraocular muscle function, and decreased visual acuity (corneal or optic nerve involvement).
The skin is smooth and flushed, with excessive sweating. Muscular weakness is uncommon but may be severe enough to result in clumsiness. Reflexes are brisk, especially the return phase of the Achilles reflex. Many of the findings in Graves disease result from hyperactivity of the sympathetic nervous system.
Tachycardia, palpitations, dyspnea, and cardiac enlargement and insufficiency cause discomfort but rarely endanger the patient’s life. Atrial fibrillation is a rare complication. Mitral regurgitation, probably resulting from papillary muscle dysfunction, is the cause of the apical systolic murmur present in some patients. The systolic blood pressure and the pulse pressure are increased.
Thyroid crisis, or thyroid storm, is a form of hyperthyroidism manifested by an acute onset, hyperthermia, severe tachycardia, heart failure, and restlessness. There may be rapid progression to delirium, coma, and death. Precipitating events include trauma, infection, radioactive iodine treatment, or surgery.
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 below the lower range of normal. Antithyroid antibodies, including thyroid peroxidase antibodies, are often present.
Most patients with newly diagnosed Graves disease have measurable TRSAb; the two methods to measure TRSAb are thyroid-stimulating immunoglobulin (TSI) or thyrotropin-binding inhibitor immunoglobulin (TBII). Measurement of TSI or TBII is useful in confirming the diagnosis of Graves disease.
Differential Diagnosis
Differential diagnosis of Graves disease is conducted for diseases accompanied by hyperthyroidism, goiter, tachycardia. Toxic adenoma and hyper functioning cancer of thyroid gland, TTG productive pituitary adenoma developing thyrotoxicosis are rarely registered for children.
Differentiation of Graves disease with autoimmune thyroiditis has current importance. The last one, differently from Graves disease, is characterized by: thickening of capsule, presence of nodules, heterogeneity of echogenic structure during ultrasonic examination, mosaic accumulation of radioactive isotope during scanning, reduction of iodine absorption function of thyroid gland, increase of the antibody titer to thyreoglobulin and peroxidase, more easy course of thyrotoxicosis which has good results of conservative therapy and can terminate spontaneously.
Sporadic (non–toxic) goiter is characterized by absence of thyrotoxicosis, sometimes even hypothyroidism is possible conversely, which is confirmed by detection of hormone levels.
When hyperthyroxinemia is caused by exogenous thyroid hormone, levels of free T4 and TSH are the same as those seen in Graves disease, but the level of thyroglobulin is very low, whereas in patients with Graves disease, it is elevated.
Treatment
Conservative therapy is the main method of Graves disease treatment for children. On the first stage child must be admitted to hospital. Thyreostatic drugs are being prescribed, and methimazole is preferred. It is highly effective (not only blocks synthesis of thyroid hormones, but inhibits creation of auto antibodies as well) and is less toxic. The initial dosage of methimazole is 0.25-1.0 mg/kg/24 hr given once or twice daily. Smaller initial dosages should be used in early childhood. Careful surveillance is required after treatment is initiated. Rising serum levels of TSH to greater thaormal indicates overtreatment and leads to increased size of the goiter. Clinical response becomes apparent in 3-6 wk, and adequate control is evident in 3-4 mo. The dose is decreased to the minimal level required to maintain a euthyroid state.
Most studies report a remission rate of approximately 25% after 2 years of antithyroid drug treatment in children. Some studies find that longer treatment is associated with higher remission rates, with one study reporting a 50% remission rate after 4.5 years of drug treatment. If a relapse occurs, it usually appears within 3 mo and almost always within 6 mo after therapy has been discontinued. Therapy may be resumed in case of relapse. Patients older than 13 yr of age, boys, those with a higher body mass index, and those with small goiters and modestly elevated T3 levels appear to have earlier remissions.
A β-adrenergic blocking agent such as propranolol (0.5-2.0 mg/kg/24 hr orally, divided 3 times daily) or atenolol (1-2 mg/kg orally given once daily) is a useful supplement to antithyroid drugs in the management of severely toxic patients.
Radioiodine treatment or surgery is indicated when adequate cooperation for medical management is not possible, when adequate trial of medical management has failed to result in permanent remission, or when severe side effects preclude further use of antithyroid drugs. Either of these treatments may also be preferred by the patient or parent.
Subtotal thyroidectomy is done only after the patient has been brought to a euthyroid state. This may be accomplished with methimazole over 2-3 mo. After a euthyroid state has been attained, a saturated solution of potassium iodide, 5 drops/24 hr, are added to the regimen for 2 wk before surgery to decrease the vascularity of the gland. Complications of surgical treatment are rare and include hypoparathyroidism (transient or permanent) and paralysis of the vocal cords. The incidence of residual or recurrent hyperthyroidism or hypothyroidism depends on the extent of the surgery. Most recommend near-total thyroidectomy. The incidence of recurrence is low, and most patients become hypothyroid.
The ophthalmopathy remits gradually and usually independently of the hyperthyroidism. Severe ophthalmopathy can require treatment with high-dose prednisone, orbital radiotherapy (of questionable value), or orbital decompression surgery. Cigarette smoking is a risk factor for thyroid eye disease and should be avoided or discontinued to avoid progression of eye involvement.
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