Difficult Diagnoses in Pediatrics

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Diagnostic Dilemma The Goiter

Craig Alan Alter, MD,* and Thomas Moshang, Ir, MDt

Many pediatricians are comfortable ordering appropriate laboratory tests in suspected cases of hyper or hypothyroidism, but the physical finding of an enlarged thyroid gland or goiter often poses a diagnostic dilemma for the pediatrician. In most cases of a goiter, the thyroid function tests are initially normal. Enlargement of the thyroid gland need not be associated with either over or underproduction activity of thyroid hormone. The morbidity of a goiter ranges from that of thyroid .carcinoma to simple cosmetic effect. It is important, therefore, for the pediatrician to feel comfortable in the workup of an enlarged thyroid gland.

INCIDENCE Prior to 1924, enlarged thyroids had an incidence of up to 70% in some areas of the United States,31 directly relating to presence or absence of iodine in the region. Since the introduction of iodized salt in 1924, the incidence has changed dramatically in industrialized areas. Two large studies of goiter in children reveal a prevalence of goiter in the United States of 3% to 7%. Trowbridge et aP1 evaluated the incidence of goiter in 7785 children. The study separated those children from several areas of presumed higher prevalence and those from a control region. The incidence of goiter for the entire population studied was 6.8% (range 4.4%-9.8%). None of the children was clinically overtly hypo or hyperthyroid. 31 In the study by Rallison et al,22 5179 children had an incidence of goiter of 3.9% (3% in males, 5% in females), confirming that goiter is a significant medical From the Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania *Pediatric Endocrinology Fellow tProfessor of Pediatrics and Director of Training Programs

Pediatric Clinics of North America-Vo!. 38, No, 3, June 1991

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CRAIG ALAN ALTER AND THOMAS MOSHANG, JR

problem. Many regions of the world still have iodine deficiency, and thus, the incidence of goiter in those regions is much higher.

DETECTION

In order to detect enlargement of the thyroid gland in children, inspection, palpation, and auscultation of the neck should be performed routinely. In preadolescent children, the thyroid gland is small and virtually nonpalpable. A fat neck may be caused by adipose tissue, large sternocleidomastoid muscles, cysts, nonthyroidal neoplasms (such as lymphoma, teratoma, or hygroma), or a goiter. Inspection of the neck includes having the child swallow (water, if necessary). Palpation is best done from behind the patient. Feel for the thyroid cartilage and cricoid cartilage to locate the isthmus of the thyroid gland, which is just below the cricoid cartilage. After delineating the lobes of the thyroid gland for approximate size, feel for nodules, granularity, and degree of firmness of the gland. The detection of a bruit in a goiter is indicative of a hypervascular gland, suggestive of hyperthyroidism. A modification of the World Health Organization criteria31 can be used for recording the size of the goiter for records: Grade Grade Grade Grade

1: 2: 3: 4:

Easily palpable goiter not visible even with the neck extended. A visibly enlarged thyroid gland when the neck is extended. A visibly enlarged thyroid gland in the normal neck position. A very large goiter.

A goiter may be diffusely enlarged, nodular, or asymmetric. The evaluation of a nodular or asymmetric gland is more intensive because of the increased likelihood of cancer in children. A granular or pebbly thyroid suggests chronic lymphocytic thyroiditis. A unilateral enlargement represents either a solitary nodule or unilateral agenesis of the thyroid. A firm gland suggests an infiltrative process, whereas a very hard gland is more suggestive of a neoplasm. A painful gland is often an acute inflammatory process, which is treated differently than a more chronic condition. One must also examine adjacent lymph nodes. A malignancy can metastasize to local nodes before the detection of a nodule. Finally, one should again consider that the swelling is not caused by thyroid tissue but by some other process involving a cyst, lymph node, fat, muscle, or a nonthyroidal neoplasm (teratoma or lymphoma). In addition, a midline dysgenetic thyroid or an aberrant thyroid may simulate a solitary nodule.

HISTORY

The child with a goiter is usually clinically euthyroid. The most common presentation is either parental observation or physician detection during a routine examination. The historical information most useful to determine whether one is hyperthyroid or hypothyroid in childhood relates to growth, activity, emotional lability, and appetite. In prepubertal hyperthyroidism, the most common historical findings include hyperactivity, irritability, and

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hyperphagia. In childhood hypothyroidism, the child is often described as sedentary, quiet, gaining weight without excessive appetite, and constipated. The most common complaint for the hypothyroid child is short stature. Signs of thyroid disease unique to children include growth retardation or rapid growth, abnormal bone age, sexual precocity or infantilism, and poor school performance. In addition to seeking signs and symptoms of thyroid disease, one should consider the possibility of medications and diet as a possible cause of goiter. Nutritional causes are extremely rare, except in those families with unusual dietary practices. Drug-related causes of goiter are occasionally found in asthmatic or allergic children with cough who use drugs with a significant iodide content. An unusual ingestion was seen recently at the Children's Hospital of Philadelphia in a mentally retarded child who had eaten the magnets from magnetic alphabets. The magnets contained iron and cobalt, which caused a large goiter and polycythemia in the child. Table 1 lists various drug and dietary goitrogens. 5 There is an association of autoimmune thyroiditis with various medical disorders. Goiters and thyroid disease are more commonly seen with trisomy 21, Turner's syndrome, type I diabetes mellitus, and other autoimmune disorders. 6, 8

DIFFERENTIAL DIAGNOSIS OF GOITER The differential diagnosis of a goiter is separated based on whether the thyroid gland is diffusely or focally enlarged. In general, a diffuse process suggests that the gland is either being globally stimulated to grow (by thyroid-stimulating hormone [TSH] or by an antibody) or is being infiltrated throughout. These diffusely enlarged glands may be composed of many discrete nodules, as in a multinodular goiter. The solitary nodule is of concern because of the high incidence of malignancy in children with a single nodule. Although the various disorders may overlap in their presentation (i. e., a malignancy may be diffusely infiltrative or chronic lymphocytic thyroiditis may cause a multinodular goiter), the differential diagnosis and evaluation of a goiter proceeds after one decides whether the thyroid gland is or is not diffusely enlarged.

Table 1. Medicinal and Dietary Goitrogens Selected anions Cations Drugs

Dietary goitrogens

Iodide (all halogens), perchlorate, thiocyanate Lithium, cobalt, arsenic Antithyroid (propylthiouracil, methimazole) Aminosalicylic acid, aminoglutethimide, phenylbutazone, PAS, amiodorone, oral contraceptives Brassicae (cabbage, rutabagas, turnip), soybean, cassava

Adapted from Fisher D; The thyroid. In Kaplan S (ed); Clinical Pediatric Endocrinology, ed 2. Philadelphia, W. B. Saunders Company, 1990, p 87; Taylor S; Non-toxic goiter. In Werner S, Ingbar S (eds); The Thyroid, ed 4. Hagerstown, Harper and Row, 1978, p 505.

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DIFFUSE GOITER

The three most common causes of a diffusely enlarged thyroid are Hashimoto's thyroiditis (chronic lymphocytic thyroiditis), simple colloid goiter, and Graves' disease. Table 2 contains a more complete list of the differential diagnosis of the diffuse goiter. Autoimmune thyroid disease accounts for most of these cases. The differential diagnosis of a diffusely enlarged thyroid gland is made simpler by dividing the cases into euthyroid, hypothyroid, and hyperthyroid goiters. After detection of a diffusely enlarged goiter, the clinician searches for signs and symptoms of thyroid dysfunction. The thyroid function tests (total T 4 , TSH, T3RU, or another measure of thyroid-binding protein level, free thyroid index, and T3 in suspected hyperthyroidism) should confirm clinical impressions. Occasionally, subclinical thyroid disease is revealed by thyroid function tests, altering the approach to further evaluation. The differential diagnosis of the diffuse goiter is considered first by clinical status and then by disease process. Euthyroid By far, most patients found to have a goiter in Trowbridge's and Rallison's studies were euthyroid. Thus, confirmatory thyroid tests usually reveal a normal TSH and free thyroid index. The two most common diagnoses to consider are simple colloid goiter and chronic lymphocytic thyroiditis (CLT). A granular or pebbly gland on examination is suggestive of CLT. The pathophysiology of these two disorders is quite different. Chronic Lymphocytic Thyroiditis. CLT is an autoimmune disease. Pathologically, the thyroid gland demonstrates diffuse lymphocytic infiltration. Either or both anti thyroglobulin or antimicrosomal antibodies is elevated in 85% to 90% of biopsy-proven cases of CLT. 21 In addition, a child occasionally has another autoimmune disorder. Rarely, CLT may be part of the autoimmune polyglandular syndrome and be associated with a number of autoimmune endocrine and nonendocrine disorders. AutoimTable 2. Differential Diagnosis of an Enlarged Thyroid USUALLY DIFFUSE

USUALLY PRESENT AS A SOLITARY NODULE

Autoimmune Chronic lymphocytic thyroiditis Graves' disease Simple colloid goiter* Compensatory (goiter due to increased TSH) Dyshormonogenesis Goitrogens Iodine deficiency Drugs Thyroxine resistance TSH-secreting adenoma (rare) Inflammatory conditions Acute thyroiditis Subacute thyroiditis Granulomatous

Congenital abnormalities Ectopic gland Unilateral agenesis Thyroglossal duct remnant Cystic hygroma Dermoid cyst Other non thyroidal disease Neoplasia Benign (e.g., adenoma) Malignant (1) Papillary carcinoma (2) Follicular carcinoma (3) Papillary-follicular carcinoma (4) Medullary carcinoma (5) Anaplastic carcinoma

* Possibly autoimmune.

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mune diseases associated with CLpo include hypoparathyroidism, Addison's disease, diabetes mellitus, chronic mucocutaneous candidiasis, premature gonadal failure, celiac disease, vitiligo, myasthenia gravis, chronic active hepatitis, and pernicious anemia. In Rallison's study,22 one third of the patients with goiter had CLT. Eighty-seven percent of these children with CLT were clinically euthyroid; 3% were clinically hyperthyroid, and 3% to 10% were hypothyroid. Of the hypothyroid children, 30% were clearly hypothyroid, whereas the other 70% had only mild signs of hypothyroidism. CLT, therefore, is most often associated with a euthyroid child. The patients with hyperthyroidism have been referred to as having thyroiditic thyrotoxicosis or hashitoxicosis. Simple Colloid Goiter (Adolescent Goiter, Nontoxic Goiter). The patient with a simple colloid goiter is euthyroid and, unlike those with CLT, not at risk for developing hypothyroidism. The disease seems to follow an autosomal inheritance, with greater penetration in the female, and most commonly affects high school-aged patients. Recent evidence suggests that some cases result from a thyroid growth-stimulating immunoglobulin (TGI).2.7 Pathologically, the gland is normal, except for the enlarged colloid follicles. Thyroid function tests are normal, and the gland diminishes in size with thyroxine therapy. Compensatory Goiters. Mild cases of inborn errors of thyroid synthesis (dyshormonogenesis), various drugs, dietary ingestion of goitrogens, and iodine deficiency may cause a diffuse goiter from increased TSH. If the defects are mild, the patients are usually euthyroid. An uncommon but more frequently recognized cause of goiter with an inappropriate elevation of TSH is the familial syndrome of thyroxine resistance. This syndrome is associated with a goiter in patients who have an elevated or high normal TSH, despite elevated levels of T4. The families may have only central (pituitary) resistance to thyroxine and are clinically hyperthyroid or they have generalized resistance and are euthyroid or hypothyroid. The diagnosis of thyroxine resistance should be suspected in a child with a goiter associated with elevated T4 levels but a normal or a paradoxically elevated TSH. 13 Hypothyroid In patients with diffuse goiter and suspected hypothyroidism, the TSH should be elevated. Most of these cases are caused by CLT and, thus, 85% to 90% of patients have elevated antimicrosomal or antithyroglobulin antibodies. Other causes include drugs (see Table 1) and dyshormonogenesis. CLT, in those cases without detectable antibodies, can be separated from other causes such as drugs or dyshormonogenesis by 1231 scan and uptake. Uncommonly, a patient will have thyroid resistance and will have an elevated T4 despite clinical hypothyroidism, as discussed earlier. Hyperthyroid

Graves' Disease. In Graves' disease, another autoimmune disorder, the pathogenesis of the hyperthyroidism is caused by antibodies that stimulate the TSH receptor. These antibodies can be determined and measured as thyroid-stimulating immunoglobulins (TSI). The antimicrosomal and antithyroglobulin thyroid antibodies, which are more commonly

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detected in CLT, may be present in Graves' disease but usually in low titers. Thyroid function tests are diagnostic with elevations of T4 or T3 but suppressed or undetectable TSH levels. In the new sensitive assays, one can distinguish between a normal TSH and a low TSH. Exophthalmos is seen frequently in pediatric patients; however, in contrast to adult patients, it is rarely progressive. Painful Thyroid

Subacute Thyroiditis. Subacute thyroiditis is a self-limiting illness often associated with an upper respiratory tract infection. It occurs predominantly in adults and is extremely rare in children. Typically, the patient is mildly thyrotoxic, with a tender goiter and no ophthalmologic signs of Graves' disease. The T4 and T3levels are elevated, and the TSH is suppressed. The radioactive iodine uptake distinguishes Graves' disease from subacute thyroiditis. The uptake is high in Graves' disease because of a hyperstimulated gland but low in subacute thyroiditis because the hormone stems from destroyed thyroid cells and subsequent release of thyroxine. Symptoms persist for about 1 to 4 weeks and may be followed by a period of transient hypothyroidism. The illness may last from 2 to 9 months. 5 Treatment, when necessary, includes nonsteroidal anti-inflammatory agents and glucocorticoids in severe cases. In general, the patient fully recovers. Acute Suppurative Thyroiditis. Acute suppurative thyroiditis is characterized by fever, dysphagia, hoarse voice, painful neck, and abscess formation. The infected thyroid gland may be caused by staphylococci or mixed aerobes and anaerobes. There is often a congenital pharyngeal sinus tract defect that predisposes the thyroid gland to acute bacterial infection. The patients are usually euthyroid and laboratory tests reveal an increased white blood cell count and erythrocyte sedimentation rate but normal thyroid function tests. Treatment with salicylates and an individualized approach with antibiotics are required. Incision and drainage may be necessary, but the long-term outcome for the thyroid is good. Evaluation of the Diffuse Goiter After detection of a diffusely enlarged goiter and having assured oneself that the gland is not nodular, the examiner should decide if the gland is hard or soft, pebbly, irregular or smooth, painful or nonpainful, and listen for the presence or absence of a bruit. In children, the painful gland is almost certainly acute suppurative thyroiditis or not related to the thyroid at all. The examiner should decide on clinical grounds, based on history and physical examination, whether the patient is euthyroid, hypothyroid, or hyperthyroid (Fig. 1). The euthyroid patient with a goiter is most likely to have CLT. T4, T3 resin uptake, TSH, and both antithyroglobulin and antimicrosomal antibodies should be obtained. In 80% to 90% of patients with CLT, antibodies are detectable. In the euthyroid patient (both clinically and biochemically), even in the absence of detectable antibodies, the diagnosis is most likely CLT or a colloid goiter. An 1231 scan separates the two because CLT characteristically has a rapid early high uptake of iodine, dischargeable with perchlorate, and a patchy, irregular scan of a diffusely enlarged gland.

Clinical and lab Impressions

/

,EuthYroid]

+

!IOWTSH

highTSH /

I

TSH

Exophthalmos?

higt

~lno r------,

GRAVES'

/

no

1

Patchy Uptake?

~

""-l W

ClT

~-----

ICLT I

.. yes

ICLT I

1

, Hypothyroidism'

1

Thyroid Antibodies?

'7

1"0

ICLT I

yes

Iodine 123 Scan Patchy Uptake?

no ~ (diffusely high uptake)

~ormal

Iodine 123 Scan 1r:S::-:-im-p-Ie-C-ollo-i-d-G-.-I

Tender Gland?

DISEASE

Thyroid Antibodies?

~no

Central T4 Resistance TSH adenoma

~

1

,Hyperthyroidism . - -----rll

123 Uptake) Figure 1. Evaluation of a diffuse goiter.

ClT Dyshormonogenesis Peripheral T4 Resistance: hi T4 and TSH Drugs

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CRAIG ALAN ALTER AND THOMAS MOSHANG, JR

Slight elevations of TSH with a normal T4 suggest compensatory hypothyroidism. If antibodies are not present, this may either be because of drugs, dyshormonogenesis, or CLT. If a patient is clinically hypothyroid, CLT is the most common cause, although hypothyroidism because of CLT is most often notable for the absence of a goiter. CLT in general produces hypothyroidism after chronic infiltration and inflammation of the gland, with resultant absence of a goiter. Nevertheless, hypothyroidism is so frequently caused by CLT in children statistically (as compared to dyshormonogenesis, goitrogens, or peripheral resistance to thyroxine) that thyroid function tests and antithyroglobulin and antimicrosomal thyroid antibodies are sufficient for initial evaluation. An enlarged gland with extremely patchy and low uptake of 1231 distinguishes CLT from goitrogens, drugs, and dyshormonogenesis. If a patient is clinically hyperthyroid, an elevated T4 and a suppressed TSH confirm the clinical diagnosis. If, however, the T4 is normal and the TSH suppressed, a T3 should be obtained because it is likely that the child has T3 toxicosis. Thyroid scan, 1231 uptake, TSI determinations, and thyrotropin-releasing hormone testing are generally not necessary to make the diagnosis of Graves' disease. In a rare situation, the patient who is clinically hyperthyroid is found to have an elevated T4 but with a normal or high TSH, and the diagnosis of central resistance to thyroxine is probable. The diagnosis of a TSH adenoma is rare.

SOLITARY NODULES

Although thyroid carcinoma is much more common in the adult population, the risk of a solitary nodule being malignant is greater in children. The incidence of carcinoma in a solitary thyroid nodule in normal children ranges from 14% to 40% in different series. 12, 14, 15, 26, 28 Therefore, the detection of a probable thyroid nodule requires a systematic approach to evaluation, The differential diagnosis (see Table 2) other than thyroid carcinoma includes thyroid follicular adenoma, cystadenoma, a functioning adenoma (Plummer syndrome), and follicular nodules of CLT. Other disorders that may mimic a thyroid nodule include congenital lesions such as unilateral agenesis, cystic hygroma, dermoid cysts, teratoma, and infections such as pyogenic, viral, or granulomatous. A prior history of radiation exposure to the neck of the child, especially in infancy, and any family history of thyroid carcinoma increase the likelihood that the solitary nodule may be a carcinoma. In the 1950s, neck irradiation for thymic enlargement in newborns, for tonsillar hypertrophy, facial hemangiomata, and other disorders was a common treatment modality.28 Subsequently, studies showed that dosages in the order of magnitude of 300 to 1500 cGy (rads) may yield thyroid malignancies in up to 30% of patients. 3 However, much higher exposure, as occurs with 1311 ablation therapy in Graves' disease (lO,ooO cGy), does not seem to be a significant risk factor, as this dosage causes cell death prior to malignant degeneration. 17 Radiation is no longer a common risk factor, except in tumor therapy and

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hone marrow transplantation. Thyroid disease does not confer an increased risk of thyroid neoplasia. Hashimoto's disease carries an increased risk of lymphoma but not of thyroid carcinoma. 26 Other risk factors include the presence of a rapidly growing mass (rare in children, even with malignancy) and a family history of thyroid cancer. The latter is especially significant for medullary carcinoma of the thyroid. Techniques used in the evaluation of the solitary nodule include physical examination, blood tests, ultrasonography, radionuclide scanning, fine-needle aspiration, and open biopsy. Each has its advantages and limitations. Physical Examination Certain findings on physical examination may suggest malignancy. A single, rock-hard, irregular nodule is highly suspicious. Multinodular goiter is much more likely caused by benign conditions such as CLT rather than malignancy. Obstructive symptoms such as hoarseness, obstruction, and dysphagia are more often suggestive of malignancy but certainly are not diagnostic, because benign multinodular goiters may produce these symptoms as well. 26 Thyroid carcinomas frequently metastasize to adjacent lymph nodes. Hence, it is important to check for anterior cervical adenopathy as well as adenopathy in the tracheoesophageal or deep jugular chain. 14 Lahoratory Evaluation There are no specific blood tests that delineate thyroid malignancy from other disorders in the differential diagnosis. Thyroid function tests are useful because malignancy is usually accompanied by normal thyroid functions. For example, if the TSH is elevated, the pathologic diagnosis is more likely to be CLT than malignancy. However, hypothyroidism can occur in malignancy, and thyroid antibodies can be found in occasional patients with thyroid carcinoma. Thyroglobulin may be increased in carcinoma of the thyroid but it is normal or decreased in anaplastic or medullary carcinoma. Furthermore, thyroglobulin may be increased in benign illnesses such as Graves' disease, Hashimoto's disease, nontoxic goiter, and subacute thyroiditis. The utility of thyroglobulin is for following the progress of patients after ablatement of carcinoma. 26 Rarely, carcinoembryonic antigen is elevated in cases of thyroid carcinoma. Calcitonin is increased in 75% of patients with medullary carcinoma of the thyroid and should be measured, especially if there is a family history of thyroid disease. Chest radiographs should be obtained to screen for the presence of metastatic lesions. Ultrasonography Ultrasonography is useful to measure the number and size of the nodules. 27 With more than 90% accuracy, it allows one to ascertain if a nodule is cystic, solid, or mixed. 26 Cystic lesions are generally considered benign. 14 These cysts often result from necrosis and degeneration of previous nodules. Most cystic lesions are therefore mixed with some solid components. A predominantly cystic lesion is usually benign. In one series of 17 children with cold nodules,14 9 had a cystic component: 6 were follicular adenomas, 1 was a colloid goiter, and 2 were thyroglossal duct cysts. Rarely,

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CRAIG ALAN ALTER AND THOMAS MOSHANG, JR

however, a mixed cystic lesion may be a degenerating carcinoma. If a thyroid nodule is completely cystic, then a more conservative approach, such as fine-needle biopsy, may be used diagnostically. Radionuclide Imaging Classically, two different isotopes are used in radionuclide scanning: (iodine) and OOmTc (pertechnetate). Radionuclide scans are used to determine whether the thyroid nodule is functioning normally (warm), hyperfunctioning (hot), or hypofunctioning (cold). In addition, a scan occasionally reveals that the nodule is actually an ectopic thyroid that may be the sole functioning thyroid tissue. Radiolabeled tracer is given orally and the thyroid is scanned for uptake of the tracer. Iodine is the more physiologic isotope, as it is needed for thyroid hormone synthesis. Thus, trapping and uptake can both be studied. 1231 has a shorter chemical half-life than 1311, which is used for ablation. 12 Scintiscanning with OOmTc delivers less radiation to the thyroid and offers the advantage of only a 20-minute wait between intake and the scan. However, there are several disadvantages. The technetium isotope occasionally results in a hot scan that is cold by radioactive iodine testing. Thus, the determination of a hot nodule by technetium needs to be confirmed with 1231, although a cold technetium scan result is adequate. In addition, OOmTc results in more radiation exposure to the large intestine, bone marrow, and gonads than does a similar dose of 1231. 17 Malignancies of the thyroid are typically cold lesions. However, most solitary thyroid nodules are cold. In addition, a rare carcinoma is hot. Thus, although radionuclide scanning is not a perfect test, if a nodule is warm or hot and unaccompanied by a clinical risk factor for malignancy, then a more conservative approach might be taken, such as a trial of thyroxine suppression. Thyroid suppression may reduce the size of a warm nodule caused by CLT but does not generally affect a hot nodule. The progress of a patient with a hot nodule should be followed for signs of thyrotoxicosis as well as enlargement of the nodule; if either occurs, the nodule is resected. 1231

Fine-needle Aspiration Versus Open Biopsy Fine-needle aspiration biopsy has emerged as a common technique for evaluating the solitary nodule in the adult population. Because the use of this technique among children has been more limited, it should be used in low-risk cases (for example, under conditions of no family history, no neck irradiation, no suspicion of metastases present, no rapid growth of the mass, and no evidence for lymphadenopathy) and in a purely cystic nodule. In addition, a child less than 8 years old represents an increased risk for mortality from thyroid carcinoma and treatment should proceed directly to open biopsy Y The accuracy of the technique depends largely on the physician performing the procedure and, more importantly, the pathologist. The result of a fine-needle aspiration is characterized as either malignant, benign, or suspicious. False-negative results may occur with small lesions and with cystic lesions when only liquid is aspirated. A suspicious result in a child must be followed by an open biopsy because of the increased

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incidence of malignancy in thyroid nodules in children. Fine-needle aspiration is not only cost effective,26 but can be done with intramuscular or intravenous sedation (e.g., Demerol, Thorazine, and Phenergan 17). However, unless a pathologist experienced in evaluating thyroid needle aspirations is available, the most judicious course is open biopsy in cases of cold, noncystic, solitary thyroid nodules. SUMMARY The incidence of goiters in children is about 4% to 5%. The first step in the evaluation is to decide whether the swelling indeed involves the thyroid. After careful examination, one determines if the thyroid is diffusely or focally enlarged. A solitary nodule merits an extensive workup because of the high rate of malignancy. The evaluation of a diffuse goiter proceeds after deciding if the patient is euthyroid, hypothyroid, or hyperthyroid. In most cases, the child is euthyroid and the diagnosis is either CLT or simple colloid goiter. Laboratory tests for thyroid function and antibodies usually make the diagnosis. The hypothyroid patient most likely has CLT, although drugs or goitrogens, dyshormonogenesis, and thyroid resistance are also possible. The hyperthyroid patient usually has Graves' disease. The incidence of malignancy of solitary thyroid nodules is 15% to 40%; therefore, evaluation must be sensitive enough not to miss cancer. Ultrasonography helps to delineate the anatomy and to reveal if the nodule is cystic. Radionuclide scans are useful, as warm or hot lesions are rarely malignant. Cold nodules require further investigation, and in most institutions, this amounts to open biopsy. Fine-needle aspiration may be used if the clinician and pathologist are experienced. With this aggressive approach to thyroid nodules, malignancies are given early treatment. The prognosis is good in most thyroid carcinomas. REFERENCES 1. Blum M, Rothschild M: Improved nonoperative diagnosis of the solitary "cold" thyroid nodule. JAMA 243:242, 1980 2. Drexhage H, Bottazzo G, Doniach, et al: Evidence for thyroid-growth-stimulating immunoglobulins in some goitrous thyroid diseases. Lancet 2:287, 1980 3. Favus M, Schneider A, Stachura M: Thyroid cancer occurring as a late consequence of head and neck irradiation: Evaluation of 1056 patients. N Engl J Med 294:1019, 1976 4. Field J, Bloom G, Chou M, et al: Effects of thyroid-stimulating hormone on human thyroid carcinoma and adjacent normal tissue. J Clin Endocrinol Metab 47:1052, 1978 5. Fisher D: The thyroid. In Kaplan S (ed): Clinical Pediatric Endocrinology, ed 2. Philadelphia, W. B. Saunders Company, 1990, p 87 6. Fisher D. Pandian M, Carlton E: Autoimmune thyroid disease: An expanding spectrum. Pediatr Clin North Am 34:907, 1987 7. Gaag R, Drexhage H, Wiersinga W: Further studies of thyroid growth-stimulating immunoglobulins in euthyroid nonendemic goiter. J Clin Endocrinol Metab 60:972, 1985 8. Germain E, Plotnick L: Age-related anti-thyroid antibodies and thyroid abnormalities in Turner syndrome. Acta Paediatr Scand 75:750, 1986

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9. Gershengorn M, McClung M, Chu E, et al: Fine-needle aspiration cytology in the preoperative diagnosis of thyroid nodules. Ann Intern Med 87:265, 1977 10. Gilani B, MacGillivray M, Voorhess M, et al: Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children. J Pediatr 105:218, 1984 11. Gorton C, Sadeghi-Nejad A, Senior B: Remission in children with hyperthyroidism treated with propylthyouracil. Am J Dis Child 141:1084, 1987 12. Hopwood N, Carroll R, Kenny F, et al: Functioning thyroid masses in childhood and adolescence. J Pediatr 89:710, 1976 13. Hopwood N, Sauder S, Shapiro B: Familial partial peripheral and pituitary resistance to thyroid hormone: A frequently missed diagnosis? Pediatrics 78:1114, 1986 14. Hung W, August G, Randolph J, et al: Solitary thyroid nodules in children and adolescents. J Pediatr Surg 17:225, 1982 15. Kirkland R, Kirkland J, Rosenberg J, et al: Solitary thyroid nodules in 30 children and report of a child with a thyroid abscess. Pediatrics 51:85, 1973 16. Lucky A, Howley P, Megyesi K, et al: Endocrine studies in cystinosis: Compensated primary hypothyroidism. J Pediatr 91:204, 1977 17. Mahoney C: Differential diagnosis of goiter. Pediatr Clin North Am 34:891, 1987 18. Miller J, Zafar S, Karo J: The cystic thyroid nodule. Radiology 110:257, 1974 19. Muir A, Daneman A, Ehrlich R: Thyroid scanning, ultrasound, and serum thyroglobulin in determining the origin of congenital hypothyroidism. Am J Dis Child 142:214, 1988 20. Olambiwonnu N, Penny R, Frasier S: Roentgenographic calcifications in carcinoma of the thyroid. Am J Dis Child 129:371, 1975 21. Rallison M, Dobyns B, Keating F, et al: Occurrence and natural history of chronic lymphocytic thyroiditis in children. J Pediatr 86:675, 1975 22. Rallison M, Dobyns B, Keating F, et al: Thyroid disease in children: A survey of subjects potentially exposed to fallout radiation. Am J Med 56:457, 1974 23. Rallison M, Dobyns B, Keating R, et al: Thyroid nodularity in children. JAMA 233:1069, 1975 24. Reiter E, Root A, Rettig K, et al: Childhood thyromegaly: Recent developments. J Pediatr 99:507, 1981 25. Rivkees S, Bode H, Crawford J: Long-term growth in juvenile acquired hypothyroidism. N Engl J Med 318:599, 1988 26. Rojeski M, Gharib H: Nodular thyroid disease: Evaluation and management. N Engl J Med 315:428, 1985 27. Scheible W, Leopold G, Woo V, et al: High-resolution real-time ultrasonography of thyroid nodules. Radiology 133:413, 1979 28. Scott M, Crawford J: Solitary thyroid nodules in childhood: Is the incidence of thyroid carcinoma declining? Pediatrics 58:521, 1976 29. Taylor, S: Non-toxic goiter. In Werner S, Ingbar S (eds): The Thyroid, ed 4. Hagerstown, Harper and Row, 1978, p 505 30. Trence D, Morley J, Handwerger B: Polyglandular autoimmune syndromes. Am J Med 77:107, 1984 31. Trowbridge F, Matovinovic J, McLaren G, et al: Iodine and goiter in children. Pediatrics 56:82, 1975

Address reprint requests to Thomas Moshang, Jr, MD Division of Endocrinology Children's Hospital of Philadelphia 34th St. and Civic Center Blvd. Philadelphia, PA 19104

Diagnostic dilemma. The goiter.

The incidence of goiters in children is about 4% to 5%. The first step in the evaluation is to decide whether the swelling indeed involves the thyroid...
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