the diagnostic use of radionuclides in the thyroid disorders of childhood

The Diagnostic Use of Radionuclides in the Thyroid Disorders of Childhood

By ALBERTO HAYEK AND JOHN B. STANBLqAY

The radioisotopes of iodine have proven useful in the differential diagnosis of thyroid disorders in infancy and childhood. Their use has been somewhat limited for technical reasons and because of concern that radiation from any source is particularly hazardous in this age group. The introduction of 99r~Tc-labeled pertechnetate and of radioisotopes of iodine that are free of beta emission or that have a short half-life, or both, and instrumentation that permits measurement in the nanocurie range are advances that promise to extend into the pediatric group the full range of diagnostic techniques employing these agents. Although exact measurements of thyrotropin and

circulating thyroid hormones have reduced substantially the need for diagnostic procedures employing radionn- clides, there are still occasions when the added information provided by these tests is invaluable. Included in this list are measurements of thyroid function for the diagnosis of hyper- or hypothyroidism, thyroid scanning for the activity of discrete nodules or of metastatic disease in areas remote from the thyroid, defini- tion of the nature of certain rare inborn metabolic errors that impair thyroid function, studies on thyroiditis, and differential diagnosis of certain hypothyroid states due to defective embryological development.

T HYROID DISEASE may pursue a subtle course in childhood. Signs may be masked and symptoms poorly communicated. Inherited disorders may

give paradoxical results when routine tests of glandular function are applied. It often is essential to have available multiple laboratory resources when the diagnosis is uncertain, and this may imply the use of radionuclides, even though one might prefer to avoid them in the growing child. When used, the thyroid tests with radioiodine, or more recently with radiotechnetiurn, may be uniquely valuable in illuminating an abnormal physiological process or an anatomical derangement.

The use of radioactive substances in pediatric practice involves special problems of radiation dosage and technical difficulties, as well as physiological variants that are peculiar to the age group. Fortunately, the introduction of new radionuclides, such as technetium, and improved detection instrumentation have reduced substantially the radiation dose received in most tests. By judicious choice of nuclide and test procedures, it is now possible to develop information that may be critical in management. Even so, one must accept the premise that any amount of radiation is undesirable and, accordingly, employ these tests with discernment and careful weighing of value versus risk.

From the Department of Pediatrics, Massachusetts General Hospital, Boston, Mass., and the Unit of Experimental Medicine, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass.

ALBERTO HAYEK, M.D., AND JOHN" B. STAXBUBV, M.D.: Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass.

334 SEXIINARS IN NVCLEAr~ MEDXClNE, VOL. 1, NO. 3 (jtmY), 1971

THYROID DISORDERS O F C H I L D H O O D 335

CHOICE OF NUCLIDES

The nuclide most widely used in the evaluation of children with thyroid disorders is lSlI. This choice is due mainly to its availability from commercial sources, low cost, excellent standardization, and convenient half-life. Its principal disadvantage is the high radiation dose to the thyroid, a considera- tion that is particularly important in the child. The radiation delivered to the thyroid by 1 ~tCi of 131I is approximately 1.52 rad in the adult I and 0.83 tad in the fetus, z Radiation exposure is significantly greater postnatally (first week of life) because of the high thyroidal uptake and is linearly related to gland weight and dosage throughout infancy and childhood.

There is abundant evidence that radiation may be particularly hazardous in the young. The peculiar susceptibility of the growing thyroid to radiation damage was first described by Duffy and Fitzgerald 3 and abundantly con- firmed by the studies of Winship et al. 4 of children who had received radiation of the thyroid area for various reasons, and of Conrad et al. 5 with children of the Marshall Islands who sustained heavy accidental thyroid irradiation in the course of a bomb test in the Pacific. Dolphin has assembled and summarized the relevant information. 6 He has estimated the risk at 100 cancers per million persons per tad, based on the incidence of thyroid cancer after X-ray treatment of the neck for thyrnic enlargement or for other reasons. There are no data on the radiation effects associated with diagnostic doses currently employed. 7

As a result of increasing awareness of the risks of radiation iniury to the thyroid, physicians have explored the investigational uses of short-lived radionuclides such as 13zI (half-life, 2-3 hr), 123I (half-life, 13 hr), and the longer lived 125I, which has a half-life of 59.9 days. Experience with l~aI has been unavailable until recently; it is cyclotron produced (see article by Wellman in this issue), l~nI is advantageous because it lacks a beta emission, but its extremely low-energy gamma ray limits its applicability for in vivo diagnostic procedures. 13~I has a short half-life but can be obtained efficiently with a commercial generator column from which a supply of the nuclide can be derived by a simple "milking" process.

Technetium 99m (99mTc) as the pertechnetate ion is concentrated in the thyroid gland but it is not organified. 8, 9 The absence of particulate beta radiation and a half-life of only 6 hr make its use particularly suitable for young patients. The radiation dose to the thyroid gland from 1 ~Ci is about 0.2 • 10 .3 rad, a value significantly below that of all the radioisotopes of iodine used in thyroid research. This ion has proved to have special utility in thyroid-scanning techniques, since large doses can be used safely (see discussion by Atkins). Since the nuclide only labels the iodide space of the thyroid, its total concentration in the gland is low and its transit time is short. The favorable gamma energy, the short half-life, and the short transit time more than offset the disadvantage of lack of organic binding. Moreover, iodide trapping is almost invariably a good indicator of total thyroid function. Occasionally, thyroids with metabolic blocks or tumors may have iodide trapping without organification; in these

336 HAYEK AND STANBUBY

instances, 99roTe-labeled pertechnetate has a positive advantage over iodide. This nuclide has the inconvenience however that it is given intravenously. Sterile 99Mo-99mTc generators are now available from commercial firms and overcome the practical difficulties of daily work with a short-half-life radionu- elide. The radiation doses of the most commonly used radionuclides are summarized in Table 1.

THE UPTAKE TEST

The domain of pediatrics extends from the moment of conception. Occa- sionally, a pregnant woman may be exposed inadvertently to a diagnostic dose of radioiodine. One could hardly ignore the questions that arise concerning uptake by the fetal thyroid. Concentration of radioiodine begins at about the 12th week. Thereafter there is a progressive increment of uptake until a maxi- mum of about 5% per g is reached near the 5th month) ~ Immediately after birth and for the first 3 days, the newborn has an elevated radioiodine uptake that may be as high as 70~. 11,12 This is at least partly in accord with the elevated plasma thyrotropin of the neonate) a Even though there is a significant lower- ing of uptake after the 1st week, mean thyroid hormone levels in plasma remain elevated above adult values up to the age of 1 yr) 4 Radioiodine uptake in the normal child rarely exceeds 45g thereafter, but other tests such as the PB 1311 have shown values higher than those of adults in children up to age 4 yr) 5

The radioiodine uptake test as usually performed employs 1 to 5 ~Ci of 131I. \Vith care in positioning, attention to statistical detail, and use of a sensitive crystal, sufficiently accurate results should be obtainable with no more than 1 ~Ci. This dose delivers approximately 8 x 10-5 rad to the gonads, a value substantially less than that received during a 24-hr period from natural radiation.

The normal range of radioiodine uptake may be taken as 20 to 45g of the administered dose at 24 hr, except during early infancy, when the values may be somewhat higher, as already mentioned. This range applies only when the ambient intake of iodine is sufficient to prevent growth of the gland but not so large as to inhibit uptake. In fact, there is a clear relationship between average intake of stable iodine and radioiodine uptake: when intake of iodine is low, the uptake of radioiodine is high, and vice versa. In interpreting a given uptake value, one requires some knowledge of the ingestion of stable iodine either in the diet or as a component of numerous nonprescription drugs,

Table 1.-Comparlson of Radiation Dose of Different Nuclides (rad/gCi) Between Adult and Fetal Thyroid (Adapted from Goolden et al.) 1

Nuclide Adult Fetus

132I 0.017 0.072 125I 1.12 0.085 131I 1.52 0.830 99roTe 0.0002 --*

*Not determined.


such as certain cough syrups. Many contrast substances used in diagnostic radiology also contain large amounts of iodine, and these may reduce radioiodine uptake. A current review of iodine intake in the United States is available, 16 and Pittman et al. 17 have demonstrated a significant decrease in the mean 24-hr uptake in the Birmingham area as a result of the introduction of iodine-containing conditioners in bread-baking by a continuous mixing process.

A high uptake may be expected in association with endemic goiter. Since a deficiency of iodine "~s by far the most common cause of this disorder, there is compensatory growth and increased avidity for the iodine that is available. 18 In addition to geographical considerations, an abnormally high uptake should raise a suspicion of recent or accidental ingestion of goitrogens, and a low uptake might indicate current ingestion of a goitrogen or ingestion of thyroid hormone. In older children, particularly adolescents, antithyroid drugs or tablets of thyroid may be ingested in a suicidal attempt or for other psycho- pathological reasons.

In the absence of iodine deficiency or an excessive intake of iodine, uptake values above 50% are generally indicative of hyperthyroidism, while those below 15~o are consistent with a hypothyroid state. Overlap in the lower ranges of uptake is much more frequent and troublesome than in the higher ranges. Accordingly, the uptake test is of more value in diagnosing hyperthyroidism.

In certain special circumstances, as in the investigation of inherited metabolic blocks in hormone synthesis and in thyrotoxicosis, when the iodine pool in the thyroid gland may be small, measurement of uptake earlier than 24 hr may be informative because the iodine turnover can be so rapid that the uptake value is higher at 4 hr than at 24 hr. To avoid this potential error, in some clinics it has been customary to take readings both at 4 hr and at 24 hr.

Occasionally, routine diagnostic aids are borderline or obscured for various reasons or are not entirely consistent with the clinical pattern. In such an event, the thyroid suppression test may be of considerable value. For this pur- pose, triiodothyronine is administered after an initial uptake has been obtained. The usual dose is 75 ~g/day for 8 to 10 days, but alternative schemes have recommended a shorter period of "suppression." When the triiodothyronine has been given for the appropriate period, a repeat 24-hr uptake test is done and the results compared with the base-line value. The criteria for "suppressibility" have not been uniform, but in general a decrease of at least 509~ below base-line uptake is required as an indication of "normal suppressibility." Failure to suppress is generally accepted as an indication of thyrotoxicosis. Cassidy 1~ has suggested that the suppression test might be useful in prognosticating the outcome of a long course of antithyroid drugs in a patient who has received them for many months or years. Thus, suppressibility would ensure a pro- longed remission or cure after withdrawal of the drug. Absence of suppressibility would indicate persistent disease, early recurrence, or the need for further continuation of therapy. Although this test seems to have prognostic implica- tions in some patients, it fails so often that it has only limited value as a therapeutic guide. Alexander et al. ~0 have employed a 20-min uptake test with intravenous 132I and report that suppression to 8~ uptake or less is consistent

338 H A Y E K AND STANBURY

with remission of thyrotoxieosis. Unfortunately, they have found a 30~o relapse rate in the "suppressed" group. At present this test does not appear to be particularly helpful in prognosticating tile long-term results of a course of antithyroid drug therapy in the treatment of Graves' disease.

In the adult, uptake tests using 99mTc generally separate normal subjects from patients with thyrotoxicosis, ~1,22 and uptake is suppressed in the usual way by administration of exogenous thyroid hormone. 22 The test has not yet been extended widely to pediatric practice.

In theory, the radioactivity in a few nanocuries is ample for accurate measurement of radionuclide uptake in the thyroid. Measurements are complicated by absorption of the emission in the body tissues, the sensitivity of detecting devices, and geometrical factors. One promising solution to the problem of minimizing radiation dosage has been proposed by ~rellman et al. ~3 They utilize a sensitive dual-crystal system and doses as small as 10 ~tCi. Their results suggest that in the near future it may be possible to reduce the dosage to extremely low levels.

One of the problems in measuring radioactive iodine uptake is background radiation emanating from blood perfusing the neck. This problem is particularly troublesome in children because the usual collimator subtends a large fraction of the infant's body. The problem can be corrected in part by a simul- taneous measurement of radiation emanating from the thigh. One must be careful to exclude radiation from any radionuclide that may be present in the bladder or in clothing soiled by urine.

The recent introduction of highly accurate measurements of total ~4 and free thyroxine ~5 in the serum by sensitive binding techniques and equilibrium- dialysis methods has greatly improved the accuracy of diagnosis for thyroid disease in childhood (see article by Murphy). Rapid advances in the methodol- ogy for measuring plasma triiodothyronine 26 have been important additional steps toward precise laboratory diagnosis. The suggestion thus has been made that the availability of these tests should go far in eliminating the need for the radioactive iodine uptake test in the diagnosis of thyrotoxicosis. This may be indeed the case except in the few instances where the values returned to the physician are borderline. On the other hand, when the results are borderline there usually is no need for treatment until the clinical and laboratory findings are unequivocal.

Measurement of radioactive iodine uptake is a necessary prelude to radioactive iodine therapy for thyrotoxicosis. 2v Although the precise level of uptake is not generally employed as a guide to dosage, there are so many instances when uptake is reduced to low values even in the face of thyrotoxicosis that failure to take uptake into account, within broad limits, would raise the possibility of giving the patient a grossly inadequate therapeutic dose.

SCANNING

Scanning of the thyroid is not often needed in infancy or childhood. It may be helpful occasionally in the study of nodules in the thyroid or of aberrant tissue in the neck or elsewhere. In the adult, the conventional dose of lslI


for scanning is from 25 to 50 ~Ci. This delivers an average of 40 to 80 rad to the thyroid, a dose clearly far beyond the permitted 6 rad per year in childhood. Currently. available rectilinear scanning devices require 10 to 20 ~Ci for adequate images when uptake is normal. Although some success has at- tended the use of 1~5I, a pure gamma emitter, its energy is so low that satis- factory resolution may be obtained only with great difficulty or not at all.

Recently the pure photon emitter 99mTc has been introduced for thyroid scanning and offers improvement in the dose-benefit ratio. The nuclide is given intravenously~ The short half-life of 99~Tc and the rapid turnover of pertechnetate in the thyroid allow doses in the millicurie range for low-rad doses to the thyroid. The scans are made with a special collimator system designed to provide high resolution in the presence of low-energ~ photons. 2s In children, the scans are made 30 rain after intravenous administration of the nuclide. An additional modification is the use of the Anger camera to record the display. Further developments are in progress, such as activation scanning with an americium source (described in detail in the article by Hoffer et al.).

The principal application of thyroid scanning in children has been for the evaluation of single thyroid nodules. Except in association with endemic goiter, single nodules of the thyroid are unusual in children and, when present, carry a high risk of malignant change, particularly if the nodules are nonfunc- tioning.29. ~o The opposite condition is the so-called "hot nodule," with activity suppressed in the rest of the gland. One could argue that a wise procedure for precise diagnosis would be either an open or a punch biopsy. It has been the policy of the Children's Service at the Massachusetts General Hospital to scan children with solitary, nodules and to remove the nodules if they prove to be nonfunctional. A report has recently appeared of 99~Tc concentration in a localized follicular carcinoma in the thyroid of an adult. 3I Autoradiographs after removal failed to disclose significant retention of 1~5I. Whether the retention of 99~"Tc in the nodule was artifactual or a biological peculiarity of the particular tumor is not clear in this case. Nonetheless, the finding suggests a need for caution in interpretation of the results of 99"Tc as a guide to subsequent management.

Hung and LoPresti 32 have reported that children with clinical lymphocytic thyroiditis, the most common cause of nontoxic diffuse goiter in the age group, 33 have an "abnormal thyroid scan due to irregular and patchy distribution of radioisotope." The value of scanning is not great in this type of thyroid disease because the same kind of distribution of the radionuclide is seen in a number of thyroid disorders. ~4

It is now well established that hypothyroid children frequently have an aberrant remnant of thyroid tissue, often at the root of the tongue. Scanning could be useful diagnostically in this situation, but the dose of nuclide required is high even with the best instruments available. 99"Tc may prove to be espe- cially valuable for study of this type of patient, as has been reported recently. 35 There are few studies of the use of 99mTc in children, s2.35,~6

In summary, scanning has limited usefulness at present in the study of thyroid disease in infancy and childhood because of dosage limitations, technical diffi-

3,~0 HAYEK AND STANBU'ftY

culties, and the rarity with which the information provided has value in guiding therapy.

Examples of scans utilizing 99mTc are shown in Figs. 1 and 2. Figure 1 is a 'qaot nodule" in the right thyroid lobe with suppression of uptake in the rest of the gland in a 16-yr-old girl. The patient of Fig. 2 had severe myxedema at 12 yr of age. Radioiodine uptake was 2~. After a dose of 1 ~tCi of 99~Tc, the scan demonstrated a normal thyroid silhouette. Such a low uptake would have required an exceedingly high dose of ]31I for a comparable picture.

RADIOIODINE IN METABOLIC EB~ORS

Children rarely have an inherited metabolic error of thyroid function. When errors occur, they usually give rise to hypothyroidism, but growth of a goiter may permit virtually complete compensation for impaired hormone synthesis. To make a firm diagnosis of these disorders, special tests have been devised, s7

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Fig. 1.--99'~Tc pertechnetate photoscan of a 16-yr-old girl with a "hot nodule."


Some of the disorders are described briefly in the following paragraphs. Iodide Transport Defect: This very rare inborn error is characterized by

the inability of the thyroid to trap iodide. The defect is shared by the gastric mucosa and by the salivary glands. Uptake of radioactive iodine is low. The distinctive finding is that the ratio of iodide in the plasma to that in the saliva is 1 or close to 1, whereas normally the saliva contains at least 20 times the iodide concentration of plasma taken at the same time. The same ratio can be demonstrated for iodide in the gastric fluid and in both salivary and gastric fluids with respect to thiocyanate. The test is simple to perform and is diagnostic when a low ratio is observed. Recently a partial defect has been reported. 38

"Peroxidase" Defect: In this disorder, organification of iodide is blocked. q~ae result is an expanded intrathyroid iodide space but little or no accumula- tion of organic, bound iodine. The central laboratory finding is an immediate and profound discharge of accumulated radioiodide after administration of perchlorate or thiocyanate. PB 131I is also absent from the plasma.

Pendred Syndrome: This inherited disorder is characterized by mild to moderate hypothyroidism, goiter, and nerve deafness. It shares with the "peroxidase" defect a pool of iodide in the thyroid which is readily discharge- able with thiocyanate or perchlorate. The defect in organifieation appears not to be as complete as in the "peroxidase" defect.

Dehalogenase Defect: In this disease thyroidal iodide derived from deiodina- tion of iodotyrosine is not reutilized because the enzyme that customarily

Fig. 2.-99mTc pertechnetate photoscan of a 12-yr-old girl with a 3111 uptake of 2~.

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349. HAYEK AND STANBURY

performs the deiodinating function is lacking. The iodotyrosines and their derivations therefore escape into the blood and urine. Characteristically, such patients have a high uptake of radioactive iodine and rapid turnover. Diagnosis is established by identification of labeled mono- and diiodotyrosine in the blood and urine after administration of a suitable dose of radioiodide or by demonstration of a failure to metabolize administered diiodotyrosine.

Other inherited disorders of the thyroid cannot be diagnosed so directly. Among them is a familial insensitivity, to thyrotropic hormone, familial insensitivity to thyroxine, familial failure to synthesize the thyroid-specific protein thyrdglobulin, and familial failure of the immediate precursors of thyroxine and triiodothyronine to undergo the complex coupling reactions that result in the synthesis of these hormones. There are doubtlessly other defects. Precise diagnosis of these diseases generally requires research facilities and the attention of an investigator with a special interest in these problems, The techniques employed are kinetic analysis of iodine metabolism and biochemical analysis of thyroid tissue removed at surgery, or biopsy.

RADIONUCLIDES IN CHILDHOOD THYROID CANCER

The authors have not yet encountered any child who has had a metastatic thyroid cancer that was revealed by studies with radioactive iodine. Although occasionally an adult may have unsuspected metastases of well-differentiated thyroid carcinoma that can be localized in bone, lung, or elsewhere by radioactive iodine, this seems to be a rare occnrrence in childhood. Perhaps the principal reason is that most childhood carcinomas of the thyroid are papillary and do not function as thyroid tissue.

The use of radionuclides in the study of solitary nodules has already been described. The question arises as to whether one should vigorously pursue studies with radioactive iodine in a child in whom a diagnosis of thyroid carcinoma has been established. At the present state of our information, we con- sider the answer to this question to be negative unless the histology of the tumor indicates the presence of follicular elements or of metastatic disease that can be shown to have extended beyond the possibility of surgical attack. In such a patient a full study with radioactive iodine would perhaps be justified. It would include prior stimulation with thyrotropin for several days, followed by scanning after a large dose of radioactive iodine. One would undertake this only after accepting the risk that the incidence of leukemia is significant after radioiodine in the doses required for tumor therapy. The infant or child is also at increased risk of other complications of radiation, such as bone marrow depression and possibly genetic damage.

TSH-STIMULATION TEST FOR THE DIAGNOSIS OF PRIMARY VERSUS

SECONDARY HYPOTHYROIDISM

Assay for TSH in the serum by radioimmunossay a9 is the most direct, simplest, and most sensitive method for differentiating primary hypothyroidism from that resulting from pituitary failure. At present this assay is not generally available, and it may be necessary to resort to the TSH-stimulation test. In this test, I0 units of bovine TSH are given intramuscularly daily for 3 days; uptake is measured prior to the first and immediately after the last TSH dose. When

THYROID DISORDERS OF CHILDHOOD 343

the second uptake is substantially greater than the base-line value, one may assume that the disorder is pituitary in origin; a damaged or absent thyroid fails to respond. A rise in plasma thyroxine is strong confirmatory evidence.

The need for this differential diagnosis arises when hypothyroidism has been established and the thyroid cannot be felt. The test has not been widely applied in infants. I t is qui te possible that a thyroid which had failed to develop because of pituitary failure would also fail to respond to a few days of TSH administration. As a minimum, one would require strong supporting clinical and laboratory evidence for final diagnostic assignment.

THE IODIDE-PERCHLORATE DISCHARGE TEST IN HASHIMOTO'S THYROIDITIS

Recently, Takeuchi et al. 4~ have reported studies on eight adults with Hashimoto's thyroiditis. Positive lSq-discharge tests were obtained when percldorate was given after pre t rea tment with a single dose of 500 ~g of 1271. Normal subjects do not release iodide under similar circumstances.

If further experience establishes the value of this test in the diagnosis of lymphocytic thyroiditis, it might be of value in the differential diagnosis of goiter in the young. Even so, it would provide only supporting evidence, and immunological tests or a biopsy by needle, or both, would be required. The test could surely be done with a far smaller dose than that used by Takeuchi et al. but would still require several microcuries. Perhaps the test could be adapted to 99~Tc pertechnetate.

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6. Dolphin, G. W.: The risk of thyroid cancer following irradiation. Health Phys. 15:219, 1968.

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13. - , and Odell, W. C.: Acute release of thyrotropin in the newborn. J. Clin. Invest. 8:1670, 1969.

14. Danowski, T. S., Johnston, M. S., Price, W. C., McKelvy, M., Stevenson, S. S., and McCluskey, E. R.: Protein-bound iodine in infants from birth to one year of age. Pediatrics 7:240, 1951.

15. Kohlenbrener, R. N., Fields, T., and Kunstadter, R. H.: Thyroid function studies

344 H A Y E K A N D S T A N B U R Y

in children: Normal values for thyroidal 131I uptake and pB1311 uptake and PB131I levels up to the age of 18. J. Clin. Endocr. 17:61, 1957.

16. Oddie, T. H., Fisher, D. A., McCona- hey, W. M., and Thompson, C. S.: Iodine intake in the United States: A reassessment. J. Clin. Endocr. 30:659, 1970.

17. Pittman, J. A., Dailey, G. E., and Beschi, R. J.: Changing normal values for thyroidal radioiodine uptake. New Eng. J. Med. 280:1431, 1969.

18. Stanbury, J. B., Brownell, G. L., Riggs, D., Pernetti, H., Itoiz, J., and Del Castollo, E. B.: Endemic Goiter: The Adap- tations of Man to Iodine Deficiency. Cam- bridge, Harvard University Press, 1954.

19. Cassidy, C. E.: Use of a thyroid suppression test as a guide to prognosis of hyperthyroidism treated with the antithyroid drugs..|. Clin. Endocr. 25:155, 1965.

20. Alexander, W. D., McLarty, D. G., Robertson, J., Shimmins, j., Brownlie, B. E., Harden, R. MEG., and Patel, A. R.: Predic- tion of long-term results of antithyroid drugs for therapy of thyrotoxicosis, j. Clin. Endocr. 30:540, 1970.

21. DeGarreta, A. C., Glass, H. I., and Goolden, A. W.: Measurements of the uptake of 09"To by the thyroid. Brit. J. Radiol. 41 : 896, 1968.

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31. Steinberg, M., Cavalieri, R. R., and Choy, S. H.: Uptake of technetium 99-pertechnetate in a primary thyroid carcinoma: need for caution in evaluating nodules. J. Clin. Endocr. 30:800, 1970.

32. Hung, W., and LoPresti, J. M.: Thyroid scintiscan in children and adolescents with chronic lymphocytic thyroiditis. J. Pediat. 77:302, 1970.

33. Saxena, K. M., and Craw~ord, j. D.: Juvenile lymphocytic thyroiditis. Pediatrics 30:917, 1962.

34. Charles, D.: Limitations of scintilla- tion scanning, I. Pediat. 77:351, 1970.

35. Dodds, W'. J., and Powell, M. R.: Lingual thyroid scanned with technetium- 99m pertechnetate. Report of two cases. Amer. J. Roentgen. 100:786, 1967.

36. Cross, H. E., Hollander, C. S., Rimoin, D. L., and McKusick, V. A.: Familial goi- trous cretinism accompanied by muscular hypertrophy. Pediatrics 41:413, 1968.

37. Stanbury, J. B.: Familial goiter. In: Wyngaarden, j. B., Stanbury, j. B., and Fredrickson, D. S. (Eds.): Metabolic Basis of Inherited Disease (ed. 3). New York, McGraw-Hill, 1971.

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the diagnostic use of radionuclides in the thyroid disorders of childhood

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