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A new rapid technique for the localization of abnormalities in migration of the thyroid gland
870
Brief clinical and laboratory observations
a congenita! scar occurring as the sole evidence of malformation. It is of interest, however, that 2 of the children reported here each had a close relative who had a cleft lip (a sibling of Patient A. R. and the mother of Patient L. S.). This fact suggests, despite the previous lack of documentation, that this entity may be a minor expression of cleft lip. Further support exists in that Case 3 showed notching of the lip, which is recognized as a microform of cleft lip.
A new rapid technique for the localization of abnormalities in migration of the thyroid gland Fuad S. Ashkar, M.D., ~ Robert Miller, M.D., William M. Smoak, III, M.D., and William W. Cleveland, M.D. MIAMI, FLA.
A z~ o M A L I E S in the pattern of embryogenesis and migration of the human thyroid have frequently led to misdiagnosis as well as to overvigorous therapy. We are presenting 3 pediatric patients who had abnormal migration of the thyroid. These cases demonstrate the usual method in diagnosing this type of thyroid anomaly by conventional scanning procedures and illustrate the usefulness of the thyroid dynamic study, an excellent diagnostic tool with a high diagnostic yield and a low radiation dose exposure to the patient.
From the Division of Nuclear Medicine and the Department of Pediatrics, University of Miami School of Medicine. ~-Reprlnt address: Division of Nuclear M q ~ i ~ Memorial Hospital, Miami, Fla. 33136.
Jackson
The ]ournal o[ Pediatrics May 1971
REFERENCES 1. Schaffer, A. J.: Diseases of the newborn, ed. 2, Philadelphia, 1965, W. B. Saunders Company, p. 804. 2. Einhorn, A. H.: The mouth, in Barnett, H. L., editor: Pediatrics, New York, 1968, Appleton-Century-Crofts, Inc., p. 1648. 3. Arey, L. B.: Developmental anatomy, ed. 7, Philadelphia, 1965, W. B. Saunders Company, p. 207. 4. Patten, B. M.: Human embryology, ed. 3, New York, 1968, McGraw-Hill Book Company, pp. 356-357.
METHOD OF STUDY The patients were investigated with the conventional thyroid scanning procedure, whereby a patient is given an oral dose of 50 /~Ci of 1~I and an uptake and scan are performed 24 hours later on a 3 inch rectilinear scanner? In our thyroid dynamic study, 2 a PhoG a m m a I I I scintillation camera with a 4000hole straight-bore, low-energy collimator is used. T h e patient is seated facing the detector. The neck is extended and positioned so that the chin is at the apex of the collimator and the thyroid cartilage is in the center. The patient can be secured in this position by a piece of tape around the back of the head. A bolus of 5 to 10 mCi. of 99mTc pertechnetate is injected in an anticubital vein. Upon starting the injection, the camera and imaging devices are also started. The 35 ram. and 16 ram. cameras are programmed to image serially for 30 seconds. The 35 turn. camera, when hyperthyroidism is suspected, is programmed to image at 1.0 second intervals; in euthyroid and hypothyroid patients, the 35 ram. camera is programmed to image at 2.5 second intervals. The subclavian vein is the first structure seen after the injection (Fig. 1) ; cardiac pool, lungs, and carotid arteries are seen next. The thyroid is visualized after the carotid arteries are seen. The carotid thyroid time is the interval of time between visualizing the carotid arteries and the appearance of the thyroid gland.
Volume 78 Number 5
Brie[ clinical and laboratory observations
871
Fig. 1. Dynamic thyroid study recording. Image sequence is 2.5 seconds; note the sequential appearance of the subclavian vein, eardiopulmonary structures, carotid arteries, then the thyroid gland. The static scan reveals the gland in normal position in the neck. O t h e r structures in the area can be easily identified, including the submandibular glands and the upper mediastinum; the position of the thyroid in relation to these organs can be easily ascertained (Fig. 1). U p o n completion of the dynamic phase of the study (the first 30 seconds after injection), 3 static images are obtained for an accumulation of 100,000, 200,000, and 300,000 counts, each taking approximately 30 seconds. T h e total time interval for the above procedure is approximately 4 to 6 minutes. Technetium is supplied commercially in generator form as 99mTc pertechnetate. I t is the isotope of choice because of its short half-life of 6 hours, moderately low-energy g a m m a emissions (140 Kev.), virtually no beta emissions, and the fact that it can be efficiently collimated. T h e dose to the thyroid in this procedure is 2 rad as compared to 50 rad when a3aI is used. T h e possibility of administering millicurie quantities of activity without delivering a high radiation dose to the patient allows studies to be performed rapidly and accurately. Because of these
characteristics, the isotope has been widely used as a scanning agent. We have recently had the opportunity to study 3 pediatric patients who had abnormal migration of the thyroid gland. CASE REPORTS
Case 1. A 7-year-old gM was presented to a surgeon with a mass on the base of the tongue. The surgeon recognized this as a possible sublingual thyroid. Uptake of ~31I over the neck was only 3 per cent, yet the patient was clinically euthyroid; the protein-bound iodine was 6 /xg per cent. A dynamic thyroid study was performed on this patient, which also revealed the gland to be located at the base of the tongue; the static image is shown in Fig. 2. Case 2. A 6-year-old boy presented to a pediatrician with a mass in his neck. An 131I scan revealed the lalI concentration along the tract of descent of the thyroid gland. The patient was clinically euthyroid but had a low radioactive iodine uptake of 8 per cent and a protein-bound iodine level of 5 ktg per cent. Case 3. A 4-year-old boy was brought to his pediatrician with a neck mass of 6 months' duration. An 13~I scan of this mass revealed it to be thyroid tissue that had failed to descend corn-
8 7 2 Brief clinical and laboratory observations
The ]ournal o[ Pediatrics May 1971
Fig. 2. Dynamic thyroid study with enlarged static image of a 7-year-old glrl with a sublingual thyroid; note the position of the thyroid between the parotid glands. pletely. Again the patient was clinically euthyroid, with a low radioactive iodine uptake of 10 per cent and a protein-bound iodine level of 7 l~g per cent. DISCUSSION
At one month after conception, the thyroid anlage appears as a thickening of epithelium in the pharyngeal floor. As development continues, the thyroid moves caudally, assumes a bilobate shape, and fuses in the central aspect of the fourth pharyngeal pouch. By 12 weeks the gland is capable of trapping iodine, and by 14 to t5 weeks is able to synthesize thyroid hormone, s, 4 Failure of caudal migration of the human thyroid anlage can result in anomalies of anatomical development. The sublingual thyroid is rare and may be the only functioning thyroid tissue. More commonly, the thyroglossal duct may persist and result in the formation of a thyroglossal duct cyst. The thyroid may terminate its caudal movement anywhere from the tongue to the neck
and may even migrate with the cardiovascular structures and come to occupy a place in the mediastinum. Anomalies in migration of the thyroid frequently result in confusing clinical findings when studied by the conventional scanning method. The typical presentation is a euthyroid patient with a low radioactive iodine uptake. The explanation for this is that the probe is placed over the neck, where the thyroid is expected to be, resulting in a low uptake of aalI. This difficulty, in addition to other disadvantages of the conventional technique, which include high radiation dose to the patient and prolonged technical time, can be circumvented by use of the new procedure, called the dynamic thyroid study, as previously described3 This study demonstrates in a short time and with minimal exposure to radiation all functioning thyroid tissue whether in the neck, mouth, or mediastinum. Ill any child in whom a mass in the tongue or neck is suspected, a thyroid dynamic study
Volume 78 Number 5
will quickly, accurately, and safely demonstrate or rule out the possibility of abnormal thyroid migration.
SUMMARY
Brief clinical and laboratory observations
873
camera; it is fast and accurate and subjects the patient to less radiation than does the conventional technique.
REFERENCES
Three children with abnormal migration of the thyroid are presented. Anomalies of migration of the thyroid can present the physician with confusing clinical findings due to the abnormal position of the gland, which results in false l~I-uptake results and athyroidic scans done by conventional techniques. We are introducing a new method of study called the dynamic thyroid study, utilizing 99roTe pertechnetate and the scintillation
I. Hutchison, R.: In Mason, A. S., editor: The thyroid and its diseases, Philadelphia, 1963, J. B. Lippincott Company, p. 39. 2. Ashkar, F. S.: The dynamic thyroid study: A rapid evaluation of thyroid function and anatomy using 99roTepertechnetate, Southern Med. J. 63: 1365, 1970. 3. Patten, B. M.: Human embryology, New York, 1953, McGraw-Hill Book Company. 4. Boyd, J. D. : Development of the human thyroid gland, in Pitt-Rivers, R., and Trotter, W, R., editors: The thyroid gland, Washington, 1964, Butterworth & Co., Ltd.
Familial selective deficiency
4 members had selective deficiency of IgA; these authors proposed an autosomal dominant mode of inheritance. In an effort to further delineate the possible genetic mechanisms in this disorder, we studied the family of a healthy 10-year-old child who had a selective deficiency of IgA. The findings of numerous aberrations in the serum immunoglobulin levels of family members, ineluding 2 with deficiencies of IgA and one with agammaglobulinemia, strongly suggest that this immune defect was under genetic control.
of IgA Steven D. Douglas, M.D.,* Leonard S. Goldberg, M.D., and H. Hugh Fudenberg, M.D.** SAN
FRANCISCO, CALIF.
F A M I L Y S T O n I ~ S of patients with selective deficiency of IgA have yielded limited and somewhat divergent genetic information. Serum immunoglobulin levels in the immediate family members of these individuals have shown either no abnormalities ~ or only minor aberrations of IgG and IgM levels. 2 More recently, however, Stocker and associates s described a Swiss family in which From the Department o[ Medicine, University of California. Supported in part by grants from the United States Public Health Service (AI-09145) and (GM-15759), and a Clinical Investigationship from the Veterans Administration (Study No. 15-69). *TrMnee in Academic Hematology (United States Public Health .bervice it raining Grant hE-05677). Present address: Department o/Medicine, Mount Sinai School of Medicine of the City University o[ New York, New York, N. Y. **Reprint address: Department o] Medicine, Unlversity oI California, San Francisco, Cali]. 94122.
METHOD Serum immunoglobulin levels were determined by radial immunodiffusion. ~ Normal values (+2 S.D.) for adults were: IgG, 1,200 mg. per 100 ml. (_+490); IgA, 200 mg. per 100 ml. (_+140); and IgM, 110 mg. per 100 ml. (_+80). Normal levels for children were expressed as percentages of the normal adult values as described by Stiehm and Fudenberg? Those sera in which IgA was not detected by radial diffusion were tested in agar gel double diffusion against antiserum monospecific for IgA; this antiserum could detect IgA at a concentration of 38 txg per milliliter. All sera were tested for antiglobulins, antinuclear antibodies and antibodies to thyroid microsomal antigen, adrenal tissue, and gastric parietal cells.
Brief clinical and laboratory observations
a congenita! scar occurring as the sole evidence of malformation. It is of interest, however, that 2 of the children reported here each had a close relative who had a cleft lip (a sibling of Patient A. R. and the mother of Patient L. S.). This fact suggests, despite the previous lack of documentation, that this entity may be a minor expression of cleft lip. Further support exists in that Case 3 showed notching of the lip, which is recognized as a microform of cleft lip.
A new rapid technique for the localization of abnormalities in migration of the thyroid gland Fuad S. Ashkar, M.D., ~ Robert Miller, M.D., William M. Smoak, III, M.D., and William W. Cleveland, M.D. MIAMI, FLA.
A z~ o M A L I E S in the pattern of embryogenesis and migration of the human thyroid have frequently led to misdiagnosis as well as to overvigorous therapy. We are presenting 3 pediatric patients who had abnormal migration of the thyroid. These cases demonstrate the usual method in diagnosing this type of thyroid anomaly by conventional scanning procedures and illustrate the usefulness of the thyroid dynamic study, an excellent diagnostic tool with a high diagnostic yield and a low radiation dose exposure to the patient.
From the Division of Nuclear Medicine and the Department of Pediatrics, University of Miami School of Medicine. ~-Reprlnt address: Division of Nuclear M q ~ i ~ Memorial Hospital, Miami, Fla. 33136.
Jackson
The ]ournal o[ Pediatrics May 1971
REFERENCES 1. Schaffer, A. J.: Diseases of the newborn, ed. 2, Philadelphia, 1965, W. B. Saunders Company, p. 804. 2. Einhorn, A. H.: The mouth, in Barnett, H. L., editor: Pediatrics, New York, 1968, Appleton-Century-Crofts, Inc., p. 1648. 3. Arey, L. B.: Developmental anatomy, ed. 7, Philadelphia, 1965, W. B. Saunders Company, p. 207. 4. Patten, B. M.: Human embryology, ed. 3, New York, 1968, McGraw-Hill Book Company, pp. 356-357.
METHOD OF STUDY The patients were investigated with the conventional thyroid scanning procedure, whereby a patient is given an oral dose of 50 /~Ci of 1~I and an uptake and scan are performed 24 hours later on a 3 inch rectilinear scanner? In our thyroid dynamic study, 2 a PhoG a m m a I I I scintillation camera with a 4000hole straight-bore, low-energy collimator is used. T h e patient is seated facing the detector. The neck is extended and positioned so that the chin is at the apex of the collimator and the thyroid cartilage is in the center. The patient can be secured in this position by a piece of tape around the back of the head. A bolus of 5 to 10 mCi. of 99mTc pertechnetate is injected in an anticubital vein. Upon starting the injection, the camera and imaging devices are also started. The 35 ram. and 16 ram. cameras are programmed to image serially for 30 seconds. The 35 turn. camera, when hyperthyroidism is suspected, is programmed to image at 1.0 second intervals; in euthyroid and hypothyroid patients, the 35 ram. camera is programmed to image at 2.5 second intervals. The subclavian vein is the first structure seen after the injection (Fig. 1) ; cardiac pool, lungs, and carotid arteries are seen next. The thyroid is visualized after the carotid arteries are seen. The carotid thyroid time is the interval of time between visualizing the carotid arteries and the appearance of the thyroid gland.
Volume 78 Number 5
Brie[ clinical and laboratory observations
871
Fig. 1. Dynamic thyroid study recording. Image sequence is 2.5 seconds; note the sequential appearance of the subclavian vein, eardiopulmonary structures, carotid arteries, then the thyroid gland. The static scan reveals the gland in normal position in the neck. O t h e r structures in the area can be easily identified, including the submandibular glands and the upper mediastinum; the position of the thyroid in relation to these organs can be easily ascertained (Fig. 1). U p o n completion of the dynamic phase of the study (the first 30 seconds after injection), 3 static images are obtained for an accumulation of 100,000, 200,000, and 300,000 counts, each taking approximately 30 seconds. T h e total time interval for the above procedure is approximately 4 to 6 minutes. Technetium is supplied commercially in generator form as 99mTc pertechnetate. I t is the isotope of choice because of its short half-life of 6 hours, moderately low-energy g a m m a emissions (140 Kev.), virtually no beta emissions, and the fact that it can be efficiently collimated. T h e dose to the thyroid in this procedure is 2 rad as compared to 50 rad when a3aI is used. T h e possibility of administering millicurie quantities of activity without delivering a high radiation dose to the patient allows studies to be performed rapidly and accurately. Because of these
characteristics, the isotope has been widely used as a scanning agent. We have recently had the opportunity to study 3 pediatric patients who had abnormal migration of the thyroid gland. CASE REPORTS
Case 1. A 7-year-old gM was presented to a surgeon with a mass on the base of the tongue. The surgeon recognized this as a possible sublingual thyroid. Uptake of ~31I over the neck was only 3 per cent, yet the patient was clinically euthyroid; the protein-bound iodine was 6 /xg per cent. A dynamic thyroid study was performed on this patient, which also revealed the gland to be located at the base of the tongue; the static image is shown in Fig. 2. Case 2. A 6-year-old boy presented to a pediatrician with a mass in his neck. An 131I scan revealed the lalI concentration along the tract of descent of the thyroid gland. The patient was clinically euthyroid but had a low radioactive iodine uptake of 8 per cent and a protein-bound iodine level of 5 ktg per cent. Case 3. A 4-year-old boy was brought to his pediatrician with a neck mass of 6 months' duration. An 13~I scan of this mass revealed it to be thyroid tissue that had failed to descend corn-
8 7 2 Brief clinical and laboratory observations
The ]ournal o[ Pediatrics May 1971
Fig. 2. Dynamic thyroid study with enlarged static image of a 7-year-old glrl with a sublingual thyroid; note the position of the thyroid between the parotid glands. pletely. Again the patient was clinically euthyroid, with a low radioactive iodine uptake of 10 per cent and a protein-bound iodine level of 7 l~g per cent. DISCUSSION
At one month after conception, the thyroid anlage appears as a thickening of epithelium in the pharyngeal floor. As development continues, the thyroid moves caudally, assumes a bilobate shape, and fuses in the central aspect of the fourth pharyngeal pouch. By 12 weeks the gland is capable of trapping iodine, and by 14 to t5 weeks is able to synthesize thyroid hormone, s, 4 Failure of caudal migration of the human thyroid anlage can result in anomalies of anatomical development. The sublingual thyroid is rare and may be the only functioning thyroid tissue. More commonly, the thyroglossal duct may persist and result in the formation of a thyroglossal duct cyst. The thyroid may terminate its caudal movement anywhere from the tongue to the neck
and may even migrate with the cardiovascular structures and come to occupy a place in the mediastinum. Anomalies in migration of the thyroid frequently result in confusing clinical findings when studied by the conventional scanning method. The typical presentation is a euthyroid patient with a low radioactive iodine uptake. The explanation for this is that the probe is placed over the neck, where the thyroid is expected to be, resulting in a low uptake of aalI. This difficulty, in addition to other disadvantages of the conventional technique, which include high radiation dose to the patient and prolonged technical time, can be circumvented by use of the new procedure, called the dynamic thyroid study, as previously described3 This study demonstrates in a short time and with minimal exposure to radiation all functioning thyroid tissue whether in the neck, mouth, or mediastinum. Ill any child in whom a mass in the tongue or neck is suspected, a thyroid dynamic study
Volume 78 Number 5
will quickly, accurately, and safely demonstrate or rule out the possibility of abnormal thyroid migration.
SUMMARY
Brief clinical and laboratory observations
873
camera; it is fast and accurate and subjects the patient to less radiation than does the conventional technique.
REFERENCES
Three children with abnormal migration of the thyroid are presented. Anomalies of migration of the thyroid can present the physician with confusing clinical findings due to the abnormal position of the gland, which results in false l~I-uptake results and athyroidic scans done by conventional techniques. We are introducing a new method of study called the dynamic thyroid study, utilizing 99roTe pertechnetate and the scintillation
I. Hutchison, R.: In Mason, A. S., editor: The thyroid and its diseases, Philadelphia, 1963, J. B. Lippincott Company, p. 39. 2. Ashkar, F. S.: The dynamic thyroid study: A rapid evaluation of thyroid function and anatomy using 99roTepertechnetate, Southern Med. J. 63: 1365, 1970. 3. Patten, B. M.: Human embryology, New York, 1953, McGraw-Hill Book Company. 4. Boyd, J. D. : Development of the human thyroid gland, in Pitt-Rivers, R., and Trotter, W, R., editors: The thyroid gland, Washington, 1964, Butterworth & Co., Ltd.
Familial selective deficiency
4 members had selective deficiency of IgA; these authors proposed an autosomal dominant mode of inheritance. In an effort to further delineate the possible genetic mechanisms in this disorder, we studied the family of a healthy 10-year-old child who had a selective deficiency of IgA. The findings of numerous aberrations in the serum immunoglobulin levels of family members, ineluding 2 with deficiencies of IgA and one with agammaglobulinemia, strongly suggest that this immune defect was under genetic control.
of IgA Steven D. Douglas, M.D.,* Leonard S. Goldberg, M.D., and H. Hugh Fudenberg, M.D.** SAN
FRANCISCO, CALIF.
F A M I L Y S T O n I ~ S of patients with selective deficiency of IgA have yielded limited and somewhat divergent genetic information. Serum immunoglobulin levels in the immediate family members of these individuals have shown either no abnormalities ~ or only minor aberrations of IgG and IgM levels. 2 More recently, however, Stocker and associates s described a Swiss family in which From the Department o[ Medicine, University of California. Supported in part by grants from the United States Public Health Service (AI-09145) and (GM-15759), and a Clinical Investigationship from the Veterans Administration (Study No. 15-69). *TrMnee in Academic Hematology (United States Public Health .bervice it raining Grant hE-05677). Present address: Department o/Medicine, Mount Sinai School of Medicine of the City University o[ New York, New York, N. Y. **Reprint address: Department o] Medicine, Unlversity oI California, San Francisco, Cali]. 94122.
METHOD Serum immunoglobulin levels were determined by radial immunodiffusion. ~ Normal values (+2 S.D.) for adults were: IgG, 1,200 mg. per 100 ml. (_+490); IgA, 200 mg. per 100 ml. (_+140); and IgM, 110 mg. per 100 ml. (_+80). Normal levels for children were expressed as percentages of the normal adult values as described by Stiehm and Fudenberg? Those sera in which IgA was not detected by radial diffusion were tested in agar gel double diffusion against antiserum monospecific for IgA; this antiserum could detect IgA at a concentration of 38 txg per milliliter. All sera were tested for antiglobulins, antinuclear antibodies and antibodies to thyroid microsomal antigen, adrenal tissue, and gastric parietal cells.