I N A recently concluded statistical analysis of pertechnetate versus iodine

Transcription

1 AUGUST, 1911 THYRODAL PERTECHNETATE UPTAKE N HASHMOTO S DSEASE* Downloaded from by on 08/23/18 from P address Copyright ARRS. For personal use only; all rights reserved By WOLFGANG HAUSER, M.D., HAROLD L. ATKNS, M.D., WLLAM C. ECKELMAN, PH.D., and POWELL RCHARDS, B.S. N A recently concluded statistical analysis of pertechnetate versus iodine 131 for the diagnosis of thyroid function, we have suggested that technetium 99 is the most suitable radionuclide for routine clinical thyroid studies.3 The diagnostic accuracv of thvroidal pertechnetate uptakes is at least as good as that of 24 hour radioiodine uptakes, and technetium 99 p05- sesses advantages over the various radioiodines in thyroid diagnostic procedures in terms of availability, cost, rapidity with which information can be obtained and, above all, low patient radiation dose. n this report we wish to present the data of all the patients with chronic thyroiditis which had been omitted from the study mentioned above. n patients with chronic thyroiditis there are several metabolic abnormalities which lead to discrepancies in the results ofvarious thyroid function tests, and which had made it, therefore, inadvisable to include these data in the abovementioned statistical analysis. n an earlier report on the assessment of thyroid function with technetium 99 as pertechnetate, it had been noted that the pertechnetate uptake b the thyroid is elevated above the range of normal in patients with hvperthvroidism and also in patients with thyroiditis.4 Since then, it has been found that some euthyroid patients who are taking oral contraceptive medication also have elevated pertechnetate uptakes.3 The purpose of the present report is to amplify the previously noted observation and to discuss the metabolic abnormality in the patients who had high pertechnetate uptakes but who were neither hyperthyroid nor taking oral contraceptive medication. UPTON, NEW YORK To complete the picture, all other patients who have had a definite diagnosis of chronic thyroiditis will also be described. MATERAL AND METHOD. SUBJECTS Nineteen patients are included in this study. Eight of them have had the diagnosis of Hashimoto s thyroiditis confirmed by surgery or by the finding of high antithyroglobulin antibody titers in the serum. The other patients had elevated thyroidal pertechnetate uptakes but were not hyperthyroid and did not take any medication containing estrogens. Like most of our patients, they had been referred as outpatients for thyroid scannings because of an enlarged and/or nodular thyroid gland. Before the scanning and uptake studies a diagnosis of the functional state of the thyroid was made on the basis of signs and symptoms. The laboratory data shown in Table were used for confirmation of that diagnosis.. PROCEDURES Thyroid scanning was started about minutes after the intravenous administration of millicuries of Tc99m04. mmediately after the patient was scanned, the pertechnetate uptake was determined by scanning a phantom containing 3 per cent of the dose given to the patient. The method for the calculation of the thyroidal pertechnetate uptake has been described before.. - Measurements of protein-bound iodine (PB), thyroxine iodine (T4-) an(l cholesterol were performed on serum obtained at the time of the thyroid scanning. odine * From the Medical Research Center and Department of Applied Science, Brookhaven National Laboratory, Upton, New York. Research supported by the United States Atomic Energy Commission. 720

2 VOL. 112, No. Thyroidal Pertechnetate Uptake in Hashimoto s Disease 72! Downloaded from by on 08/23/18 from P address Copyright ARRS. For personal use only; all rights reserved 131 thyroidal uptakes were measured at 24 hours, and the PBP3 values were determined 72 hours after the oral administration of the tracer. Standard laboratory procedures were carried out for all the tests listed above except for the PB 3 which was determined by the following technique: the free iodide was separated from the proteinbound iodide by use of a Dowex 5o anion exchange resin. One ml. of the resin was packed into a 2.5 ml. disposable syringe and equilibrated with isotonic saline. Two ml. of a plasma sample was adsorbed to the column followed by i ml. of saline wash. Three additional ml. of saline were added to further wash the column. The saline washes and the column were counted to determine the protein-bound iodide. Circulating antibodies to thyrogiobulin were measured by agglutination of formolized thyroglobulin-coated sheep cells.8 Patient RESULTS The results of all in vivo and in vitro Age (yr.) Histology+. DR i6 2. MK Circulating TABLE studies are shown in Table i. The patients are separated into 3 groups. Group i (Cases and 2) includes 2 patients in whom the clinical diagnosis ofhashimoto s thyroiditis was confirmed by histologic examination and who had little or no thyroid autoantibodies in their serum. n the 6 patients in Group! (Cases 3-8) the clinical diagnosis of Hashimoto s thyroiditis was supported by the presence of thyroid autoantibodies in high titers in the serum. The patients in Group (Cases 9-19) are those who had high pertechnetate uptakes but no histologic diagnosis and either no thyroid autoantibodies or no determination for them. The data for these 3 groups are summarized in Table, in which they are shown together with the findings in a control group of 53 patients with nontoxic nodular goiter. AGE AND SEX All 19 patients are women. The age range in the groups is similar. n Groups and it is years, and in Group, RESULTS OF N VVO AND N VTRO THYROD FUNCTON TESTS Duration Symptoms Mo. Yr. of Uptake Radioiodine Studies Serum 24 Hour Uptake 72 Hour PB! Antithyroglobulin Cholesterol (mg./oo ml.) PB! (Mg./oo ml.) Tel (,ig./100 ml.) TcsSmO4- Normal Range <0.! < 50 ntibodies+ 3. EN LF MWa CM FL 5 8. ML 36 Tc 04 LTptake 9. CC BK 30. JD RR KM CP,8 5. RD 31 i6. MB so 17. LH 26,8. MWe o 19. JZ >20 >15 > S? i z o.o o oil 0.05) o.o ! o i ,192 1:25,000 1:1, ,000 1:250,000 1:512 1:25 1:25 Titer

3 722 Hauser, Atkins, Eckelman and Richards AUGUST, 1971 TABLE COM ARSON OF THE RESULTS OF THYROD FUNCTON TESTS N 19 PAENTS WTH HASHMOTO S 1HYROD115 WTH THOSE OBTANED N 53 PATENTS WTH NONTOXC NODULAR GOTER Downloaded from by on 08/23/18 from P address Copyright ARRS. For personal use only; all rights reserved \ontoxic goiter (53)* nodular Groups and 11(8) (;roj) () Tc99#{176}04Uptakes.69±o.77t 3.98 ± 2.09 (o.ooi) 6.05 ± Groups, 11 and 5.18± ±14.3 lpl 26.0± 7.2 (l.5r ±13.0 (NS) 4.5 ± 14.9 combined (19) (o.ool) (0.025) * No. of patients in group. t Mean ±50. Probability that the value in the test group is identical with the corresponding value in the control group NS = Not significant (p= o.o) s ears. Patients and 7 are daughter and mother. CLNCAL FNDNGS Of the 9 patients examined, 5 had consuited their referring physician because of the goiter- the other because of symptoms of hypothyroidism. Almost all patients could give a date on which they first noticed the goiter. n most patients the thyroid enlargement was readily noticeable; the enlargement was usually estimated to be 2-4 times normal size. On physical examination the glands were generally firm and diffusely enlarged. The scans, however, not infrequently showed irregular distribution of radioactivity without any defmite nodule formation. LABORATORY FNDNGS The results of the serum PB, T4- and cholesterol generally confirmed the clinical impression of eu- or hypothyroidism. A PB-T4- difference of greater than 1.5 jg./ 100 ml. was found in only 2 patients. Since all our patients had been referred for scanning only, no extensive investigati()n was (lone before this pattern of high pertechnetate uptake in eu- or hypothyroid patients was recognized. Tests for thyroid autoantibodies and PB 3 values were obtaine(l only recently. n 3 patients neither 1131 Uptakes (0.01) ± ±1.5 ll 5.0± ± ±0.9 study was done. Out of7 patients in Group, in whom iodide turnover studies were carried out, PB 3 values were found to be above the normal range in 4 patients; out of4 patients with elevated antibody titers, 2 were found to have elevated PB 3 values. The 2 patients who underwent surgery (Group i) had normal antibody titers; 6 patients (Group ) had elevated titers; and 9 patients in Group with high pertechnetate uptakes had no elevation of antibody titers. ODDE AND PERTECHNET.AE METABOLSM Table iii shows a comparison of the data obtained. Of the 8 patients in Groups i and, 4 had normal and had elevated pertechnetate uptakes. Six patients in Groups and ii had normal 24 hour iodide uptakes; however, of them had a high 72 hour PBP3 value. Of the remaining 2 patients in Groups and ii, i had a low and the other had an elevated iodide uptake. The PBP3 value in the patient with the low Uptake was, on the other hand, elevated. The patients in Group iii were selected because they had high pertechnetate uptakes. Eight of patients in that group had normal 24 hour iodide uptakes; of the 8 patients had elevated 72 hour PB 3 values. Two patients in Group T! had ele-

4 VoL. 112, No. Thvroidal Pertechnetate Uptake in Hashimoto s Disease 723 TABLE COMPARSON OF THE RESULTS OF ERTECHNETATE UPTAKES WTH THOSE OF ODDE UPTAKES AND PB1131 Tc 910Qr Uptake j131 Uptake PB 3 Downloaded from by on 08/23/18 from P address Copyright ARRS. For personal use only; all rights reserved Groups and 11 Euthvroid ()* Hypothyroid (3) Group Euthyroid () Hypothyroid (4) * No. of patients in group. vated iodide uptakes, in i of them in whom it was examined, the PBP31 was normal. DSCUSSON The concept that Hashimoto s struma and acquired hypothyroidism represent clinical variants of the same disease process,#{176} or that the former may lead to the latter 4 makes it important that goiters due to this disease process are definitely separated from goiters due to other causes, particularly from the more commonly occurring nontoxic nodular goiter dii?o Unknown cause. 2 t is generally considered that the clinical diagnosis of Hashimoto s thyroiditis should be confirmed on the basis of: (i) a biopsy; (2) demonstration of thyroid autoantibodies; (3) a TSH (thyroid stimulating hormone) test; and/or ( 4) discrepancies in the results of various thyroid function tests. When the first of the patients described in this series was seen, the pertechnetate uptake had not been firmly established as a thyroid function test in this laboratory, and, therefore, the diagnosis of Hashimoto s thyroiditis was only suggested because of the clinical symptoms and signs. n a recent summary of our experience3 we have now shown that the pertechnetate uptake is at least as good an indicator of thyroid function in eu- and hyperthyroid patients as is the iodide uptake. n this study we would like to draw attention to the discrepancy in the results of Normal Elevated Normal or Low Normal Elevated the pertechnetate uptake and other thyroid function tests in patients with chronic thyroiditis. Table iii shows that in 6 out of 8 patients with a definite diagnosis of Hashimoto s thyroiditis (Groups i and ii) there was a discrepancy between the pertechnetate uptake and the functional state of the thyroid gland. Although the diagnosis of the patients in Group H is not confirmed by the same criteria listed above, Table shows that the results of the thyroid function tests in this group are similar to those in Groups i and ii, and significantly different from those found in a group of patients with simple nontoxic nodular goiter. n Table iii it is shown, in addition, that hypothyroid patients had high pertechnetate uptakes and normal iodide uptakes, and that, of 7 euthyroid patients, 2 had elevated PB113 values; i.e., in 4 of these 7 patients an abnormality in the conventional iodide studies could also be demonstrated. This leaves only 3 patients (Cases 12, 13 and 15) in whom the pertechnetate uptake was the only abnormalitsr. n summary, then, we have found that there is a discrepancy between the results of the pertechnetate uptake and the functional state of the thyroid gland in 6 out of 8 patients with Hashimoto s thyroiditis, confirmed by histology or elevated antibody titer. n a second group of other patients with a clinical diagnosis of Hashimoto s disease, the elevated pertechnetate uptake was associated with irregular results

5 724 Flauser, Atkins, Eckelman and Richards AUGUST, 1971 Downloaded from by on 08/23/18 from P address Copyright ARRS. For personal use only; all rights reserved of iodide metabolism studies in 8 patients. The finding of an elevated pertechnetate uptake in patients with Hashimoto s thyroiditis is not surprising in view of the known elevation of serum TSH levels in hypothyroid patients. 5 9 TSH plays a main role in the regulation of thyroidal iodide transport,1#{176} and pertechnetate is trapped to an extent almost identical to iodide in the thyroid gland.2 The results of the radioiodine uptake in Hashimoto s thyroiditis have been more variable, probably because of a decreased iodine pool in the thyroid gland,1 defective iodide organification, 3 and a subsequent rapid turnover of iodide in the gland.7 Early hour uptakes have, however, shown good correlation with elevated TSH levels.9 Our study would suggest that pertechnetate uptakes probably correlate more closely with TSH levels than radioiodide uptakes. The routine use of the pertechnetate uptake as a test of thyroid function has not been found to be a problem because the time required for calculations is only about 2-3 minutes and the time needed for the additional scanning of the phantom is short. Scannings of the thyroid gland with pertechnetate take less over-all time than those with iodide because a larger dose o the radionuclide can be administered, while the radiation dose absorbed by the thyroid gland is considerably lower.3 The importance of our observation is two-fold: (i) it gives another indicator for the confirmation of Hashimoto s thyroiditis, so that the diagnosis can be established without surgery; and (2) it enables identification of individuals who, although euthyroid at the time of the examination, should be followed closely because of the possibility of the development of hypothyroidism. S UMM A RY Two conditions other than hyperthroidism will lead to an elevation of the thyroidal pertechnetate uptake. The first situation is in patients taking medication containing estrogens. The second situation is in patients with chronic thyroiditis. n patients with this disorder the pertechnetate uptake was consistently higher than expected from over-all thyroid function. n 19 patients the mean pertechnetate uptake was 5.18 ± 2.73 per cent compared to a mean of 1.69 ±0.77 per cent in 53 patients with nontoxic nodular goiter. This finding is of importance because it aids in the diagnosis of Hashimoto s disease without surger and it allows identification of individuals who may become hypothyroid in the future. Wolfgang Hauser, M.D. Medical Department Brookhaven National Laboratory Upton, L.., New York RE FERENCES. ADAMS, D. D., and KENNEDY, T. H. Measurements of thyroid stimulating hormone content ofserum from hypothyroid and euthyroid people. 7. Clin. Endocrinol., 1968, 28, ANDROS, G., HARPER, P. V., LATHROP, K. A., and MCCARDLE, R. J. Pertechnetate-99m localization in man with application to thyroid scanning and study of thyroid physiology. 7. Clin. Endocrinol., 1965, 25, ATKNS, H. L., HAUSER, W., and RCHARDS, P. Pertechnetate-99m versus iodine-131 for thyroid diagnosis. To be published. 4. ATKNS, H. L., and RCHARDS, P. Assessment of thyroid function and anatomy with technetium-99m as pertechnetate. 7. Nuclear Med., 1968, 9, BONNYNS, M., and BASTENE, P. A. Serum thyrotrophin in myxedema and in asymptomatic atrophic thyroiditis. 7. C/in. Endocrinol., 1967, 27, BUCHANAN, W. W., and HARDEN, R. MCG. Primary hypothyroidism and Hashimoto s thyroiditis. 7. C/in. Endocrinol., 1961, 2!, 8o6-8i6. 7. BUCHANAN, W. W., KOUTRAS, D. A., ALEX- ANDER, W. D., CROOKS, J., RCHMOND, M. H., MACDONALD, E. M., and WAYNE, E. J. odine metabolism in Hashimoto s thyroiditis. 7. C/in. Endocrino/., 1961, 2!, 8o6-8i6. 8. FULTHORPE, A. J., ROTT,. M., DONACH, D., and COUCHMAN, K. Stable sheep cells preparation for detecting thyroglobulin auto-antibodies and its clinical application. 7. C/in. Path., 1961, 14, GREENBERG, A. H., CZERNCHOW, P., HUNG, W., SHELLEY, W., WNS-P, T., and BLZZARD, R. M. Juvenile chronic lymphocytic thy-

6 VoL. 112, No. Thyroidal Pertechnetate Uptake in Hashimoto s Disease 725 Downloaded from by on 08/23/18 from P address Copyright ARRS. For personal use only; all rights reserved roiditis: clinical, laboratory and histological correlation. 7. C/in. Endocrinol., 1970, 30, JO. HALM, N. S. Thyroidal odide Transport: Vitamins and Hormones. Academic Press, nc., New York, 1961, 19, KVKANGAS, V., LAMBERG, B. A., and MXENPA, J. Thyroidal iodine and proteins in autoimmune thyroiditis. Scandinav. 7. C/in. & Lab. nvest., 1970, 25, LNG, S. M., KAPLAN, S. A., WETZMANN, J. J., REED, G. B., COSTN, G., and LANDNG, B. H. Euthyroid goiters in children: correlation of needle biopsy with other clinical and laboratory findings in chronic lymphocytic thyroiditis and simple goiter. Pediatrics, 1969, 44, TAKEUCH, K., SUZUK, H., HORUCH, Y., and MA5HM0, K. Significance of iodide-perchlorate discharge test for detection of iodine organification defect of thyroid. 7. C/in. Endocrino/., 1970,31, WNTER, J., EBERLEN, W. R., and BoNclo- VANN, A. M. Relationship of juvenile hypothyroidism to chronic lymphocytic thyroiditis. 7. Pediat., 1966, 69,

7 This article has been cited by: Downloaded from by on 08/23/18 from P address Copyright ARRS. For personal use only; all rights reserved 1. Maria S. Sucupira, Edwaldo E. Camargo, Eileen L. Nickoloff, Philip O. Alderson, Henry N. Wagner The role of 99mTc pertechnetate uptake in the evaluation of thyroid function. nternational Journal of Nuclear Medicine and Biology 10:1, [CrossRef] 2. James R. Hurley Thyroiditis. Disease-a-Month 24:3, [CrossRef] 3. P.H. Wise, A. Ahmad, P.E. Harding, R.B. Burnet NTENTONAL RADOODNE ABLATON N GRAVES' DSEASE. The Lancet 306:7947, [CrossRef]