- Email: [email protected]
Biological half-time of tritiated water: Comparison of hyperthyroid and hypothyroid patients
Nucl. Med. Eiol. Vol. 13, No. 3, ht. 1. Radiat. Appl. h.Wwn. Printed in Great Britnin
pp. 231-233, 1986
0883.2897/86 s3.00 + 0.00 Pcrg4monJourn& Ltd
Part B
Biological Half-time of Tritiated Water: Comparison of Hyperthyroid and Hypothyroid Patients PETER EBERSTADT’, OFELIA GONZALEZ2 M. VICTORIA GUASTI FERNANDEZ’
and
‘Centro de Estudios Nuckares, Univctidad National Autbnoma de M&X and zclinica de Tiroides de1 Institute National de la Nutricibn, “Salvador Zubiran”, M&co (Received
11 February 1986)
The half-time values of tritiated water were explored in eleven hyperthyroid patienta and in two hypothyroid ona~ For reasona of comparability the numbers are exprcaed in days per square meter (d/m3 of bcdy surface. Against the estimated 5.4 d/m’ in normal subjects, the hyperthy~ok& re&ted 3.9 f 0.66 and the two determinations on hypothyroids were 6.42 and 7.13, qxctively. During the study neither diagnostic nor therapeutic procedures were ever postponed. The half-time values are not representative of extrane conditions in hypcr- or hypothyroids, but are suflkkntly ckar to indiatte well-d&al differences from normal peopk. The total exposure to radiation for the exploratory procedure was minimal, estimated at ltss than 12 mrem for the normal standard man.
IlltdUCtIOll
The earliest determination of the half-time of water on human beings appeared in 1934.“) The study was
carried out with deuterium oxide, using a very ingenuous gravimetric procedure, rendering a value of 9-10 days. During a certain period of years only, subsequent studies with deuterium oxide or tritium oxide on normal subjects gave quite similar results,‘“) depending on a number of factors which have to be taken into account. For example, high ambient temperatures can reduce the ciphers considerably.cn Absolute values under some controlled conditions could not be representative of the desired natural ones. However, a comparative criterion becomes essential if departures from a normal pattern are to he appreciated. Considering differences in height and weight between individuals, a unifying criterion could very well be the half-time of water, related to a square meter of body surface, thus achieving the desired comparability. The square meter values have rendered acceptable linear correlations in well known metabolic studies: the cardiac index can be stated, as well as the glomerular filtration rate for renal functional studies. Since the turnover of water is quite a similar metabolic process, the above proposed criterion should Correspondence should be addressed to: Peter Ebcrstadt, Centro de F-studios Nuckarcs. U.N.A.M. Circuit0 Exterior, C.U. A. Postal 70-543 Mkxico. D.F. MCxico. 231
render fruitful results and indeed has. To infer normal figures, using the above-mentioned proposition, the paper of Richmond et al. was consulted;Q here the given half-time obtained on five normal human subjects of both sexes was 9.46 f0.88 days. The average weight given is 67.3 kg, which is very near to that of the standard man, and assuming a body surface of 1.75 mu0 the half-time value could be estimated as 5.4 days, in good agreement with previous sttKhes.‘r The total radiation dose for a normal standard man with the assumed values and the amounts of Mated water employed would be less than 12 mrem.(‘)
Materials qod Method The 13 subjects being studied for their half-times of tritiated water, were chosen from the Mexican population and were receiving attention in the “Hospital for Nutritional Diseases”; eleven were hyperthyroid and only two hypothyroid. Twelve were female with ages ranging between 17 and 62 years, body weights between 37 and 81.5 kg and body surfaces between 1.24 and 1.74 m2. All body surface areas were determined with the aid of Dubois’ formula. All patients were subjected to a careful clinical study: thyroid uptakes with ‘)‘I including y camera scintiscans, routine laboratory studies, I,(RIA), FT, determinations and also when indicated, TSH determinations and antithyroid antibody studies. Special
232
PETER EBERSTADTet al.
procedures included a pathologic appraisal of a papillary carcinoma in one of the cases who was considered hypothyroid and who also happened to be the last case in the study. When convenient to the managing physician 1 mL of water containing 71 PCi of tritiated water was given orally. Thereafter at regular intervals, urine specimens were collected; the first one 48 h after the tritiated water was given, and then usually at weekly intervals thereafter up to the time significant readings could be obtained, up to periods of 50 days in some cases. The urine samples were processed with an internal standard method@) using liquid scintillation equipment expressing the results in dpm. The half-time values were calculated for each time interval and showed good agreement, although therapeutic effects became evident as time passed, in some cases. To give a general view, however, the least squares method was employed to determine the overall value. The drop in radioactivity follows an exponential law; the values on the ordinates were introduced as natural logarithms. Correlation coefficients were calculated for each case and considered as oxm
is the slope). Results
The results of the study are presented in Table 1 and Fig. 1. Since the majority of cases were hyperthyroid an average was calculated for the half-time values m2 of body surface, being 3.9 f 0.66 days. With one exception (case S), they all belonged to the female sex. In spite of the fact that the t,,r values could vary between sample intervals, probably reflecting changes due to therapeutic measures taken, the individual overall correlations were excellent, practically 0.99 in all hyperthyroid patients studied, and in the two hypothyroids, who were numbered as cases 12 and 13, the first one was a post-thyroiditis case and the second one had a papillary carcinoma. Table I. Results of the study. All but case 5 be1011gedto the female sex. Case-s I to 11 were hypcrthyroids, cases 12 and 13 were hypothyroid Age
Body surface
CaSe
cv)
(m2)
1
62 36 17 32 30 41 26 35
1.24 1.53
2 3 4 5 6 7 8 9 IO 11 12 13
iii 38 50 58
1.42 1.54 1.64 I .47 I .32 1.74 1.50 1.69 1.51 1.78 1.55
5
1 .5
Fig. 1. The ordinates on a logarithic scale represent dpm. Abscissa: time in days. The numerals indicate the biological decay OF I-Hyperthyroids, 2-euthyroids, 3-hypothyroids.
The graph of Fig. 1 does not represent a collection of extreme instances in the pathologic cases, and should not be considered as such.
Discussion
CY (m
10
tv
observed (days)
+lm*
5.06 6.16 5.4 5.48 8.28 3.84 4.80 5.48 6.65 6.91 6.21 11.43 11.05
4.08 4.42 3.80 3.56 5.05 2.61 3.64 3.15 4.43 4.09 4.11 6.42 7.13
Differences of the biological half-time values of tritiated water became quite evident in this study. In the hyperthyroids the values are shortened in comparison to normals, and in the hypothyroids they are lengthened. A clear cut differentiation may become difficult, as in many other tests, if they are to be considered diagnostic. The reference here is made towards borderline cases. The only instance in which some discussion may arise refers to case 5, the only male who had a normal half-time during the entire observation period, and who had really been hyperthyroid but received a therapeutic dose of 13’1and additional medication. The inclusion of this case elevates the general average, which however does not pretend to be characteristic with such a limited number of cases. The implications as viewed on an individual criterion may reflect the severity of Graves’ disease, and inferences towards water turnover rates may well be extended toward electrolyte, mineral and even general metabolism; they may be indicative of the general wear and tear of tissues all over the body, which is no novelty, but may promote a more quantitative approach and further studies using larger sample sizes. The two hypothyroid patients do not represent the extreme cases as athyriosis would, since they received substitution therapy. Here again, a speculative approach towards a new follow-up procedure could shed light upon aspects concerning the optimization of the afore-mentioned substitution therapy, if normal turnover rates are re-acquired. Acknowledgements-The authors wish to express their appreciation to Dr Jorge Maisterrena, head of the Department
Half-time of water in thyroid patients of Endocrinology of the National Institute for Nutritional ~se.a.ses: “Salvador Zubirbn” in Mexico City, has his valuable assistance rendered in making this study possible.
References 1. von Hevesy G. Hofer. Klin. Wochenschr. 13, 1524 (1934). 2. Schloerb P. R., Friis-Hansen B. J., Edelman I. S., Solomon A. K. and Moore F. D. J. Clin Invest. 29, 1296 (1950).
233
3. Pinson E. A. and Langham W. H. J. Appl. Physiol. 10, 108 (1957). 4. Fallot P., Aaberhardt A. and Masson J. Inc. J. Appl. Radiat. Isot. 1, 237 (1957). 5. Foy J. M. and Schnieden H. J. Physiol. 154, 169 (1960). 6. Richmond C. R., Langham W. H. and Trujillo T. T. J. Cell. Camp. Physiolr59, 45 (1962). 7. Koipp A. K., Sweet W. J., Jawetz E., Bigheri E. G. and Roe R. L. Physicians Handbook, p. 683 (Dange Medical
Publications, 1975). 8. Eberstadt P. L. Inr. J. Nucl. Med. Biol. 1, 191 (1974). 9. Blahd W. H. Nuclear Medicine. p. 117. (McGraw-Hill. New York, 1971).
pp. 231-233, 1986
0883.2897/86 s3.00 + 0.00 Pcrg4monJourn& Ltd
Part B
Biological Half-time of Tritiated Water: Comparison of Hyperthyroid and Hypothyroid Patients PETER EBERSTADT’, OFELIA GONZALEZ2 M. VICTORIA GUASTI FERNANDEZ’
and
‘Centro de Estudios Nuckares, Univctidad National Autbnoma de M&X and zclinica de Tiroides de1 Institute National de la Nutricibn, “Salvador Zubiran”, M&co (Received
11 February 1986)
The half-time values of tritiated water were explored in eleven hyperthyroid patienta and in two hypothyroid ona~ For reasona of comparability the numbers are exprcaed in days per square meter (d/m3 of bcdy surface. Against the estimated 5.4 d/m’ in normal subjects, the hyperthy~ok& re&ted 3.9 f 0.66 and the two determinations on hypothyroids were 6.42 and 7.13, qxctively. During the study neither diagnostic nor therapeutic procedures were ever postponed. The half-time values are not representative of extrane conditions in hypcr- or hypothyroids, but are suflkkntly ckar to indiatte well-d&al differences from normal peopk. The total exposure to radiation for the exploratory procedure was minimal, estimated at ltss than 12 mrem for the normal standard man.
IlltdUCtIOll
The earliest determination of the half-time of water on human beings appeared in 1934.“) The study was
carried out with deuterium oxide, using a very ingenuous gravimetric procedure, rendering a value of 9-10 days. During a certain period of years only, subsequent studies with deuterium oxide or tritium oxide on normal subjects gave quite similar results,‘“) depending on a number of factors which have to be taken into account. For example, high ambient temperatures can reduce the ciphers considerably.cn Absolute values under some controlled conditions could not be representative of the desired natural ones. However, a comparative criterion becomes essential if departures from a normal pattern are to he appreciated. Considering differences in height and weight between individuals, a unifying criterion could very well be the half-time of water, related to a square meter of body surface, thus achieving the desired comparability. The square meter values have rendered acceptable linear correlations in well known metabolic studies: the cardiac index can be stated, as well as the glomerular filtration rate for renal functional studies. Since the turnover of water is quite a similar metabolic process, the above proposed criterion should Correspondence should be addressed to: Peter Ebcrstadt, Centro de F-studios Nuckarcs. U.N.A.M. Circuit0 Exterior, C.U. A. Postal 70-543 Mkxico. D.F. MCxico. 231
render fruitful results and indeed has. To infer normal figures, using the above-mentioned proposition, the paper of Richmond et al. was consulted;Q here the given half-time obtained on five normal human subjects of both sexes was 9.46 f0.88 days. The average weight given is 67.3 kg, which is very near to that of the standard man, and assuming a body surface of 1.75 mu0 the half-time value could be estimated as 5.4 days, in good agreement with previous sttKhes.‘r The total radiation dose for a normal standard man with the assumed values and the amounts of Mated water employed would be less than 12 mrem.(‘)
Materials qod Method The 13 subjects being studied for their half-times of tritiated water, were chosen from the Mexican population and were receiving attention in the “Hospital for Nutritional Diseases”; eleven were hyperthyroid and only two hypothyroid. Twelve were female with ages ranging between 17 and 62 years, body weights between 37 and 81.5 kg and body surfaces between 1.24 and 1.74 m2. All body surface areas were determined with the aid of Dubois’ formula. All patients were subjected to a careful clinical study: thyroid uptakes with ‘)‘I including y camera scintiscans, routine laboratory studies, I,(RIA), FT, determinations and also when indicated, TSH determinations and antithyroid antibody studies. Special
232
PETER EBERSTADTet al.
procedures included a pathologic appraisal of a papillary carcinoma in one of the cases who was considered hypothyroid and who also happened to be the last case in the study. When convenient to the managing physician 1 mL of water containing 71 PCi of tritiated water was given orally. Thereafter at regular intervals, urine specimens were collected; the first one 48 h after the tritiated water was given, and then usually at weekly intervals thereafter up to the time significant readings could be obtained, up to periods of 50 days in some cases. The urine samples were processed with an internal standard method@) using liquid scintillation equipment expressing the results in dpm. The half-time values were calculated for each time interval and showed good agreement, although therapeutic effects became evident as time passed, in some cases. To give a general view, however, the least squares method was employed to determine the overall value. The drop in radioactivity follows an exponential law; the values on the ordinates were introduced as natural logarithms. Correlation coefficients were calculated for each case and considered as oxm
is the slope). Results
The results of the study are presented in Table 1 and Fig. 1. Since the majority of cases were hyperthyroid an average was calculated for the half-time values m2 of body surface, being 3.9 f 0.66 days. With one exception (case S), they all belonged to the female sex. In spite of the fact that the t,,r values could vary between sample intervals, probably reflecting changes due to therapeutic measures taken, the individual overall correlations were excellent, practically 0.99 in all hyperthyroid patients studied, and in the two hypothyroids, who were numbered as cases 12 and 13, the first one was a post-thyroiditis case and the second one had a papillary carcinoma. Table I. Results of the study. All but case 5 be1011gedto the female sex. Case-s I to 11 were hypcrthyroids, cases 12 and 13 were hypothyroid Age
Body surface
CaSe
cv)
(m2)
1
62 36 17 32 30 41 26 35
1.24 1.53
2 3 4 5 6 7 8 9 IO 11 12 13
iii 38 50 58
1.42 1.54 1.64 I .47 I .32 1.74 1.50 1.69 1.51 1.78 1.55
5
1 .5
Fig. 1. The ordinates on a logarithic scale represent dpm. Abscissa: time in days. The numerals indicate the biological decay OF I-Hyperthyroids, 2-euthyroids, 3-hypothyroids.
The graph of Fig. 1 does not represent a collection of extreme instances in the pathologic cases, and should not be considered as such.
Discussion
CY (m
10
tv
observed (days)
+lm*
5.06 6.16 5.4 5.48 8.28 3.84 4.80 5.48 6.65 6.91 6.21 11.43 11.05
4.08 4.42 3.80 3.56 5.05 2.61 3.64 3.15 4.43 4.09 4.11 6.42 7.13
Differences of the biological half-time values of tritiated water became quite evident in this study. In the hyperthyroids the values are shortened in comparison to normals, and in the hypothyroids they are lengthened. A clear cut differentiation may become difficult, as in many other tests, if they are to be considered diagnostic. The reference here is made towards borderline cases. The only instance in which some discussion may arise refers to case 5, the only male who had a normal half-time during the entire observation period, and who had really been hyperthyroid but received a therapeutic dose of 13’1and additional medication. The inclusion of this case elevates the general average, which however does not pretend to be characteristic with such a limited number of cases. The implications as viewed on an individual criterion may reflect the severity of Graves’ disease, and inferences towards water turnover rates may well be extended toward electrolyte, mineral and even general metabolism; they may be indicative of the general wear and tear of tissues all over the body, which is no novelty, but may promote a more quantitative approach and further studies using larger sample sizes. The two hypothyroid patients do not represent the extreme cases as athyriosis would, since they received substitution therapy. Here again, a speculative approach towards a new follow-up procedure could shed light upon aspects concerning the optimization of the afore-mentioned substitution therapy, if normal turnover rates are re-acquired. Acknowledgements-The authors wish to express their appreciation to Dr Jorge Maisterrena, head of the Department
Half-time of water in thyroid patients of Endocrinology of the National Institute for Nutritional ~se.a.ses: “Salvador Zubirbn” in Mexico City, has his valuable assistance rendered in making this study possible.
References 1. von Hevesy G. Hofer. Klin. Wochenschr. 13, 1524 (1934). 2. Schloerb P. R., Friis-Hansen B. J., Edelman I. S., Solomon A. K. and Moore F. D. J. Clin Invest. 29, 1296 (1950).
233
3. Pinson E. A. and Langham W. H. J. Appl. Physiol. 10, 108 (1957). 4. Fallot P., Aaberhardt A. and Masson J. Inc. J. Appl. Radiat. Isot. 1, 237 (1957). 5. Foy J. M. and Schnieden H. J. Physiol. 154, 169 (1960). 6. Richmond C. R., Langham W. H. and Trujillo T. T. J. Cell. Camp. Physiolr59, 45 (1962). 7. Koipp A. K., Sweet W. J., Jawetz E., Bigheri E. G. and Roe R. L. Physicians Handbook, p. 683 (Dange Medical
Publications, 1975). 8. Eberstadt P. L. Inr. J. Nucl. Med. Biol. 1, 191 (1974). 9. Blahd W. H. Nuclear Medicine. p. 117. (McGraw-Hill. New York, 1971).