58 part by grant AM02375 from the National Institute of Arthritis and Metabolic Diseases and the Fluid Research Fund, Children’s Hospital of Los Angeles.
Requests for reprints should be addresses to R.B.E., Department of Surgery, University of California, Los Angeles, California 90024,
related to changes in free hormones or binding proteins. Adrenal glucocorticoids may have a pathophysiological role in modulating the peripheral metabolism of thyroid hormones in stress.
U.S.A.
Introduction REFERENCES 1. Patel, R., Terasaki, P. I. New Engl. J. Med. 1969, 280, 735. 2. Terasaki, P. I., Marchioro, T. H., Starzl, T. E. in Conference on Histocompatibility Testing (edited by P. S. Russel and H. J. Winn); p.83. Washington D.D., 1965. 3. Terasaki, P. I., Kreisler, M., Mickey, R. M. Postgrad. med. J. 1971, 47, 89. 4. Beleil, O. M., Mickey, M. R., Terasaki, P. I. Transplantation, 1972, 13, 493. 5. Myburgh, J. A., Maier, G., Smit, J. A., Shapiro, M., Meyers, A. M., Rabkin, R., van Blerk, P. J. P., Jersky, J. ibid. 1974, 18, 213. 6. Winchester, R. J., Fu, S. M., Wernet, P., Kunkel, H. G., Dupont, B., Jersild, C. J. exp. Med. 1975, 141, 924. 7. Ting, A., Mickey, M. R., Terasaki, P. I. ibid. 1976, 143, 981. 8. van Rood, J. J., van Leeuwen, A., Keuning, J. J., Blusse van Oud Alblas, Tissue Antigens, 1975, 5, 73. 9. Arbeit, R. D., Sachs, D. H., Amos, D. B., Dickler, H. B. J. Immun. 1975, 10.
reported an acute fall in serum-3,3’,5-triiodothyronine (T3) concentration and acute rise in serum-3,3’,5’-triiodothyronine (reverse T3 or rT3) concentration after surgical operation.’ Similar findings have been reported in various diseases2 and after caloric restriction.3 It was suggested that the peripheral monodeiodination of thyroxine (T4) might be altered in the above conditions, with an increase in peripheral deiodination from the tyrosyl ring and reduced deiodination from the phenolic ring. This would lead to increased formation of metabolically inactive rT3 4and decreased formation of metabolically active T3. The factors governing peripheral formation of rT3 and T3 are not yet understood, but several of the conditions in which high rT3 concentrations have been WE have
115, 117. Ettenger, R. B., Terasaki, P. I., Ting, A., Malekzadeh, M. H., Pennisi, Uittenbogaart, C., Fine, R. N. New Engl. J. Med. (in the press).
A.
J.,
Davies, D. A. L., Alkins, B. J. Nature, 1974, 247, 295. Soulillou, J. P., Carpenter, C. B., d’Apice, A. J. F., Strom, T. B. J. exp. Med. 1976, 143, 405. 13. Terasaki, P. I., McClelland, J. D. Nature, 1974, 204, 998. 14. Ting, A., Hasegawa, T., Ferrone, S., Reisfield, R. A. Transplantn Proc.
11. 12.
1973, 5, 813. Ting, A., Terasaki, P. I. Lancet, 1975, i, 304. Williams, G. M., Hume, D. M., Hudson, R. P., Morris, P. J., Kano, K., Milgrom, F. New Engl. J. Med. 1968, 279, 611. 17. Mittal, K. K., Mickey, M. R., Singal, D. P., Terasaki, P. I. Transplantation, 1968, 6, 913. 18. Nelken, D., Cohen, I., Furcaig, I. ibid. 1970, 10, 346. 19. Gibofsky, A., Terasaki, P. I. ibid. 1972, 15, 192. 20. Rogentine, G. N., Plocinik, B. A. ibid. 1967, 5, 1323. 15. 16.
21. Pierce, J. C., Waller, M., Phibbs, M., ibid. 1975, 19, 343. 22. Forbes, J. F., Morris, P. J. ibid. 1972, 13, 444. 23. Hasegawa, T., Graw, R. G., Terasaki, P. I. ibid. 1973, 15, 492. 24. Morris, P. J., Dumble, L. J. Lancet, 1973, ii, 16. 25. Mann, D. L., Abelson, L., Harris, S., Amos, D. B. J. exp. Med., 1975, 142, 84. 26. Preud, ’Homme, J.-L., Seligmann, M. in Progress in Clinical Immunology (edited by R. S. Schwartz); p.125. New York, 1974. 27. Diaz-Jouanen, E., Williams, R. C., Jr, Strickland, R. G. Lancet, 1975, i, 688. 28. Steel, C. M., Evans, J., Smith, M. A. Nature, 1974, 247, 387. 29. Myburgh, J. A., Maier, G., Smit, J. A., Shapiro, M., Meyers, A. M., Rabkin, R., van Blerk, P. J. P., Jersky, J. Transplantation, 1974, 18, 206. 30. Opelz, G., Terasaki, P. I. ibid. (in the press).
found
are
associated with
stress.
We therefore investi-
gated the possible role of glucocorticoids in altering the peripheral metabolism of T4. Dexamethasone has been reported to cause an acute lowering of serum-T3 concentration in both euthyroid 6and thyrotoxic* individuals. The fall in serum-T3 has been shown to accompany a rise in rT3 in the serum of thyrotoxic patients and in hypothyroid patients treated with T4.’ Other synthetic glucocorticoids have been shown to have marked effects on the binding protein, thyroxine-binding pre-albumin (T.B.P.A.).’o 11 Here we describe the acute effects of a single dose of dexamethasone on serum T3, rT3, T4, and T.S.H. concentrations, and the relationship of changes in total hormone concentration to the values of free hormones and binding proteins. Methods
euthyroid volunteers (six male, four female, aged 20-40 were treated with L-thyroxine 0.2 mg daily for two weeks. On the fourteenth day, each received 12 mg of dexamethasone orally in a single dose, while continuing to take T4. Serum samples were obtained before the study, before taking dexamethasone, and daily thereafter for three days. Serum T3, rT3, and T4 were measured by specific radioimmunoassays.12 13 Serum-T.s.H. was measured by radioimmunoassay using reagents obtained from the National Institute of Arthritis and Metabolic Diseases, Bethesda, Maryland. Percentage free T4 and T3 were measured by a modification of Ten
years) EFFECT OF A SINGLE DOSE OF DEXAMETHASONE ON SERUM CONCENTRATIONS OF THYROID HORMONES W. A. BURR D. B. RAMSDEN E. G. BLACK R. S. GRIFFITHS R. HOFFENBERG
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH H. MEINHOLD
K. W. WENZEL
Thyroid Research Group, Department of Nuclear Medicine and Endocrinology, Klinikum Steglitz, Freie Universität Berlin, 1000 Berlin 45, West Germany In ten euthyroid subjects, in whom endogenous thyroid-stimulating hormone (T.S.H.) production was suppressed by oral thyroxine (T4), a single dose of dexamethasone resulted in reduced serum-3,3’,5-triidothyronine (T3) concentration and raised serum-3,3’,5’-triiodothyronine (reverse T3 or rT3) concentration after 24 h. These changes were not
Summary
the method of Lee et al.,14 in which labelled free hormones are bound to ’Sephadex G-25’ on a small column which is then counted in a well-type ·ounter. Serum T.B.G. and T.B.P.A. concentrations were measured by Laurell monorocket im-
munoelectrophoresis.15 of the method of Drysdale et al.,16 using an antibody to human a-globulins and labelling of samples with 125l-T4 followed by of the electrophoresis plate. Monospecific anti-T.B.P.A. was produced in rabbits by repeated intradermal injections of 200 p.g purified human T.B.P.A. in Freund’s complete adjuvant, and serum-T.B.P.A. was measured from the area of precipitation seen after protein staining without addition of radioactive tracers of T4.
autoradiography
Results Serum
The
T4, T3, and rT3
accompanying table shows
the pretreatment
59 SERUM CONCENTRATIONS OF
T4, T3
N.D.=not
values of serum T4, T3, and rT3, and the values after two weeks’ treatment with T4 and 1, 2, and 3 days after dexamethasone. Changes in serum T3 and rT3 are
AND
rT3
Ill1701
done.
shown in fig. 1. Treatment with T4 caused an increase in concentration of serum T4 and rT3 but not T3. The serum-T.S.H. concentration was reduced from a mean pretreatment value (±S.E.M.) of 1.5±0.12 mU/1 to undetectable levels (< 1.2 mU/1) in nine out of ten subjects after T4 and in all subjects on day 1 after dexamethasone.
Serum-T3 was decreased and serum-rT3 was increased 24 h after dexamethasone. The mean serum-T3 (is.E.M.) before dexamethasone was 3.06±0·21 nmol/1, decreasing to a mean of 2.62±0·24 nmol/1 after 24 h, with return to pretreatment values after 48 h. The mean serum-rT3 (is.E.M.) pre-dexamethasonewas 0-37±0.04 nmol/1 increasing to 0.63±0.07 nmol/1 after 24 h, and 0.41±0.04 nmol/1 after 48 h. Concentration of rT3 returned to pre-dexamethasone values after 72 h. Serum-T4 concentration did not change after dexamethasone.
Serum T.BPA., T.B.G., and Free Hormones Serum T.B.P.A. and T.B.G. results are shown in
fig. 2,
nuur
Fig. 1-Pereentage change
in
T3, rT3, and T4 concentrations after
Fig. 2—Percentage change
dexamethasone.
Significant difference **P
Requests for reprints should be addresses to R.B.E., Department of Surgery, University of California, Los Angeles, California 90024,
related to changes in free hormones or binding proteins. Adrenal glucocorticoids may have a pathophysiological role in modulating the peripheral metabolism of thyroid hormones in stress.
U.S.A.
Introduction REFERENCES 1. Patel, R., Terasaki, P. I. New Engl. J. Med. 1969, 280, 735. 2. Terasaki, P. I., Marchioro, T. H., Starzl, T. E. in Conference on Histocompatibility Testing (edited by P. S. Russel and H. J. Winn); p.83. Washington D.D., 1965. 3. Terasaki, P. I., Kreisler, M., Mickey, R. M. Postgrad. med. J. 1971, 47, 89. 4. Beleil, O. M., Mickey, M. R., Terasaki, P. I. Transplantation, 1972, 13, 493. 5. Myburgh, J. A., Maier, G., Smit, J. A., Shapiro, M., Meyers, A. M., Rabkin, R., van Blerk, P. J. P., Jersky, J. ibid. 1974, 18, 213. 6. Winchester, R. J., Fu, S. M., Wernet, P., Kunkel, H. G., Dupont, B., Jersild, C. J. exp. Med. 1975, 141, 924. 7. Ting, A., Mickey, M. R., Terasaki, P. I. ibid. 1976, 143, 981. 8. van Rood, J. J., van Leeuwen, A., Keuning, J. J., Blusse van Oud Alblas, Tissue Antigens, 1975, 5, 73. 9. Arbeit, R. D., Sachs, D. H., Amos, D. B., Dickler, H. B. J. Immun. 1975, 10.
reported an acute fall in serum-3,3’,5-triiodothyronine (T3) concentration and acute rise in serum-3,3’,5’-triiodothyronine (reverse T3 or rT3) concentration after surgical operation.’ Similar findings have been reported in various diseases2 and after caloric restriction.3 It was suggested that the peripheral monodeiodination of thyroxine (T4) might be altered in the above conditions, with an increase in peripheral deiodination from the tyrosyl ring and reduced deiodination from the phenolic ring. This would lead to increased formation of metabolically inactive rT3 4and decreased formation of metabolically active T3. The factors governing peripheral formation of rT3 and T3 are not yet understood, but several of the conditions in which high rT3 concentrations have been WE have
115, 117. Ettenger, R. B., Terasaki, P. I., Ting, A., Malekzadeh, M. H., Pennisi, Uittenbogaart, C., Fine, R. N. New Engl. J. Med. (in the press).
A.
J.,
Davies, D. A. L., Alkins, B. J. Nature, 1974, 247, 295. Soulillou, J. P., Carpenter, C. B., d’Apice, A. J. F., Strom, T. B. J. exp. Med. 1976, 143, 405. 13. Terasaki, P. I., McClelland, J. D. Nature, 1974, 204, 998. 14. Ting, A., Hasegawa, T., Ferrone, S., Reisfield, R. A. Transplantn Proc.
11. 12.
1973, 5, 813. Ting, A., Terasaki, P. I. Lancet, 1975, i, 304. Williams, G. M., Hume, D. M., Hudson, R. P., Morris, P. J., Kano, K., Milgrom, F. New Engl. J. Med. 1968, 279, 611. 17. Mittal, K. K., Mickey, M. R., Singal, D. P., Terasaki, P. I. Transplantation, 1968, 6, 913. 18. Nelken, D., Cohen, I., Furcaig, I. ibid. 1970, 10, 346. 19. Gibofsky, A., Terasaki, P. I. ibid. 1972, 15, 192. 20. Rogentine, G. N., Plocinik, B. A. ibid. 1967, 5, 1323. 15. 16.
21. Pierce, J. C., Waller, M., Phibbs, M., ibid. 1975, 19, 343. 22. Forbes, J. F., Morris, P. J. ibid. 1972, 13, 444. 23. Hasegawa, T., Graw, R. G., Terasaki, P. I. ibid. 1973, 15, 492. 24. Morris, P. J., Dumble, L. J. Lancet, 1973, ii, 16. 25. Mann, D. L., Abelson, L., Harris, S., Amos, D. B. J. exp. Med., 1975, 142, 84. 26. Preud, ’Homme, J.-L., Seligmann, M. in Progress in Clinical Immunology (edited by R. S. Schwartz); p.125. New York, 1974. 27. Diaz-Jouanen, E., Williams, R. C., Jr, Strickland, R. G. Lancet, 1975, i, 688. 28. Steel, C. M., Evans, J., Smith, M. A. Nature, 1974, 247, 387. 29. Myburgh, J. A., Maier, G., Smit, J. A., Shapiro, M., Meyers, A. M., Rabkin, R., van Blerk, P. J. P., Jersky, J. Transplantation, 1974, 18, 206. 30. Opelz, G., Terasaki, P. I. ibid. (in the press).
found
are
associated with
stress.
We therefore investi-
gated the possible role of glucocorticoids in altering the peripheral metabolism of T4. Dexamethasone has been reported to cause an acute lowering of serum-T3 concentration in both euthyroid 6and thyrotoxic* individuals. The fall in serum-T3 has been shown to accompany a rise in rT3 in the serum of thyrotoxic patients and in hypothyroid patients treated with T4.’ Other synthetic glucocorticoids have been shown to have marked effects on the binding protein, thyroxine-binding pre-albumin (T.B.P.A.).’o 11 Here we describe the acute effects of a single dose of dexamethasone on serum T3, rT3, T4, and T.S.H. concentrations, and the relationship of changes in total hormone concentration to the values of free hormones and binding proteins. Methods
euthyroid volunteers (six male, four female, aged 20-40 were treated with L-thyroxine 0.2 mg daily for two weeks. On the fourteenth day, each received 12 mg of dexamethasone orally in a single dose, while continuing to take T4. Serum samples were obtained before the study, before taking dexamethasone, and daily thereafter for three days. Serum T3, rT3, and T4 were measured by specific radioimmunoassays.12 13 Serum-T.s.H. was measured by radioimmunoassay using reagents obtained from the National Institute of Arthritis and Metabolic Diseases, Bethesda, Maryland. Percentage free T4 and T3 were measured by a modification of Ten
years) EFFECT OF A SINGLE DOSE OF DEXAMETHASONE ON SERUM CONCENTRATIONS OF THYROID HORMONES W. A. BURR D. B. RAMSDEN E. G. BLACK R. S. GRIFFITHS R. HOFFENBERG
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH H. MEINHOLD
K. W. WENZEL
Thyroid Research Group, Department of Nuclear Medicine and Endocrinology, Klinikum Steglitz, Freie Universität Berlin, 1000 Berlin 45, West Germany In ten euthyroid subjects, in whom endogenous thyroid-stimulating hormone (T.S.H.) production was suppressed by oral thyroxine (T4), a single dose of dexamethasone resulted in reduced serum-3,3’,5-triidothyronine (T3) concentration and raised serum-3,3’,5’-triiodothyronine (reverse T3 or rT3) concentration after 24 h. These changes were not
Summary
the method of Lee et al.,14 in which labelled free hormones are bound to ’Sephadex G-25’ on a small column which is then counted in a well-type ·ounter. Serum T.B.G. and T.B.P.A. concentrations were measured by Laurell monorocket im-
munoelectrophoresis.15 of the method of Drysdale et al.,16 using an antibody to human a-globulins and labelling of samples with 125l-T4 followed by of the electrophoresis plate. Monospecific anti-T.B.P.A. was produced in rabbits by repeated intradermal injections of 200 p.g purified human T.B.P.A. in Freund’s complete adjuvant, and serum-T.B.P.A. was measured from the area of precipitation seen after protein staining without addition of radioactive tracers of T4.
autoradiography
Results Serum
The
T4, T3, and rT3
accompanying table shows
the pretreatment
59 SERUM CONCENTRATIONS OF
T4, T3
N.D.=not
values of serum T4, T3, and rT3, and the values after two weeks’ treatment with T4 and 1, 2, and 3 days after dexamethasone. Changes in serum T3 and rT3 are
AND
rT3
Ill1701
done.
shown in fig. 1. Treatment with T4 caused an increase in concentration of serum T4 and rT3 but not T3. The serum-T.S.H. concentration was reduced from a mean pretreatment value (±S.E.M.) of 1.5±0.12 mU/1 to undetectable levels (< 1.2 mU/1) in nine out of ten subjects after T4 and in all subjects on day 1 after dexamethasone.
Serum-T3 was decreased and serum-rT3 was increased 24 h after dexamethasone. The mean serum-T3 (is.E.M.) before dexamethasone was 3.06±0·21 nmol/1, decreasing to a mean of 2.62±0·24 nmol/1 after 24 h, with return to pretreatment values after 48 h. The mean serum-rT3 (is.E.M.) pre-dexamethasonewas 0-37±0.04 nmol/1 increasing to 0.63±0.07 nmol/1 after 24 h, and 0.41±0.04 nmol/1 after 48 h. Concentration of rT3 returned to pre-dexamethasone values after 72 h. Serum-T4 concentration did not change after dexamethasone.
Serum T.BPA., T.B.G., and Free Hormones Serum T.B.P.A. and T.B.G. results are shown in
fig. 2,
nuur
Fig. 1-Pereentage change
in
T3, rT3, and T4 concentrations after
Fig. 2—Percentage change
dexamethasone.
Significant difference **P
