Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Editor's mail Robert M. Gabrielson & Paul F. Gilliland To cite this article: Robert M. Gabrielson & Paul F. Gilliland (1975) Editor's mail, Postgraduate Medicine, 58:6, 33-36, DOI: 10.1080/00325481.1975.11714194 To link to this article: http://dx.doi.org/10.1080/00325481.1975.11714194
Published online: 07 Jul 2016.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [Australian Catholic University]
Date: 31 August 2017, At: 04:46
OOilorS mail
Downloaded by [Australian Catholic University] at 04:46 31 August 2017
THYROID DISEASE TREATMENT DEBATED To the Editor: We appreciate the fact that the subject of thyroidology is extremely complex and the literature on the subject is truly vast. lt is thus understandable that Dr. Paul F. Gilliland encountered sorne problems in summarizing such complex material in a few pages in the June issue of POSTGRADUATE MEDICINE. For example, we differ strongly with his statement on purified thyroglobulin (Proloid) in which he states that its effects on blood tests of thyroid function are not consistent or predictable and with his statement that "this preparation does not offer advantages over thyroid USP." Thyroid USP is a poorly defined product with only the percentage of iodine being specified. The ratio of thyroxine (T.) to triiodothyronine (T,) is not defined, and this can vary widely depending, for example, on the animal source or method of preparation. Even the actual thyroactive potency can vary considerably from one USP brand to another because sorne products may contain more of the less active thyroactive compounds and, conversely, other batches high in T, or highly active thyroid compounds could possibly be superpotent. These defects are peculiar only to certain brands of USP thyroid, however. Proloid, on the other hand, has the following characteristics. 1. lt meets the USP requirement for iodine content. 2. lt is specially standardized by an antigoitrogenic bioassay method that Dr. Robert Kroc, of our research institute, developed. lt is now an accepted bioassay method for thyroid products. 3. At one time, accurate quantitative chemical assays of the relative amounts of T, and T. in thyroid products were not possible. The advances in quantitative chemistry, however, have enabled us to define precisely the amounts of T. and T, in Proloid, and the ratio is held within fairly rigid tolerances in our manufacturing process. Thus, we have the third Proloid control, namely, chromatographie chemical assay for T4 /T 3 ratio. 4. Lest any of these laboratory methods suffer from pitfalls or unforeseen deficiencies, Proloid is routinely tested in human subjects in leading thyroid clinics to make sure that Proloid administration in normal maintenance doses will maintain the patient in a euthyroid status. Finally, the laboratory
Vol. 58 • No. 6 • November 1975 • POSTGRADUATE MEDICINE
parameters of these subjects are checked to ascertain that they fall within normal ranges. We therefore feel confident that Proloid offers significant advantages over generic USP thyroid from unknown sources. We realize at the same time that even though these great precautions are taken to keep Proloid as uniform as possible, we are still talking about narrowly defined ranges rather than precise amounts. lt was exactly for this reason that Warner 1Chilcott introduced Euthroid, which is a precise mixture of T. and T, at a 4:1 ratio which produces laboratory values in the normal range when the patient is euthyroid. We thus disagree with Dr. Gilliland's statement that a disadvantage of combination therapy with 1- T. and /-T, is poor correlation with results of blood tests of thyroid function with the patient's clinical status, thus making therapy difficult to monitor. The following bibliography amply substantiates the fact that a patient made euthyroid with Euthroid will have normal laboratory values. This is quite unlike therapy with either T4 alone or T, alone. Robert M. Gabrielson, MD Warner 1Chilcott Morris Plains, New Jersey
BIBLIOGRAPHY Aguil6 F Jr, Gândara JR, Martlnez Rovira GR: Clinical experience with Euthroid: A new drug for thyroid replacement therapy. Bol Asoc Med PR 65: 267-279, 1973 Danowski TS, Moses C: Thyroid indices during replacement with desiccated thyroid and Proloid. Metabolism 14:99-103, 1965 Farmer TA Jr, Smitherman TC, Beschi RJ, et al: Effect of triiodothyronine administration on serum PBI in hypothyroid patients maintained on constant doses of thyroxine. J Clin Endocrinol 29: 781-785, 1969 Hamburger JI, Meier DA: Which thyroid hormone preparation is best? Mich Med 70:119-120, 1971 Mangieri CN, Lund MH: Potency of United States Pharmacopeia dessicated thyroid tablets as determined by the antigoitrogenic assay in rats. J Clin Endocrinol 30:102-104, 1970 Nahum LH: Desiccated thyroid vs. synthetic thyroid preparations. (Editorial) Conn Med 31:757, 1967 Sachs, BA, Wolfman L, Murthy G: Lipid and clinical response to a new thyroid hormone combination. Am J Med Sei 256:232-238, 1968 Selenkow HA, Refetoff S: Common tests of thyroid function in serum. JAMA 202:153-154, 1967 ~
33
editor's mail _ _ _ _ _ _ _ _ _ __ Thyroid, thyroxine and triiodothyronine. Med Lett Drugs Ther 5:69-71, 30 Aug 1963 Wool MS, Selenkow HA: Physiologie combinations of synthetic thyroid hormones in myxedema. Clin Pharmacol Ther 6:710-715, 1965 Workman JB, Lund MH: Serum protein-bound iodine response to thyroglobulin (Proloid). Curr Ther Res 12:828-830, 1970
Announclng
•
two
Downloaded by [Australian Catholic University] at 04:46 31 August 2017
Dr. Gabrielson's comments were sent to Dr. Gilliland, whose reply follows. To the Editor: 1 certainly agree with Dr. Gabrielson that the literature on thyroidology is quite vast, and it contains reports of some important recent work not cited by him. The point is not whether Proloid is better than thyroid USP. The point is that there is something better than either of them. lt is now known that in the normal human the thyroid gland secretes mainly T4; the circulating T3 is largely derived from peripheral deiodination of circulating T4 • lt recently has been fou nd that athyreotic humans who are rendered euthyroid by administration of /-T4 (as judged by the minimal dose necessary to suppress plasma TSH into the normal range) have normal concentrations of circulating T4 and T3, and these concentrations do not change appreciably throughout a 24-hour period. lt also is known that in normal humans without thyroid disease, T4 and T3 concentrations are relatively constant throughout the 24-hour period. Treatment with preparations containing both T3 and T4 (ie, TrT4 combinations or thyroid USP) results in serum T3 concentrations that are in the thyrotoxic range for up to ten hours after ingestion of the medication. Although Proloid has not been tested in this system, it is likely that the T3 in it also will produce thyrotoxic serum concentrations for several hours after the dose is taken. This marked increase in serum T3 concentration for several hours after ingestion of T3-T4 combinatians or desiccated thyroid could be harmful to persons with cardiac disease, and it will cause difficulty in interpreting serum T3 concentration data unless one knows precisely when the previous dose was taken. A crossover study comparing T4-T3 combinatians (4: 1 ratio) with /-thyroxine showed clearly that a significant number of patients taking the TrT4 combination had symptoms of thyrotoxicosis, and many of them discontinued taking the medication because of this. This occurred at a time when protein-bound iodine and resin T3 uptake values were in the normal range. ln summary, 1 think that use of synthetic /-T4 has the following advantages: First, serum T4 and T3 concentrations are constant throughout the 24-hour period, which mimics the values seen in normal humans much more closely than do the results seen when natural products containing T3 and T4 or synthetic combinations are used. Second, there is no risk of marked increases in serum T3 concentration, which might be hazardous in patients with cardiac disease. Furthermore, the long-term results of serum
definitive pedlattlc tefetences New 5th Edition!
PEDIATRie THERAPY This new edition presents essential information on the treatment of virtually every condition affecting infants and children within the context of total patient care. From the bread range of pediatrie medicine, the authors provide specifie detai is on drug therapy, adverse drug reactions, generai therapy and treatment of symptoms, and management of disorders of each body system. Edited by Harry C. Shirkey, B.S. (Pharm.), M.D., F.A.A.P.; with 4 associa te editors and 117 contributors. November, 1975. Approx. 1,344 pages, 7Y4" x 10Y2", 498 illustrations in 410 figures. About $34.50.
A New Book!
THE PRAeTieE OF PEDIATRie NEUROLOGY This book is an orderly approach to the study of various conditions which afflict the nervous system in children. Using a general approach, Section 1discusses normal growth and development in childhood, and proceeds into historicai, physical and laboratory examinations. Section Il covers specifie symptoms and signs of neurologicai disease in children. Section Ill provides detailed discussions of individual childhood neurologie disorders. By Kenneth F. Swaiman, M.D. and Francis S. Wright, M.D.; with the collaboration of 42 contributors. November, 1975.2 volumes, approx. 1,360 pages, 8Y2" x 11", 457 illustrations plus 4 full-color illustrations and 1 two-color illustration. About $115.00.
MOSBV TIMES
MU~ROR
THE C.V. MOSBY COMPANY 11830 WESTLINE INDUSTRIAL DRIVE ST. LOUIS. MISSOURI 63141 Vol. 58 • No. 6 • November 1975 • POSTGIRADUATE MEDICINE
editor's
maü1-----------
TJ concentrations in the thyrotoxic range for many hours each day are not known. The bibliography that follows should correct any false impressions readers may have regarding Proloid and Euthroid. Paul F. Gilliland, MD Scott and White Clinic Temple, Texas
Downloaded by [Australian Catholic University] at 04:46 31 August 2017
BIBLIOGRAPHY Braverman LE, Vagenakis A, Downs P, et al: Effects of replacement doses of sodium-L-thyroxine on the peripheral metabolism of thyroxine and triiodothyronine in man. J Clin lnvest 52:10101017, 1973 Smith RN, Taylor SA, Massey JC: Controlled clinical trial of combined triiodothyronine and thyroxine in the treatment of hypothyroidism. Br Med J 4:145-148, 1970 Stock JM, Surks Ml, Oppenheimer JH: Replacement dosage of L-thyroxine in hypothyroidism: A reevaluation. N Engl J Med 290:529-533, 1974 Surks Ml, Schadlow AR, Oppenheimer JH: A new radioimmunoassay for plasma L-triiodothyronine: Measurements in thyroid disease and in patients maintained on hormonal replacement. J Clin lnvest 51:3104-3113, 1972 Surks Ml, Schadlow AR, Stock JM, et al: Determination of iodothyronine absorption and conversion of L-thyroxine (T 4) to L-triiodothyronine (T 3) using turnover rate techniques. J Clin lnvest 52: 805-811, 1973
NATIONAL STUDENT RESEARCH FORUM The 1976 AMSA-UTMB National Student Research Forum, sponsored by the American Medical Student Association and The University of Texas Medical Branch, will be held in Galveston April 21 to 24, 1976. The forum is open to medical students, graduate students associated with medical schools, and interns and residents, who will cornpete in one of these categories based on their classification at the time of participation. Research in both clinical and basic sciences will be included. Participants are selected solely on the basis of an abstract of the presentation, which must be submitted with the formai application before February 2, 1976. Participants in competition for the Excellence of Research Awards will be required to submit a formai manuscript. Monetary and plaque awards will be given in the following categories: liver disease, demyelinating diseases, cardiovascular research, immunology and infectious diseases, and neuroscience. For further information and application forms, contact: AMSA-UTMB National Student Research Forum, Room 209, Basic Sciences Building, The University of Texas Medical Branch, Galveston, TX 77550.
36
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Editor's mail Robert M. Gabrielson & Paul F. Gilliland To cite this article: Robert M. Gabrielson & Paul F. Gilliland (1975) Editor's mail, Postgraduate Medicine, 58:6, 33-36, DOI: 10.1080/00325481.1975.11714194 To link to this article: http://dx.doi.org/10.1080/00325481.1975.11714194
Published online: 07 Jul 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [Australian Catholic University]
Date: 31 August 2017, At: 04:46
OOilorS mail
Downloaded by [Australian Catholic University] at 04:46 31 August 2017
THYROID DISEASE TREATMENT DEBATED To the Editor: We appreciate the fact that the subject of thyroidology is extremely complex and the literature on the subject is truly vast. lt is thus understandable that Dr. Paul F. Gilliland encountered sorne problems in summarizing such complex material in a few pages in the June issue of POSTGRADUATE MEDICINE. For example, we differ strongly with his statement on purified thyroglobulin (Proloid) in which he states that its effects on blood tests of thyroid function are not consistent or predictable and with his statement that "this preparation does not offer advantages over thyroid USP." Thyroid USP is a poorly defined product with only the percentage of iodine being specified. The ratio of thyroxine (T.) to triiodothyronine (T,) is not defined, and this can vary widely depending, for example, on the animal source or method of preparation. Even the actual thyroactive potency can vary considerably from one USP brand to another because sorne products may contain more of the less active thyroactive compounds and, conversely, other batches high in T, or highly active thyroid compounds could possibly be superpotent. These defects are peculiar only to certain brands of USP thyroid, however. Proloid, on the other hand, has the following characteristics. 1. lt meets the USP requirement for iodine content. 2. lt is specially standardized by an antigoitrogenic bioassay method that Dr. Robert Kroc, of our research institute, developed. lt is now an accepted bioassay method for thyroid products. 3. At one time, accurate quantitative chemical assays of the relative amounts of T, and T. in thyroid products were not possible. The advances in quantitative chemistry, however, have enabled us to define precisely the amounts of T. and T, in Proloid, and the ratio is held within fairly rigid tolerances in our manufacturing process. Thus, we have the third Proloid control, namely, chromatographie chemical assay for T4 /T 3 ratio. 4. Lest any of these laboratory methods suffer from pitfalls or unforeseen deficiencies, Proloid is routinely tested in human subjects in leading thyroid clinics to make sure that Proloid administration in normal maintenance doses will maintain the patient in a euthyroid status. Finally, the laboratory
Vol. 58 • No. 6 • November 1975 • POSTGRADUATE MEDICINE
parameters of these subjects are checked to ascertain that they fall within normal ranges. We therefore feel confident that Proloid offers significant advantages over generic USP thyroid from unknown sources. We realize at the same time that even though these great precautions are taken to keep Proloid as uniform as possible, we are still talking about narrowly defined ranges rather than precise amounts. lt was exactly for this reason that Warner 1Chilcott introduced Euthroid, which is a precise mixture of T. and T, at a 4:1 ratio which produces laboratory values in the normal range when the patient is euthyroid. We thus disagree with Dr. Gilliland's statement that a disadvantage of combination therapy with 1- T. and /-T, is poor correlation with results of blood tests of thyroid function with the patient's clinical status, thus making therapy difficult to monitor. The following bibliography amply substantiates the fact that a patient made euthyroid with Euthroid will have normal laboratory values. This is quite unlike therapy with either T4 alone or T, alone. Robert M. Gabrielson, MD Warner 1Chilcott Morris Plains, New Jersey
BIBLIOGRAPHY Aguil6 F Jr, Gândara JR, Martlnez Rovira GR: Clinical experience with Euthroid: A new drug for thyroid replacement therapy. Bol Asoc Med PR 65: 267-279, 1973 Danowski TS, Moses C: Thyroid indices during replacement with desiccated thyroid and Proloid. Metabolism 14:99-103, 1965 Farmer TA Jr, Smitherman TC, Beschi RJ, et al: Effect of triiodothyronine administration on serum PBI in hypothyroid patients maintained on constant doses of thyroxine. J Clin Endocrinol 29: 781-785, 1969 Hamburger JI, Meier DA: Which thyroid hormone preparation is best? Mich Med 70:119-120, 1971 Mangieri CN, Lund MH: Potency of United States Pharmacopeia dessicated thyroid tablets as determined by the antigoitrogenic assay in rats. J Clin Endocrinol 30:102-104, 1970 Nahum LH: Desiccated thyroid vs. synthetic thyroid preparations. (Editorial) Conn Med 31:757, 1967 Sachs, BA, Wolfman L, Murthy G: Lipid and clinical response to a new thyroid hormone combination. Am J Med Sei 256:232-238, 1968 Selenkow HA, Refetoff S: Common tests of thyroid function in serum. JAMA 202:153-154, 1967 ~
33
editor's mail _ _ _ _ _ _ _ _ _ __ Thyroid, thyroxine and triiodothyronine. Med Lett Drugs Ther 5:69-71, 30 Aug 1963 Wool MS, Selenkow HA: Physiologie combinations of synthetic thyroid hormones in myxedema. Clin Pharmacol Ther 6:710-715, 1965 Workman JB, Lund MH: Serum protein-bound iodine response to thyroglobulin (Proloid). Curr Ther Res 12:828-830, 1970
Announclng
•
two
Downloaded by [Australian Catholic University] at 04:46 31 August 2017
Dr. Gabrielson's comments were sent to Dr. Gilliland, whose reply follows. To the Editor: 1 certainly agree with Dr. Gabrielson that the literature on thyroidology is quite vast, and it contains reports of some important recent work not cited by him. The point is not whether Proloid is better than thyroid USP. The point is that there is something better than either of them. lt is now known that in the normal human the thyroid gland secretes mainly T4; the circulating T3 is largely derived from peripheral deiodination of circulating T4 • lt recently has been fou nd that athyreotic humans who are rendered euthyroid by administration of /-T4 (as judged by the minimal dose necessary to suppress plasma TSH into the normal range) have normal concentrations of circulating T4 and T3, and these concentrations do not change appreciably throughout a 24-hour period. lt also is known that in normal humans without thyroid disease, T4 and T3 concentrations are relatively constant throughout the 24-hour period. Treatment with preparations containing both T3 and T4 (ie, TrT4 combinations or thyroid USP) results in serum T3 concentrations that are in the thyrotoxic range for up to ten hours after ingestion of the medication. Although Proloid has not been tested in this system, it is likely that the T3 in it also will produce thyrotoxic serum concentrations for several hours after the dose is taken. This marked increase in serum T3 concentration for several hours after ingestion of T3-T4 combinatians or desiccated thyroid could be harmful to persons with cardiac disease, and it will cause difficulty in interpreting serum T3 concentration data unless one knows precisely when the previous dose was taken. A crossover study comparing T4-T3 combinatians (4: 1 ratio) with /-thyroxine showed clearly that a significant number of patients taking the TrT4 combination had symptoms of thyrotoxicosis, and many of them discontinued taking the medication because of this. This occurred at a time when protein-bound iodine and resin T3 uptake values were in the normal range. ln summary, 1 think that use of synthetic /-T4 has the following advantages: First, serum T4 and T3 concentrations are constant throughout the 24-hour period, which mimics the values seen in normal humans much more closely than do the results seen when natural products containing T3 and T4 or synthetic combinations are used. Second, there is no risk of marked increases in serum T3 concentration, which might be hazardous in patients with cardiac disease. Furthermore, the long-term results of serum
definitive pedlattlc tefetences New 5th Edition!
PEDIATRie THERAPY This new edition presents essential information on the treatment of virtually every condition affecting infants and children within the context of total patient care. From the bread range of pediatrie medicine, the authors provide specifie detai is on drug therapy, adverse drug reactions, generai therapy and treatment of symptoms, and management of disorders of each body system. Edited by Harry C. Shirkey, B.S. (Pharm.), M.D., F.A.A.P.; with 4 associa te editors and 117 contributors. November, 1975. Approx. 1,344 pages, 7Y4" x 10Y2", 498 illustrations in 410 figures. About $34.50.
A New Book!
THE PRAeTieE OF PEDIATRie NEUROLOGY This book is an orderly approach to the study of various conditions which afflict the nervous system in children. Using a general approach, Section 1discusses normal growth and development in childhood, and proceeds into historicai, physical and laboratory examinations. Section Il covers specifie symptoms and signs of neurologicai disease in children. Section Ill provides detailed discussions of individual childhood neurologie disorders. By Kenneth F. Swaiman, M.D. and Francis S. Wright, M.D.; with the collaboration of 42 contributors. November, 1975.2 volumes, approx. 1,360 pages, 8Y2" x 11", 457 illustrations plus 4 full-color illustrations and 1 two-color illustration. About $115.00.
MOSBV TIMES
MU~ROR
THE C.V. MOSBY COMPANY 11830 WESTLINE INDUSTRIAL DRIVE ST. LOUIS. MISSOURI 63141 Vol. 58 • No. 6 • November 1975 • POSTGIRADUATE MEDICINE
editor's
maü1-----------
TJ concentrations in the thyrotoxic range for many hours each day are not known. The bibliography that follows should correct any false impressions readers may have regarding Proloid and Euthroid. Paul F. Gilliland, MD Scott and White Clinic Temple, Texas
Downloaded by [Australian Catholic University] at 04:46 31 August 2017
BIBLIOGRAPHY Braverman LE, Vagenakis A, Downs P, et al: Effects of replacement doses of sodium-L-thyroxine on the peripheral metabolism of thyroxine and triiodothyronine in man. J Clin lnvest 52:10101017, 1973 Smith RN, Taylor SA, Massey JC: Controlled clinical trial of combined triiodothyronine and thyroxine in the treatment of hypothyroidism. Br Med J 4:145-148, 1970 Stock JM, Surks Ml, Oppenheimer JH: Replacement dosage of L-thyroxine in hypothyroidism: A reevaluation. N Engl J Med 290:529-533, 1974 Surks Ml, Schadlow AR, Oppenheimer JH: A new radioimmunoassay for plasma L-triiodothyronine: Measurements in thyroid disease and in patients maintained on hormonal replacement. J Clin lnvest 51:3104-3113, 1972 Surks Ml, Schadlow AR, Stock JM, et al: Determination of iodothyronine absorption and conversion of L-thyroxine (T 4) to L-triiodothyronine (T 3) using turnover rate techniques. J Clin lnvest 52: 805-811, 1973
NATIONAL STUDENT RESEARCH FORUM The 1976 AMSA-UTMB National Student Research Forum, sponsored by the American Medical Student Association and The University of Texas Medical Branch, will be held in Galveston April 21 to 24, 1976. The forum is open to medical students, graduate students associated with medical schools, and interns and residents, who will cornpete in one of these categories based on their classification at the time of participation. Research in both clinical and basic sciences will be included. Participants are selected solely on the basis of an abstract of the presentation, which must be submitted with the formai application before February 2, 1976. Participants in competition for the Excellence of Research Awards will be required to submit a formai manuscript. Monetary and plaque awards will be given in the following categories: liver disease, demyelinating diseases, cardiovascular research, immunology and infectious diseases, and neuroscience. For further information and application forms, contact: AMSA-UTMB National Student Research Forum, Room 209, Basic Sciences Building, The University of Texas Medical Branch, Galveston, TX 77550.
36
