J. Endocrinol. Invest. 15: 513-517,1992
The management of hyperthyroidism due to Graves' disease in the former USSR in 1991: results of a survey G. Gerasimov*, O. Judenitch*, E. Zdanova*, N. Jurieva*, I. Korostishevskaja*, K. Mushinskaja*, I. Dedov*, and D. Glinoer** *National Endocrinology Research Centre, Moscow, Russia, and **Hopital Universitaire Saint-Pierre, Department of Internal Medicine, Brussels, Belgium ABSTRACT. A survery of the current management of Graves' disease was performed in the USSR among members of All Union Endocrine Society. The questionnaire was based on the format used previously for a survey of members of European Thyroid Association. The aim of a similar survery in the USSR was to obtain a comprehensive pattern of management of Graves' disease in Soviet endocrinology clinics and to compare medical attitudes in the former USSR to those in other European countries. One hundred and twenty questionnaires were mailed with 55 returned (46%). The responses originated from 33 cities, representing major endocrinology centers of the former Soviet Republics. Initial diagnosis was conducted both in hospitals (55%) and ambulatory care settings (45%). Thyroid scintigraphy was requested by 42.3% of the respondents; a majority of
them (90%) used 1311. Thyroid ultrasonography was performed in more than 50% of cases. Measurements of cholesterol, total T4 and T3 were the most frequent laboratory tests requested to confirm the diagnosis. For the treatment with ATD, methimazole was the exclusive choice (PTU is not currently in use in the USSR). Beta-blocking agents were prescribed by a majority of respondents. For the long term treatment, a combination procedure of MMI and thyroid hormones was clearly preferred by almost 3/4 of the respondents. A fixed period of treatment was preferred by 62% of the respondents, with a duration of therapy of 18-24 months. Surgery for treatment of the index patient was chosen by only 6%, and radioiodine by 3%. The number of responses was too limited to attempt any characterization of the two latter modalities.
INTRODUCTION
distinctions, as well as similarities in the diagnostic and therapeutic approaches to the management of hyperthyroidism due to Graves'/Basedow disease (HGBD) in the different countries surveyed. Since no data were available from "Eastern" Europe, the aim of a similar survey in the USSR was to obtain an accurate comprehensive pattern of the management of HGBD in endocrinology clinics and to compare medical attitudes in the USSR to those in other European countries,
In 1987, the results of a survey of the members of the European Thyroid Association (ETA) on the management of Graves'/Basedow disease were reported by Glinoer et al. (1). The aim of the survey was to evaluate how expert thyroidologists employ the available diagnostic procedures and carry out therapy, given three therapeutic options of antithyroid drugs (ATD), radioiodine (RI) and surgery (S). Shortly thereafter, national surveys in Europe, based on the questionnaire employed for the ETA survey, were carried out in the Netherlands (2), Austria (3), Germany (4), France (5) and Spain (6). More recently, similar surveys were conducted in the United States (7) and Japan (8), and the comparative results of the three regional surveys have recently been reported (9). The surveys showed both striking
MATERIALS AND METHODS The questionnaire employed in the present survey was based on the original format proposed by ETA in 1986 (1). The questionnaire was translated into Russian with only minor modification and adaptation. The questionnaire was divided into two sections. In the first section, the case of a hypothetical patient was presented and respondents were asked to select in vivo and in vitro tests as they would in their daily practice. The second section dealt with the choice of therapy for the index patient. It was subdivided in three parts, according to
Key-words: Graves', Basedow disease, thyroid, hyperthyroidism, antithyroid drugs. Correspondence: Dr. D. Glinoer. Laboratory of Radioisotopes, Hopital Saint-Pierre, 322 rue Haute, B-1 000 Brussels, Belgium. Reiceived January 16,1992; accepted May 14,1992.
513
G. Gerasimov, 0. Judenitch, E. Zdanova, et al.
the choice of therapy, and dealt specifically with information on how the chosen treatment was implemented. The questionnaire was mailed to all senior members of the Soviet Endocrine Society, to local endocrinology dispensaries* and also to the endocrinology departments of High Medical Schools, Universities and Research Institutes. Participants were kept strictly confidential. The data analysis was performed in the National Endocrinology Research Centre in Moscow using conventional statistical methods. The index patient was described as follows: "A 43yr-old woman with moderate and overt signs of hyperthyroidism of 2-3 month duration. She is healthy, takes no medication and leads an active working life. She has two children and does not plan on being pregnant again. This is her first episode of hyperthyroidism. She has a diffuse goiter of 40-50 g, pulse rate of 105 beats/min and regular, and typical but minimal eye signs." Finally, in the questionnaire used for the ETA survey, there was also a section dealing with clinical variations of the index patient, in relation to the age, sex, severity of disease, size of goiter, etc. This section of the original survey was not assessed in the present study.
Table 1 - Frequency of ordered in vivo diagnostic tests for workup of the index patient by 55 centers of the former USSR. Test
Response*
Scintigraphy**
42
131 1
89 with uptake
82
without uptake
11
no answer 99m-Tc
7
11
with uptake (20 min)
33
without uptake
67
Ultrasonography**
53
Fine needle aspiration**
20
*Percent of positive answers. "Percentage of all responses.
netium pertechnetate (Tc-99m); 123 1 is not currently available in the USSR. Most respondents (82%) performed a thyroidal uptake with the scan. Thyroid ultrasonography was performed in more than 50% of the cases, mainly in association with thyroid scintigraphy. A fine needle aspiration of the thyroid was carried out by 20% of the respondents. Responses for in vitro laboratory tests are given in Table 2. Respondents were given a choice of 10 tests and were asked to select those they would actually use for the index patient. Measurements of cholesterol, total T4, T3 and basal TSH were the
RESULTS Survey responses One hundred and twenty questionnaires were mailed with 55 returned and completed (46%), and included in the data analysis. Twenty-two responses originated from single individuals and 33 were presented by teams. A total of 146 specialists in endocrinology/thyroidology took part in the survey. The responses originated from 33 cities, representing most major endocrinology centers of the former Soviet Republics: city hospitals (25.8%), endocrinology dispensaries (19.7%), Endocrine Research Institutes (31.8%), and High Medical Schools (22.7%).
Table 2 - Frequency of ordered in vitro diagnostic tests for workup of the index patient by 55 centers of the former USSR. Tests*
Diagnostic procedures Initial diagnosis was conducted both in hospitals (55%) and ambulatory (45%) care settings. Table 1 presents the results for in vivo tests. A thyroid scintigraphy would be obtained by only 42.4% of the respondents. Among them, the majority (90%) used 131 1 as primary isotope and only 10% - tech-
Frequency ("!o)
1. cholesterol
78.8
2. total T3
68.2
3. total T4
66.7
4. basal TSH
56.1
5. thyroglobulin autoantibodies
47
6. microsomal autoantibodies
21.2
7. serum thyroglobulin
21.2
8. TSH receptor antibodies
7.6
9. urinary iodine excretion
1.5
10. TRH test
o
Each test is considered as an individual item separate from any other test.
*Endocrinology dispensaries are specialized medical institutions (formerly-Antigoiter Stations) for outpatient and inpatient care.
*Listed in decreaSing order of frequency.
514
Treatment of Graves' disease in the former USSR
most frequent laboratory tests requested to confirm the diagnosis. The other in vitro tests were employed less frequently. The respondents from institutions with well equipped diagnostic departments made a larger use of tests. For example, total T4 determinations represented 86% of responses from Endocrine Research Institutes and Medical Schools, compared to 47% in Hospitals and 39% in Dispensaries.
Iy 6% and radioiodine therapy by 3% of the respondents. MODALITIES OF TREATMENT
1. A TO (Table 3). For the treatment with ATD, methimazole (MMI) represented the exclusive choice, since PTU is not currently in use in the USSR. Therapy was initiated with a daily dose of 25-40 mg (85% of respondents). The initial treatment was modified when the patient reached a euthyroid state (64% of responses), according to both clinical and laboratory criteria (70% of responses). Beta-blocking agents were prescribed by a majority of respondents, mainly during initial phase of treatment. Respondents were also asked whether the long term administration of ATD would consist of adapting the dose of MMI used alone, or in combination with thyroid hormones. The combination procedure was clearly preferred by almost three quarters of the respondents. Questions were asked in the survey in relation to duration of treatment and criteria used to withdraw ATD. A fixed period of treatment was preferred by 62% of the respondents and among them, the overwhelming preference was for a long duration of therapy: 18-24 month. Criteria used for withdrawal of therapy were clinical and biochemical euthyroidism (91% of responses). Those respondents associated with Research Institutes and High Medical Schools, and hence who disposed more easily of laboratory facilities, included the normalization of TSH-receptor antibodies and/or basal TSH in sensitive assays among the criteria. 2. Surgery. This modality for treatment of the index patient was chosen by only 6% of the respondents. Preoperative medical preparation associated MMI, Lugol solution and beta-bloking agents. The aim of surgery was conservative in all responses, i.e. minimal resection in order to keep the patient euthyroid without medication. After the surgery, follow up was organized in local policlinics. Moreover, 25% of the respondents indicated that organization of the follow up would influence the surgical strategy. 3. Radioiodine administration. Only 3% of the respondents chose this modality. The number of responses was too limited to attempt any characterisation of the modalities employed.
Therapeutic choices Once the diagnosis was established, the question asked was: "In this patient, what is the basic treatment that you would advocate, assuming that the patient leaves the decision of therapy entirely to you?" For this case of moderate hyperthyroidism, clinicians almost unanimously recommended treatment with ATD (91 %). Surgery was chosen by on-
Table 3 - Modalities of antithyroid drug treatment employed by specialists of 55 centers of the former USSR. Initial dose of MMI 20mg
Frequency (%) 5
20-30 mg
13.3
30mg
55
30-40 mg
15.2
>40mg
6.7
no information
3.3
Modification of initial treatment after reaching a euthyroid state
64
after a fixed period
26
2-3 weeks
18
3-4 weeks
4
up to 3 months
4
according to pulse rate
10
Criteria of modification laboratory data alone
o
clinical findings alone
30
both
70
Beta-blocking agents during initial treatment
70
throughout medical treatment
23.3
not at all Combination of MMI and thyroid hormones
DISCUSSION The present survey represented an effort to analyze medical strategies for the management of Graves' disease within the former USSR. The design previously used for the ETA survey, with slight modifica-
7.7 73.3
MMI - methimazole.
515
G. Gerasimov, 0. Judenitch, E. Zdanova, et at.
tion, was used to organize the questionnaire which was mailed to all senior members of AUES (All Union Endocrine Society), the local Endocrine dispensaries, the divisions of Endocrinology of High Medical Schools and Universities. The response rate, although below 50%, represents most important thyroid centers in our country. It should also be noted that the original ETA survey, and its application to the USA and Japan more recently (7, 8) included an important section dealing with clinical variations of the index case, namelyon the influence of the age and sex of patients, severity of disease, and recurrence of hyperthyroidism on the responses. Since it was known that in the USSR the major form of therapy was the administration of ATD, this part of the original questionnaire was deleted from the present survey. The results of the present survey should primarily be compared with those obtained in Europe and Japan, since the overall modalities of the management of Graves' hyperthyroidism are strikingly different in the USA. Table 4 lists the main results in the USSR, Europe (ETA) and Japan. There was consensus in Europe (ETA) and Japan for the evaluation of patients in an outpatient setting, while in the USSR the situation was markedly different. Most patients are evaluated in a hospital setting in the USSR because of the lack of facilities and qualified endocrinologists in many local policlinics. Also, the main radionuclide used for in vivo testing was 131 1, because 123 1 is not available in the USSR and the supply of Tc-99m generators remains presently insufficient. The soviet radiopharmaceutical industry produces RIA kits for the determination of total T4 and T3, thyroglobulin and TG-antibodies. The determination of serum TSH (including second generation "sensitive" assays) depends on import from the West, and is therefore practically not available.
These factual constraints explain why fewer in vitro tests are carried out in the USSR and only the determination of total T4 and T3 remains the most common method used for the in vitro evaluation of thyroid function. Similarly, since immunological techniques, such as the determination of microsomal and TSH-receptor antibodies, are only available in specialized Research Institutes - and their use hence limited in current medical practice - fine needle aspiration and ultrasonography of the thyroid gland are more frequently used in the USSR. One of the major findings of the present survey was the almost unanimous choice of antithyroid drugs for the treatment of the index case. This is in keeping with the results observed in Europe (ETA) and Japan, and in contrast with USA, where 70% of the respondents preferred radioiodine therapy. Methimazole was used in all instances and the shortage of laboratory facilities was the main reason for adjusting the dosage of MMI according mainly to clinical criteria. As in Europe (ETA), a fixed period before the withdrawal of treatment was the preferred choice of a majority of respondents. Medical treatment was of long duration, 2 yr in average. The "block and replace" technique, i.e. the combination of ATD and thyroid hormones was employed more frequently in the USSR, in comparison with Europe (ETA) and Japan. In regard to the use of surgical thyroidectomy, the present survey as well as previous ones in different parts of the world, showed that its use was extremely limited for Graves' disease. The main indications for the surgical treatment of toxic diffuse goiter in the USSR are limited to goiters of large size, recurrence of thyrotoxicosis after treatment with ATD and rare instances, such as hematologic or allergic complications from ATD. The presence of a large goiter was the only occurrence in the
Table 4 - Summary of the major differences between the results in Japan, Europe (ETA) and the USSR. Japan
Europe (ETA)
USSR
Radionuclide
123 1
1231/99mTc
131 1
Use of in vitro diagnostic tests
many
moderate
moderate
Ultrasonography
25%
21%
53%
Fine needle aspiration
rare
rare
relatively frequent
Use of ATD
MMI/PTU
MMI/PTU
MMlonly
adjustment of the daily dosage
according to thyroid function
after a fixed period
according to clinical Criteria
long term follow up
ATD alone in 93%
ATD alone/ATD+ TH 55%/45%
ATD+ TH 73%
withdrawal of ATD treatment
use of specific criteria
after a fixed period (12 month)
after a fixed period (24 month)
MMI - methimazole, PTU - propylthiouracil, ATD - antithyroid drugs, TH - thyroid hormones.
516
Treatment of Graves' disease in the former USSR
Acta Med. Aust. 14: 61, 1987.
Europe (ETA) and Japanese surveys in which surgery represented a significant fraction of the respondents' choice, respectively 51 % and 31 %. In conclusion, the survey has outlined the present trends for the management of hyperthyroidism due to Graves' disease in the USSR. The comparison with similar surveys in other parts of the world, and more significantly with Europe, provides guidelines for the improvement of medical care and future research in thyroidology in our country.
4. Auf'mkolk M., Lagasse R., Glinoer D., Hesch D. Diagnostic und Therapie der Basedow-hyperthyreose. Ergebnis der Bundesdeutchen Umfrage 1987. Med. Klin. 83: 590, 1988. 5. Malinsky M., Glinoer D., Lagasse R. Le Traitement de la maladie de Basedow - resultats d'une enquete en 1987. Ann. Endocrinol. (Paris) 48: 185, 1987. 6. Fdez Soto M., Escobar-Jimenez F., Gonzales Jimenez A., Sanches Franco F. Diagnostico y tratamento de la enfermedad de Graves. Resultados de una encuesta nacional en 1987. Endocrinologie 35: 166, 1988.
REFERENCES 1. Glinoer D., Hesch D., Lagasse R., Laurberg P. The management of hyperthyroidism due to Graves' disease in Europe in 1986. Results of an international survery. Acta Endocrinol. (Copenh.) 115 (Suppl. 285): 1, 1987. 2. Glinoer D., Hesch D., Laurberg P., Malinsky P., Haak B., Fritzsche H., Lagasse R. Europe: "Between Country" diversity in the management of hyperthyroidism due to Graves' disease. In: Nagataki S., Torizuka K. (Eds.), The Thyroid. Excerpta Medica, Amsterdam, New York, Oxford 1988, p. 63. 3. Fritzsche H. Diagnose und Therapie der BasedowHyperthyreose.
7. Solomon B., Glinoer D., Lagasse R., Wartofsky L. Current trends in the management of Graves' disease. J. Clin. Endocrinol. Metab. 70: 1518, 1990. 8. Nagayama Y., Izumi M., Nagataki S. The management of hyperthyroidism due to Graves' disease in Japan in 1988. Endocrinol. Jpn. 36: 299, 1989. 9. Wartofsky L., Glinoer D., Solomon B., Nagataki S., Lagasse R., Nagayama Y., Izumi M. Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan, and the United States. Thyroid 1: 129, 1991.
517
The management of hyperthyroidism due to Graves' disease in the former USSR in 1991: results of a survey G. Gerasimov*, O. Judenitch*, E. Zdanova*, N. Jurieva*, I. Korostishevskaja*, K. Mushinskaja*, I. Dedov*, and D. Glinoer** *National Endocrinology Research Centre, Moscow, Russia, and **Hopital Universitaire Saint-Pierre, Department of Internal Medicine, Brussels, Belgium ABSTRACT. A survery of the current management of Graves' disease was performed in the USSR among members of All Union Endocrine Society. The questionnaire was based on the format used previously for a survey of members of European Thyroid Association. The aim of a similar survery in the USSR was to obtain a comprehensive pattern of management of Graves' disease in Soviet endocrinology clinics and to compare medical attitudes in the former USSR to those in other European countries. One hundred and twenty questionnaires were mailed with 55 returned (46%). The responses originated from 33 cities, representing major endocrinology centers of the former Soviet Republics. Initial diagnosis was conducted both in hospitals (55%) and ambulatory care settings (45%). Thyroid scintigraphy was requested by 42.3% of the respondents; a majority of
them (90%) used 1311. Thyroid ultrasonography was performed in more than 50% of cases. Measurements of cholesterol, total T4 and T3 were the most frequent laboratory tests requested to confirm the diagnosis. For the treatment with ATD, methimazole was the exclusive choice (PTU is not currently in use in the USSR). Beta-blocking agents were prescribed by a majority of respondents. For the long term treatment, a combination procedure of MMI and thyroid hormones was clearly preferred by almost 3/4 of the respondents. A fixed period of treatment was preferred by 62% of the respondents, with a duration of therapy of 18-24 months. Surgery for treatment of the index patient was chosen by only 6%, and radioiodine by 3%. The number of responses was too limited to attempt any characterization of the two latter modalities.
INTRODUCTION
distinctions, as well as similarities in the diagnostic and therapeutic approaches to the management of hyperthyroidism due to Graves'/Basedow disease (HGBD) in the different countries surveyed. Since no data were available from "Eastern" Europe, the aim of a similar survey in the USSR was to obtain an accurate comprehensive pattern of the management of HGBD in endocrinology clinics and to compare medical attitudes in the USSR to those in other European countries,
In 1987, the results of a survey of the members of the European Thyroid Association (ETA) on the management of Graves'/Basedow disease were reported by Glinoer et al. (1). The aim of the survey was to evaluate how expert thyroidologists employ the available diagnostic procedures and carry out therapy, given three therapeutic options of antithyroid drugs (ATD), radioiodine (RI) and surgery (S). Shortly thereafter, national surveys in Europe, based on the questionnaire employed for the ETA survey, were carried out in the Netherlands (2), Austria (3), Germany (4), France (5) and Spain (6). More recently, similar surveys were conducted in the United States (7) and Japan (8), and the comparative results of the three regional surveys have recently been reported (9). The surveys showed both striking
MATERIALS AND METHODS The questionnaire employed in the present survey was based on the original format proposed by ETA in 1986 (1). The questionnaire was translated into Russian with only minor modification and adaptation. The questionnaire was divided into two sections. In the first section, the case of a hypothetical patient was presented and respondents were asked to select in vivo and in vitro tests as they would in their daily practice. The second section dealt with the choice of therapy for the index patient. It was subdivided in three parts, according to
Key-words: Graves', Basedow disease, thyroid, hyperthyroidism, antithyroid drugs. Correspondence: Dr. D. Glinoer. Laboratory of Radioisotopes, Hopital Saint-Pierre, 322 rue Haute, B-1 000 Brussels, Belgium. Reiceived January 16,1992; accepted May 14,1992.
513
G. Gerasimov, 0. Judenitch, E. Zdanova, et al.
the choice of therapy, and dealt specifically with information on how the chosen treatment was implemented. The questionnaire was mailed to all senior members of the Soviet Endocrine Society, to local endocrinology dispensaries* and also to the endocrinology departments of High Medical Schools, Universities and Research Institutes. Participants were kept strictly confidential. The data analysis was performed in the National Endocrinology Research Centre in Moscow using conventional statistical methods. The index patient was described as follows: "A 43yr-old woman with moderate and overt signs of hyperthyroidism of 2-3 month duration. She is healthy, takes no medication and leads an active working life. She has two children and does not plan on being pregnant again. This is her first episode of hyperthyroidism. She has a diffuse goiter of 40-50 g, pulse rate of 105 beats/min and regular, and typical but minimal eye signs." Finally, in the questionnaire used for the ETA survey, there was also a section dealing with clinical variations of the index patient, in relation to the age, sex, severity of disease, size of goiter, etc. This section of the original survey was not assessed in the present study.
Table 1 - Frequency of ordered in vivo diagnostic tests for workup of the index patient by 55 centers of the former USSR. Test
Response*
Scintigraphy**
42
131 1
89 with uptake
82
without uptake
11
no answer 99m-Tc
7
11
with uptake (20 min)
33
without uptake
67
Ultrasonography**
53
Fine needle aspiration**
20
*Percent of positive answers. "Percentage of all responses.
netium pertechnetate (Tc-99m); 123 1 is not currently available in the USSR. Most respondents (82%) performed a thyroidal uptake with the scan. Thyroid ultrasonography was performed in more than 50% of the cases, mainly in association with thyroid scintigraphy. A fine needle aspiration of the thyroid was carried out by 20% of the respondents. Responses for in vitro laboratory tests are given in Table 2. Respondents were given a choice of 10 tests and were asked to select those they would actually use for the index patient. Measurements of cholesterol, total T4, T3 and basal TSH were the
RESULTS Survey responses One hundred and twenty questionnaires were mailed with 55 returned and completed (46%), and included in the data analysis. Twenty-two responses originated from single individuals and 33 were presented by teams. A total of 146 specialists in endocrinology/thyroidology took part in the survey. The responses originated from 33 cities, representing most major endocrinology centers of the former Soviet Republics: city hospitals (25.8%), endocrinology dispensaries (19.7%), Endocrine Research Institutes (31.8%), and High Medical Schools (22.7%).
Table 2 - Frequency of ordered in vitro diagnostic tests for workup of the index patient by 55 centers of the former USSR. Tests*
Diagnostic procedures Initial diagnosis was conducted both in hospitals (55%) and ambulatory (45%) care settings. Table 1 presents the results for in vivo tests. A thyroid scintigraphy would be obtained by only 42.4% of the respondents. Among them, the majority (90%) used 131 1 as primary isotope and only 10% - tech-
Frequency ("!o)
1. cholesterol
78.8
2. total T3
68.2
3. total T4
66.7
4. basal TSH
56.1
5. thyroglobulin autoantibodies
47
6. microsomal autoantibodies
21.2
7. serum thyroglobulin
21.2
8. TSH receptor antibodies
7.6
9. urinary iodine excretion
1.5
10. TRH test
o
Each test is considered as an individual item separate from any other test.
*Endocrinology dispensaries are specialized medical institutions (formerly-Antigoiter Stations) for outpatient and inpatient care.
*Listed in decreaSing order of frequency.
514
Treatment of Graves' disease in the former USSR
most frequent laboratory tests requested to confirm the diagnosis. The other in vitro tests were employed less frequently. The respondents from institutions with well equipped diagnostic departments made a larger use of tests. For example, total T4 determinations represented 86% of responses from Endocrine Research Institutes and Medical Schools, compared to 47% in Hospitals and 39% in Dispensaries.
Iy 6% and radioiodine therapy by 3% of the respondents. MODALITIES OF TREATMENT
1. A TO (Table 3). For the treatment with ATD, methimazole (MMI) represented the exclusive choice, since PTU is not currently in use in the USSR. Therapy was initiated with a daily dose of 25-40 mg (85% of respondents). The initial treatment was modified when the patient reached a euthyroid state (64% of responses), according to both clinical and laboratory criteria (70% of responses). Beta-blocking agents were prescribed by a majority of respondents, mainly during initial phase of treatment. Respondents were also asked whether the long term administration of ATD would consist of adapting the dose of MMI used alone, or in combination with thyroid hormones. The combination procedure was clearly preferred by almost three quarters of the respondents. Questions were asked in the survey in relation to duration of treatment and criteria used to withdraw ATD. A fixed period of treatment was preferred by 62% of the respondents and among them, the overwhelming preference was for a long duration of therapy: 18-24 month. Criteria used for withdrawal of therapy were clinical and biochemical euthyroidism (91% of responses). Those respondents associated with Research Institutes and High Medical Schools, and hence who disposed more easily of laboratory facilities, included the normalization of TSH-receptor antibodies and/or basal TSH in sensitive assays among the criteria. 2. Surgery. This modality for treatment of the index patient was chosen by only 6% of the respondents. Preoperative medical preparation associated MMI, Lugol solution and beta-bloking agents. The aim of surgery was conservative in all responses, i.e. minimal resection in order to keep the patient euthyroid without medication. After the surgery, follow up was organized in local policlinics. Moreover, 25% of the respondents indicated that organization of the follow up would influence the surgical strategy. 3. Radioiodine administration. Only 3% of the respondents chose this modality. The number of responses was too limited to attempt any characterisation of the modalities employed.
Therapeutic choices Once the diagnosis was established, the question asked was: "In this patient, what is the basic treatment that you would advocate, assuming that the patient leaves the decision of therapy entirely to you?" For this case of moderate hyperthyroidism, clinicians almost unanimously recommended treatment with ATD (91 %). Surgery was chosen by on-
Table 3 - Modalities of antithyroid drug treatment employed by specialists of 55 centers of the former USSR. Initial dose of MMI 20mg
Frequency (%) 5
20-30 mg
13.3
30mg
55
30-40 mg
15.2
>40mg
6.7
no information
3.3
Modification of initial treatment after reaching a euthyroid state
64
after a fixed period
26
2-3 weeks
18
3-4 weeks
4
up to 3 months
4
according to pulse rate
10
Criteria of modification laboratory data alone
o
clinical findings alone
30
both
70
Beta-blocking agents during initial treatment
70
throughout medical treatment
23.3
not at all Combination of MMI and thyroid hormones
DISCUSSION The present survey represented an effort to analyze medical strategies for the management of Graves' disease within the former USSR. The design previously used for the ETA survey, with slight modifica-
7.7 73.3
MMI - methimazole.
515
G. Gerasimov, 0. Judenitch, E. Zdanova, et at.
tion, was used to organize the questionnaire which was mailed to all senior members of AUES (All Union Endocrine Society), the local Endocrine dispensaries, the divisions of Endocrinology of High Medical Schools and Universities. The response rate, although below 50%, represents most important thyroid centers in our country. It should also be noted that the original ETA survey, and its application to the USA and Japan more recently (7, 8) included an important section dealing with clinical variations of the index case, namelyon the influence of the age and sex of patients, severity of disease, and recurrence of hyperthyroidism on the responses. Since it was known that in the USSR the major form of therapy was the administration of ATD, this part of the original questionnaire was deleted from the present survey. The results of the present survey should primarily be compared with those obtained in Europe and Japan, since the overall modalities of the management of Graves' hyperthyroidism are strikingly different in the USA. Table 4 lists the main results in the USSR, Europe (ETA) and Japan. There was consensus in Europe (ETA) and Japan for the evaluation of patients in an outpatient setting, while in the USSR the situation was markedly different. Most patients are evaluated in a hospital setting in the USSR because of the lack of facilities and qualified endocrinologists in many local policlinics. Also, the main radionuclide used for in vivo testing was 131 1, because 123 1 is not available in the USSR and the supply of Tc-99m generators remains presently insufficient. The soviet radiopharmaceutical industry produces RIA kits for the determination of total T4 and T3, thyroglobulin and TG-antibodies. The determination of serum TSH (including second generation "sensitive" assays) depends on import from the West, and is therefore practically not available.
These factual constraints explain why fewer in vitro tests are carried out in the USSR and only the determination of total T4 and T3 remains the most common method used for the in vitro evaluation of thyroid function. Similarly, since immunological techniques, such as the determination of microsomal and TSH-receptor antibodies, are only available in specialized Research Institutes - and their use hence limited in current medical practice - fine needle aspiration and ultrasonography of the thyroid gland are more frequently used in the USSR. One of the major findings of the present survey was the almost unanimous choice of antithyroid drugs for the treatment of the index case. This is in keeping with the results observed in Europe (ETA) and Japan, and in contrast with USA, where 70% of the respondents preferred radioiodine therapy. Methimazole was used in all instances and the shortage of laboratory facilities was the main reason for adjusting the dosage of MMI according mainly to clinical criteria. As in Europe (ETA), a fixed period before the withdrawal of treatment was the preferred choice of a majority of respondents. Medical treatment was of long duration, 2 yr in average. The "block and replace" technique, i.e. the combination of ATD and thyroid hormones was employed more frequently in the USSR, in comparison with Europe (ETA) and Japan. In regard to the use of surgical thyroidectomy, the present survey as well as previous ones in different parts of the world, showed that its use was extremely limited for Graves' disease. The main indications for the surgical treatment of toxic diffuse goiter in the USSR are limited to goiters of large size, recurrence of thyrotoxicosis after treatment with ATD and rare instances, such as hematologic or allergic complications from ATD. The presence of a large goiter was the only occurrence in the
Table 4 - Summary of the major differences between the results in Japan, Europe (ETA) and the USSR. Japan
Europe (ETA)
USSR
Radionuclide
123 1
1231/99mTc
131 1
Use of in vitro diagnostic tests
many
moderate
moderate
Ultrasonography
25%
21%
53%
Fine needle aspiration
rare
rare
relatively frequent
Use of ATD
MMI/PTU
MMI/PTU
MMlonly
adjustment of the daily dosage
according to thyroid function
after a fixed period
according to clinical Criteria
long term follow up
ATD alone in 93%
ATD alone/ATD+ TH 55%/45%
ATD+ TH 73%
withdrawal of ATD treatment
use of specific criteria
after a fixed period (12 month)
after a fixed period (24 month)
MMI - methimazole, PTU - propylthiouracil, ATD - antithyroid drugs, TH - thyroid hormones.
516
Treatment of Graves' disease in the former USSR
Acta Med. Aust. 14: 61, 1987.
Europe (ETA) and Japanese surveys in which surgery represented a significant fraction of the respondents' choice, respectively 51 % and 31 %. In conclusion, the survey has outlined the present trends for the management of hyperthyroidism due to Graves' disease in the USSR. The comparison with similar surveys in other parts of the world, and more significantly with Europe, provides guidelines for the improvement of medical care and future research in thyroidology in our country.
4. Auf'mkolk M., Lagasse R., Glinoer D., Hesch D. Diagnostic und Therapie der Basedow-hyperthyreose. Ergebnis der Bundesdeutchen Umfrage 1987. Med. Klin. 83: 590, 1988. 5. Malinsky M., Glinoer D., Lagasse R. Le Traitement de la maladie de Basedow - resultats d'une enquete en 1987. Ann. Endocrinol. (Paris) 48: 185, 1987. 6. Fdez Soto M., Escobar-Jimenez F., Gonzales Jimenez A., Sanches Franco F. Diagnostico y tratamento de la enfermedad de Graves. Resultados de una encuesta nacional en 1987. Endocrinologie 35: 166, 1988.
REFERENCES 1. Glinoer D., Hesch D., Lagasse R., Laurberg P. The management of hyperthyroidism due to Graves' disease in Europe in 1986. Results of an international survery. Acta Endocrinol. (Copenh.) 115 (Suppl. 285): 1, 1987. 2. Glinoer D., Hesch D., Laurberg P., Malinsky P., Haak B., Fritzsche H., Lagasse R. Europe: "Between Country" diversity in the management of hyperthyroidism due to Graves' disease. In: Nagataki S., Torizuka K. (Eds.), The Thyroid. Excerpta Medica, Amsterdam, New York, Oxford 1988, p. 63. 3. Fritzsche H. Diagnose und Therapie der BasedowHyperthyreose.
7. Solomon B., Glinoer D., Lagasse R., Wartofsky L. Current trends in the management of Graves' disease. J. Clin. Endocrinol. Metab. 70: 1518, 1990. 8. Nagayama Y., Izumi M., Nagataki S. The management of hyperthyroidism due to Graves' disease in Japan in 1988. Endocrinol. Jpn. 36: 299, 1989. 9. Wartofsky L., Glinoer D., Solomon B., Nagataki S., Lagasse R., Nagayama Y., Izumi M. Differences and similarities in the diagnosis and treatment of Graves' disease in Europe, Japan, and the United States. Thyroid 1: 129, 1991.
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