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During July 2019 to August 2020, a single-blind clinical trial was done to 36 patients with Graves' disease. At the beginning of the study, subjects were accommodated into 2 groups, 17 into PTU groups and 19 into methimazole groups. There were 24 subjects who finished the study, 13 from PTU group and 11 from methimazole group. Blood serum was collected for HOMA-IR, LDL-R, NFĸB, sICAM-1, sVCAM-1 and sE-selectin examination. Meanwhile stiffness and thickness of carotid artery was measured using PWV and cIMT.
This study was a single blind, randomized clinical trial study, conducted in Cipto Mangunkusumo National Referral Hospital from January 2019 to August 2020. We included all adult patient aged 18-65 years with newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month, who agreed to participate in the study. The exclusion criteria was pregnancy, history of coronary heart disease, known malignancy, current use of immunosuppressive medication, sepsis, thyroid crisis, or having allergic reaction to anti-thyroid drugs and other severe side effect. Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine, Universitas Indonesia with approval number KET-784/UN.2.F1/ETIK/PPM.00.02/2019.
Study participant was observed every month for 3 months. Anti-thyroid drugs (PTU or methimazole) were given according to true simple randomization with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist. At baseline visit, first and third month follow up, blood serum was collected to analyse HOMA-IR, LDL-R, NFĸB, sICAM-1, sVCAM-1 and sE-selectin, meanwhile PWV and cIMT were measured using radiofrequency ultrasound examination of carotid arteries.
Categorical data was presented in frequency (%), while numerical data was presented using mean (SD) if normally distributed or median (IQR) if not normally distributed. Correlation Pearson test was performed for normal distributed data and Spearman test for not normal distributed data. To analyze the changes in parameter from baseline, first and third month, repeated ANOVA and General Linear Model test was performed. For not normally distributed data, transformation into normally distributed data was performed and the data was presented as geometric mean (CI 95%).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PTU Group | Active Comparator | Propylthiouracil (PTU) was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist |
|
| Methimazole Group | Active Comparator | Methimazole was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propylthiouracil | Drug | PTU were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pulse Wave Velocity | Pulse wave velocity was measured using radio frequency ultrasound in supine position at both left and right carotid artery | Change from Baseline to 3 month follow-up |
| carotid intima media thickness | cIMT was measured using radio frequency ultrasound in supine position at both left and right carotid artery | Change from Baseline to 3 month follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| HOMA-IR | HOMA-IR was calculated from patient fasting blood glucose and fasting insulin, which both were obtained through serum of the patient. Fasting blood glucose was measured using ECLIA methods with Abbott reagent, while fasting insulin were measured using ELISA with D&G International Inc. kit | Change from Baseline to 3 month follow-up |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Indonesia | Jakarta Pusat | Jakarta Special Capital Region | 10430 | Indonesia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29089349 | Background | Bano A, Chaker L, Mattace-Raso FUS, van der Lugt A, Ikram MA, Franco OH, Peeters RP, Kavousi M. Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study. Circ Res. 2017 Dec 8;121(12):1392-1400. doi: 10.1161/CIRCRESAHA.117.311603. Epub 2017 Oct 31. | |
| 21660244 | Background |
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IPD would be share under specific request to the investigator
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| ID | Term |
|---|---|
| D006980 | Hyperthyroidism |
| D006111 | Graves Disease |
| D050197 | Atherosclerosis |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D005094 | Exophthalmos |
| D009916 | Orbital Diseases |
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| ID | Term |
|---|---|
| D011441 | Propylthiouracil |
| D008713 | Methimazole |
| ID | Term |
|---|---|
| D013889 | Thiouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 |
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This study was a single blind, randomized clinical trial study, conducted in Cipto Mangunkusumo National Referral Hospital from January 2019 to August 2020. We included all adult patient aged 18-65 years with newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month, who agreed to participate in the study. The exclusion criteria was pregnancy, history of coronary heart disease, known malignancy, current use of immunosuppressive medication, sepsis, thyroid crisis, or having allergic reaction to anti-thyroid drugs and other severe side effect.
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The care providers gave two choice of drug doses to the research assistant. The research assistant then give the participant their drugs based on the assignment from the randomisation.
The investigator and outcome assessor were blinded to the drugs which the participants received
| Methimazole | Drug | methimazole were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist. |
|
| LDL-R |
LDL-R was measured from the patient serum using ELISA with D&G International Inc. kit |
| Change from Baseline to 3 month follow-up |
| NFkB | NFkB was measured from the patient serum using ELISA with Cusabio kit | Change from Baseline to 3 month follow-up |
| sICAM-1 | sICAM-1 was measured from the patient serum using ELISA with D&G International Inc. kit | Change from Baseline to 3 month follow-up |
| sVCAM-1 | sVCAM-1 was measured from the patient serum using ELISA with D&G International Inc. kit | Change from Baseline to 3 month follow-up |
| sE-selectin | sE-selectin was measured from the patient serum using ELISA with D&G International Inc. kit | Change from Baseline to 3 month follow-up |
| Rizos CV, Elisaf MS, Liberopoulos EN. Effects of thyroid dysfunction on lipid profile. Open Cardiovasc Med J. 2011;5:76-84. doi: 10.2174/1874192401105010076. Epub 2011 Feb 24. |
| 21825964 | Background | Bilir C, Gokosmanoglu F, Caliskan M, Cinemre H, Akdemir R. Regression of the carotid intima media thickness by propylthiouracil therapy in Graves' hyperthyroidism. Am J Med Sci. 2012 Apr;343(4):273-6. doi: 10.1097/MAJ.0b013e31822a8284. |
| 12199623 | Background | Inaba M, Henmi Y, Kumeda Y, Ueda M, Nagata M, Emoto M, Ishikawa T, Ishimura E, Nishizawa Y. Increased stiffness in common carotid artery in hyperthyroid Graves' disease patients. Biomed Pharmacother. 2002 Jul;56(5):241-6. doi: 10.1016/s0753-3322(02)00195-6. |
| 27839806 | Background | Upala S, Wirunsawanya K, Jaruvongvanich V, Sanguankeo A. Effects of statin therapy on arterial stiffness: A systematic review and meta-analysis of randomized controlled trial. Int J Cardiol. 2017 Jan 15;227:338-341. doi: 10.1016/j.ijcard.2016.11.073. Epub 2016 Nov 9. |
| 39355401 | Derived | Wisnu W, Alwi I, Nafrialdi N, Pemayun TGD, Pantoro NI, Wijaya CN, Tahapary DL, Tarigan TJE, Subekti I. The Effects of Anti-thyroid Drugs on Lipoproteins and Insulin Resistance in Graves' Disease: A Randomized Clinical Trial. J Lipid Atheroscler. 2024 Sep;13(3):358-370. doi: 10.12997/jla.2024.13.3.358. Epub 2024 Jun 12. |
| D005128 |
| Eye Diseases |
| D006042 | Goiter |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |