Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis

Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis: Review on the Pathway of Insulin Resistance, Lipid, Inflammation, and Endothelial Dysfunction to Pulse Wave Velocity and Carotid Intima-Media Thickness

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%).

Hyperthyroidism, Graves Disease, Atherosclerosis, Pathophysiology, Insulin Resistance, Lipid Marker, Inflammatory Marker, PWV, 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.

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

Propylthiouracil (PTU) was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist

Methimazole was given with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist

PTU were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.

methimazole were given to participants with adjusted dosage according to patient clinical assessment at every visit by their own endocrinologist.

Pulse wave velocity was measured using radio frequency ultrasound in supine position at both left and right carotid artery

cIMT was measured using radio frequency ultrasound in supine position at both left and right carotid artery

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

Inclusion Criteria: Adult patients aged 18-65 years Newly diagnosed Graves' disease or no prior anti-thyroid drugs medication for more than 1 month Agreed to participate in the study Exclusion Criteria: Pregnancy History of coronary heart disease Known malignancy Current use of immunosuppressive medication sepsis, thyroid crisis Having allergic reaction to anti-thyroid drugs and other severe side effect

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