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Abstrak :
Penyakit Graves merupakan penyakit autoimun pada kelenjar tiroid dengan manifestasi berbagai sistem organ, termasuk sistem kardiovaskular akibat hipertiroid. Pada pasien hipertiroid terjadi peningkatan fungsi sistolik ventrikel kiri dibandingkan populasi normal. Beberapa penelitian tentang kadar hormon tiroid mendapatkan hasil yang berbeda-beda. Hipotesis pada penelitian ini adalah peningkatan kadar hormon tiroid akan diikuti peningkatan fungsi ventrikel kiri. Tujuan Diketahui korelasi kadar tiroksin bebas dan fraksi ejeksi ventrikel kiri pada pasien Graves yang belum diobati. Metode Pada penelitian potong lintang ini digunakan kadar tiroksin bebas sebagai parameter hormon tiroid dan fraksi ejeksi ventrikel kiri (LVEF) menurut cara Simpson yang dimodifikasi dengan ekokardiografi sebagai parameter fungsi sistolik ventrikel kiri. Kadar tiroksin bebas diperiksa di laboratorium sedangkan fraksi ejeksi ventrikel kiri cara Simpson dinilai dengan alat ekokardiografi. Hasil Didapatkan 10 pasien, 7 laki-laki dan 3 perempuan, dengan usia 18-52 tahun. Lama gejala dirasakan pasien 2-12 bulan. Pada pasien didapatkan rerata kadar fT4 5,75 (SB 0,96) ngldL dan rerata fraksi ejeksi ventrikel kiri 70,57 (SB 4,50) %. Didapatkan koefisien korelasi positif antara kadar tiroksin bebas dan fraksi ejeksi ventrikel kiri (r=0,711, p=0,021) pada pasien Graves yang belum diobati Kesimpulan Pada penelitian ini didapatkan korelasi positif kuat antara kadar tiroksin bebas (fT4) dan fraksi ejeksi ventrikel kiri (LVEF) pada pasien Grave yang belum mendapat pengobatan.

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Graves' disease is an autoimmune disease of thyroid gland which can be manifested in many organ system, especially cardiovascular system due to hyperthyroid. Hyperthyroid patients have a higher left ventricular systolic function than normal. Several studies of correlation between thyroid hormone level and cardiac function have showed different results. The hypotesis tested in this study is the increasing thyroid level will followed by the increase of left ventricular systolic function in Graves' disease. Objective To determine the correlation between thyroid hormone level and left ventricular ejection fraction in newly diagnosed Graves' patients. Methods In this cross-sectional study, we use the free thyrosine level as a parameter of thyroid hormon and use left ventricular ejection fraction as a parameter of left ventricular systolic function. Free thyroxine level was measured in the laboratory and the LVEF were assessed by Simpson's methods of echocardiography study. Results Ten patients (7 men and 3 women; age 18-52 years old) were studied. Their average of ff4 was 5.75 (SD 0.96) ngldL and their average of LVEF was 70.57 (SD 4.50) %. There was positive correlation coefficient between free thyroxine level and left ventricular ejection fraction (r=0.711, p=0.021) in newly diagnosed Graves' patients. Conclusion In this study there was strong positive correlation between free thyroxine (fT4) and left ventricular ejection fraction (LVEF) in newly diagnosed Graves' patients.

Abstrak :
Latar belakang. Pada penyakit graves (GD), konsentrasi vitamin D berbanding terbalik dengan titer antibodi dan berbanding lurus dengan status remisi. Pembentukan autoantibodi diawali dari pajanan self antigen oleh sel dendritik (DC), sebagai antigen presenting cell (APC), ke sel T naif. Kemampuan DC sebagai APC ditentukan oleh tingkat kematangannya. Sel dendritik, APC utama pada GD, bersifat lebih aktif dalam respons imun dibandingkan dengan subjek sehat. Studi pada SLE, MS, dan penyakit crohn menunjukkan efek imunoregulator vitamin D terutama melalui hambatan pematangan DC sehingga fungsi imunogenitasnya berkurang. Tujuan. Mengetahui efek 1,25-D3 in vitro dan 1α-D3 in vivo terhadap pematangan DC pasien GD Metode. Pada periode Mei 2014 sampai dengan Maret 2015 dilakukan studi eksperimental dan klinis, masing-masing pada 12 dan 25 pasien GD fase hipertiroid. Pada studi eksperimental, dilakukan kultur monocyte derived dendritic cell (MDDC) pasien GD dengan atau tanpa intervensi 1,25-D3 in vitro pada tahap monosit dan maturasi distimulasi dengan lipopolysaccharide (LPS). Pada studi klinis, sebanyak 12 dan 13 pasien GD, masing-masing mendapatkan 1α-D3 dan plasebo selama 8 minggu, di samping mendapatkan terapi standar PTU 100 mg 3 kali sehari. Kultur MDDC dilakukan sebelum dan sesudah suplementasi dan dilakukan perbandingan pematangan DC sebelum dan sesudah suplementasi pada kedua kelompok. Pematangan DC dilihat dari ekspresi penanda DC (HLA-DR, CD80, CD40, CD83, CD14, dan CD206) dan rasio sitokin IL-12/IL-10 pada supernatan kultur. Hasil. Pada studi in vitro, pascastimulasi LPS, DC yang dikultur dengan 1,25-D3 menunjukkan ekspresi HLA-DR, CD80, CD40, dan CD83 lebih rendah serta ekspresi CD14 dan CD206 yang lebih tinggi dibandingkan dengan DC yang dikultur dengan LPS saja. Pada DC yang dikultur dengan 1,25-D3, didapatkan rasio IL-12/IL-10 lebih rendah daripada DC tanpa 1,25-D3. Pada studi klinis, apabila dibandingkan antara ekspresi penanda DC serta rasio IL-12/IL-10 sebelum dan sesudah suplementasi 1α-D3 selama 8 minggu, belum didapatkan perbedaan yang bermakna pada ekspresi penanda DC dan rasio sitokin IL-12/IL-10. Simpulan. Pemberian 1,25-D3 in vitro menghambat pematangan DC pasien GD, sedangkan efek pemberian 1α-D3 in vivo terhadap pematangan DC belum dapat ditunjukkan pada penelitian ini. ...... Background. In graves? disease (GD), vitamin D levels is inversely proportional to antibody titer and proportionally associated with remission status. The development of autoantibody is initiated by self-antigen exposure by dendritic cells (DC) as the antigen presenting cells (APC) to the naïve T cells. The ability of DC as APC is determined by its maturity level. Dendritic cells, the major APC in GD, have more active immune responses than those in healthy subjects. Studies on systemic lupus erythematosus (SLE), multiple sclerosis (MS) and crohn?s disease have demonstrated immunoregulator effects of vitamin D, mainly through inhibition of DC maturation, which may lead to lower immunogenic function. Aim. To identify the effect of 1,25-D3 in vitro and 1α-D3 in vivo on DC maturation in patients with GD. Method. Our study consisted of an experimental and a clinical study started from May 2014 until March 2015, which was conducted in 12 and 25 GD patients with thyrotoxicosis, respectively. In the experimental study, cultures of monocyte derived dendritic cell (MDDC) of GD patients were performed, with or without intervention of 1,25-D3 in vitro at monocytic phase and the maturation was stimulated by lipopolysaccharide (LPS). In the clinical study, there were 12 GD patients who received 1α-D3 supplementation and 13 GD patients who received placebo for 8 weeks, in addition to the standard treatment of PTU 100 mg three times a day. MDDC cultures and comparison of DC maturation were performed before and after the supplementation for both groups. DC maturation was evaluated based on the expression of DC markers (HLA-DR, CD80, CD40, CD83, CD14 and CD206) and the ratio of cytokines IL-12/IL-10 levels in the culture supernatants. Results. In the in vitro study and following the LPS stimulation, DC cells cultured with 1,25-D3 showed lower expression of HLA-DR, CD80, CD40 and CD83 and higher expression of CD14 and CD206 compared to DC cultured with LPS alone. DC, which were cultured with 1,25-D3 had lower ratio of IL-12/IL-10 levels than those cultured without 1,25-D3. In the clinical study, when the expression of DC marker as well as the ratio of IL-12/IL-10 levels between before and after the 8-week supplementation of 1α-D3 were compared, we found no significant difference on the expression of DC markers and the ratio of IL-12/IL10. Conclusion. In vitro 1,25-D3 supplementation inhibits DC maturation in patients with GD; while the effects of in vivo 1α-D3 treatment on DC maturation have not been clearly demonstrated in the present study yet.

Abstrak :
Latar belakang: Sekitar 50% pasien penyakit Graves mengalami kekambuhan setelah obat antitiroid diberhentikan. Padahal penyakit Graves yang kambuh umumnya bersifat lebih berat, sehingga membutuhkan terapi yang lebih agresif. Dengan demikian penting untuk mengetahui faktor untuk memprediksi kekambuhan penyakit Graves. Faktor risiko kekambuhan penyakit Graves di antaranya adalah usia, tanda klinis, faktor lingkungan, serta faktor genetik. Gen SCGB3A2 merupakan salah satu gen yang berkaitan dengan penyakit Graves. Genotip AA dan GA, serta alel A gen SCGB3A2 rs1368408 diketahui merupakan faktor risiko timbulnya penyakit Graves. Namun, gen SCGB3A2 rs1368408 belum diketahui asosiasinya dengan kekambuhan penyakit Graves. Tujuan: Mengetahui hubungan polimorfisme gen SCGB3A2 rs1368408 dengan kekambuhan penyakit Graves. Metode: Desain penelitian ini adalah penelitian potong lintang dengan total 77 sampel. Sampel yang digunakan adalah DNA yang telah diisolasi dari pasien yang telah menjalani terapi obat antitiroid selama ≥12 bulan. Sampel dipilih dengan metode consecutive sampling. Data yang diambil yaitu genotip dan alotip gen SCGB3A2 rs1368408 melalui teknik tetra-primer ARMS-PCR. Sampel dikelompokkan sesuai dengan kekambuhannya dan dilihat frekuensi genotip dan alotip dari masing-masing kelompok. Data juga dianalisis dengan uji chi-square atau uji Fisher untuk melihat asosiasi genotip dan alotip gen SCGB3A2 rs1368408 dengan kekambuhan penyakit Graves. Hasil: Frekuensi genotip pada keseluruhan sampel pasien penyakit Graves didapatkan 98,7% GG dan 1,3% GA. Pada kelompok kambuh didapatkan genotip 97,8% GG dan 2,2% GA, serta alotip 98,9% alel G dan 1,1% alel A. Sedangkan pada kelompok tidak kambuh 100% memiliki genotip GG, sehingga didapatkan frekuensi alotip 100% alel G. Dari analisis menggunakan uji Fisher, tidak didapatkan perbedaan signifikan antara genotip gen SCGB3A2 rs 1368408 dan kekambuhan penyakit Graves (p=1.000). Analisis uji Fisher pada alotip gen SCGB3A2 rs1368408 juga menunjukkan tidak adanya perbedaan signifikan dengan kekambuhan penyakit Graves (p=1.000). Simpulan: Tidak terdapat asosiasi genotip atau alotip gen SCGB3A2 rs1368408 dengan kekambuhan penyakit Graves. ...... Background: Approximately 50% of Graves’ disease patients experience a relapse after discontinuation of antithyroid drugs. Relapsed Graves’ disease patients are generally more severe and require more aggressive therapy. Thus, it is important to know the factors that can predict the relapse of Graves’ disease. Age, clinical signs, environment, and genetic are some of the risk factors for Graves’ disease relapse. SCGB3A2 gene is one of the genes associated with Graves’ disease. Genotype GA and AA, as well as alelle A of SCGB3A2 gene rs1368408 are known to be risk factors for Graves’ disease. However, the association between SCGB3A2 gene rs1368408 and relape of Graves’ disease is not yet known. Objective: To determine the correlation between the polymorphism of SCGB3A2 gene rs1368408 and Graves' disease relapse. Methods: Study design of this study was cross-sectional with a total of 77 samples. The sample used in this study was DNA that had been isolated from patients who have received antithyroid drug treatment for ≥12 months. Samples were selected through consecutive sampling method. The data taken were genotypes and allotypes of SCGB3A2 gene rs1368408 using tetra-primer ARMS-PCR technique. Samples were grouped according to the incidence of relapse. The genotype and allotype frequency of each group was observed. Data were also analyzed using chi-square test or Fisher’s exact test to determine the association of genotype and allotype of SCGB3A2 gene rs1368408 with Graves’ disease relapse. Results: The genotype frequency in the entire sample of patients with Graves’ disease was found to be 98.7% GG and 1.3% GA. In the relapse group, the genotype observed was 97.8% GG and 2.2% GA whereas the allotype frequency in this group was 98.9% G allele and 1.1% A allele. All samples in non-relapse group had GG genotype (100%), thus the allotype frequency was 100% G allele. Analysis using Fisher’s exact test showed no significant difference between genotype of SCGB3A2 gene rs1368408 and Graves’ disease relapse (p=1.000). Fisher's exact analysis of SCGB3A2 gene rs1368408 allotype also found no significant difference with Graves' disease recurrence (p=1.000). Conclusions: There was no association between genotype or allotype of SCGB3A2 gene rs1368408 and Graves' disease relapse.

Abstrak :
ABSTRAK
LATAR BELAKANG: Oftalmopati adalah manifestasi ekstratiroid yang paling umum dan serius pada penderita penyakit Graves. Oftalmopati Graves terjadi karena adanya inflamasi autoimun kronis pada jaringan orbita dan retro-orbita. Keadaan oftalmopati secara signifikan menurunkan kualitas hidup penderita penyakit Graves. Patofisiologi oftalmopati Graves melibatkan ikatan CD154 dan CD40 yang transkripsinya diregulasi oleh faktor transkripsi AKNA. Pada penelitian ini dianalisis variasi genetik gen AKNA rs3748178 dan kadar sCD154 serta hubungannya dengan derajat oftalmopati pada penderita penyakit Graves. METODE: Penelitian ini merupakan studi potong lintang dengan melibatkan 60 sampel yang dikelompokkan berdasarkan sistem klasifikasi NOSPECS. Analisis variasi genetik dilakukan dengan teknik PCR-RFLP dan pengukuran kadar sCD154 dengan teknik ELISA. Analisis statistik yang digunakan adalah uji chi-square dan uji Kruskal-Wallis, dengan kemaknaan p<0,05. HASIL: Hasil penelitian menunjukkan adanya hubungan yang bermakna antara genotip gen AKNA rs3748178 dengan derajat oftalmopati Graves pada kelompok derajat 1-3 dan 4-6 yang dibandingkan dengan kelompok derajat 0 (p=0,011). Genotip GG berisiko 14 kali lebih besar untuk mengalami oftalmopati derajat 4-6. Terdapat hubungan yang bermakna antara alotip gen AKNA rs3748178 dengan derajat oftalmopati Graves pada kelompok derajat 1-3 dan 4-6 yang dibandingkan dengan kelompok derajat 0 (p=0,003). Alotip A berisiko 13 kali lebih besar untuk mengalami oftalmopati derajat 4-6. Kadar sCD154 berbanding lurus dengan derajat keparahan oftalmopati Graves (p<0,001). Genotip GG gen AKNA rs3748178 pada kelompok derajat 4-6 menunjukkan kadar sCD154 yang paling tinggi (p=0,01). KESIMPULAN: Variasi genetik AKNA ekson 11 rs3748178 dan kadar sCD154 berperan terhadap derajat keparahan oftalmopati Graves

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ABSTRACT
BACKGROUND: Ophthalmopathy is the most common and serious extrathyroidal manifestation of Graves' disease. Graves? Ophthalmopathy occurs due to chronic autoimmune inflammatory of orbital and retro-orbital tissue. Graves? Ophthalmopathy significantly impairs the quality of life of patients with Graves' disease. Pathophysiology of Graves? Ophthalmopathy involves CD154-CD40 binding which regulated by transcription factor AKNA. This study analyzed the genetic variation of AKNA rs3748178 and sCD154 levels associated with ophthalmopathy grade of patients with Graves' disease. METHODS: This research is a cross sectional study examining 60 samples grouped according to NOSPECS classification system. Genetic variation was analyzed with PCR-RFLP. Serum sCD154 level was measured with ELISA. Chi-square and Kruskal-Wallis test used for statistical analysis, p value less than 0,05 was considered significant. RESULTS: The results showed a significant relationship between genotype of AKNA rs3748178 with Graves? ophthalmopathy severity (p=0.011). There is a significant relationship between alotype of AKNA rs3748178 with Graves? ophthalmopathy severity (p=0.003). Level of sCD154 in serum was considered significant with Graves? ophthalmopathy severity (p<0.001). Genotype GG of AKNA rs3748178 in grade 4-6 group showed the highest level of sCD154 (p=0.01). CONCLUSIONS: Genetic variation of AKNA rs3748178 and sCD154 level contribute to the severity of Graves? ophthalmopathy

Abstrak :
Latar Belakang: Penelitian ini bertujuan untuk mengetahui faktor-faktor yang memengaruhi terjadinya kekambuhan seperti, faktor klinis yaitu usia dan jenis kelamin, riwayat keluarga, besarnya ukuran kelenjar tiroid, ada tidaknya oftalmopati; faktor genetik yang berperan pada kejadian GD; dan faktor imunologi yaitu jumlah sel T regulator, kadar interleukin 10 (IL-10), interleukin 17 (IL-17) dan antibodi pada reseptor tiroid (TRAb). Metode: Penelitian ini merupakan studi kasus kontrol yang membandingkan 36 pasien GD yang kambuh dan 36 pasien GD yang tidak kambuh. Pemeriksaan polimorfisme gen dilakukan dengan metode PCR RFLP. Pemeriksaan jumlah sel T regulator dengan flowsitometri. Pemeriksaan IL-10, IL-17 dan TRAb dengan ELISA. Hasil: Analisis hasil penelitian membuktikan hubungan antara kekambuhan dengan faktor keluarga (p 0,008), usia saat didiagnosis (p 0,021), oftalmopati derajat 2 (p 0,001), kelenjar tiroid yang membesar melebihi tepi lateral muskulus sternokleidomastoideus (p 0,040), lamanya periode remisi (p 0,029), genotip GG gen CTLA-4 nukleotida 49 kodon 17 pada ekson 1 (p 0,016), genotip CC gen tiroglobulin nukleotida 5995 kodon 1980 pada ekson 33 (p 0,017), genotip CC gen TSHR SNP rs2268458intron 1 (p 0,003), jumlah sel T regulator (p 0,001), kadar IL-10 (p 0,012) dan kadar TRAb (p 0,002). Penelitian ini juga membuktikan hubungan antara faktor klinis yaitu faktor keluarga, usia, oftalmopati, pembesaran kelenjar tiroid dan lamanya periode remisi; dengan faktor genetik dan respons imun. Simpulan: Polimorfisme genotip gen CTLA-4 nukleotida 49 kodon 17 ekson 1, gen tiroglobulin nukleotida 5995 kodon 1980 ekson 33, gen TSHR SNP rs2268458 intron 1 dan sel T regulator berperan sebagai faktor risiko kambuh pada pasien penyakit Graves. ...... Background: The management of Graves? disease (GD) is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission and more than 50 percent of patients who had remission may be at risk for relapse after the drug is stopped. This study was aimed to identify factors affecting relapse of Graves? Disease Methods: This was a case-control study comparing 36 patients relapsed GD and 36 patients who did not relapse. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure serum IL-10, IL-17 and TRAb. Results: The analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p 0.008), age at diagnosis (p 0.021), 2nd degree of Graves? ophthalmopathy (p 0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p 0.040), duration of remission period (p 0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p 0.016), CC genotype of thyroglobulin gene on the nucleotide 5995 at codon 1980 of exon 33 (p 0.017), CC genotype of TSHR gene on the rs2268458 of intron 1 (p 0.003), the number of regulatory T cells (p 0.001), the levels of IL-10 (p 0.012) and TRAb levels (p 0.002). This study also showed the association between clinical factors, which included family factors, age at diagnosis, ophthalmopathy, thyroid gland enlargement and the long periods of remission with genetic factors and immune response. Conclusion: Genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, thyroglobulin gene on the nucleotide 5995 at codon 1980 of exon 33, TSHR gene SNP rs2268458 of intron 1 and regulatory T cells play a role as risk factors for relapse in patients with Graves? disease.

Abstrak :
Penyakit Graves (GD) merupakan penyakit autoimun yang menyerang kelenjar tiroid dan menjadi penyebab utama terjadinya hipertiroidisme. Manifestasi klinis ekstratiroid yang umum terjadi pada pasien GD ialah oftalmopati Graves (OG). Salah satu penentu genetik yang terkait dengan respon autoimunitas baik pada GD atau OG ialah gen CD40. Penelitian ini dilakukan untuk melihat hubungan variasi genetik CD40 (rs1883832 dan rs11086998) dan kadar sCD40 terhadap derajat keparahan oftalmopati pada penderita Graves. Studi potong lintang ini menggunakan 60 sampel DNA dan serum pasien Graves yang dikategorikan ke dalam tiga kelompok, yaitu kelompok OG kelas 0, kelas I-III, dan kelas IV-VI. Analisis variasi genetik dilakukan dengan metode PCR-RFLP dan pengukuran kadar sCD40 menggunakan metode ELISA. Derajat keparahan OG dinilai menggunakan klasifikasi NOSPECS yang mana data diperoleh dari rekam medik pasien. Hasil yang diperoleh menunjukkan bahwa variasi gen CD40 pada bagian 5’UTR rs1883832 tidak memiliki hubungan yang bermakna dengan kadar sCD40 dan derajat keparahan OG (p>0,05), sedangkan pada ekson 9 rs11086998 tidak ditemukan variasi genetik (hanya diperoleh genotip CC dan alel C). SNP gen CD40 pada rs1883832 menunjukkan genotip TT dan alel T memiliki rata-rata kadar sCD40 yang lebih tinggi dibandingkan kelompok variasi genetik lainnya pada penderita Graves. Disimpulkan, variasi genetik CD40 pada 5’UTR rs1883832 dan ekson 9 rs11086998 tidak berhubungan dengan derajat keparahan OG. ......Graves' Disease (GD) is an autoimmune disease which causes hyperthyroidism by attacking the thyroid gland. The most common extra thyroid manifestation in GD is Graves' ophthalmopathy (OG). One of the genetic determinants associated with the autoimmune response to GD and OG is the CD40 gene. The aim of this study is to determine the association between genetic variation of CD40 gene (rs1883832 and rs11086998) and the serum level of sCD40 to the degree of ophthalmopathy severity in patients with Graves' disease. In this cross- sectional study, 60 DNA and serum of Graves patients were categorized into three groups; namely OG class 0, class I-III, and class IV-VI. Analysis of genetic variations were carried out using the PCR-RFLP method and ELISA method for the measurement of sCD40 levels. The severity of OG was assessed using NOSPECS classification where the data was obtained from medical records. The results showed that the genetic variation of the CD40 gene at 5’UTR rs1883832 does not have a significant association with sCD40 levels and degree of OG severity (p> 0.05). There was no genetic variation found in exon 9 rs11086998 with only CC genotypes and alleles C were obtained. SNP rs1883832 of the CD40 gene indicates that the TT genotype and the T allele have higher average of sCD40 levels compare to the other group of genetic variation in patient with Graves' disease. In conclusion, genetic variation in 5’UTR rs1883832 and exon 9 rs11086998 of CD40 gene have no correlation with the severity degree of OG.

Abstrak :
Latar belakang: Penyakit Graves merupakan penyakit autoimun yang memiliki kemungkinan untuk kambuh setelah remisi. Sebanyak 50% pasien berisiko mengalami kekambuhan setelah menyelesaikan terapi obat antitiroid (OAT). Salah satu prediktor kekambuhan penyakit Graves adalah faktor genetik. Gen PTPN22 rs2476601 merupakan gen yang berperan dalam persinyalan sel T. Polimorfisme pada gen ini dapat memicu proses autoimun pada penyakit Graves. Tujuan: Mengetahui hubungan polimorfisme gen PTPN22 rs2476601 terhadap risiko kekambuhan penyakit Graves. Metode: Penelitian ini adalah penelitian observasional dengan metode cross sectional. Subjek penelitian merupakan 80 sampel DNA pasien penyakit Graves yang telah mendapatkan terapi OAT selama >12 bulan. Kekambuhan pada pasien dinilai dalam 12 bulan pasca pasien berhenti menggunakan OAT. Pemeriksaan genotip gen PTPN22 rs2476601 dilakukan menggunakan teknik Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Hasil: Pada pasien penyakit Graves di Jakarta, frekuensi genotip GA ditemukan paling tinggi (77.5%) dibandingkan GG (18.75%) dan AA (3.75%). Genotip AA lebih sering ditemukan pada kelompok kambuh (6%) dibandingkan tidak kambuh (0%). Sementara itu, Genotip GA dan GG lebih sering ditemukan pada kelompok tidak kambuh (79% dan 21%) dibandingkan kambuh (77% dan 17%). Namun, hasil uji fisher tidak menunjukkan adanya perbedaan yang bermakna antara genotip gen PTPN22 rs2476601 dengan kekambuhan penyakit Graves (p=0.264). Frekuensi alotip alel A ditemukan lebih tinggi pada kelompok kambuh (45%) dibandingkan tidak kambuh (39%). Sedangkan, frekuensi alotip alel G ditemukan lebih tinggi pada kelompok tidak kambuh (61%) dibandingkan kambuh (53%). Namun, hasil uji chi-square juga tidak menunjukkan adanya perbedaan yang bermakna antara alotip gen PTPN22 rs2476601 dengan kekambuhan penyakit Graves (p=0.505). Kesimpulan: Polimorfisme gen PTPN22 rs2476601 tidak berhubungan dengan kekambuhan penyakit Graves pada populasi di Jakarta ......Background: Graves’ disease is an autoimmune disease that has a chance to recur after remission. 50% of patients have the risk of recurrence after completed anti-thyroid drugs (ATD) therapy. One of the recurrence predictors of Graves’ disease is the genetic factor. The PTPN22 rs2476601 gene is a gene involved in T cell signaling. Polymorphism in this gene may trigger the autoimmune process in Graves’ disease. Aim: Determine the association between PTPN22 rs2476601 gene polymorphism and the recurrence risk of Graves’ disease. Methods: This study was an observational study with a cross-sectional design. The subjects of this study were 80 DNA samples from patients with Graves’ disease who received ATD therapy for >12 months. Recurrence of the disease was assessed within 12 months after patients completed ATD therapy. Genotype examination of PTPN22 rs2476601 gene was performed using Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique. Results: Patients with Graves’ disease in Jakarta had the highest genotype frequency of GA (77.5%) compared to GG (18.75%) and AA (3.75%). AA genotype was more frequent in the recurrence group (6%) compared to non-recurrence (0%). In contrast, GA and GG genotype were more frequent in the non-recurrence group (79% and 21%) compared to recurrence (77% and 17%). However, the result of fisher test showed there was no significant difference between the genotype of PTPN22 rs2476601 gene and recurrence of Graves’ disease (p=0.264). The allotype frequency of A allele was higher in the recurrence group (45%) compared to non-recurrence (39%). Meanwhile, the allotype frequency of G allele was higher in the non-recurrence group (61%) compared to recurrence (53%). However, the result of chi-square test also showed there was no significant difference between the allotype of PTPN22 rs2476601 gene and recurrence of Graves’ disease (p=0.505). Conclusion: PTPN22 rs2476601 gene polymorphism is not associated with the recurrence of Graves’ disease in Jakarta’s population.

Abstrak :
Latar Belakang. Kualitas hidup merupakan keluaran klinis yang seringkali terlupakan pada pengkajian pasien penyakit Graves. Saat ini belum ada kuesioner kualitas hidup pasien gangguan tiroid yang tervalidasi dalam Bahasa Indonesia. Penelitian terkait kualitas hidup belum pernah dilakukan pada pasien penyakit Graves di Indonesia. Metode. Penelitian ini menggunakan desain potong lintang yang terbagi ke dalam dua tahap yaitu (1) validasi kuesioner ThyPRO dalam Bahasa Indonesia dan (2) pengambilan data kualitas hidup pasien penyakit Graves dan faktor-faktor yang memengaruhinya. Studi ini dikerjakan pada bulan Maret sampai November 2022 di Poliklinik Endokrin Metabolik RSCM, Jakarta, Indonesia. Hasil. 50 subjek pasien gangguan tiroid dan 150 subjek pasien penyakit Graves berpartisipasi masingmasing pada tahap pertama dan kedua penelitian ini. Tahap pertama studi ini menghasilkan kuesioner ThyPROid (Thyroid-Related Patient-Reported Outcome Indonesian version) atau “Kuesioner Kualitas Hidup Pasien Tiroid Berbahasa Indonesia” yang secara keseluruhan valid dan reliabel. Kualitas hidup pasien penyakit Graves yang diperoleh pada penelitian ini adalah baik (72,7%) dan kurang (27,3%). Faktor-faktor yang memengaruhi kualitas hidup kurang pada penelitian ini adalah Indeks Wayne dengan skor di atas 19 dan oftalmopati derajat sedang-berat dan aktif. Riwayat sudah diobati, baik dengan obat anti-tiroid, pembedahan maupun terapi iodium radioaktif merupakan faktor protektif bagi kualitas hidup kurang. Kesimpulan. Menggunakan kuesioner ThyPROid yang sudah divalidasi dalam Bahasa Indonesia, sebagian besar pasien penyakit Graves memiliki kualitas hidup yang baik. Faktor yang memengaruhi kualitas hidup kurang adalah Indeks Wayne, oftalmopati derajat sedang-berat dan aktif. Riwayat sudah diobati, baik dengan obat anti-tiroid, pembedahan maupun terapi iodium radioaktif, merupakan faktor protektif kualitas hidup kurang. Kata kunci. Penyakit Graves, kualitas hidup, Indonesia, ThyPRO, Indeks Wayne, oftalmopati, pengobatan, obat anti-tiroid, pembedahan, terapi iodium radioaktif. ......Introduction. Quality of life is a clinical outcomes which frequently forgotten in any assessment of patients with Graves’ disease. There is currently no questionnaire for quality of life assessment for patients with thyroid disease which are validated in Bahasa Indonesia. Study about quality of life has never been conducted in patients with Graves’ disease in Indonesia. Methods. This cross-sectional study divided into two phases, that is: (1) ThyPRO questionnaire validation in Bahasa Indonesia, and (2) data collection on quality of life in patients with Graves’ disease and the factors affected it. This study was conducted on March to November 2022 in Endocrine & Metabolic Polyclinic Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Results. 50 subjects of patients with thyroid disease and 150 subjects of patients with Graves’ disease participated each in the first and the second phase of the study. First phase of the study resulted with ThyPROid questionnaire (Thyroid-Related Patient Reported Outcome Indonesian version) which overall is valid and reliable. Quality of life in patients with Graves’ disease that were obtained from this study was good (72,7%) and poor (27,3%). Factors that affected poor quality of life in this study was higher score of Wayne Index (total score > 19) and moderate-to-severe degree and active Graves’ ophthalmopathy. History of treatment, either with anti-thyroid medication, surgery, or radioactive iodine therapy, was protective factor for poor quality of life. Conclusion. Using ThyPROid questionnaire which were validated in Bahasa Indonesia, most of the patients with Graves’ disease in this study has good quality of life. Factors which affected poor quality of life was high Wayne Index and moderate-to-severe degree and active Graves’ ophthalmopathy. History of treatment, either with anti-thyroid medication, surgery, or radioactive iodine therapy, was protective factor for poor quality of life.

Abstrak :
Background: graves disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA 4 gene on nucleotide 49 at codon 17 of exon 1, CTLA 4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves disease in Indonesia. Methods: this was a case control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. Results: the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA 4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). Conclusion: genetic polymorphisms of CTLA 4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in patients with Graves disease.