Hasil Pencarian  ::  Simpan CSV :: Kembali

Abstrak :
Defisiensi enzim 5 alfa-reduktase tipe 2 (D5AR2) merupakan penyakit genetik, yang disebabkan gangguan konversi testosteron (T) menjadi dihidrotestosteron (DHT). Diagnosis D5AR2 pada umumnya ditegakkan dengan rasio T/DHT dan analisis DNA gen SRD5A2, namun rasio T/DHT sering tidak konklusif, sehingga diperlukan pemeriksaan alternatif dalam diagnosis D5AR2, dalam hal ini dipilih rasio metabolit 5β/5αsteroid urin yakni rasio etiokolanolon/androsteron (Et/An) urin karena telah dilaporkan oleh beberapa peneliti dan juga karena tersedia di Indonesia. Penelitian ini bertujuan untukmembandingkan akurasi rasio T/DHT dan Et/An urin dalam diagnosis penyandang dan pembawa sifat D5AR2. Selain itu mengetahui pola mutasi gen SRD5A2 dan hubungan genotipe-fenotipe. Studi deskriptif potong-lintang dilakukan untuk mengetahui pola mutasi gen SRD5A2 dan hubungan genotipe-fenotipe dilakukandi Lembaga Eijkman, Jakarta sejak Juli 2016–September 2018. Studi komparatif dilakukan untuk membandingkan akurasi rasio T/DHT (dilakukan di Laboratorium Terpadu FKUI) dan rasio Et/An urin (dilakukan di Laboratorium Kesehatan Daerah DKI Jakarta) dalam mendiagnosis penyandang dan pembawa sifat D5AR2, dilanjutkan dengan analisis kurva ROC (receiver operating characteristics) masing-masing rasio, dengan baku emas analisis DNA gen SRD5A2. Enam puluh enam subjek penyandang 46,XY DSD dan 95 subjek keluarga peyandang direkrut dalam penelitian ini. Hasil analisis DNA gen SRD5A2 membagi subjek penyandang 46,XY DSD menjadi 37 subjek penyandang D5AR2 dan 29 subjek bukan penyandang D5AR2, dan subjek keluarga menjadi 53 subjek pembawa sifat dan 42 subjek bukan pembawa sifat D5AR2. Rasio T/DHT tidak berbeda bermakna antara penyandang dan bukan penyandang D5AR2, dan juga tidak berbeda bermakna antara pembawa sifat dan bukan pembawa sifat D5AR2. Nilai AUC rasio Et/An urin dalam mendiagnosis penyandang D5AR2 adalah 79,7% (IK 95% 69,0–90,4%, p < 0,001). Dengan nilai titik potong >0,95 didapatkan sensitivitas rasio Et/An urin dalam diagnosis D5AR2 adalah 67,57% dan spesifisitas 86,21%. Dengan nilai titik potong >0,99 didapatkan sensitivitas rasio Et/An urin dalam mendiagnosis pembawa sifat D5AR2 adalah 67,92% dan spesifisitas73,81%. Kombinasi rasio Et/An urin subjek penyandang dan salah satu keluarga dekatnya meningkatkan perkiraan akurasi diagnostik menjadi sangat baik (AUC menjadi 84,1% (IK 95% 74,3–93,9%, p < 0,001), dengan sensitivitas sangat baik (89,19%), namun spesifisitas kurang baik (57,69%). Enam jenis mutasi baru dideteksi, yaitu c.34delGinsCCAGC, R50H, W136stop, G191R, F194I, I253V, dan 7 mutasi lain. Tidak ada hubungan nyata genotipe dan fenotipe. ......The 5 alpha-reductase type 2 deficiency (5ARD2) is a genetic condition associated with impairment in conversion of testosterone (T) to dihydrotestosterone (DHT), leading to undervirilization in 46,XY individuals. Diagnosis of 5ARD2 is mainly established by T/DHT ratio and molecular analysis. Yet, the T/DHT ratio often yielded in conflicting results, and the available urinary ratio of etiocholanolone/androsterone (Et/An) was selected as an alternative test. This study aimedto compare the accuracy of T/DHT and urinary Et/An ratios in diagnosing 5ARD2 cases and carriers and to elaborate the molecular characteristics of SRD5A2 gene in 5ARD2 cases and the genotype and phenotype correlations. Descriptive and comparative cross-sectional studies were conducted at the Eijkman Institute, Jakarta in year 2016–2018. The accuracy of T/DHT and Et/An ratios were compared using ROC (receiver operating characteristics) curve analysis in the cases and carriers group with molecular analysis of SRD5A2 gene as the gold standard. The molecular characterization of SRD5A2 gene and genotype-phenotype correlations were described. Sixty six 46,XY DSD subjects and 95 subjects of their family members, who gave written consent or parental approval were recruited. Thirty seven 5ARD2 cases and 29 control were identified in 46,XY DSD subjects, and 53 carriers and 42 control of family members were confirmed by molecular analysis of SRD5A2 gene. The T/DHT ratios were not different significantly in cases and carriers group, while the AUC (area under the curve) of urinary Et/An showed 79.7% (95% CI 69.0–90.4%, p < 0.001). After determining cutoff values for diagnosing cases (>0.95) and carriers (>0.99), the sensitivity and specificity of urinary Et/An ratio in cases groups were 67.57% and 86.21%, respectively, and in carrier groups 67.92% and 73.81%, respectively. Simultaneous urinary Et/An ratios of cases and one of their closed family members increased the diagnostic accuracy with AUC of 84.1% (95% CI 74.3–93.9%, p < 0,001) and sensitivity 89.19%, yet the specificity of only 57.69%. Six novel mutations (c.34delGinsCCAGC, R50H, W136stop, G191R, F194I, and I253V), and 7 other mutations, which were G34Fs, c.699-1 G>T, V89L, Y128C, N193S, R227Q, and g.5352+15 T>C, in the SRD5A2 gene were detected. There were no clear genotype-phenotype correlations found. Conclusion: The diagnostic accuracy of urinary Et/An ratio was good in 5ARD2 cases and carriers, and the accuracy was very good if the urinary Et/An ratios of cases and their closed family members were combined. The T/DHT ratio was inaccurate in diagnosing 5ARD2 cases. Six new mutations were detected.

Abstrak :
Follicle-stimulating hormone (FSH) dan Testosteron merupakan hormon penting untuk spermatogenesis. Peningkatan FSH serum dan penurunan testosteron berhubungan dengan spermatogenesis abnormal. Azoospermia dapat diklasifikasikan sebagai azoospermia obstruktif dan nonobstruktif. Penelitian ini bertujuan untuk mengetahui nilai batas untuk pemeriksaan testosteron dan FSH dalam memprediksi azoospermia obstruktif dan non-obstruktif. Dari 1.064 pasien, 120 pasien memenuhi kriteria inklusi dan eksklusi. Terdapat 66,7% pada kelompok obstruktif dengan 33,3% pada kelompok non-obstruktif. Tidak ada perbedaan dalam hal usia (36,83 vs 36,62 tahun). Testosteron adalah 405.54 ± 186.14 ng/dL vs 298.84 ± 161.45 ng/dL (p = 0.002) sedangkan FSH adalah 8,53 ± 8,43 mIU/mL vs 20,12 ± 11,89 mIU / mL (p <0,001) untuk azoospermia obstruktif dan non-obstruktif masing-masing. Rata-rata testis 17,74 ± 4,03 cc dan 17,50 ± 4,23 cc sedangkan pada kelompok non obstruktif masing-masing 12,97 ± 5,18 cc dan 13,37 ± 5,31 cc untuk testis kiri dan kanan. Nilai FSH diatas 10,36 mIU/mL mempunyai sensitivitas 82,1% dan spesifisitas 79,5% untuk memprediksi azoospermia non obstruktif. Sayangnya, Testosteron tidak dapat digunakan untuk memprediksi klasifikasi azoospermia. Azoospermia obstruktif dan non-obstruktif dapat diprediksi menggunakan FSH tetapi tidak dengan kadar serum testosteron. Populasi testosteron yang lebih tinggi harus digunakan untuk studi lebih lanjut. ......Follicle-stimulating hormone (FSH) and Testosterone are important for spermatogenesis. Increased serum FSH and decreased testosterone are related to abnormal spermatogenesis. Azoospermia can be classified as obstructive and nonobstructive azoospermia. This study aims to discover cut-off value of Testosterone and FSH in predicting obstructive and non-obstructive azoospermia. From 1064 patients, 120 fulfilled inclusion and exclusion criteria. There were 66.7% in obstructive with 33.3% in non-obstructive group. No difference in terms of age (36,83 vs 36,62 y.o). Testosterone were 405.54 ± 186.14 ng/dL vs 298.84 ± 161.45 ng/dL (p = 0.002) while FSH was 8,53 ± 8,43 mIU/mL vs 20,12 ± 11,89 mIU/mL (p < 0.001) for obstructive and non-obstructive azoospermia respectively. Average testicular were 17.74 ± 4.03 cc and 17.50 ± 4.23 cc while in non-obstructive group are 12.97 ± 5.18 cc and 13.37 ± 5.31 cc for right and left testis respectively. FSH value above 10.36 mIU/mL has sensitivity 82.1% and specificity 79.5% for predicting non-obstructive azoospermia. Unfortunately, Testosterone could not be used in predicting azoospermia classification. Obstructive and non-obstructive azoospermia could be predicted using FSH but not testosterone serum level. Higher testosterone population should be used for further study.