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The Shadow of Deficiency: Vitamin D Status as a Critical Determinant of Antithyroid Drug Efficacy in Graves’ Disease – Insights from an Indonesian Cohort Ratna Maila Dewi Anggraini; Intan Fajrin Karimah; Eddy Yuristo; Yulianto Kusnadi; Erwin Sukandi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 8 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i8.1356

Background: Graves' disease (GD), an autoimmune hyperthyroid condition, presents significant management challenges, particularly concerning variable remission rates with antithyroid drugs (ATDs). Vitamin D, with its established immunomodulatory properties, is hypothesized to influence autoimmune processes, including those in GD. However, its precise impact on ATD treatment outcomes in diverse populations, especially in regions like Indonesia with high vitamin D deficiency prevalence, remains insufficiently elucidated. Methods: This retrospective cohort study was conducted at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia, analyzing data from 73 newly diagnosed adult GD patients (diagnosed January 2022 - December 2023). Patients had confirmed GD based on hyperthyroidism with orbitopathy or positive TRAb and were followed until May 2025. Baseline serum 25-hydroxyvitamin D [25(OH)D], free T4 (fT4), and TSH levels were recorded. Vitamin D deficiency (VDD) was defined as <20 ng/mL. The primary outcome was non-remission after ATD therapy, defined as failure to achieve stable euthyroidism for ≥6 months on minimal ATD doses. Multivariate Poisson regression was used to assess predictors of non-remission. Results: Of 73 patients (mean age 36.2 years; 62% female), 55 (75.3%) exhibited VDD. Multivariate analysis identified VDD as a significant independent predictor of non-remission (adjusted Relative Risk [aRR] 11.81; 95% CI 1.88–74.20; p=0.008). Elevated baseline fT4 levels (≥5 ng/dL; aRR 4.61; 95% CI 1.13–18.70; p=0.032) and older age (>48 years; aRR 0.078; 95% CI 0.06–0.95, indicating a protective effect of older age against non-remission) were also significant predictors. Conclusion: Baseline vitamin D deficiency is a potent independent risk factor for non-remission in Indonesian Graves' disease patients receiving antithyroid drug therapy. These findings underscore the potential importance of assessing and addressing vitamin D status in the management of Graves' disease to optimize therapeutic outcomes.

The Shadow of Deficiency: Vitamin D Status as a Critical Determinant of Antithyroid Drug Efficacy in Graves’ Disease – Insights from an Indonesian Cohort Ratna Maila Dewi Anggraini; Intan Fajrin Karimah; Eddy Yuristo; Yulianto Kusnadi; Erwin Sukandi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 8 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i8.1356

Background: Graves' disease (GD), an autoimmune hyperthyroid condition, presents significant management challenges, particularly concerning variable remission rates with antithyroid drugs (ATDs). Vitamin D, with its established immunomodulatory properties, is hypothesized to influence autoimmune processes, including those in GD. However, its precise impact on ATD treatment outcomes in diverse populations, especially in regions like Indonesia with high vitamin D deficiency prevalence, remains insufficiently elucidated. Methods: This retrospective cohort study was conducted at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia, analyzing data from 73 newly diagnosed adult GD patients (diagnosed January 2022 - December 2023). Patients had confirmed GD based on hyperthyroidism with orbitopathy or positive TRAb and were followed until May 2025. Baseline serum 25-hydroxyvitamin D [25(OH)D], free T4 (fT4), and TSH levels were recorded. Vitamin D deficiency (VDD) was defined as <20 ng/mL. The primary outcome was non-remission after ATD therapy, defined as failure to achieve stable euthyroidism for ≥6 months on minimal ATD doses. Multivariate Poisson regression was used to assess predictors of non-remission. Results: Of 73 patients (mean age 36.2 years; 62% female), 55 (75.3%) exhibited VDD. Multivariate analysis identified VDD as a significant independent predictor of non-remission (adjusted Relative Risk [aRR] 11.81; 95% CI 1.88–74.20; p=0.008). Elevated baseline fT4 levels (≥5 ng/dL; aRR 4.61; 95% CI 1.13–18.70; p=0.032) and older age (>48 years; aRR 0.078; 95% CI 0.06–0.95, indicating a protective effect of older age against non-remission) were also significant predictors. Conclusion: Baseline vitamin D deficiency is a potent independent risk factor for non-remission in Indonesian Graves' disease patients receiving antithyroid drug therapy. These findings underscore the potential importance of assessing and addressing vitamin D status in the management of Graves' disease to optimize therapeutic outcomes.

Impaired Stimulated Pancreatic β-Cell Responsiveness is a Dominant Feature of Bisphenol A-Associated Metabolic Dysfunction in Type 2 Diabetes: A Cross-Sectional Analysis of Adjusted Associations in an Indonesian Cohort Yulianto Kusnadi; Ardianto Ardianto; Ratna Maila Dewi Anggraini; Sudarto Sudarto; Imran Imran
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 10 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i10.1410

Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is a suspected contributor to the type 2 diabetes mellitus (T2DM) pandemic. This study aimed to move beyond simple correlation and investigate the adjusted association between urinary BPA and the dual pathophysiological defects of T2DM—insulin resistance and pancreatic β-cell failure—with a novel emphasis on contrasting basal versus stimulated β-cell function in an understudied Indonesian cohort. Methods: In a cross-sectional study, 40 patients with T2DM were recruited from a tertiary hospital in Palembang, Indonesia. Urinary BPA was quantified by liquid chromatography–mass spectrometry (LCMS). Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). β-cell function was evaluated using the C-peptide index (CPI) at fasting and 1-hour post-75g oral glucose tolerance test (OGTT). Multivariable linear regression models were constructed to determine the association between urinary BPA (log-transformed) and metabolic indices, adjusting for age, gender, and body mass index (BMI). Results: After adjusting for confounders, higher log-urinary BPA remained a significant independent predictor of higher log-HOMA-IR (β = 0.58, 95% CI: 0.31-0.85, p < 0.001). BPA was also independently associated with poorer β-cell function, showing a significant inverse association with the fasting CPI (β = -0.45, 95% CI: -0.73 to -0.17, p = 0.003). Critically, this association was markedly stronger and more profound with the 1-hour stimulated CPI (β = -0.79, 95% CI: -0.99 to -0.59, p < 0.001). The variance in stimulated CPI explained by the model (R2) was substantially higher than for other indices. Conclusion: Higher environmental BPA exposure is independently associated with both heightened insulin resistance and compromised β-cell function in T2DM. The distinctly stronger association with impaired stimulated β-cell secretion, even after adjusting for key confounders, identifies a critical mechanism by which BPA may accelerate functional β-cell exhaustion, the pivotal event in T2DM progression.

Beyond Viral Load: The Clinical and Endocrine Profile of ART-Naive HIV-Infected Men with Hypogonadism, Opportunistic Infections, and Malnutrition Yulianto Kusnadi; Fahrenheit; Harun Hudari
Open Access Indonesian Journal of Medical Reviews Vol. 5 No. 5 (2025): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v5i5.792

In patients with advanced human immunodeficiency virus (HIV), the clinical presentation often extends beyond immunodeficiency to a syndemic of interacting comorbidities. Male hypogonadism is a critical but often under-recognized endocrine dimension of this syndrome. This study aimed to characterize the clinical, metabolic, and endocrine profile of antiretroviral therapy (ART)-naive men to provide a comprehensive baseline understanding of this syndemic state before therapeutic intervention. An analytical cross-sectional study was conducted from April to October 2024, enrolling 64 consecutively presenting ART-naive men with HIV at a tertiary hospital in Palembang, Indonesia. We performed a comprehensive assessment including WHO clinical staging, nutritional evaluation (BMI), and screening for comorbidities. Endocrine status was assessed by measuring total testosterone, Luteinizing Hormone (LH), and serum albumin, from which bioavailable testosterone was calculated using the Vermeulen formula. Bivariate correlations and comparative analyses were conducted to explore relationships between variables. The cohort presented with profound immunodeficiency (median CD4 count: 23.5 cells/µL) and advanced disease (92.2% in WHO Stage 3 or 4). A high burden of opportunistic infections (40.6% pulmonary tuberculosis) and malnutrition (48.4% underweight; median serum albumin: 3.25 g/dL) was observed. Based on total testosterone (<300 ng/dL), the prevalence of hypogonadism was 32.8%. However, analysis using the more physiologically relevant calculated bioavailable testosterone (<70 ng/dL) revealed a higher prevalence of 42.2%. Secondary (hypogonadotropic) hypogonadism was the overwhelmingly dominant etiology (28.1%). Bioavailable testosterone was significantly and positively correlated with both CD4 count (ρ=0.35, p=0.005) and BMI (ρ=0.41, p=0.001). In conclusion, ART-naive men presenting with advanced HIV in this setting are caught in a syndemic of immunodeficiency, infectious disease, malnutrition, and profound endocrine dysfunction. The high prevalence of secondary hypogonadism, strongly associated with the severity of immune collapse and poor nutritional status, highlights the HPG axis as a key casualty of systemic illness. These findings provide a compelling rationale for integrating routine hormonal and metabolic screening into the initial assessment of all men newly diagnosed with HIV.

The Inflammatory Correlates of Hypothalamic-Pituitary-Gonadal Axis Dysfunction in Antiretroviral-Naïve Men with HIV: A Cross-Sectional Analysis of the TNF-α and Testosterone Relationship Hudari, Harun; Yulianto Kusnadi; Risfandi Ahmad Taskura
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 11 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i11.1440

Background: In men with untreated Human Immunodeficiency Virus (HIV), the mechanisms underlying testosterone deficiency remain incompletely defined. Chronic inflammation is hypothesized to be a key factor in disrupting the hypothalamic-pituitary-gonadal (HPG) axis. This study aimed to investigate the association between the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the HPG axis and to assess this relationship while accounting for nutritional status in ART-naïve men. Methods: We conducted a cross-sectional study of 40 ART-naïve men with HIV in Palembang, Indonesia. We measured serum total testosterone, Luteinizing Hormone (LH), TNF-α, Interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). Hypogonadism was classified as primary (low testosterone, high LH) or secondary (low testosterone, low/normal LH). Spearman’s correlation was used to assess bivariate relationships. A multiple linear regression analysis was performed to determine the independent association of TNF-α and Body Mass Index (BMI) with testosterone levels. Results: All 40 participants (100%) presented with secondary (hypogonadotropic) hypogonadism, characterized by a median total testosterone of 6.48 pg/mL and an inappropriately normal median LH of 3.86 mIU/mL. Serum TNF-α was significantly elevated (median: 10.32 pg/mL). A moderate negative correlation was found between TNF-α and total testosterone (ρ = -0.411, p = 0.008). In the multivariate regression model, both higher TNF-α levels (β = -0.38, p = 0.011) and lower BMI (β = 0.45, p = 0.003) were significant, independent predictors of lower total testosterone. The model explained 34.6% of the variance in testosterone levels (Adjusted R² = 0.346). Conclusion: Our findings demonstrate a universal prevalence of secondary hypogonadism in ART-naïve men with HIV. This HPG axis dysfunction is strongly and independently associated with both the magnitude of systemic inflammation, marked by TNF-α, and the severity of malnutrition. These results suggest a complex interplay where inflammation and poor nutritional status act as distinct, synergistic contributors to the profound endocrine disruption seen in untreated HIV infection.

DIAGNOSTIC ACCURACY OF CLINICAL SCORING SYSTEMS (NSS, NDS, AND TCSS) COMPARED TO ELECTROPHYSIOLOGICAL TESTING IN DIABETIC NEUROPATHY AMONG T2DM PATIENTS Muhlisa, Safitri; Theresia Christin; Yulianto Kusnadi; Erial Bahar
Jurnal Kedokteran dan Kesehatan : Publikasi Ilmiah Fakultas Kedokteran Universitas Sriwijaya Vol. 12 No. 3 (2025): Jurnal Kedokteran dan Kesehatan : Publikasi Ilmiah Fakultas Kedokteran Univers
Publisher : Fakultas Kedokteran Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32539/jkk.v12i3.689

Diabetic neuropathy is one of the most common chronic complications in diabetes mellitus patients and can significantly impair quality of life. Early diagnosis is essential, but limited availability of diagnostic tools such as electrophysiological testing in many healthcare facilities calls for more practical and efficient alternatives. This study aimed to compare the diagnostic accuracy of three clinical scoring systems—NSS (Neuropathy Symptom Score), NDS (Neuropathy Disability Score), and TCSS (Toronto Clinical Scoring System)—in detecting diabetic neuropathy among Type 2 DM patients at Dr. Mohammad Hoesin Hospital, Palembang. A cross-sectional design was employed, and findings revealed that TCSS had the highest accuracy (90.3%) compared to NDS (85.5%) and NSS (85.4%). TCSS also demonstrated the best balance of sensitivity (95.4%) and specificity (77.8%). All three instruments can serve as effective early screening tools, especially in healthcare settings with limited access to electrophysiological diagnostic facilities.

Impaired Stimulated Pancreatic β-Cell Responsiveness is a Dominant Feature of Bisphenol A-Associated Metabolic Dysfunction in Type 2 Diabetes: A Cross-Sectional Analysis of Adjusted Associations in an Indonesian Cohort Yulianto Kusnadi; Ardianto Ardianto; Ratna Maila Dewi Anggraini; Sudarto Sudarto; Imran Imran
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 10 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i10.1410

Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is a suspected contributor to the type 2 diabetes mellitus (T2DM) pandemic. This study aimed to move beyond simple correlation and investigate the adjusted association between urinary BPA and the dual pathophysiological defects of T2DM—insulin resistance and pancreatic β-cell failure—with a novel emphasis on contrasting basal versus stimulated β-cell function in an understudied Indonesian cohort. Methods: In a cross-sectional study, 40 patients with T2DM were recruited from a tertiary hospital in Palembang, Indonesia. Urinary BPA was quantified by liquid chromatography–mass spectrometry (LCMS). Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). β-cell function was evaluated using the C-peptide index (CPI) at fasting and 1-hour post-75g oral glucose tolerance test (OGTT). Multivariable linear regression models were constructed to determine the association between urinary BPA (log-transformed) and metabolic indices, adjusting for age, gender, and body mass index (BMI). Results: After adjusting for confounders, higher log-urinary BPA remained a significant independent predictor of higher log-HOMA-IR (β = 0.58, 95% CI: 0.31-0.85, p < 0.001). BPA was also independently associated with poorer β-cell function, showing a significant inverse association with the fasting CPI (β = -0.45, 95% CI: -0.73 to -0.17, p = 0.003). Critically, this association was markedly stronger and more profound with the 1-hour stimulated CPI (β = -0.79, 95% CI: -0.99 to -0.59, p < 0.001). The variance in stimulated CPI explained by the model (R2) was substantially higher than for other indices. Conclusion: Higher environmental BPA exposure is independently associated with both heightened insulin resistance and compromised β-cell function in T2DM. The distinctly stronger association with impaired stimulated β-cell secretion, even after adjusting for key confounders, identifies a critical mechanism by which BPA may accelerate functional β-cell exhaustion, the pivotal event in T2DM progression.

The Inflammatory Correlates of Hypothalamic-Pituitary-Gonadal Axis Dysfunction in Antiretroviral-Naïve Men with HIV: A Cross-Sectional Analysis of the TNF-α and Testosterone Relationship Hudari, Harun; Yulianto Kusnadi; Risfandi Ahmad Taskura
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 11 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i11.1440

Background: In men with untreated Human Immunodeficiency Virus (HIV), the mechanisms underlying testosterone deficiency remain incompletely defined. Chronic inflammation is hypothesized to be a key factor in disrupting the hypothalamic-pituitary-gonadal (HPG) axis. This study aimed to investigate the association between the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the HPG axis and to assess this relationship while accounting for nutritional status in ART-naïve men. Methods: We conducted a cross-sectional study of 40 ART-naïve men with HIV in Palembang, Indonesia. We measured serum total testosterone, Luteinizing Hormone (LH), TNF-α, Interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). Hypogonadism was classified as primary (low testosterone, high LH) or secondary (low testosterone, low/normal LH). Spearman’s correlation was used to assess bivariate relationships. A multiple linear regression analysis was performed to determine the independent association of TNF-α and Body Mass Index (BMI) with testosterone levels. Results: All 40 participants (100%) presented with secondary (hypogonadotropic) hypogonadism, characterized by a median total testosterone of 6.48 pg/mL and an inappropriately normal median LH of 3.86 mIU/mL. Serum TNF-α was significantly elevated (median: 10.32 pg/mL). A moderate negative correlation was found between TNF-α and total testosterone (ρ = -0.411, p = 0.008). In the multivariate regression model, both higher TNF-α levels (β = -0.38, p = 0.011) and lower BMI (β = 0.45, p = 0.003) were significant, independent predictors of lower total testosterone. The model explained 34.6% of the variance in testosterone levels (Adjusted R² = 0.346). Conclusion: Our findings demonstrate a universal prevalence of secondary hypogonadism in ART-naïve men with HIV. This HPG axis dysfunction is strongly and independently associated with both the magnitude of systemic inflammation, marked by TNF-α, and the severity of malnutrition. These results suggest a complex interplay where inflammation and poor nutritional status act as distinct, synergistic contributors to the profound endocrine disruption seen in untreated HIV infection.

Relapse of Pheochromocytoma with Hipertensive Heart Disease Mildly Reduced Left Ventricle Ejection Fraction Filianty Sipayung, Merylla; Kusnadi, Yulianto; Shahab, Alwi; Maila Dewi, Ratna; Soleh, Imran; Pramudhya Hoesain, Fadil
Journal of World Science Vol. 2 No. 9 (2023): Journal of World Science
Publisher : Riviera Publishing

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.58344/jws.v2i9.427

Pheochromocytoma is a tumor originating from the medulla of the adrenal gland. This tumor is rare and is caused by excessive production of catecholamines. There are three classic triads of pheochromocytoma: diaphoresis, palpitations and headaches. Elevated metanephrines and normetanephrine in plasma or urine confirm the diagnosis. At the same time, radiological examination helps in the tumor's location and the presence of local invasion or metastasis. Hypertension is a health problem that is quite dangerous worldwide because it is a significant risk factor for cardiovascular diseases such as heart attack, heart failure, stroke, and kidney disease. Hypertension can cause Hypertensive Heart Disease, which is a significant cause of morbidity and mortality due to cardiovascular disease. This scientific report presents a case study of a 19-year-old woman diagnosed with relapsed pheochromocytoma and hypertensive heart disease with mildly reduced left ventricular ejection fraction. This patient was previously diagnosed at the age of 13 with pheochromocytoma, where the patient experienced symptoms of headache, sweating, especially in the forehead area, trembling hands, and hypertension. Hence, the patient had to be treated. The patient underwent further examination and found a right adrenal tumor, so an adrenalectomy was performed on the patient. Similar complaints appeared again in the patient, and further examination was carried out. Moreover, an increase in plasma metanephrine and normetanephrine levels was found. A CT scan of the abdomen revealed a right adrenal tumor, so this patient underwent another adrenalectomy.

Seluang Fish (Rasbora sp.) Oil Improves Interleukin-17 Levels and Disease Activity in Rheumatoid Arthritis Partan, Radiyati Umi; Mikhael, Rodry; Adinata, Triawan; Darma, Surya; Reagan, Muhammad; Kriswiastiny, Rina; Kusnadi, Yulianto; Salim, Eddy Mart
The Indonesian Biomedical Journal Vol 15, No 1 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i1.2085

BACKGROUND: Vitamin D has a role in downregulating the proinflammatory cytokines as well as promoting the antiinflammatory pathway in rheumatoid arthritis (RA). Seluang fish (Rasbora sp.) has potency as a new source of vitamin D. Previous study had proven Seluang fish oil efficacy in systemic lupus erythematosus. However, there are no trials that prove its efficacy in RA yet. Hence, this study was conducted to find out the ability of Seluang fish oil to improve proinflammatory cytokines, vitamin D levels, and disease activity in RA.METHODS: A clinical trial with a randomized and double-blind method was done in two groups, each one consisting of 17 RA subjects. One group was given 500 mL of a Seluang fish oil capsule (contains 665 IU cholecalciferol), while the other group was given a placebo daily, for 12 consecutive weeks. Measurements of the RA disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR) and DAS28 C-reactive protein (DAS28-CRP), as well as measurement of interleukin (IL)-6, IL-17, and vitamin D levels by using immunoassay method were performed before and after the supplementation.RESULTS: Significant alterations in the lower levels of IL-17 were observed in the Seluang fish oil group (p=0.031), but not in the placebo group (p=0.320). Reduction of DAS28-ESR (p=0.000) and DAS28-CRP (p=0.000) score demonstrated that the Seluang fish oil supplementation was useful in reducing RA disease activity. No significant shift was observed in either vitamin D (p=0.967) or IL-6 levels (p=0.076) after Seluang Fish Oil supplementation.CONCLUSION: Seluang fish oil is effective in lowering IL-17 levels, DAS28-ESR, and DAS28-CRP, but not in improving vitamin D level or lowering IL-6 level in RA patients.KEYWORDS: rheumatoid arthritis, seluang fish oil, interleukin-6, interleukin-17, vitamin D, DAS28

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