Changing the patterns of hospitalized diabetic foot ulcer (DFU) over a 5-year period in a multi-disciplinary setting in Thailand.

BACKGROUND: After years of decline, the rate of amputations was reported to increase by 50% in the U.S. population between 2009 and 2015. Few studies have examined the most recent trends in hospitalized diabetic foot ulcer (DFU) in Asian patients. This study aimed to examine recent trends and outcomes in hospitalized DFU at a tertiary diabetes center in Bangkok. METHODS: We conducted a retrospective study from consecutive hospitalized DFU admissions from 2014 to 2018 at Theptarin Hospital, a multi-disciplinary diabetes center, led by diabetologists. RESULTS: During the study period, 290 patients (male 57.4%, age 65.5 ± 13.3 years, T2DM 99.4%, DM duration 18.8 ± 11.5 years, A1C 8.6 ± 2.3%) with 350 admissions were included. DFU were classified into neuropathic wounds (38.0%), ischemic wounds (2.6%), and mixed-type wounds (59.4%). The median length of stay was 8 days. Severe DFU (Wagner grade 3-5) composed 68.3% of all DFU and one-third of patients had prior history of amputations. Complete healing was achieved in 73.5% of the patients. Major amputation was performed in 16 (4.6%) and minor amputation was performed in 78 (22.3%) of all DFU. The mortality rate at 1 year after discharge was 12.0%. Advanced diseases with higher co-morbidities were associated with worse outcomes. When compared with our previous published data from 2009 to 2013, the annual rate of ischemic wounds from peripheral arterial diseases (PAD) and severity of DFU were increased in this study period. The major amputation rate slightly decreased from 6.0 to 4.6% but the minor amputation rate increased from 18.7 to 22.3%. CONCLUSION: The changing trend of DFU provides an excellent outlook into the inadequacies of our current diabetes care systems and global trend of aging population. After considerable successes in reducing major amputations over the past decade, the current analysis revealed a discouraging change in the healing rate of DFU and a stable pattern of major amputation. The prevalence of PAD among Thai patients with DFU increased significantly and affected the results of DFU treatments. Redefined organization of care with multidisciplinary team approach and coordination with referral centers are urgently required to improve outcomes of DFU.

Performance of HbA1c versus oral glucose tolerance test (OGTT) as a screening tool to diagnose dysglycemic status in high-risk Thai patients.

BACKGROUND: Dysglycemic status defined by prediabetes and diabetes is known to be related with future risk of diabetic complications and cardiovascular diseases. Herein, we aimed to determine the diagnostic accuracy of glycated hemoglobin (HbA1c) when compared with oral glucose tolerance test (OGTT) as a reference test in identifying dysglycemic status among high-risk Thai patients receiving care in an out-patient setting. METHODS: An 11-year retrospective cross-sectional study of high-risk Thai patients who underwent OGTT during 2007-2017 was analysed. The OGTT was used as a reference test to identify subjects of dysglycemic status. The diagnostic accuracy of HbA1c and the agreement between HbA1c and OGTT were examined. Validated Thai diabetes risk score, Thai cardiovascular risk score (Thai CV risk score), and visceral fat area (VFA) were also compared in each glycemic status from OGTT as surrogate markers for future diabetes and cardiovascular diseases. RESULTS: A total of 512 subjects (females 60.5%, mean age of 50.3 ± 12.7 years, BMI of 26.5 ± 4.6 kg/m2) were reviewed. Normal glucose tolerance (NGT) was found in 220 patients (43.0%), impaired glucose tolerance (IGT) in 191 patients (37.3%), and diabetes in 101 patients (19.7%). The prevalence of diabetes using OGTT was approximately two times higher than those defined by HbA1c (19.7% versus 11.1%). There were poor agreements between the classifications of prediabetes and diabetes defined by OGTT and HbA1c (Cohen's Kappa 0.154 and 0.306, respectively). Using a cut-off value for HbA1c ≥6.5% as a threshold for HbA1c-defined criteria of diabetes, sensitivity was 32% (95% CI 23-41%) and specificity was 94% (95% CI 92-96%). The optimal cut-off HbA1c value for detecting diabetes by Youden's index was at HbA1c 6.2%. Thai CV risk score was much higher among the OGTT-defined diabetes group when compared with the NGT group (median score 10 vs. 3, p-value < 0.001). CONCLUSIONS: Despite the practicality and validity of HbA1c as a diagnostic test, our study suggested that HbA1c as a screening tool for diabetes in high-risk Thai patients is much inferior to OGTT. With limitations of HbA1c, physicians should continue to advocate OGTT as a screening tool for the identification of dysglycemic status in high-risk Thai patients.

Development of New Lemon-Lime Flavored Beverage for OGTT: Acceptability and Reproducibility.

BACKGROUND: The oral glucose tolerance test (OGTT) is essential procedure in both screening and diagnosis of impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes mellitus (DM), but it is not easy to perform because of intense sweetness of the 75-g glucose test beverage causing abdominal discomfort post-testing. Therefore, the new formula of non-carbonated lemon-lime flavored beverage was developed to increase its palatability and better compliance. OBJECTIVE: To develop a new non-carbonated lemon-lime flavored beverage to replace the standard beverage for OGTT Subsequently, the diagnostic value and acceptability between the new formula and the traditional 75-g OGTT formula were compared in healthy subjects. MATERIAL AND METHOD: The new lemon-lime flavored formula was developed to replace the standard beverage for OGTT by adding 1,000 milligram of citric acid and 0.03 gram of lime flavor to 75 gram of anhydrous glucose to a final volume of 300 ml. The study was conducted in 30 healthy subjects who underwent the traditional 75-gram OGTT test and the new formula of OGTT beverage one week later, or vice versa, to access acceptability, indices markers of insulin secretion, and insulin sensitivity. Palatability was determined by rating on a 9-point Hedonic Scale. RESULTS: Thirty healthy subjects (15 females) with the age of 33.2 ± 7.5 years and body mass index of 22.9 ± 3.5 kg/m² were enrolled. No significant difference was found between plasma glucose in 0, 30, 60, 90, and 120 minutes, insulin level (0 and 120 minutes) and four insulin surrogate markers in both traditional 75-gram OGTT and new formula of lemon-lime flavored OGTT beverage. The overall satisfaction score of the new formula OGTT was better when compared with the scores of the traditional OGTT (7.1 ± 1.8 vs. 4.7 ± 2.0). Only one subject complained about abdominal discomfort in both episode of OGTT CONCLUSION: The modified lemon-lime flavored beverage for OGTT demonstrated better acceptance in the subjects without difference in plasma glucose values and OGTT derived parameters responses to OGTT in comparison to the traditional formula.

Metformin-Associated Vitamin B12 Deficiency: An Underrecognized Complication.

Metformin-associated vitamin B12 deficiency is a well-established side effect, especially in patients taking higher doses of metformin or who have existing risk factors. Severe deficiency causes a wide range of systemic disorders. Gait instability, which leads to frequent falling, is usually an underrecognized side effect. Older patients are more likely to develop chronic subdural hematoma even with minor trauma. We present a case of 84-year-old man with type 2 diabetes mellitus with acute-on-chronic subdural hematoma from frequent falls. Metformin therapy at dose of 1700 mg/day was given for more than 25 years. He had been in his usual state of health until 10 months ago when he began to have frequent fallings and fatigue. Physical examination in this admission revealed new-onset impaired vibratory sensation and proprioception in both feet and positive Romberg test. Subsequent evaluations demonstrated undetectable plasma vitamin B12 level and elevated plasma homocysteine. Improvement in neurological symptoms occurred within 1 week of vitamin B12 replacement and surgical hematoma evacuation. This case highlights the importance of awareness and periodic monitoring of vitamin B12 status among older patients taking metformin.

Clinical inertia in thyrotropin suppressive therapy for low-risk differentiated thyroid cancer: A real-world experience at an endocrine center in Bangkok.

The management of low-risk differentiated thyroid cancer (DTC) has evolved over time toward treatment de-escalation. However, overtreatment with supraphysiological dose of levothyroxine (LT4) continues to be observed despite current clinical guideline. This study aimed to assess the actual thyrotropin suppressive therapy for low-risk DTC patients at an endocrine center in Bangkok. This retrospective study included patients with low-risk DTC who were regularly follow-up for at least 18 months at Theptarin Hospital between 2016 and 2022. The serum thyroid stimulating hormone (TSH) levels were stratified as TSH < 0.1 mIU/L; TSH 0.1 to 0.5 mIU/L; TSH 0.5 to 2.0 mIU/L; and TSH > 2.0 mIU/L. The initial risk stratification (IRS) and dynamic risk stratification were determined at 12 months of follow-up after completing the initial treatment and at the last visit. The clinical factors associated with overtreatment with LT4 were analyzed. A total of 102 patients (83.3% female, age at diagnosis 41.8 ±â€…13.6 years, mean tumor size 1.6 ±â€…1.0 cm) were evaluated with a mean follow-up of 5.9 years. The IRS classified 92.2% of patients after the initial treatment and 93.1% of patients at the last follow-up visit into the excellent response category. The mean LT4 daily dosage at the last follow-up was 121.3 ±â€…44.8 µg/day. Serum TSH levels were in an appropriate target range according to IRS in only 8.8% (9/102) of the patients and then improved to 19.6% (20/102) at the last follow-up visit. Further analysis showed that treating physicians with ≥10 years of practice was associated with severe TSH suppression therapy (TSH < 0.1 mIU/L). Despite the current clinical guideline recommendations and scientific evidences, less than one-fifth of low-risk DTC patients achieved the appropriate serum TSH target. While the proportion of an optimum LT4 suppressive had improved during the study period, further efforts are needed to overcome this clinical inertia.

Real-World Use of Once-Weekly Semaglutide in Thai Patients With Type 2 Diabetes Mellitus in a Private Hospital Setting.

Objective: To evaluate the real-world use of once-weekly semaglutide among Thai patients with type 2 diabetes (T2DM) in a private hospital setting. Methodology: A retrospective review of Thai patients with T2DM who have initiated semaglutide for at least 1 month between June 2020 and March 2022 at Theptarin Hospital, Bangkok, Thailand. Results: A total of 58 patients (50% female, mean age 55.6 ± 15.9 years, with duration of diabetes 12.6 ± 10.3 years, BMI 31.5 ± 4.4 kg/m2, baseline HbA1c 7.9 ± 1.9%, with prior GLP-1 RA use 24.1%, and concomitant SGLT2i intake (41.4%) were included. During a median follow-up of 6 months, the mean serum HbA1c level reduction was 1.3 ± 1.7% with weight loss of 4.7 ± 4.1 kg. The proportion of patients who achieved optimal and sustainable glycemic control (HbA1c < 7.0%) increased from 43.1% to 55.8% at the last follow-up. The proportion of patients reaching both HbA1c targets of <7.0% and 5% weight loss was 27.8%. No cases of pancreatitis, cancer, or progressive retinopathy were observed. Conclusions: In this single center undertaking, it was shown that in among persons with T2DM and obesity in Thailand, semaglutide was associated with short-term glycemic control and weight loss comparable with what has been observed in randomized clinical trials and other RWE.

Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus.

AIMS: To investigate epigenomic indices of diabetic kidney disease (DKD) susceptibility among high-risk populations with type 2 diabetes mellitus. METHODS: KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines were used to classify people living with or without DKD. Differential gene methylation of DKD was then assessed in a discovery Aboriginal Diabetes Study cohort (PROPHECY, 89 people) and an external independent study from Thailand (THEPTARIN, 128 people). Corresponding mRNA levels were also measured and linked to levels of albuminuria and eGFR. RESULTS: Increased DKD risk was associated with reduced methylation and elevated gene expression in the PROPHECY discovery cohort of Aboriginal Australians and these findings were externally validated in the THEPTARIN diabetes registry of Thai people living with type 2 diabetes mellitus. CONCLUSIONS: Novel epigenomic scores can improve diagnostic performance over clinical modelling using albuminuria and GFR alone and can distinguish DKD susceptibility.

Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes.

Diabetic nephropathy (DN) is a polygenic disorder with few risk variants showing robust replication in large-scale genome-wide association studies. To understand the role of DNA methylation, it is important to have the prevailing genomic view to distinguish key sequence elements that influence gene expression. This is particularly challenging for DN because genome-wide methylation patterns are poorly defined. While methylation is known to alter gene expression, the importance of this causal relationship is obscured by array-based technologies since coverage outside promoter regions is low. To overcome these challenges, we performed methylation sequencing using leukocytes derived from participants of the Finnish Diabetic Nephropathy (FinnDiane) type 1 diabetes (T1D) study (n = 39) that was subsequently replicated in a larger validation cohort (n = 296). Gene body-related regions made up more than 60% of the methylation differences and emphasized the importance of methylation sequencing. We observed differentially methylated genes associated with DN in 3 independent T1D registries originating from Denmark (n = 445), Hong Kong (n = 107), and Thailand (n = 130). Reduced DNA methylation at CTCF and Pol2B sites was tightly connected with DN pathways that include insulin signaling, lipid metabolism, and fibrosis. To define the pathophysiological significance of these population findings, methylation indices were assessed in human renal cells such as podocytes and proximal convoluted tubule cells. The expression of core genes was associated with reduced methylation, elevated CTCF and Pol2B binding, and the activation of insulin-signaling phosphoproteins in hyperglycemic cells. These experimental observations also closely parallel methylation-mediated regulation in human macrophages and vascular endothelial cells.

Kratom-Associated Mixed Cholestatic-Hepatocellular Liver Injury in a Patient With Long COVID: A case Report.

Introduction: Mitragyna speciosa (commonly known as kratom) has both opioid and stimulant-like effects. Recently, Thailand decriminalized the possession and sale of kratom which led people in many areas to seek income from the sale of kratom at a time of widespread unemployment due to COVID-19. Here, we report a patient with post-COVID syndrome who developed a mixed cholestatic-hepatocellular liver injury secondary to kratom. Case presentation: A 23-year-old Thai man was seen for an evaluation of fatigue and nausea which was soon followed by pruritus, dark urine and jaundice. The patient had no known underlying disease but had been treated with mild COVID-19 pneumonia in the past 2 months. He reported taking kratom recreationally for 2 weeks as a treatment for his post-COVID insomnia. Kratom was purchased from a friend and used in a homemade iced cocktail called "4 × 100" consisting of Coca-Cola, tea made from boiled kratom leaves, and diphenhydramine-containing cough syrup which has been popular in Southernmost provinces of Thailand. His lab workup showed his total bilirubin to be 10.6 mg/dL, aspartate aminotransferase was 642 U/L, and alanine aminotransferase was 1635 U/L. Extensive workups including viral etiologies was negative. Abdominal ultrasound revealed normal liver and no cirrhosis. The case was managed conservatively for 5 days in the hospital by giving intravenous fluid and stopping all medications. Urine toxicology screening confirmed the presence of mitragynine and diphenhydramine. He was in a stable condition with normalized liver function tests at 3 months after discharge. Conclusion: The COVID-19 pandemic has posed unprecedented challenges to health consequences and this case highlights the importance of kratom as potential cause of acute liver injury. Future studies should accumulate further case series and identify kratom-user subgroups or the polydrug patterns of kratom use that are at heightened risk of severe liver injury.

Diabetes mellitus and insulin resistance associated with Kabuki syndrome-A case report and literature review.

Kabuki syndrome (KS) is a genetic disorder characterized by distinctive facies, intellectual disability, and multi-organ anomalies. This case report highlights the importance of clinical recognizable phenotype in patients with diabetes. The development of diabetes should be considered an endocrine complication in KS patients.

Profile of Levothyroxine Replacement Therapy in Graves' Disease Patients with Hypothyroidism Post-Radioactive Iodine Ablation: Focus on Different Weight-Based Regimens.

Objective: To evaluate the status of euthyroidism achieved among Thai patients with post-ablative hypothyroidism and to examine the difference between various weight-based daily levothyroxine (LT4) replacement regimens in these patients. Methodology: We conducted a retrospective review of Thai patients with Graves' disease (GD) who developed hypothyroidism following radioactive iodine treatment from 2016 to 2020 at Theptarin hospital. Daily LT4 dose was calculated based on actual body weight (ABW), ideal body weight (IBW), and estimated lean body mass (LBM). Results: We reviewed a total of 271 patient records. Of these, 81.2% were females with a mean age of 40.8±11.7 years, LT4 intake duration of 27.1±14.6 months, and LT4 dose/kg ABW of 1.4±0.5 µg/kg/day. At the final follow-up, 62.4% of patients achieved thyroid-stimulating hormone (TSH) levels within the reference interval, 15.5% had TSH levels over, and 22.1% had TSH levels under the reference range. Obese patients required a lower daily LT4 dose relative to ABW and higher daily LT4 dose relative to IBW to attain euthyroidism (ABW 1.1±0.4 µg/kg/day and IBW 2.0±0.8 µg/kg/day). Estimated daily LT4 dose based on LBM showed a constant dosage of 2.0 µg/kg/day in all BMI categories. Conclusions: Suboptimum LT4 replacement therapy was found in almost half of hypothyroid patients with GD treated with radioactive iodine. Estimated LBM was a better indicator for dosing calculation in these patients compared with ABW and IBW.

Hypertriglyceridemia as a main feature associated with 17q12 deletion syndrome-related hepatocyte nuclear factor 1ß-maturity-onset diabetes of the young.

Summary: Hepatocyte nuclear factor 1ß (HNF1B) gene is located on chromosome 17q12. It is a transcription factor implicated in the early embryonic development of multiple organs. HNF1B-associated disease is a multi-system disorder with variable clinical phenotypes. There are increasing reports suggesting that the 17q12 deletion syndrome should be suspected in patients with maturity-onset diabetes of the young type 5 (MODY5) due to the deletion of HNF1B gene. In contrast to classical 17q12 syndrome in childhood with neurological disorders and autism, patients with HNF1B-MODY deletion rarely had neuropsychological disorders or learning disabilities. The diagnosis of 17q12 deletion syndrome highlighted the phenotypic heterogeneity of HNF1B-MODY patients. In this study, we report the clinical course of a Thai woman with young-onset diabetes mellitus and hypertriglyceridemia as a predominant feature due to HNF1B deletion as part of the 17q12 deletion syndrome. Our findings and others suggest that hypertriglyceridemia should be considered a syndromic feature of HNF1B-MODY. Our case also highlights the need to use sequencing with dosage analyses to detect point mutations and copy number variations to avoid missing a whole deletion of HNF1B. Learning points: Maturity-onset diabetes of the young type 5 (MODY5) may be caused by heterozygous point mutations or whole gene deletion of HNF1B. Recent studies revealed that complete deletion of the HNF1B gene may be part of the 17q12 deletion syndrome with multi-system involvement. The length of the deletion can contribute to the phenotypic variability in patients with HNF1B-MODY due to whole gene deletion. Using next-generation sequencing alone to diagnose MODY could miss a whole gene deletion or copy number variations. Specialized detection methods such as microarray analysis or low-pass whole genome sequencing are required to accurately diagnose HNF1B-MODY as a component of the 17q12 deletion syndrome. Molecular diagnosis is necessary to distinguish other acquired cystic kidney diseases in patients with type 2 diabetes which could phenocopy HNF1B-MODY. Hypertriglyceridemia is a possible metabolic feature in patients with HNF1B-MODY due to 17q12 deletion syndrome.

Unilateral gynecomastia as an initial presentation of hyperthyroid Graves' disease.

SUMMARY: Graves' disease is an autoimmune condition leading to the activation of and an increase in thyroid hormone secretion. Manifestations of hyperthyroidism in Graves' disease can vary among people. In this case, we report a 24-year-old Thai man with a rare presentation of unilateral gynecomastia along with symptoms of thyrotoxicosis. Physical examination revealed a 3 cm non-tender palpable glandular tissue beneath and around the left areola without nipple discharge and moderately diffuse thyroid enlargement with thyroid bruit. Thyroid function test showed a typical thyrotoxicosis state with elevated serum-free T4 and decreased serum TSH. His diagnosis of Graves' disease was confirmed biochemically with a highly elevated anti-TSH receptor antibody. Early treatment with anti-thyroid medication was given first, followed by Radioiodine treatment (RAI) for definitive treatment due to high level of anti-TSH receptor antibody, enlarged thyroid and severe thyrotoxicosis presentation at a young age, which might not resolve by anti-thyroid medication alone. The patient responded well to treatment and achieved complete resolution of unilateral gynecomastia with clinically and biochemically euthyroid within 3 months after treatment. No recurrent gynecomastia was found during the 2-year follow-up. LEARNING POINTS: Characteristic of gynecomastia in hyperthyroidism is usually presented with bilateral progressive gynecomastia; however, unilateral gynecomastia is occasionally found as a presentation of hyperthyroidism. Complete resolution of gynecomastia without recurrence can be achieved within a few months of treatment after thyrotoxicosis is resolved in patients with hyperthyroidism with the recent development of gynecomastia. RAI for definitive treatment is recommended in young adult patients expressing very high anti-TSH antibody level with severe thyrotoxicosis.

Phenotypic and Genetic Heterogeneity in a Thai Glucokinase MODY Family Reveals the Complexity of Young-Onset Diabetes.

Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY) is characterized by asymptomatic, non-progressive and fasting hyperglycemia, albeit not without phenotypic variability. We used next generation sequencing (NGS) to screen for 34 MODY genes in a non-obese person with familial young-onset diabetes followed by screening in 24 family members within three generations with varying presentations of young-onset diabetes and sensorineural hearing loss. The index patient was found to carry a paternally-inherited heterozygous missense variant (c.716 A>G) of GCK in exon 7 with amino acid change (Q239R). This variant was associated with phenotypic heterogeneity ranging from normal glucose tolerance to diabetes with complications amongst the siblings which might be modified by obesity and chronic hepatitis B infection. Two paternally-inherited variants of SLC29A3 encoding a nucleoside transporter protein and Apo-A1 genes also co-segregated with glucose and lipid traits. Co-occurrence of diabetes and deafness in maternal aunts led to discovery of WFS1 (Wolfram syndrome type 1) as a cause of non-syndromic deafness in multiple members of the maternal pedigree. Our findings highlight the complex causes of familial young-onset diabetes and the need of a multidisciplinary approach to interpret the clinical relevance of discoveries made by NGS in this era of genomic medicine.

Celiac Disease as a Cause of Anemia and Brittle Diabetes in Type 1 Diabetes Mellitus.

Untreated celiac disease (CD) leads to an increased risk for hypoglycemia and diabetic complications. However, the diagnosis of CD can be challenging and some extra-gastrointestinal tract manifestations could be a presenting symptom. We report a case of a 29-year-old Indian male with brittle T1DM whose underlying CD was discovered from a work-up for anemia. After an introduction of a gluten-free diet, he gained 5 kgs in two months, was responsive to oral iron supplement, and had stable glycemic control with much less hypoglycemia. Even though this disease is rare in Asian populations, the diagnosis of celiac disease should always be kept in mind when people with T1DM present with unexplained microcytic anemia and/or unexplained hypoglycemia.

Serum T3 Level and Duration of Minimum Maintenance Dose Therapy Predict Relapse n Methimazole-Treated Graves Disease.

BACKGROUND: Methimazole (MMI) has been advocated as a preferred option for most Graves disease (GD) patients. However, long-term remission after a course of MMI treatment is achieved in only 20% to 40% of patients, depending on the duration of follow-up. OBJECTIVE: To evaluate clinical factors for predicting relapse of GD in Thai patients after MMI treatment. METHODS: A retrospective analysis was performed of newly diagnosed patients with GD who achieved remission of hyperthyroid GD after at least 12 months of MMI treatment. Long-term outcomes were assessed and predictive factors of early and late relapse were evaluated. RESULTS: A total of 443 patients with newly diagnosed GD who were treated with MMI for at least 12 months from 1985 to 2019, and were able to discontinue medication, were studied. The mean age at diagnosis was 37.0 ±â€…11.4 years and 81.7% were female. Of the 320 patients (72.2%) who achieved initial remission after MMI treatment for 23 months, 106 patients (33.1%) experienced late relapse during the mean follow-up duration of 9.7 years after MMI withdrawal. The remission rates decreased from 36.4% at the first year after stopping MMI to only 20.7% at 10 years. High initial serum triiodothyronine (T3) level and duration of minimum maintenance dose therapy (MMDT) of <6 months were associated with late disease relapse after remission. CONCLUSION: The long-term remission rate of Graves hyperthyroidism was achieved in one-fifth of MMI-treated Thai patients. Predictive markers for late relapse included high initial serum T3 level and a duration of MMDT of <6 months.

Prolonged Honeymoon Period in a Thai Patient with Adult-Onset Type 1 Diabetes Mellitus.

OBJECTIVE: To describe a usual case of adult-onset T1DM with prolonged honeymoon period for more than 5 years. METHODS: Repeated mixed meal stimulation tests for a period of 6-12 months together with monitoring pancreatic autoantibodies and laboratory data were followed following the onset of diagnosis. RESULTS: We report a 24-year-old Thai patient with T1DM with sustained remission without antidiabetic medication for more than 5 years while maintaining low-carbohydrate intake and regular exercise. Repeated mixed meal stimulation tests for a period of 6-12 months revealed preserved beta-cell functions. Interestingly, repeated pancreatic autoantibodies at 5 years after diagnosis still showed positive anti-GAD, anti-IA2, and anti-ZnT8. CONCLUSION: Restored beta-cell function with complete insulin withdrawal in new-onset T1DM has been reported in very few cases with some common factors as in our patient (low-carbohydrate intake with regular exercise). Delaying autoimmune activity by reducing metabolic load in newly diagnosed T1DM might play a role in maintaining the honeymoon period and could lead to an innovative therapeutic option in new-onset T1DM.

Impacts of the American Joint Committee on Cancer (AJCC) 8th edition tumor, node, metastasis (TNM) staging system on outcomes of differentiated thyroid cancer in Thai patients.

BACKGROUND: In 2018, the American Joint Committee on Cancer (AJCC) 8th edition (AJCC8) was introduced to replace the previous version (AJCC7) due to superiority of AJCC8 over AJCC7 for better prediction of survival from thyroid cancer. AIM: To compare AJCC staging systems with the American Thyroid Association (ATA) risk classification for the prediction of 5-year disease-free survival (DFS), and 5-year disease-specific survival (DSS) in Thai patients. METHODS: We retrospectively reviewed all patients with histopathologic diagnosis of DTC who were treated at Theptarin Hospital, Bangkok, Thailand from 1987 to 2019. RESULTS: The study cohort included 262 differentiated thyroid cancer (DTC) patients (papillary thyroid cancer 89.7% with a median time of follow-up 7.8 years). The number (%) of patients within each stage group by AJCC7 and AJCC8 respectively are as follows: Stage I: 173 (66.0%) vs. 232 (88.5%), Stage II: 33 (12.6%) vs. 24 (9.2%), Stage III: 36 (13.7%) vs. 2 (0.8%), Stage IV: 20 (7.7%) vs. 4 (1.5%). The ATA high risk group was found in 24.3% of AJCC7 Stage I compared with 23.7% of AJCC8 Stage I. The 5-year DFS rates in patients classified as stages I, II, III, and IV by AJCC8 were 87.9%, 45.8%, 0% and 25%, respectively. The 5-year DSS rates in patients classified as stages I, II, III and IV by AJCC8 were 98.7%, 100%, 100% and 0%, respectively. AJCC8 was more predictive of DFS rate than AJCC7. CONCLUSIONS: Our study is in accord with previous studies that AJCC8 downstage a significant percentage of patients with DTC and correlated with better prognostic validity. However, even a person at low risk for mortality can be at high risk for recurrence.

Practice patterns and outcomes in the management of Thai patients with Graves' disease.

BACKGROUND: The treatment of hyperthyroid Graves' disease (GD) varies considerably among geographic areas. In this study, we aimed to evaluate practice patterns and treatment outcomes in Thai patients with hyperthyroid GD. METHODS: A retrospective cohort study over 35 years (1985-2019) in patients with hyperthyroid GD was conducted. The trends of treatment options were compared periodically during the study period and the overall remission rate from each option was determined. RESULTS: A total of 2736 hyperthyroid GD patients were treated and followed-up for at least 3 months over the study period (female 82.0%, mean age at diagnosis 36.3 ± 12.0 years, median duration of follow-up 74.5 months). Anti-thyroid drug (ATD) was the most commonly used treatment (78.0%), followed by RAI (21.0%), and surgery (1.0%). There was a significant downward trend for surgery, from 12.3% in the 1980s to only 0.2% in last phase of the study period. The preference for RAI therapy has also decreased in the last 5 years. Among ATD-treated patients, the remission rate was achieved only in 30.7 and 16.0% of all ATD-treated patients were eventually treated with RAI. Spontaneous hypothyroidism developed in 2.7% of the ATD-treated patients during a follow-up period. Almost all RAI-treated patients (97.1%) developed hypothyroidism. CONCLUSIONS: Our present study highlighted the changing landscape of primary treatments for hyperthyroid GD toward ATD and the sharp downward trend in the surgical option. Even though ATD was associated with a low remission rate, it was preferred by many patients and physicians. The use of RAI as the primary treatment decreased in the last decade. However, RAI was a very effective treatment for Graves' hyperthyroidism but will inevitably induce hypothyroidism and a requirement for life-long replacement therapy.

Impact of first-line treatment choice on long-term outcomes of hyperthyroid Graves' disease patients with thyrotoxic periodic paralysis.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a unique manifestation of Graves' disease. While it is uncommon in Asian, it is extremely rare in Caucasian patients (0.1-0.2%). Previous studies suggested that TPP indicate more severity of Graves' disease and definitive treatments should be used to prevent relapses. AIM: To describe clinical features and impact of first-line treatment on long-term outcomes of TPP patients. METHOD: A retrospective cohort study over 35 years (1985-2019) of TPP from Graves' disease patients was conducted. All cases were analyzed and their clinical courses were compared between those who received anti-thyroid drugs (ATD) versus radioactive iodine (RAI) as a primary treatment. None of them underwent surgery. RESULTS: A total of 2964 hyperthyroid Graves' disease patients were treated and followed-up at least 3 months over the study period. TPP was identified in 63 cases (2.1%) of all patients. There were 60 males and only 3 females with age at presentation of 35.0 ± 8.2 years. TPP was the first presentation of hyperthyroid Graves' disease in 82.5% of them. During the acute attack of TPP, all patients presented with bilateral lower limb flaccid weaknesses with median serum potassium of 2.1 mmol/L. No fatal TPP cases were found. RAI was selected as primary treatment in 27 patients (42.9%). Nearly all RAI-treated patients rendered hypothyroidism with the median RAI dose at 15 mCi. No patients who were in remission after RAI treatment developed recurrent attack of TPP. In the remaining 36 ATD-treated patients with mean follow-up time at 9.1 years, relapse was found in 10 patients (27.8%) after the drug discontinuation and 6 patients suffered recurrent TPP. Only 8 ATD-treated TPP patients (22.2%) went into remission. CONCLUSIONS: TPP is a rare complication of hyperthyroid Graves' disease. Definitive treatment with RAI or thyroidectomy should be employed to prevent relapse and further attacks of TPP.