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.

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.

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.

ANGPTL3 and ANGPTL8 in Thai subjects with hyperalphalipoproteinemia and severe hypertriglyceridemia.

BACKGROUND: The role of ANGPTL3 and ANGPTL8 in lipid regulation in patients with very high levels of HDL-cholesterol and triglyceride is unknown. OBJECTIVE: We examined plasma levels of ANGPTL3 and ANGPTL8 in subjects with hyperalphalipoproteinemia (HALP) and in those with severe hypertriglyceridemia (HTG). METHODS: Plasma ANGPTL3 and ANGPTL8 levels were measured by ELISA in 320 subjects, consisting of HALP subjects with HDL-cholesterol ≥100 mg/dl (n=90) and healthy controls (n=90) and subjects with triglyceride ≥886 mg/dl (n=89) and control subjects (n=51). RESULTS: The mean plasma ANGPTL3 level was significantly higher in the HALP group compared to that of the controls (297 ± 112 ng/mL vs. 230 ± 100 ng/mL, p<0.001). Similarly, the mean plasma ANGPTL8 level was also higher in the HALP group (30 ± 11 ng/mL vs. 20 ± 8 ng/mL, p<0.001). Both ANGPTL3 and ANGPTL8 levels positively correlated with HDL-cholesterol levels. In the severe HTG group, plasma ANGPTL3 level was significantly higher than those in the control group (223 ± 105 ng/mL vs. 151 ± 60 ng/mL, p<0.001), but not ANGPTL8 (23 ± 20 ng/mL vs. 31 ± 23 ng/mL in controls, p=0.028). Only ANGPTL3, but not ANGPTL8, levels positively correlated with triglyceride levels. CONCLUSION: Plasma level of ANGPTL3 was increased in both HALP and severe HTG whereas an increase in plasma level of ANGPTL8 was found only in HALP, and not in severe HTG, suggesting that both ANGPTL3 and ANGPTL8 might play distinct roles in lipid regulation on these two extremes of dyslipidemia.

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.

Recurrence Factors and Characteristic Trends of Papillary Thyroid Cancer over Three Decades.

BACKGROUND: The prevalence of thyroid cancer is rising worldwide. Although thyroid cancer has a favorable prognosis, up to 20% of patients experienced recurrent disease during the follow-up period. The present study aimed to examine the trend of incidence and factors associated with recurrence and outcomes of papillary thyroid cancer (PTC) in Thai patients over the last 30 years. METHODS: We reviewed the clinical data of all patients with PTC who were treated between 1987 and 2019 at Theptarin Hospital. Clinical characteristics, epidemic trend, factors associated with the persistence/recurrence of the disease, overall disease-specific survival rate, and overall disease-free survival rate were analysed. RESULTS: A total of 235 patients with PTC who were registered between 1987 and 2019 were reviewed. The mean age was 42.5 ± 14.3 years, with a mean follow-up of 9.5 years. Papillary thyroid microcarcinoma (PTMC) was consistently increased and accounted for 21.4% (50/235) of total cases. The American Thyroid Association (ATA) risk stratification was high in 24% of all PTMCs in the last decade, and 16.0% of these patients experienced local recurrence during the follow-up period. Coexistence with Hashimoto's thyroiditis (HT) was found in one-fifth of the patients with PTC and was correlated with a low recurrence rate (HR: 0.16, P=0.013). Only age ≥55 years associated with the persistence/recurrence of the disease. The overall disease-free survival and disease-specific survival rates were 77.4% and 98.3%, respectively. CONCLUSIONS: The prognosis of PTC is generally considered favorable. However, approximately one-fourth of patients with PTMC demonstrated more aggressive clinical behavior, particularly in the last decade of the study. Coexistence of HT contributed to a better prognosis.

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.

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.

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.