Resistance to Thyroid Hormone Beta Due to THRB Mutation in a Patient Misdiagnosed With TSH-Secreting Pituitary Adenoma.

Elevated concentrations of T3 and T4 concomitant with nonsuppressed TSH are found in both TSH-producing tumors and resistance to thyroid hormone beta (RTHß), posing a diagnostic challenge. We demonstrate here a 54-year-old female who presented with palpitations, goiter, and elevated free T4 with nonsuppressed TSH concentrations (TSH 2.2 mIU/L [normal range, NR 0.27-4.2 mIU/L] and FT4 59.08 pmol/L [NR 12.0-22.0 pmol/L]). Because magnetic resonance imaging revealed a pituitary microadenoma (4 mm), she was diagnosed with TSH-secreting pituitary adenoma and underwent transsphenoidal surgery. Pathological reports showed no tumor cells. Subsequent genetic testing revealed a pathogenic variant in the THRB gene resulting in a His435Arg amino acid substitution in the T3 receptor isoform beta 1 (TRß1), suggestive of RTHß. In vitro and ex vivo studies revealed that the His435Arg mutated TRß1 (TRß1-H435R) completely abolishes the T3-induced transcriptional activation, nuclear receptor corepressor 1 release, steroid receptor coactivator 1 recruitment, and T3-induced thyroid hormone target gene expression, confirming the pathogenicity of this variant. The identification of a pituitary microadenoma in a patient with RTHß led to a misdiagnosis of a TSH-producing tumor and unnecessary surgery. Genetic testing proved pivotal for an accurate diagnosis, suggesting earlier consideration in similar clinical scenarios.

Effects of D-Allulose with Sucrose Beverage on Glucose Tolerance and Insulin Levels among Thai Healthy Volunteers.

D-Allulose has blood glucose suppression effects in both animal and clinical studies. The mechanism mediating glucose suppression in animals is controlled by several actions including the inhibition of sucrase. To investigate the dose-response effects of D-allulose with a sucrose beverage on glucose tolerance and insulin levels using Thai volunteers. This was a prospective, randomized, double-blinded, crossover study. Subjects had five oral sucrose tolerance tests (OSTT) with escalating doses of D-allulose (0, 2.5, 5, 7.5 or 10 g) with a 50 g sucrose beverage in a random order once a week for five consecutive weeks. The five drinks were consumed in a random order; the order being blinded for both subjects and investigators. Blood samples were drawn immediately before consumption and at 30, 60, 90 and 120 min after consumption of the study product for measurement of plasma glucose and insulin levels. Thirty healthy subjects (11 men and 19 women) completed the study. The peak postprandial glucose (PePPG) and insulin levels (PePPI) were lower when D-allulose was added in a dose-dependent manner. The lowest plasma glucose and insulin levels occurred at 120 min after OSTT in all five products and they were raised when D-allulose was added in a dose-dependent manner. D-Allulose has a suppression response on glucose and insulin shown by the decrease in postprandial plasma glucose and insulin levels following the addition of D-allulose to sucrose in a dose-dependent manner. The more D-allulose added, the less marked the glucose and insulin response occurred.

Prevalence of thyroid dysfunctions and thyroid autoantibodies in Thai patients with systemic lupus erythematosus: An age- and sex-matched controlled study.

BACKGROUND/OBJECTIVE: To determine the prevalence of thyroid dysfunctions and thyroid autoantibodies in Thai systemic lupus erythematosus (SLE) patients, and compare them with age- and sex-matched healthy controls (HCs). Associations between thyroid dysfunctions and SLE disease activity, and associated factors for thyroid dysfunctions in SLE also were determined. METHOD: One hundred SLE patients, without apparent clinical thyroid disease, attended the Rheumatology Clinic between November 2021 and October 2022, were enrolled into this study. HCs were matched to SLE cases by age and sex (ratio of 1:1). Clinical manifestations, SLE disease activity and medication received were collected in all SLE patients. Thyroid function tests and thyroid autoantibodies (anti-thyroglobulin: anti-TG and anti-thyroid peroxidase: anti-TPO) were collected from all participants. RESULTS: When compared with HCs, SLE patients had higher prevalence of thyroid dysfunctions, hypothyroidism and euthyroid sick syndrome (28% vs. 7%, p < .001, and 12% vs. 2%, p = .010, and 6% vs. 0%, p = .013, respectively). Prevalence of isolated hypothyroxinemia was higher numerically in SLE patients (9% vs. 3%, p = .074). Prevalence of anti-TG or anti-TPO was no different between SLE patients and HCs (16% vs. 18%, p = .707). There was no association between SLE disease activity and abnormal thyroid functions or thyroid autoantibodies. Family history of thyroid disease and prednisolone use (>10 mg/day) were associated factors for thyroid abnormalities with adjusted OR (95% CI) of 6.13 (1.58-23.75), p = .009 and 4.00 (1.37-11.70), p = .011, respectively. CONCLUSION: Thyroid dysfunctions were more prevalent in SLE patients. Family history of thyroid disease and prednisolone use (>10 mg/day) were independent associated factors of thyroid abnormalities.

Glycated hemoglobin variability and the risk of cardiovascular events in patients with prediabetes and type 2 diabetes mellitus: A post-hoc analysis of a prospective and multicenter study.

AIMS/INTRODUCTION: High glycated hemoglobin (HbA1c) variability has been reported to be linked with cardiovascular events in type 2 diabetes patients. Only a few studies have been carried out on Asian patients. This study aimed to investigate the association of prediabetes and type 2 diabetes in Asian patients by performing a post-hoc analysis of a multicenter, prospective, observational study. MATERIALS AND METHODS: Data for prediabetes and type 2 diabetes patients were retrieved from a multicenter national registry entitled "CORE-Thailand study." The primary outcome was 4P-MACE (major adverse cardiovascular events, including non-fatal myocardial infarction, heart failure hospitalization, non-fatal stroke and all-cause death). Patients were stratified according to quartiles of HbA1c standard deviation. The Cox proportional hazards regression model was used to estimate the association of HbA1c variability with incident cardiovascular disease. RESULTS: A total of 3,811 patients with prediabetes and type 2 diabetes were included. The median follow-up duration was 54 months. In the fully adjusted model, the highest quartile of HbA1c variability showed a statistically significant association with 4P-MACE (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.77-4.35), fatal and non-fatal myocardial infarction (HR 6.91, 95% CI 1.90-25.12), hospitalization for heart failure (HR 3.34, 95% CI 1.20-9.26) and all-cause death (HR 3.10, 95% CI 1.72-5.57). All these outcomes were statistically significantly different among four quartiles of HbA1c (log-rank P-value <0.05). Fatal and non-fatal stroke showed no statistically significant association with high HbA1c variability. CONCLUSION: High HbA1c variability in the highest quartile showed a statistically significant association with multiple adverse cardiovascular events in an Asian population. Minimizing HbA1c fluctuation during long-term follow up should be another important objective for type 2 diabetes patients.

Changes in Urinary Iodine Levels Following Bariatric Surgery.

OBJECTIVE: Obesity has become an epidemic in the United States. Although bariatric surgery can effectively achieve weight loss by altering the gastrointestinal tract, it commonly results in micronutrient deficiency, requiring supplementation. Iodine is an essential micronutrient for the synthesis of thyroid hormones. We aimed to investigate changes in urinary iodine concentrations (UIC) in patients following bariatric surgery. METHODS: 85 adults who underwent either laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass surgery were enrolled. At baseline and 3 months after surgery, we evaluated spot UIC and serum thyroid stimulating hormone (TSH), vitamin D, vitamin B12, ferritin, and folate levels. Participants provided a 24-hour diet recall for iodine-rich foods and information about multivitamin use at each time point. RESULTS: There was a significant increase in median UIC (201 [120.0 - 288.5] vs 334.5 [236.3 - 740.3] µg/L; P < .001), a significant decrease in mean body mass index (44.0 ± 6.2 vs 35.8 ± 5.9; P < .001) and a significant decrease in TSH levels (1.5 [1.2 - 2.0] vs 1.1 [0.7 - 1.6] uIU/mL; P < .001) at 3 months postoperatively compared to baseline. Body mass index, UIC, and TSH levels before and after surgery did not differ based on the type of weight loss surgery. CONCLUSION: In an iodine-sufficient area, bariatric surgery does not cause iodine deficiency nor clinically significant changes in thyroid function. Different surgical procedures with different anatomical alterations in the gastrointestinal tract do not significantly affect iodine status.

Added Value of Postoperative Radioiodine Scan for Staging and Risk Stratification in Papillary Thyroid Microcarcinoma.

OBJECTIVE: The complete staging and risk stratification of Papillary thyroid microcarcinoma (PTMC) is usually not done due to its theoretically low recurrence rates. This study aimed to determine the value of postoperative radioiodine diagnostic scan and SPECT/CT for the accurate staging and risk stratification in PTMC patients. METHODOLOGY: This study was a retrospective review of PTMC patients from January 2014 to May 2017 who underwent I-131 scans. All PTMC patients were initially staged by the 8th edition AJCC/TNM staging system and risk-stratified, based on clinical information, histopathology and stimulated thyroglobulin (sTg). After I-131 scan, staging and risk stratification were re-assessed. The proportion of patients who ended up with a higher stage and risk stratification were reported. RESULTS AND CONCLUSION: Fifty-two patients were included. The overall upgrading of cancer stage was 7.7 %. The overall higher risk stratification was 19.2% with radioiodine-avid lymph node, lung, and bone metastases. Neck and paratracheal node metastases were found in 37.3% of the initial low-risk patients with sTg less than 5 ng/mL. Lung metastasis was found in the initial intermediate-risk patient. The I-131 scan helps to localize metastatic lesions and results in a higher stage in 50% of the initial high-risk patients. This study provides some evidence showing the value of postoperative radioiodine WBS for accurate staging and risk stratification in PTMC patients. Larger studies with analytical design should be further performed to prove its significant utility.

30-Minute Delta Cortisol Post-ACTH Stimulation Test and Proposed Cut-Off Levels for Adrenal Insufficiency Diagnosis.

The ACTH stimulation test is used to diagnose adrenal insufficiency (AI). This study evaluated the diagnostic performance of serum delta cortisol from ACTH stimulation tests and determined appropriate cut-off levels of serum 30-minute delta cortisol for the diagnosis of AI, allowing a reduction in the number of 60-minute cortisol tests. A 6-year retrospective study in 471 patients was conducted. The performance of the serum delta cortisol in diagnosing AI was assessd using a multivariable logistic regression model and the area under ROC curves (AuROC). Both serum 30-minute and 60-minute delta cortisol demonstrated equally high diagnostic accuracy for AI (AuROC for LDT : 0.91 vs 0.90 ; HDT : 0.91 vs 0.92, respectively). The 30-minute delta cortisol test was chosen to develop proposed diagnostic cut-off levels due to its simplicity. The proposed lower cut-off level for 30-minute delta cortisol was Δ < 1.8 µg/dL for both LDT and HDT. The upper cut-off levels were Δ > 11.8 µg/dL for LDT and Δ > 10.5 µg/dL for HDT. These cut-off levels yielded high sensitivity and specificity > 90%. The 30-minute serum delta cortisol using the proposed cut-off levels provides diagnostic performance for AI equal to that of the 60-minute test and is more convenient, requires less time, less invasive and is cost-saving. 67 : 95-101, February, 2020.