Usefulness of Real-Time Quantitative Microvascular Ultrasonography for Differentiation of Graves’ Disease from Destructive Thyroiditis in Thyrotoxic Patients

백한상,박지연,Chaiho Jeong,하정훈,강무일,임동준 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.2

Background: Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD)and power Doppler (PD) imaging to distinguish Graves’ disease (GD) from destructive thyroiditis (DT). Methods: This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, andMVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs),which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen’s kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173). Results: The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. Theoptimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. Wefound a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method. Conclusion: In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxicpatients, with less inter-observer variability.

Long-term Cumulative Exposure to High γ-glutamyl Transferase Levels and The Risk of Cardiovascular Disease: A Nationwide Population-based Cohort Study

백한상,김봉성,이승환,임동준,권혁상,장상아,한경도,윤재승 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.6

Background: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. Methods: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. Results: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. Conclusion: Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes

백한상,박지연,유진,이준엽,양여리,하정훈,이승환,조재형,임동준,김헌성 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.4

Background: The prevalence of young-onset diabetes (YOD) has been increasing worldwide. As the incidence of YOD increases, itis necessary to determine the characteristics of YOD and the factors that influence its development and associated complications. Methods: In this retrospective study, we recruited patients who were diagnosed with type 2 diabetes mellitus between June 2001 andDecember 2021 at a tertiary hospital. The study population was categorized according to age: YOD (age <40 years), middle-age-onset diabetes (MOD, 40≤ age <65 years), and late-onset diabetes (LOD, age ≥65 years). We examined trends in glycemic control byanalyzing fasting glucose levels during the first year in each age group. A Cox proportional-hazards model was used to determine therelative risk of developing complications according to glycemic control trends. Results: The fasting glucose level at the time of diagnosis was highest in the YOD group (YOD 149±65 mg/dL; MOD 143±54mg/dL; and LOD 140±55 mg/dL; P=0.009). In the YOD group, glucose levels decreased at 3 months, but increased by 12 months. YOD patients and those with poor glycemic control in the first year were at a higher risk of developing complications, whereas therisk in patients with LOD was not statistically significant. Conclusion: YOD patients had higher glucose levels at diagnosis, and their glycemic control was poorly maintained. As poor glycemic control can influence the development of complications, especially in young patients, intensive treatment is necessary for patients with YOD.

ST elevation MI in a 17 year old man with acute lymphoblastic leukemia who received allo-SCT

백한상,박성수 대한내과학회 2017 대한내과학회 추계학술발표논문집 Vol.2017 No.1

Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes (Endocrinol Metab 2022;37:641-51, Han-sang Baek et al.)

백한상,Ji-Yeon Park,Jin Yu,이준엽,양여리,하정훈,Seung Hwan Lee,Jae Hyoung Cho,임동준,김헌성 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.6

갑상선기능항진증에서 갑상선 자가항체의 해석

백한상 ( Han-sang Baek ),임동준 ( Dong-jun Lim ) 대한내과학회 2023 대한내과학회지 Vol.98 No.3

Thyrotoxicosis is a clinical state with a variety of various etiologies that results from excess thyroid hormones, including hyperthyroidism and thyroiditis. Graves' disease (GD) is a well-known autoimmune thyroid disease that causes hyperthyroidism, and its pathogenesis is mainly driven by the thyroid-stimulating hormone receptor antibody (TSHRAb), which is highly specific for GD. Measuring the TSHRAb is a fast and accurate diagnostic tool for GD and has been used to monitor disease activity and the treatment response. However, conventional TSH-binding inhibitory immunoglobulin (TBII) does not differentiate between stimulating, blocking, or neutral antibodies. In contrast, thyroid stimulatory immunoglobulin bioassays differentiate between stimulating and blocking antibodies and have comparably high sensitivity and specificity to TBII for GD. We also discuss the role of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) in thyrotoxicosis, although they are less specific than TSHRAb for GD. TPOAb is associated with autoimmune thyroiditis, while TgAb appears with TPOAb in patients with autoimmune thyroid disease. In addition, TPOAb or TgAb may be associated with a low recurrence of GD after discontinuing anti-thyroid drugs. Clinicians should interpret thyroid autoantibodies in the context of the patient's clinical presentation and consider their implications to manage and monitor thyrotoxicosis. (Korean J Med 2023;98:132-136)

Heart Rate Variability in Postoperative Patients with Nonfunctioning Pituitary Adenoma

하정훈,백한상,정채호,여민수,이승환,조재형,백기현,강무일,임동준 대한내분비학회 2021 Endocrinology and metabolism Vol.36 No.3

Background: Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction. Methods: A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies. Results: In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007). Conclusion: HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.

The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease

유진,백한상,Chaiho Jeong,조관훈,이정민,하정훈,김민희,이정민,임동준 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.3

Background: To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatmentwith an anti-thyroid drug (ATD) can predict prognosis of Graves’ disease (GD) in real-world practice. Methods: This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline andat follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patientswho experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation(remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies includingTSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and secondvalues divided by time duration (year). Results: Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in responseto ATD than the remission group (–84.7 [TSI slope, –198.2 to 8.2] vs. –120.1 [TSI slope, –204.4 to –45.9], P=0.026), whereas theTBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII,P=0.001). Conclusion: Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginningand follow-up could help predict GD prognosis.

A Newly Developed Pancreatic Adenocarcinoma in a Patient with Advanced Thyroid Cancer under Long-Term Sorafenib Use

김민지,백한상,이성학,임동준 대한갑상선학회 2021 International Journal of Thyroidology Vol.14 No.2

Sorafenib, an oral multi-target tyrosine kinase inhibitor (MTKI) for treatment of radioiodine-refractory differentiatedthyroid cancer can induce acute or chronic pancreatitis as an adverse event. However, there have been no reportsof pancreatic cancer associated with MTKI, especially among long-term MTKI user. A 60-year-old male patientvisited our outpatient cancer clinic due to aggravated abdominal and back pain. He had been taking sorafenibfor over five years for advanced thyroid cancer with multiple lung metastases, without any adverse events exceptmild hand-foot syndrome and slightly increased liver enzymes at the initial phase. Laboratory findings showedincreasing serum amylase and lipase levels. An abdominal CT scan showed a 5.2 cm heterogeneous hypointensemass-like lesion on the pancreas distal body area. Under suspicion of pancreatic cancer, extensive surgery of distalpancreatectomy, unilateral nephrectomy, and unilateral adrenalectomy confirmed moderately differentiatedadenocarcinoma with a background of chronic pancreatitis accompanying fibrosis and fat necrosis. Pancreaticcancer should be considered as well as pancreatitis in long-term MTKI users who show abrupt increases in serumpancreatic enzymes, although a causal relationship between long-term MTKI use and pancreatic cancer has notbeen elucidated.

Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study

정채호,권혜인,백한상,김헌성,임동준,백기현,하정훈,강무일 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.4

Background: Concomitant papillary thyroid cancer (PTC) and hyperparathyroidism (HPT) have been reported in several studies. Our study aimed to investigate the incidence of concomitant PTC in HPT patients upon preoperative diagnosis and present a clinical opinion on detecting thyroid malignancy in case of parathyroidectomy. Methods: Patients who underwent parathyroidectomy between January 2009 and December 2019 in two medical centers were included. Of the 279 participants 154 were diagnosed as primary hyperparathyroidism (pHPT) and 125 as secondary hyperparathy roidism (sHPT). The incidence of concomitant PTC and its clinical characteristics were compared with 98 patients who underwent thyroidectomy and were diagnosed with classical PTC during the same period. Results: Concurrent PTC was detected in 14 patients (9.1%) with pHPT and in nine patients (7.2%) with sHPT. Ten (71.4%) and seven (77.8%) PTCs were microcarcinomas in the pHPT and sHPT cases respectively. In the pHPT patients, vitamin D was lower in the pHPT+PTC group (13.0±3.7 ng/mL) than in the pHPT-only group (18.5±10.4 ng/mL; P=0.01). Vitamin D levels were also lower in the sHPT+PTC group (12.3±5.6 ng/mL) than in the sHPT-only group (18.0±10.2 ng/mL; P=0.12). In the concomitant PTC group, lymph node ratio was higher than in the classical PTC group (P=0.00). Conclusion: A high prevalence of concomitant PTC was seen in patients with pHPT and sHPT. Those concomitant PTCs were mostly microcarcinomas and had more aggressive features, suggesting that efforts should be made to detect concomitant malignancies in the preoperative parathyroidectomy evaluation.