Sung Hye Kong

Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice

OBJECTIVE Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years. DESIGN AND METHODS This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines. RESULTS The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 μg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushings syndrome in the study. CONCLUSIONS We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.

Dietary calcium intake and risk of cardiovascular disease, stroke, and fracture in a population with low calcium intake

Background: The role of dietary calcium intake in cardiovascular disease (CVD), stroke, and fracture is controversial. Most previous reports have evaluated populations with high calcium intake.Objective: We aimed to evaluate whether high dietary calcium intake was associated with the risk of CVD, stroke, and fracture in a population with low calcium intake.Design: In a prospective cohort study beginning in 2001 in Ansung-Ansan, Korea, 2158 men and 2153 women aged >50 y were evaluated for all-cause mortality, CVD, stroke, and fractures over a median 9-y follow-up.Results: During follow-up, 242 and 100 deaths, 149 and 150 CVD events, 58 and 82 stroke events, and 211 and 292 incident fractures occurred in men and women, respectively. The first quartiles of energy-adjusted dietary calcium intake were 249 mg/d (IQR: 169 mg/d) in men and 209 mg/d (IQR: 161 mg/d) in women. Both men and women with higher dietary calcium intake tended to have higher fat, protein, sodium, phosphorus, fruit, and vegetable intakes. In men, outcomes were not significantly associated with dietary calcium intake with or without adjustments, and CVD risk tended to increase with increasing energy-adjusted dietary calcium intake, but this was not statistically significant (P = 0.078 and P = 0.093 with and without adjustment, respectively). In women, CVD risk and dietary calcium intake showed a U-shaped association; the HRs (95% CIs) without adjustment relative to the first quartile were 0.71 (0.47, 1.07), 0.57 (0.36, 0.88), and 0.52 (0.33, 0.83) for quartiles 2, 3, and 4, respectively, and the values after adjustment were 0.70 (0.45, 1.07), 0.51 (0.31, 0.81), and 0.49 (0.29, 0.83) for quartiles 2, 3, and 4, respectively.Conclusion: In Korean women, increased dietary calcium intake was associated with a decreased CVD risk, but it did not influence the risk of stroke or fracture.

Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus

Background There has been evidences of ethnic differences in the low density lipoprotein cholesterol (LDL-C) lowering effect of statin. We aimed to evaluate the efficacy of moderate-intensity statins in the treatment of dyslipidemia among Korean patients with type 2 diabetes mellitus (T2DM). Methods We analyzed a retrospective cohort that consisted of Korean patients with T2DM aged 40 to 75 years who had been prescribed any of the moderate-intensity statins (atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, or pravastatin 40 mg). Among them, only patients with baseline lipid profiles before starting statin treatment were selected, and changes in their lipid profiles before and 6 months after statin therapy were analyzed. Results Following the first 6 months of therapy, the overall LDL-C reduction was −47.4% (interquartile range, −56.6% to −34.1%). In total, 92.1% of the participants achieved an LDL-C level of <100 mg/dL, 38.3% had a 30% to 50% reduction in their LDL-C levels, and 42.3% had a reduction in their LDL-C levels greater than 50%. The response rates of each drug for achieving a LDL-C level <100 mg/dL were 81.7%, 93.1%, 95.0%, 95.0%, 96.5%, and 91.7% for treatment with atorvastatin doses of 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, and pravastatin 40 mg, respectively. Conclusion In conclusion, the use of moderate-intensity statins reduced LDL-C levels less than 100 mg/dL in most of the Korean patients studied with T2DM. The efficacies of those statins were higher than expected in about 42% of Korean patients with T2DM.

Anti-programmed cell death 1 therapy triggering diabetic ketoacidosis and fulminant type 1 diabetes.

Programmed cell death 1 (PD-1) is a co-inhibitory molecule expressed on effector T cells and is involved in regulation of immune checkpoints. One of the known ligands of PD-1 protein is programmed cell death ligand 1 (PDL1), which is expressed in many tumor cells. Activation of PD-1/PDL-1 axis results in suppression of anti-tumor immune checkpoints. Pembrolizumab is an immunoglobulin G4 monoclonal antibody targeting PD-1 molecule that increases immune response and induces anti-tumor activity. It has been approved for treating metastatic melanoma and is currently on clinical investigation for several other tumors including non-small cell lung cancer. On the other hand, PD-1 or PDL-1 blockade induced type 1 diabetes mellitus (T1DM) in non-obese prediabetic mice regardless of age [1]. In humans, few case reports of anti-PD-1 therapy induced T1DM have been reported including one case of fulminant T1DM [2, 3]. Here, we described a case of new-onset fulminant T1DM after anti-PD-1 therapy along with measures of glucose and C-peptide levels before and after the therapy. Case report

Insulin Resistance is Associated with Cognitive Decline Among Older Koreans with Normal Baseline Cognitive Function: A Prospective Community-Based Cohort Study

We evaluated whether metabolic factors were associated with cognitive decline, compared to baseline cognitive function, among geriatric population. The present study evaluated data from an ongoing prospective community-based Korean cohort study. Among 1,387 participants who were >65 years old, 422 participants were evaluated using the Korean mini-mental status examination (K-MMSE) at the baseline and follow-up examinations. The mean age at the baseline was 69.3 ± 2.9 years, and 222 participants (52.6%) were men. The mean duration of education was 7.1 ± 3.6 years. During a mean follow-up of 5.9 ± 0.1 years, the K-MMSE score significantly decreased (−1.1 ± 2.7 scores), although no significant change was observed in the homeostasis model assessment of insulin resistance (HOMA-IR) value. Participants with more decreased percent changes in K-MMSE scores had a shorter duration of education (p = 0.001), older age (p = 0.022), higher baseline K-MMSE score (p < 0.001), and increased insulin resistance (∆HOMA-IR, p = 0.002). The correlation between the percent changes in K-MMSE and ∆HOMA-IR values remained significant after multivariable adjustment (B = −0.201, p = 0.002). During a 6-year follow-up of older Koreans with normal baseline cognitive function, increased insulin resistance was significantly correlated with decreased cognitive function.

Thyroid Cancer Treatment Choice: A Pilot Study of a Tool to Facilitate Conversations with Patients with Papillary Microcarcinomas Considering Treatment Options

BACKGROUND The 2015 American Thyroid Association guidelines recognize active surveillance as an alternative to immediate surgery in patients with papillary microcarcinomas (PMCs). As a way to incorporate active surveillance as one of the management options for patients with PMCs, we developed and tested a tool to support conversations between clinicians and patients with PMCs considering treatment options. METHODS Thyroid Cancer Treatment Choice was developed using an iterative process based on the principles of interaction, design, and participatory action research. To evaluate the impact of the tool on treatment choice, a prospective study was conducted in two thyroid cancer clinics in Seongnam-si and Seoul, South Korea. Both clinics had the expertise to offer active surveillance as well as immediate surgery. One clinic was trained in the use of the conversation aid, while the other clinic continued to care for patients without access to the conversation aid. RESULTS Between May 2016 and April 2017, 278 patients, mostly women (n = 220, 79%), were included in the study; 152 (53%) received care at the clinic using the conversation aid. Age, sex, and mean (±SD) tumor size (6.6 ± 1.6 mm and 6.5 ± 1.9 mm) distributions were similar across clinics. Overall, 233 (84%) patients opted for active surveillance and 53 (16%) for thyroid surgery. Patients in the conversation aid group were more likely to choose active surveillance than the patients seen in the usual care clinic (relative risk = 1.16 [confidence interval 1.04-1.29]). Of all patients opting for active surveillance, more patients in the conversation aid group had thyroid cancer nodules >5 mm than in the usual care group (81% vs. 67%; p = 0.013). CONCLUSIONS Thyroid Cancer Treatment Choice is an evidence-based tool that supports the presentation of treatment options for PMCs. Pilot testing suggests that this conversation tool increases acceptance of active surveillance, suggesting that this option is an acceptable and preferable alternative for informed patients. Further studies are warranted to confirm this finding.

Catatonia as a presenting symptom of ectopic adrenocorticotropic hormone syndrome caused by thymic carcinoid tumor

Case description Clinical situation A previously healthy 57 ‐year ‐old man presented to our hos‐ pital due to lower extremity edema and fatigue, which started a few months earlier. He was re‐ cently diagnosed with diabetes mellitus and hy‐ pertension. However, he did not show any typi‐ cal Cushingoid features such as moon face, cen‐ tral obesity, buffalo hump, and purple striae. At the outpatient clinic, a chest X ‐ray revealed well ‐defined opacity at the right cardiac border (Figure 1A), and chest computed tomography (CT) showed a mass of approximately 6.5 cm in size along the anterior mediastinum (Figure 1B). He was admitted for further evaluation of abnormal findings confirmed by imaging studies.

Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro)

Background The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups. Methods This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis. Results Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014). Conclusion The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

Subclinical Hypothyroidism and Coronary Revascularization After Coronary Artery Bypass Grafting

We aimed to investigate long-term cardiovascular sequelae after coronary artery bypass grafting (CABG) in patients with subclinical hypothyroidism (SCH). All-cause and cardiovascular-related mortality, and cardiovascular events were retrospectively reviewed in 222 euthyroid and 36 SCH patients who underwent CABG. During a mean follow-up period of 8.2 ± 4.1 years, there were 90 incidents of all-cause deaths, 20 cardiovascular-related deaths, 70 major cardiovascular adverse events, 6 myocardial infarctions, 12 unstable anginas, 31 strokes, 23 hospitalizations due to heart failure, 15 atrial fibrillation (AF) events, and 27 coronary revascularizations. The incidence rate of coronary revascularization was significantly higher in patients with SCH (n = 6, 16.6%) than in euthyroid patients (n = 20, 9.0%), with a hazard ratio (HR) of 3.179 (95% confidence interval [CI] 1.174, 8.605; p = 0.023) after adjustment. In subgroup analysis, SCH patients who experienced postoperative AF within 3 months after CABG surgery had a significantly higher risk of coronary revascularization (n = 4, 25.0%) than euthyroid patients without AF (n = 14, 8.9%) after adjustment (HR 11.759, 95% CI 2.747, 50.343, p = 0.001). The frequency of fatal or nonfatal unstable angina was also higher in patients with SCH (n = 2, 12.5%) than in euthyroid patients (n = 4, 2.5%) (HR 16.999, 95% CI 2.242, 128.860, p = 0.006). In conclusion, preoperative SCH is associated with less favorable cardiovascular outcomes, especially coronary revascularization after CABG. Moreover, SCH patients who develop postoperative AF exhibit significantly increased risks of unstable angina and coronary revascularization. Preoperative evaluation of thyroid function may be helpful for predicting long-term outcomes after CABG.

Relation of Subclinical Hypothyroidism is Associated With Cardiovascular Events and All-Cause Mortality in Adults With High Cardiovascular Risk

The aim of this study was to determine the association between subclinical hypothyroidism and cardiovascular (CVD) events, and mortality using the atherosclerotic CVD risk score. We carried out an observational study in a prospective cohort that was followed up for 12 years. The study included 3,021 participants aged ≥ 40 years at baseline from the Ansung cohort, part of the Korean Genome and Epidemiology Study. Cox regression models were constructed to evaluate the hazards ratio (HR) and 95% confidence interval (CI) for all-cause mortality and CVD events in groups classified according to thyroid status. Subgroup analysis was performed with a cut-off age of 65 years or 7.5% of the 10-year atherosclerotic CVD risk score. The subclinical hypothyroidism group in the highest quartile of thyroid-stimulating hormone (>6.57 mIU/L) had a significantly increased risk of all-cause mortality (HR 2.12, 95% CI 1.27 to 3.56) and CVD events (HR 1.92, 95% CI 1.21 to 3.04) compared with euthyroid participants. Subgroup analysis by CVD risk revealed that participants with high CVD risk only had a high risk of all-cause mortality (HR 2.18, 95% CI 1.22 to 3.87) and CVD events (HR 2.42, 95% CI 1.35 to 4.33). Further analysis showed that participants aged <65 years with high CVD risk had the highest risk of all-cause mortality (HR 3.50, 95% CI 1.50 to 8.16) and CVD events (HR 3.37, 95% CI 1.46 to 9.57). Our results demonstrated that high thyroid-stimulating hormone levels were associated with a greater risk of mortality and new CVD risks, particularly among subjects with high CVD risk.