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Articles in E-pub version are posted online ahead of regular printed publication.

Original Articles
Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience
Jung Heo, Yeon-Lim Suh, Se Hoon Kim, Doo-Sik Kong, Do-Hyun Nam, Won-Jae Lee, Sung Tae Kim, Sang Duk Hong, Sujin Ryu, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim, Kyu Yeon Hur
Received November 8, 2023  Accepted December 21, 2023  Published online February 5, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1877    [Epub ahead of print]
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  • 16 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity.
Methods
A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared.
Results
Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered.
Conclusion
The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.
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Impact of Antidiabetic Drugs on Clinical Outcomes of COVID-19: A Nationwide Population-Based Study
Han Na Jang, Sun Joon Moon, Jin Hyung Jung, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Received October 16, 2023  Accepted January 3, 2024  Published online January 29, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1857    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
Background
Inconsistent results have been reported regarding the association between the use of antidiabetic drugs and the clinical outcomes of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of antidiabetic drugs on COVID-19 outcomes in patients with diabetes using data from the National Health Insurance Service (NHIS) in South Korea.
Methods
We analyzed the NHIS data of patients aged ≥20 years who tested positive for COVID-19 and were taking antidiabetic drugs between December 2019 and June 2020. Multiple logistic regression analysis was performed to analyze the clinical outcomes of COVID-19 based on the use of antidiabetic drugs.
Results
A total of 556 patients taking antidiabetic drugs tested positive for COVID-19, including 271 male (48.7%), most of whom were in their sixties. Of all patients, 433 (77.9%) were hospitalized, 119 (21.4%) received oxygen treatment, 87 (15.6%) were admitted to the intensive care unit, 31 (5.6%) required mechanical ventilation, and 61 (11.0%) died. Metformin was significantly associated with the lower risks of mechanical ventilation (odds ratio [OR], 0.281; 95% confidence interval [CI], 0.109 to 0.720; P=0.008), and death (OR, 0.395; 95% CI, 0.182 to 0.854; P=0.018). Dipeptidylpeptidase-4 inhibitor (DPP-4i) were significantly associated with the lower risks of oxygen treatment (OR, 0.565; 95% CI, 0.356 to 0.895; P=0.015) and death (OR, 0.454; 95% CI, 0.217 to 0.949; P=0.036). Sulfonylurea was significantly associated with the higher risk of mechanical ventilation (OR, 2.579; 95% CI, 1.004 to 6.626; P=0.049).
Conclusion
In patients with diabetes and COVID-19, metformin exhibited reduced risks of mechanical ventilation and death, DPP- 4i was linked with lower risks of oxygen treatment and death, while sulfonylurea was related to the increased risk of mechanical ventilation.
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Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Samir Kumar Talukder, Deep Dutta, Shahjada Selim
Received October 6, 2023  Accepted November 30, 2023  Published online January 23, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1839    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap.
Methods
Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events.
Results
From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, –0.58%; 95% confidence interval, –0.75 to –0.40; P<0.00001; I2=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG).
Conclusion
Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.
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Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells
Seok-Woo Hong, Jinmi Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Received August 21, 2023  Accepted November 6, 2023  Published online January 23, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1809    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Polyunsaturated fatty acids (PUFAs) reportedly have protective effects on pancreatic β-cells; however, the underlying mechanisms are unknown.
Methods
To investigate the cellular mechanism of PUFA-induced cell protection, mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis were examined.
Results
DHA treatment remarkably repressed caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of autophagy, an increase in microtubule- associated protein 1-light chain 3 (LC3)-II, autophagy-related 5 (Atg5), and decreased p62. Upstream factors involved in autophagy regulation (Beclin-1, unc51 like autophagy activating kinase 1 [ULK1], phosphorylated mammalian target of rapamycin [mTOR], and protein kinase B) were also altered by DHA treatment. DHA specifically induced phosphorylation on S2448 in mTOR; however, phosphorylation on S2481 decreased. The role of G protein-coupled receptor 120 (GPR120) in the effect of DHA was demonstrated using a GPR120 agonist and antagonist. Additional treatment with AH7614, a GPR120 antagonist, significantly attenuated DHA-induced autophagy and protection. Taken together, DHA-induced autophagy activation with protection against PA-induced apoptosis mediated by the GPR120/mTOR axis.
Conclusion
These findings indicate that DHA has therapeutic effects on PA-induced pancreatic β-cells, and that the cellular mechanism of β-cell protection by DHA may be a new research target with potential pharmacotherapeutic implications in β-cell protection.
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Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review
Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
Received July 28, 2023  Accepted November 23, 2023  Published online January 22, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1794    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).
Methods
Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.
Results
In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%–10.8% and 16.0%–25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%–1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.
Conclusion
AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.
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The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy
Hye Hyeon Moon, Sae Rom Chung, Young Jun Choi, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Jeong Hyun Lee, Jung Hwan Baek
Received September 4, 2023  Accepted November 14, 2023  Published online January 3, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1818    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB).
Methods
This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy.
Results
Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system.
Conclusion
Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.
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Effectiveness of a Social Networking Site Based Automatic Mobile Message Providing System on Glycemic Control in Patients with Type 2 Diabetes Mellitus
Kyuho Kim, Jae-Seung Yun, Joonyub Lee, Yeoree Yang, Minhan Lee, Yu-Bae Ahn, Jae Hyoung Cho, Seung-Hyun Ko
Received October 30, 2023  Accepted December 21, 2023  Published online December 27, 2023  
DOI: https://doi.org/10.3803/EnM.2023.1871    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM).
Methods
A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12.
Results
HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group.
Conclusion
An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.
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Endocrinol Metab : Endocrinology and Metabolism