Endocrinology and Metabolism

Brief Report

Adrenal gland
Comparative Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Radioimmunoassay in Determining Plasma Aldosterone Concentration and Plasma Renin Activity for Primary Aldosteronism Screening: So Yoon Kwon, Kyeong-Jin Kim, Soo-Youn Lee, Jae Hyeon Kim; Endocrinol Metab. 2024;39(6):965-969. Published online November 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.1985

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Abstract PDF Supplementary Material PubReader ePub: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) accurately measures plasma aldosterone concentration (PAC), but its correlation with radioimmunoassay (RIA), equivalent RIA levels, and optimal cutoff for PAC and aldosterone-to-renin ratio (ARR) in primary aldosteronism (PA) screening have not been determined in a Korean population. Our study of 127 patients who underwent diagnostic testing for PA showed that the LC-MS/MS and RIA methods have good correlation, with a mean bias of 29.3% for PAC. An LC-MS/MS PAC level of 11.7 ng/dL was equivalent to an RIA PAC level of 15 ng/dL. Receiver operating characteristic curve analysis showed that an LC-MS/MS PAC level of 10.3 ng/dL and LC-MS/MS ARR level of 20.0 provided sensitivity of 73.1% with a specificity of 57.3% and sensitivity of 92.3% with a specificity of 14.7%, respectively. When the LC-MS/MS method is used for PA screening, an adjustment of cutoff values is necessary.

Original Article

Hypothalamus and pituitary gland
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; Endocrinol Metab. 2024;39(2):387-396. Published online February 5, 2024; DOI: https://doi.org/10.3803/EnM.2023.1877

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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.

Citations

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TSH-secreting pituitary adenomas and bone
Marco Losa, Alberto Vassallo, Stefano Frara, Pietro Mortini, Andrea Giustina
Pituitary.2024; 27(6): 752. CrossRef

Review Article

Diabetes, obesity and metabolism
The Benefits Of Continuous Glucose Monitoring In Pregnancy: Jee Hee Yoo, Jae Hyeon Kim; Endocrinol Metab. 2023;38(5):472-481. Published online October 11, 2023; DOI: https://doi.org/10.3803/EnM.2023.1805

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Previous studies have consistently demonstrated the positive effects of continuous glucose monitoring (CGM) on glycemic outcomes and complications of diabetes in people with type 1 diabetes. Guidelines now consider CGM to be an essential and cost-effective device for managing type 1 diabetes. As a result, insurance coverage for it is available. Evidence supporting CGM continues to grow and expand to broader populations, such as pregnant people with type 1 diabetes, people with type 2 diabetes treated only with basal insulin therapy, and even type 2 diabetes that does not require insulin treatment. However, despite the significant risk of hyperglycemia in pregnancy, which leads to complications in more than half of affected newborns, CGM indications and insurance coverage for those patients are unresolved. In this review article, we discuss the latest evidence for using CGM to offer glycemic control and reduce perinatal complications, along with its cost-effectiveness in pregestational type 1 and type 2 diabetes and gestational diabetes mellitus. In addition, we discuss future prospects for CGM coverage and indications based on this evidence.

Citations

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Glucose circadian rhythm assessment in pregnant women for gestational diabetes screening
Rafael Bravo, Kyung Hyun Lee, Sarah A. Nazeer, Jocelyn A. Cornthwaite, Michal Fishel Bartal, Claudia Pedroza
International Journal of Obesity.2025; 49(1): 118. CrossRef
Quality of Life in Women With Gestational Diabetes Mellitus and Treatment Satisfaction Upon Intermittently Scanned Continuous Glucose Monitoring
Sookyung Won, Hyeon Ji Kim, Jee Yoon Park, Kyung Joon Oh, Sung Hee Choi, Hak Chul Jang, Joon Ho Moon
Journal of Korean Medical Science.2025;[Epub] CrossRef
Wearable devices for glucose monitoring: A review of state-of-the-art technologies and emerging trends
Mohammad Mansour, M. Saeed Darweesh, Ahmed Soltan
Alexandria Engineering Journal.2024; 89: 224. CrossRef
Diagnosis and Treatment of Hyperglycemia in Pregnancy
Sneha Mohan, Aoife M. Egan
Endocrinology and Metabolism Clinics of North America.2024; 53(3): 335. CrossRef

Original Article

Diabetes, obesity and metabolism
Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION): Byung Wan Lee, KyungWan Min, Eun-Gyoung Hong, Bon Jeong Ku, Jun Goo Kang, Suk Chon, Won-Young Lee, Mi Kyoung Park, Jae Hyeon Kim, Sang Yong Kim, Keeho Song, Soon Jib Yoo; Endocrinol Metab. 2023;38(3):328-337. Published online June 28, 2023; DOI: https://doi.org/10.3803/EnM.2023.1688

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Background
This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin.
Methods
In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks.
Results
The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted.
Conclusion
Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Citations

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Dual add‐on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study
Kyung Ah Han, You‐Cheol Hwang, Shin Je Moon, Ho Chan Cho, Hye Jin Yoo, Sung Hee Choi, Suk Chon, Kyoung‐Ah Kim, Tae Nyun Kim, Jun Goo Kang, Cheol‐Young Park, Jong Chul Won, Eunjoo Cho, Jeongyun Kim, Kyong Soo Park
Diabetes, Obesity and Metabolism.2024; 26(9): 3743. CrossRef

Brief Report

Adrenal Gland
Aldosterone Immunoassay-Specific Cutoff Value for Seated Saline Suppression Test for Diagnosing Primary Aldosteronism: So Yoon Kwon, Jiyun Park, So Hee Park, So Hyun Cho, You-Bin Lee, Soo-Youn Lee, Jae Hyeon Kim; Endocrinol Metab. 2022;37(6):938-942. Published online December 6, 2022; DOI: https://doi.org/10.3803/EnM.2022.1535

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A seated saline loading test (SLT) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is one of the most accepted confirmatory tests of primary aldosteronism. However, LC-MS/MS is time-consuming and is not widely available in diagnostic laboratories compared to immunoassay. With immunoassay, it is unknown whether SLT in the seated position is more accurate than that of the supine position, and a cutoff value of post-seated SLT plasma aldosterone concentration (PAC) must be established in the Korean population. Ninety-eight patients underwent SLT in both positions, and post-SLT PAC was measured by LC-MS/MS and radioimmunoassay. We confirmed primary aldosteronism if post-seated SLT PAC by LC-MS/MS exceeded 5.8 ng/dL. The area under the receiver operating characteristic curve was greater for seated than supine SLT (0.928 vs. 0.834, P=0.003). The optimal cutoff value of post-seated SLT by radioimmunoassay was 6.6 ng/dL (sensitivity 83.3%, specificity 92.2%).

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Investigating the cut-off values of captopril challenge test for primary aldosteronism using the novel chemiluminescent enzyme immunoassay method: a retrospective cohort study
Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Kengo Kambara, Hiroki Kamada, Sota Oguro, Yuto Yamazaki, Celso E. Gomez-Sanchez, Akihiro Ito, Hironobu Sasano, Kei Takase, Tetsuhiro Tanaka, Hideki Katagiri, Fumitoshi Satoh
Hypertension Research.2024; 47(5): 1362. CrossRef
Usefulness of the Upright Posture Test in the Diagnosis of Primary Aldosteronism
Nada Younes, Matthieu St-Jean, Marie-Josée Desrochers, Eric Therasse, Mathieu Latour, Isabelle Bourdeau, André Lacroix
Journal of the Endocrine Society.2024;[Epub] CrossRef
Screening and treatment of endocrine hypertension focusing on adrenal gland disorders: a narrative review
Seung Min Chung
Journal of Yeungnam Medical Science.2024; 41(4): 269. CrossRef
Comparative Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Radioimmunoassay in Determining Plasma Aldosterone Concentration and Plasma Renin Activity for Primary Aldosteronism Screening
So Yoon Kwon, Kyeong-Jin Kim, Soo-Youn Lee, Jae Hyeon Kim
Endocrinology and Metabolism.2024; 39(6): 965. CrossRef

Original Articles

Thyroid Big Data Articles (National Health Insurance Service Database)
Graves’ Disease and the Risk of End-Stage Renal Disease: A Korean Population-Based Study: Yoon Young Cho, Bongseong Kim, Dong Wook Shin, Hye Ryoun Jang, Bo-Yeon Kim, Chan-Hee Jung, Jae Hyeon Kim, Sun Wook Kim, Jae Hoon Chung, Kyungdo Han, Tae Hyuk Kim; Endocrinol Metab. 2022;37(2):281-289. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1333

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Background
Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed.
Methods
This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles.
Results
Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD.
Conclusion
This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Citations

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Chronic Kidney Disease and Thyroid Hormones
Yuan Cheng, Haofei Hu, Wangyang Li, Sheng Nie, Shiyu Zhou, Yuna Chen, Tao Cao, Hong Xu, Bicheng Liu, Chunbo Chen, Huafeng Liu, Qiongqiong Yang, Hua Li, Yaozhong Kong, Guisen Li, Yan Zha, Ying Hu, Gang Xu, Yongjun Shi, Yilun Zhou, Guobin Su, Ying Tang, Men
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism
Magdy Mohamed Allam, Hanaa Tarek El-Zawawy, Tarek Hussein El-Zawawy
Endocrine.2023; 82(1): 78. CrossRef
Effect of Hyperthyroidism on Preventing Renal Insufficiency
Tae Yong Kim
Endocrinology and Metabolism.2022; 37(2): 220. CrossRef
Effects and Clinical Value of Peritoneal Dialysis on Water and Water Balance, Adverse Reactions, Quality of Life, and Clinical Prognosis in Patients with Decompensated Chronic Nephropathy: A Systematic Review and Meta-Analysis
Xichao Wang, Miaomiao Zhang, Na Sun, Wenxiu Chang, Gang Chen
Computational and Mathematical Methods in Medicine.2022; 2022: 1. CrossRef

Adrenal Gland
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism: Ye Seul Yang, Seung Hun Lee, Jung Hee Kim, Jee Hee Yoo, Jung Hyun Lee, Seo Young Lee, A Ram Hong, Dong-Hwa Lee, Jung-Min Koh, Jae Hyeon Kim, Sang Wan Kim; Endocrinol Metab. 2021;36(4):875-884. Published online August 11, 2021; DOI: https://doi.org/10.3803/EnM.2021.1047

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Background
Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisol_nondominantperipheral) at AVS remains unclear. We aimed to investigate the clinical significance of CS and its impact on postoperative outcomes after unilateral adrenalectomy.
Methods
In this retrospective observational multi-center study, we analyzed PA patients who underwent both successful adrenocorticotropin hormone-stimulated AVS and unilateral adrenalectomy. Successful cannulation was defined as the selectivity index (cortisol_adrenal/ cortisol_peripheral) ≥3. Clinical and biochemical outcomes after unilateral adrenalectomy were evaluated based on the international Primary Aldosteronism Surgical Outcome consensus.
Results
Among 263 patients analyzed, 247 had CS (93.9%). Patients with CS had lower serum potassium levels, higher plasma aldosterone concentration, higher aldosterone-to-renin ratio (ARR), and larger adenoma size than those without CS. Those with CS showed significantly higher lateralization index than those without CS (P<0.001). Although postoperative blood pressure and ARR significantly decreased in those with CS, clinical and biochemical outcomes were comparable in both groups. When the cut-off value of age was determined using receiver operating characteristic (ROC) analysis, patients aged ≥50 years old with contralateral suppression index (CSI; the ratio between aldosterone/cortisol_nondominant and aldosterone/cortisol_peripheral) ≤0.26 had greater odds ratio (6.43; 95% confidence interval, 1.30 to 31.69) of incident chronic kidney disease than those aged <50 years with CSI >0.26 after adjusting for other factors.
Conclusion
CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Citations

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Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism
Xizi Zhang, Xiaoyu Shu, Feifei Wu, Jun Yang, Qingfeng Cheng, Zhipeng Du, Ying Song, Yi Yang, Jinbo Hu, Yue Wang, Qifu Li, Shumin Yang
Journal of Hypertension.2024; 42(3): 450. CrossRef
Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
The Journal of Clinical Endocrinology & Metabolism.2024; 109(8): e1582. CrossRef
Development of a multivariate model predictive of post-adrenalectomy renal function decline in patients with primary aldosteronism: a large-cohort single-center study
Wenhao Lin, Juping Zhao, Chen Fang, Wei He, Xin Huang, Fukang Sun, Jun Dai
World Journal of Urology.2024;[Epub] CrossRef
Prognostic value of contralateral suppression on kidney function after surgery in patients with primary aldosteronism
Nathalie Voss, Sara Mørup, Caroline Clausen, Claus larsen Feltoft, Jan Viberg Jepsen, Mads Hornum, Mikkel Andreassen, Jesper Krogh
Clinical Endocrinology.2023; 98(3): 306. CrossRef
Factors Predicting Long-term Estimated Glomerular Filtration Rate Decrease, a Reliable Indicator of Renal Function After Adrenalectomy in Primary Aldosteronism
Qiyu He, Zhimin Tan, Yu Liu, Liang Zhou
Endocrine Practice.2023; 29(3): 199. CrossRef
Prognostic value of contralateral suppression for remission after surgery in patients with primary aldosteronism
Sara Mørup, Nathalie Voss, Caroline Clausen, Claus Larsen Feltoft, Mikkel Andreassen, Jesper Krogh
Clinical Endocrinology.2022; 96(6): 793. CrossRef
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism (Endocrinol Metab 2021;36:875-84, Ye Seul Yang et al.)
Zhimin Tan, Qiyu He, Liang Zhou
Endocrinology and Metabolism.2022; 37(6): 951. CrossRef
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism (Endocrinol Metab 2021;36:875-84, Ye Seul Yang et al.)
Ye Seul Yang, Sang Wan Kim
Endocrinology and Metabolism.2022; 37(6): 953. CrossRef

Brief Report

Adrenal Gland
Urinary Free Metanephrines for Diagnosis of Pheochromocytoma and Paraganglioma: Jiyeon Ahn, Ji Yun Park, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Soo-Youn Lee, Jae Hyeon Kim; Endocrinol Metab. 2021;36(3):697-701. Published online June 1, 2021; DOI: https://doi.org/10.3803/EnM.2020.925

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Background
Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated.
Methods
This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group.
Results
Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity.
Conclusion
Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.

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Advancements in understanding the molecular mechanisms and clinical implications of Von Hippel-Lindau syndrome: A comprehensive review
Yaochun Wang, Jingzhuo Song, Shuxing Zheng, Shuhong Wang
Translational Oncology.2025; 51: 102193. CrossRef
The role of the adrenalectomy in the management of pheochromocytoma: the experience of a Portuguese referral center
Inês Costa Carvalho, Miguel V. B. Machado, João P. Morais, Filipa Carvalho, Elisabete Barbosa, José Barbosa
Endocrine.2024; 86(1): 409. CrossRef
Laparoscopic Resection of Para-Aortic Mass at the Aortic Bifurcation: An Atypical Presentation of a Tailgut Cyst
Andy Wang, Jiddu A Guart, Danielle Li, Trenton Taros, Hongyi Cui
Cureus.2024;[Epub] CrossRef
Biochemical Assessment of Pheochromocytoma and Paraganglioma
Graeme Eisenhofer, Christina Pamporaki, Jacques W M Lenders
Endocrine Reviews.2023; 44(5): 862. CrossRef
Adrenal bleeding due to pheochromocytoma - A call for algorithm
Ewelina Rzepka, Joanna Kokoszka, Anna Grochowska, Magdalena Ulatowska-Białas, Martyna Lech, Marta Opalińska, Elwira Przybylik-Mazurek, Aleksandra Gilis-Januszewska, Alicja Hubalewska-Dydejczyk
Frontiers in Endocrinology.2022;[Epub] CrossRef

Special Article

Adrenal gland
Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force: Eu Jeong Ku, Kyoung Jin Kim, Jung Hee Kim, Mi Kyung Kim, Chang Ho Ahn, Kyung Ae Lee, Seung Hun Lee, You-Bin Lee, Kyeong Hye Park, Yun Mi Choi, Namki Hong, A Ram Hong, Sang-Wook Kang, Byung Kwan Park, Moon-Woo Seong, Myungshin Kim, Kyeong Cheon Jung, Chan Kwon Jung, Young Seok Cho, Jin Chul Paeng, Jae Hyeon Kim, Ohk-Hyun Ryu, Yumie Rhee, Chong Hwa Kim, Eun Jig Lee; Endocrinol Metab. 2021;36(2):322-338. Published online April 6, 2021; DOI: https://doi.org/10.3803/EnM.2020.908

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Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

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A Prospective Comparative Study of 18F-FDOPA PET/CT Versus 123I-MIBG Scintigraphy With SPECT/CT for the Diagnosis of Pheochromocytoma and Paraganglioma
Changhwan Sung, Hyo Sang Lee, Dong Yun Lee, Yong-il Kim, Jae Eun Kim, Sang Ju Lee, Seung Jun Oh, Tae-Yon Sung, Yu-Mi Lee, Young Hoon Kim, Beom-Jun Kim, Jung-Min Koh, Seung Hun Lee, Jin-Sook Ryu
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Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study
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Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review
Kwan Hoon Jo, Jaewoong Lee, Jaeeun Yoo, Hoon Seok Kim, Eun Sook Kim, Je Ho Han, Yi Sun Jang, Jae-Seung Yun, Jang Won Son, Soon Jib Yoo, Seung Hwan Lee, Dong Jun Lim, Hyuk-Sang Kwon, Seungok Lee, Sungdae Moon, Myungshin Kim
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Screening and treatment of endocrine hypertension focusing on adrenal gland disorders: a narrative review
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D. V. Rebrova, N. V. Vorokhobina
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A Ram Hong, Hwa Young Ahn, Bu Kyung Kim, Seong Hee Ahn, So Young Park, Min-Hee Kim, Jeongmin Lee, Sun Wook Cho, Ho-Cheol Kang
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Original Article

Clinical Study
Association of Body Mass Index with the Risk of Incident Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality: A Community-Based Prospective Study: Ji Cheol Bae, Nam H. Cho, Jae Hyeon Kim, Kyu Yeon Hur, Sang-Man Jin, Moon-Kyu Lee; Endocrinol Metab. 2020;35(2):416-424. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.416

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Background
Type 2 diabetes and cardiovascular disease (CVD) are the most important sequelae of obesity and the leading cause of death. We evaluated the association between body mass index (BMI) and the risk of incident type 2 diabetes, CVD, and all-cause mortality in a prospective study of a Korean population.
Methods
The shapes of the associations were modeled by restricted cubic splines regression analysis. After categorizing all subjects (n=8,900) into octiles based on their BMI levels, we estimated the hazard ratio (HR) for the association of categorized BMI levels with the risk of incident CVD and type 2 diabetes using a Cox’s proportional hazard analysis.
Results
The mean age of participants was 52 years and 48% were men. Of the subjects at baseline, 39.0% of men and 45.6% of women were classified as obese (BMI ≥25 kg/m²). Over a mean follow-up of 8.1 years, CVD events occurred in 509 participants; 436 died; and 1,258 subjects developed type 2 diabetes. The increased risk of incident diabetes began to be significant at BMI 23 to 24 kg/m² in both sexes (HR, 1.8). For CVD events, the risk began to increase significantly at BMI 26 to 28 kg/m² (HR, 1.6). We found a reverse J-shaped relationship between BMI and all-cause mortality, with an increased risk among individuals with BMI values in lower range (BMI <21 kg/m²).
Conclusion
These results suggest that the BMI cut-off points for observed risk were varied depending on the diseases and that the BMI classification of obesity need to be revised to reflect differential risk of obesity-related diseases.

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Namgok Lecture 2019

Obesity and Metabolism
Impact of Skeletal Muscle Mass on Metabolic Health: Gyuri Kim, Jae Hyeon Kim; Endocrinol Metab. 2020;35(1):1-6. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.1

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Abstract PDF PubReader ePub

Skeletal muscle is regarded as an endocrine and paracrine organ. Muscle-derived secretory proteins, referred to as myokines, mediate interactions between skeletal muscle mass and other organs such as the liver, adipose tissue, pancreas, bone, and the cardiovascular system. As individuals age, reduced levels of physical activity and sarcopenia (loss of skeletal muscle mass and strength) are associated with physical frailty and disability. Recently, several studies have suggested that the loss of skeletal muscle mass may contribute to metabolic disease. Therefore, herein, we focus on the relationships between skeletal muscle mass and metabolic diseases, including metabolic syndrome and non-alcoholic fatty liver disease.

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Original Article

Clinical Study
Triiodothyronine Levels Are Independently Associated with Metabolic Syndrome in Euthyroid Middle-Aged Subjects: Hye Jeong Kim, Ji Cheol Bae, Hyeong Kyu Park, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Jae Hyeon Kim, Yong-Ki Min, Sun Wook Kim, Jae Hoon Chung; Endocrinol Metab. 2016;31(2):311-319. Published online May 13, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.311

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Background

Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort.

Methods

A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders.

Results

Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend <0.001) and the T3-to-T4 ratio quartile categories (P for trend <0.001). The multi-variate-adjusted OR (95% confidence interval) for MetS in the highest T3 quartile group was 1.249 (1.020 to 1.529) compared to the lowest T3 quartile group, and that in the highest T3-to-T4 ratio quartile group was 1.458 (1.141 to 1.863) compared to the lowest T3-to-T4 ratio quartile group, even after adjustment for potential confounders.

Conclusion

Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications.

Citations

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Case Report

Adrenal gland
Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently: Seung-Eun Lee, Jae Hyeon Kim, You-Bin Lee, Hyeri Seok, In Seub Shin, Yeong Hee Eun, Jung-Han Kim, Young Lyun Oh; Endocrinol Metab. 2015;30(4):607-613. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.607

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A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses.

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Problems of diagnosis and treatment of Connshing syndrome
M. S. Annaev, B. I. Geltser, K. V. Stegniy, O. I. Pak, R. A. Goncharuk, S. M. Selyutin, A. M. Morozova, O. G. Tsygankova, E. V. Maslyantsev, V. G. Fisenko
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Different cell compositions and a novel somatic KCNJ5 variant found in a patient with bilateral adrenocortical adenomas secreting aldosterone and cortisol
Liling Zhao, Jinjing Wan, Yujun Wang, Wenjun Yang, Qi Liang, Jinrong Wang, Ping Jin
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Adrenal Vein Cortisol to Metanephrine Ratio for Localizing ACTH-Independent Cortisol-Producing Adenoma: A Case Report
Rishi Raj, Philip A Kern, Neelima Ghanta, Edilfavia M Uy, Kamyar Asadipooya
Journal of the Endocrine Society.2021;[Epub] CrossRef
Adrenal Venous Sampling for Subtype Diagnosis of Primary Hyperaldosteronism
Mitsuhide Naruse, Akiyo Tanabe, Koichi Yamamoto, Hiromi Rakugi, Mitsuhiro Kometani, Takashi Yoneda, Hiroki Kobayashi, Masanori Abe, Youichi Ohno, Nobuya Inagaki, Shoichiro Izawa, Masakatsu Sone
Endocrinology and Metabolism.2021; 36(5): 965. CrossRef
Hypercortisolism and primary aldosteronism caused by bilateral adrenocortical adenomas: a case report
Kaiyun Ren, Jia Wei, Qilin Liu, Yuchun Zhu, Nianwei Wu, Ying Tang, Qianrui Li, Qianying Zhang, Yerong Yu, Zhenmei An, Jing Chen, Jianwei Li
BMC Endocrine Disorders.2019;[Epub] CrossRef

Original Articles

Adrenal gland
Using Growth Hormone Levels to Detect Macroadenoma in Patients with Acromegaly: Ji Young Park, Jae Hyeon Kim, Sun Wook Kim, Jae Hoon Chung, Yong-Ki Min, Myung-Shik Lee, Moon-Kyu Lee, Kwang-Won Kim; Endocrinol Metab. 2014;29(4):450-456. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.450

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Background

The aim of this study was to assess the clinical differences between acromegalic patients with microadenoma and patients with macroadenoma, and to evaluate the predictive value of growth hormone (GH) levels for early detection of macroadenoma.

Methods

We performed a retrospective analysis of 215 patients diagnosed with a GH-secreting pituitary adenoma. The patients were divided into two groups: the microadenoma group and the macroadenoma group, and the clinical parameters were compared between these two groups. The most sensitive and specific GH values for predicting macroadenoma were selected using receiver operating characteristic (ROC) curves.

Results

Compared with the microadenoma group, the macroadenoma group had a significantly younger age, higher body mass index, higher prevalence of hyperprolactinemia and hypogonadism, and a lower proportion of positive suppression to octreotide. However, there were no significant differences in the gender or in the prevalence of diabetes between the two groups. The tumor diameter was positively correlated with all GH values during the oral glucose tolerance test (OGTT). All GH values were significantly higher in the macroadenoma group than the microadenoma group. Cut-off values for GH levels at 0, 30, 60, 90, and 120 minutes for optimal discrimination between macroadenoma and microadenoma were 5.6, 5.7, 6.3, 6.0, and 5.8 ng/mL, respectively. ROC curve analysis revealed that the GH value at 30 minutes had the highest area under the curve.

Conclusion

The GH level of 5.7 ng/mL or higher at 30 minutes during OGTT could provide sufficient information to detect macroadenoma at the time of diagnosis.

Citations

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Does size really matter? A closer look at the absolute size of growth hormone-secreting pituitary adenomas
Katharina Schilbach, Gérald Raverot
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Jakob Dal, Benedikte G. Skov, Marianne Andersen, Ulla Feldt‐Rasmussen, Claus L. Feltoft, Jesper Karmisholt, Eigil H. Nielsen, Olaf M. Dekkers, Jens Otto L. Jørgensen
Clinical Endocrinology.2021; 94(4): 625. CrossRef
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Leila Hedayati Zafarghandi, Mohammad Ebrahim Khamseh, Milad Fooladgar, Shahrzad Mohseni, Mostafa Qorbani, Nahid Hashemi Madani, Mahboobeh Hemmatabadi, MohammadReza Mohajeri-Tehrani, Nooshin Shirzad
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Obesity and Metabolism
Association between Serum Albumin, Insulin Resistance, and Incident Diabetes in Nondiabetic Subjects: Ji Cheol Bae, Sung Hwan Seo, Kyu Yeon Hur, Jae Hyeon Kim, Myung-Shik Lee, Moon Kyu Lee, Won Young Lee, Eun Jung Rhee, Ki Won Oh; Endocrinol Metab. 2013;28(1):26-32. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.26

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Background

Serum albumin has been suggested to be associated with insulin resistance. We evaluated the association between serum albumin concentration and insulin resistance. We also investigated whether serum albumin level has an independent effect on the development of diabetes.

Methods

In our study, 9,029 subjects without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into tertiles based on their serum albumin levels at baseline. The odds ratio (OR) for the prevalence of insulin resistance, defined as the top quartile of homeostasis model assessment of insulin resistance and the presence of impaired fasting glucose and nonalcoholic fatty liver disease, was evaluated cross-sectionally. Also, the hazard ratio (HR) for incident diabetes was estimated longitudinally, according to the baseline albumin tertiles using Cox proportional hazard analysis respectively.

Results

From the lowest to the highest tertile of albumin, the multivariable-adjusted ORs of insulin resistance increased significantly in both men and women. During the mean follow-up period of nearly 4 years, 556 (6.1%) subjects progressed to diabetes. The multivariable-adjusted HR (95% confidence interval [CI]) of diabetes in men were 1, 1.09 (95% CI, 0.86 to 1.40), and 1.10 (95% CI, 0.86 to 1.41), respectively, from the lowest to the highest tertiles of baseline albumin. Corresponding values for women were 1, 1.21 (95% CI, 0.66 to 2.21), and 1.06 (95% CI, 0.56 to 2.02), respectively.

Conclusion

Our study showed that increased serum albumin level was associated with insulin resistance. However, serum albumin did not have an independent effect on the development of diabetes.

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