Endocrinology and Metabolism

Original Articles

⁶⁸Ga-DOTATOC PET/CT in the Localization of Pituitary Tumors in Cushing’s Disease: Kyungwon Kim, Dongwoo Kim, Min-Ho Lee, Yae Won Park, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Cheol Ryong Ku, Eun Jig Lee; Received November 20, 2024 Accepted January 21, 2025 Published online March 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2249 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
This study aimed to determine the value of ⁶⁸Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas.
Methods
In this retrospective cohort study, we enrolled 30 patients with Cushing’s disease and positive ACTH immunoreactivity. All patients underwent ⁶⁸Ga-DOTATOC PET/CT and pituitary magnetic resonance imaging (MRI) before transsphenoidal adenomectomy.
Results
Twenty-five patients showed ⁶⁸Ga-DOTATOC uptake in their pituitary glands on PET/CT. Median age, pre-operative ACTH levels, pre-operative cortisol, and tumor size on MRI were comparable irrespective of DOTATOC uptake. ⁶⁸Ga-DOTATOC PET/CT showed a 77% success rate for localizing adenomas, which was not statistically different from that of MRI. The ACTH level in the successful localization group was significantly higher than that in the failed group (84.41 pg/mL vs. 37.26 pg/mL, P=0.001). The ACTH level was statistically significant predictor of successful localization using ⁶⁸Ga-DOTATOC PET/CT (P=0.013). The area under the curve was 0.932 with a cutoff of 53.86 pg/mL for ACTH levels to determine successful localization. Pre-operative ACTH levels above 53.86 pg/mL showed the best diagnostic accuracy in predicting the success of localizing adenomas (sensitivity, 91.3%; specificity, 85.7%). Mean and maximum standardized uptake value of adenoma negatively correlated to pre-operative ACTH level.
Conclusion
Plasma ACTH level is a favorable predictor for the successful localization and negative correlation with ⁶⁸Ga-DOTATOC uptake of corticotroph adenomas in ⁶⁸Ga-DOTATOC PET/CT. ⁶⁸Ga-DOTATOC PET/CT did not improve tumor localization for Cushing’s disease compared with MRI alone.

Sex-Specific Cardiovascular Risks and Mortality in Patients with Panhypopituitarism: A Nationwide Cohort Study: Seung Shin Park, Hyunmook Jeong, Chang Ho Ahn, Min Jeong Park, Yong Hwy Kim, Kwangsoo Kim, Jung Hee Kim; Received September 12, 2024 Accepted December 16, 2024 Published online February 11, 2025; DOI: https://doi.org/10.3803/EnM.2024.2176 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Panhypopituitarism is a condition of combined deficiency of multiple pituitary hormones, which requires lifelong hormone replacement therapy. Hormone deficiency or inadequate hormone replacement may contribute to cardiovascular disease. Here, we aimed to investigate the burden of cardiovascular, cerebrovascular diseases and mortality in patients with panhypopituitarism.
Methods
A total of 5,714 patients with panhypopituitarism were enrolled in the Korean National Health Insurance Service database from 2003 to 2020. Panhypopituitarism was defined according to the International Classification of Diseases, 10th Revision (ICD- 10) codes for hypopituitarism, pituitary adenoma, or craniopharyngioma and the continuous prescription of thyroid hormone and glucocorticoids. The risks of all-cause mortality, coronary artery disease (CAD), heart failure (HF), ischemic stroke, and intracranial hemorrhage were compared between patients with panhypopituitarism and age-, sex-, and index year-matched controls.
Results
The mean age of patients with panhypopituitarism and matched controls was 55.1 years, and men accounted for 51.5%. Patients with panhypopituitarism showed significantly higher all-cause mortality compared to matched controls after adjustment for covariates (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.95 to 2.43 in men and HR, 3.09; 95% CI, 2.78 to 3.44 in women). Additionally, there were higher risks of CAD, HF, ischemic stroke, and intracranial hemorrhage in both sexes, except for CAD in men.
Conclusion
Patients with panhypopituitarism have elevated risks of cardiovascular and cerebrovascular diseases as well as increased mortality. These risks are particularly prominent for all-cause mortality in women. Therefore, proactive monitoring for cardiovascular and cerebrovascular complications is required in patients with panhypopituitarism.

Review Article

Hypothalamus and pituitary gland
Pituitary Neuroendocrine Tumors in Multiple Endocrine Neoplasia: Sang Ouk Chin, Constance Chik, Toru Tateno; Endocrinol Metab. 2025;40(1):39-46. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.2074

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Abstract PDF PubReader ePub: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant disorder characterized by tumors of the pituitary, parathyroid, and endocrine-gastrointestinal tract. Pituitary neuroendocrine tumors (PitNETs) occur in about 40% of MEN1 cases, with 10% being the first manifestation. Recent studies show a slight female predominance, with microPitNETs (<1 cm) being more common than macroPitNETs (>1 cm). Functional PitNETs (FPitNETs) are more frequent than non-functional ones (36% to 48%), with prolactinomas being the most common FPitNETs. MEN1-associated PitNETs are often plurihormonal, larger, and more invasive compared to sporadic types, though patient age and FPitNET proportions are similar. MEN1 mutation-negative patients tend to have larger, symptomatic PitNETs at diagnosis. Six patients with MEN1 have been reported to have pituitary carcinomas, including a mutation- negative patient. Treatment approach between PitNETs in MEN1 and sporadic types appears to be similar. PitNETs also occur in MEN4, but their epidemiology is less understood. In patients with a MEN1-like phenotype and negative genetic testing, MEN4 should be considered.

Original Articles

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

Hypothalamus and pituitary gland
Preoperative Serum Copeptin Can Predict Delayed Hyponatremia after Pituitary Surgery in the Absence of Arginine Vasopressin Deficiency: Ho Kang, Seung Shin Park, Yoo Hyung Kim, Hwan Sub Lim, Mi-Kyeong Lee, Kyoung-Ryul Lee, Jung Hee Kim, Yong Hwy Kim; Endocrinol Metab. 2024;39(1):164-175. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1792

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Background
Delayed postoperative hyponatremia (DPH) is the most common cause of readmission after pituitary surgery. In this study, we aimed to evaluate the cutoff values of serum copeptin and determine the optimal timing for copeptin measurement for the prediction of the occurrence of DPH in patients who undergo endoscopic transsphenoidal approach (eTSA) surgery and tumor resection.
Methods
This was a prospective observational study of 73 patients who underwent eTSA surgery for pituitary or stalk lesions. Copeptin levels were measured before surgery, 1 hour after extubation, and on postoperative days 1, 2, 7, and 90.
Results
Among 73 patients, 23 patients (31.5%) developed DPH. The baseline ratio of copeptin to serum sodium level showed the highest predictive performance (area under the curve [AUROC], 0.699), and its optimal cutoff to maximize Youden’s index was 2.5×10^–11, with a sensitivity of 91.3% and negative predictive value of 92.0%. No significant predictors were identified for patients with transient arginine vasopressin (AVP) deficiency. However, for patients without transient AVP deficiency, the copeptin-to-urine osmolarity ratio at baseline demonstrated the highest predictive performance (AUROC, 0.725). An optimal cutoff of 6.5×10^–12 maximized Youden’s index, with a sensitivity of 92.9% and a negative predictive value of 94.1%.
Conclusion
The occurrence of DPH can be predicted using baseline copeptin and its ratio with serum sodium or urine osmolarity only in patients without transient AVP deficiency after pituitary surgery.

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Impact Factors of Blood Copeptin Levels in Health and Disease States
Yutong Wang, Shirui Wang, Siyu Liang, Xinke Zhou, Xiaoyuan Guo, Bochuan Huang, Hui Pan, Huijuan Zhu, Shi Chen
Endocrine Practice.2024; 30(12): 1197. CrossRef

Review Article

Hypothalamus and pituitary gland
Update on Current Evidence for the Diagnosis and Management of Nonfunctioning Pituitary Neuroendocrine Tumors: Elizabeth Whyte, Masahiro Nezu, Constance Chik, Toru Tateno; Endocrinol Metab. 2023;38(6):631-654. Published online November 15, 2023; DOI: https://doi.org/10.3803/EnM.2023.1838

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Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing’s disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.

Citations

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Circulating miR-20a-5p as a biomarker associated with cabergoline responsiveness in patients with hyperprolactinemia and pituitary adenomas
Yang Jong Lee, Jae Won Hong, Yongjae Kim, Jisup Kim, Chan Woo Kang, Min-Ho Lee, Ju Hyung Moon, Eui Hyun Kim, Cheol Ryong Ku, Eun Jig Lee
European Journal of Endocrinology.2025; 192(4): 335. CrossRef
Phenotype Transformation of PitNETs
Zhenwei Li, Yinzi Wu, Guannan He, Renzhi Wang, Xinjie Bao
Cancers.2024; 16(9): 1731. CrossRef
Donor–Acceptor–Donor Strategy Rouses the Photodynamic Therapy Anticancer Activity of a Bis-terpyridyl Ru(II) Complex
Zhongyu Wang, Li Wei, Junfeng Lin, Can Huang, Huitong Chen, Dong Fan, Weiyu Hu, Jing Liu, Huaiyi Huang, Zongming Wang, Xin Wang
Journal of Medicinal Chemistry.2024; 67(15): 13435. CrossRef
A Study in Pituitary Neuroendocrine Tumors (PitNETs): Real-Life Data Amid Baseline and Serial CT Scans
Mihai Costachescu, Oana-Claudia Sima, Mihaela Stanciu, Ana Valea, Mara Carsote, Claudiu Nistor, Mihai-Lucian Ciobica
Cancers.2024; 16(20): 3477. CrossRef
Editorial: Prognostic factors in pituitary tumors: clinical, biochemical, imaging, and pathological aspects
Toru Tateno, Roxana-Ioana Dumitriu Stan, Stephanie Du Four
Frontiers in Endocrinology.2024;[Epub] CrossRef
Adaptive evaluation of gross total resection rates for endoscopic endonasal approach based on preoperative MRI morphological features of pituitary adenomas
Ao Shen, Yue Min, Dongjie Zhou, Lirui Dai, Liang Lyu, Wenyi Zhan, Shu Jiang, Peizhi Zhou
Frontiers in Oncology.2024;[Epub] CrossRef

Songwon Lecture 2022

Hypothalamus and pituitary gland
Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine: Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2023;38(5):463-471. Published online October 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1820

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The clinical characteristics and prognoses of acromegaly vary among patients. Assessment of current and novel predictors can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and a reduction in the increased morbidity and mortality associated with acromegaly. Despite advances in the diagnosis and treatment of acromegaly, its pathophysiology remains unclear. Recent advancements in multiomics technologies, including genomics, transcriptomics, proteomics, metabolomics, and radiomics, have offered new opportunities to unravel the complex pathophysiology of acromegaly. This review comprehensively explores the emerging role of multiomics approaches in elucidating the molecular landscape of acromegaly. We discuss the potential implications of multiomics data integration in the development of novel diagnostic tools, identification of therapeutic targets, and the prospects of precision medicine in acromegaly management. By integrating diverse omics datasets, these approaches can provide valuable insights into disease mechanisms, facilitate the identification of diagnostic biomarkers, and identify potential therapeutic targets for precision medicine in the management of acromegaly.

Citations

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“Micromegaly”: Acromegaly with apparently normal GH, an entity on its own?
Lucio Vilar, Luciana Ansaneli Naves, Manoel Ricardo Alves Martins, Antônio Ribeiro-Oliveira Jr
Best Practice & Research Clinical Endocrinology & Metabolism.2024; 38(3): 101878. CrossRef

Special Article

Miscellaneous
Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society: Hyemi Kwon, Eun Roh, Chang Ho Ahn, Hee Kyung Kim, Cheol Ryong Ku, Kyong Yeun Jung, Ju Hee Lee, Eun Heui Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Jun Sung Moon, Jin Hwa Kim, Mi-kyung Kim, The Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2022;37(6):839-850. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1627

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Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Citations

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Patterns of hormonal changes in hypophysitis by immune checkpoint inhibitor
Hyunji Sang, Yun Kyung Cho, Sang-hyeok Go, Hwa Jung Kim, Eun Hee Koh
The Korean Journal of Internal Medicine.2024; 39(5): 801. CrossRef
Pembrolizumab plus lenvatinib for radically unresectable or metastatic renal cell carcinoma in the Japanese population
Ryo Fujiwara, Takeshi yuasa, kenichi kobayashi, tetsuya yoshida, susumu kageyama
Expert Review of Anticancer Therapy.2023; 23(5): 461. CrossRef
Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review
Won Sang Yoo, Eu Jeong Ku, Eun Kyung Lee, Hwa Young Ahn
Endocrinology and Metabolism.2023; 38(6): 750. CrossRef

Review Articles

Hypothalamus and Pituitary Gland
Independent Skeletal Actions of Pituitary Hormones: Se-Min Kim, Farhath Sultana, Funda Korkmaz, Daria Lizneva, Tony Yuen, Mone Zaidi; Endocrinol Metab. 2022;37(5):719-731. Published online September 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.1573

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Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector glands axis. Bone cells—osteoblasts and osteoclasts—express receptors for growth hormone, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin, and vasopressin. Independent skeletal actions of pituitary hormones on bone have been studied using genetically modified mice with haploinsufficiency and by activating or inactivating the receptors pharmacologically, without altering systemic effector hormone levels. On another front, the discovery of a TSH variant (TSH-βv) in immune cells in the bone marrow and skeletal action of FSHβ through tumor necrosis factor α provides new insights underscoring the integrated physiology of bone-immune-endocrine axis. Here we discuss the interaction of each pituitary hormone with bone and the potential it holds in understanding bone physiology and as a therapeutic target.

Citations

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Cushing’s disease and bone
Aleksandra Zdrojowy-Wełna, Barbara Stachowska, Marek Bolanowski
Pituitary.2024; 27(6): 837. CrossRef
Skeletal fragility in pituitary disease: how can we predict fracture risk?
Fabio Bioletto, Alessandro Maria Berton, Marco Barale, Luigi Simone Aversa, Lorenzo Sauro, Michela Presti, Francesca Mocellini, Noemi Sagone, Ezio Ghigo, Massimo Procopio, Silvia Grottoli
Pituitary.2024; 27(6): 789. CrossRef
Role of oxytocin in bone
Tianming Wang, Jianya Ye, Yongqiang Zhang, Jiayi Li, Tianxiao Yang, Yufeng Wang, Xiao Jiang, Qingqiang Yao
Frontiers in Endocrinology.2024;[Epub] CrossRef
Plasma proteomic profiles reveal proteins and three characteristic patterns associated with osteoporosis: A prospective cohort study
Yi Zheng, Jincheng Li, Yucan Li, Jiacheng Wang, Chen Suo, Yanfeng Jiang, Li Jin, Kelin Xu, Xingdong Chen
Journal of Advanced Research.2024;[Epub] CrossRef
Modern approach to bone comorbidity in prolactinoma
Meliha Melin Uygur, Sara Menotti, Simona Santoro, Andrea Giustina
Pituitary.2024; 27(6): 802. CrossRef
New tools for bone health assessment in secreting pituitary adenomas
Meliha Melin Uygur, Stefano Frara, Luigi di Filippo, Andrea Giustina
Trends in Endocrinology & Metabolism.2023; 34(4): 231. CrossRef
A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility
Dongjin Lee, Moon Ahn
Metabolites.2023; 13(3): 372. CrossRef
The mechanism of oxytocin and its receptors in regulating cells in bone metabolism
Liu Feixiang, Feng Yanchen, Li Xiang, Zhang Yunke, Miao Jinxin, Wang Jianru, Lin Zixuan
Frontiers in Pharmacology.2023;[Epub] CrossRef
To investigate the mechanism of Yiwei Decoction in the treatment of premature ovarian insufficiency-related osteoporosis using transcriptomics, network pharmacology and molecular docking techniques
Weisen Fan, Yan Meng, Jing Zhang, Muzhen Li, Yingjie Zhang, Xintian Qu, Xin Xiu
Scientific Reports.2023;[Epub] CrossRef

Hypothalamus and Pituitary Gland
Advances in Pituitary Surgery: Yoon Hwan Byun, Ho Kang, Yong Hwy Kim; Endocrinol Metab. 2022;37(4):608-616. Published online August 19, 2022; DOI: https://doi.org/10.3803/EnM.2022.1546

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Pituitary surgery has advanced considerably in recent years with the exploration and development of various endoscopic approaches and techniques. Different endoscopic skull base approaches are being applied to access sellar tumors in different locations. Moreover, extracapsular dissection and cavernous sinus exploration have enabled gross total resection of sellar tumors where it could not have been achieved in the past. Techniques for skull base reconstruction have also progressed, allowing surgeons to remove larger and more complicated tumors than before. This review article discusses different endoscopic skull base approaches, surgical techniques for removing pituitary adenomas, and reconstruction methods for repairing postoperative low-flow and high-flow cerebrospinal fluid leakage.

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The Impact of Surgical Telementoring on Reducing the Complication Rate in Endoscopic Endonasal Surgery of the Skull Base
Janez Ravnik, Hojka Rowbottom, Carl H. Snyderman, Paul A. Gardner, Tomaž Šmigoc, Matic Glavan, Urška Kšela, Nenad Kljaić, Boštjan Lanišnik
Diagnostics.2024; 14(17): 1874. CrossRef
Obstructive Sleep Apnea Screening and Effects of Surgery in Acromegaly: A Prospective Study
Jaeyoung Cho, Jung Hee Kim, Yong Hwy Kim, Jinwoo Lee
Endocrinology and Metabolism.2024; 39(4): 641. CrossRef
Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study
Seung Shin Park, Yong Hwy Kim, Ho Kang, Chang Ho Ahn, Dong Jun Byun, Man Ho Choi, Jung Hee Kim
The Journal of Steroid Biochemistry and Molecular Biology.2023; 230: 106276. CrossRef
Pituitary disease and anaesthesia
Kim Rhodes, Robert John, Astri Luoma
Anaesthesia & Intensive Care Medicine.2023; 24(6): 348. CrossRef
Орфанні ендокринні захворювання: сучасні тенденції хірургічного лікування в Україні
M.D. Tronko, B.B. Guda
Endokrynologia.2022; 27(4): 287. CrossRef

Original Article

Hypothalamus and Pituitary Gland
Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency: Yun Jeong Lee, Yunha Choi, Han-Wook Yoo, Young Ah Lee, Choong Ho Shin, Han Saem Choi, Ho-Seong Kim, Jae Hyun Kim, Jung Eun Moon, Cheol Woo Ko, Moon Bae Ahn, Byung-Kyu Suh, Jin-Ho Choi; Endocrinol Metab. 2022;37(2):359-368. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1384

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Background
Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.
Methods
This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.
Results
Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.
Conclusion
GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

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Impact of non-weight-dependent low-dose somatropin on bone accrual in childhood-onset GH deficient in the transition: an 18-month randomized controlled trial
Valesca Mansur Kuba, Antonia B.S. Castro, Cláudio Leone, Durval Damiani
Jornal de Pediatria.2025; 101(2): 255. CrossRef
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Jiang Zhu, Tanfang Zhou, Meng Menggen, Kalibixiati Aimulajiang, Hao Wen
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
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Patricia García Navas, María Yolanda Ruíz del Prado, Pablo Villoslada Blanco, Emma Recio Fernández, María Ruíz del Campo, Patricia Pérez Matute
Anales de Pediatría.2024; 100(6): 404. CrossRef
Composition of the microbiota in patients with growth hormone deficiency before and after treatment with growth hormone
Patricia García Navas, María Yolanda Ruíz del Prado, Pablo Villoslada Blanco, Emma Recio Fernández, María Ruíz del Campo, Patricia Pérez Matute
Anales de Pediatría (English Edition).2024; 100(6): 404. CrossRef
Clinical Management of Postoperative Growth Hormone Deficiency in Hypothalamic-Pituitary Tumors
Pedro Iglesias
Journal of Clinical Medicine.2024; 13(15): 4307. CrossRef
An Overview of Cardiovascular Risk in Pituitary Disorders
Georgia Ntali, Vyron Markussis, Alexandra Chrisoulidou
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Hussein Zaitoon, Michal Yackobovitch-Gavan, Eyas Midlej, Adi Uretzky, Irina Laurian, Anna Dorfman, Hagar Interator, Yael Lebenthal, Avivit Brener
Endocrine.2024; 86(3): 1110. CrossRef
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Frontiers in Endocrinology.2024;[Epub] CrossRef
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Mirjana Doknic, Marko Stojanovic, Aleksandra Markovic
International Journal of Molecular Sciences.2024; 25(19): 10313. CrossRef
Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency - Real World Evidence
Nageswary Nadarajah, Emmanuel Ssemmondo, Shani Brooks, Remi Akinyombo, Kazeem Adeleke, Harshal Deshmukh, Thozhukat Sathyapalan
International Journal of Endocrinology and Metabolism.2024;[Epub] CrossRef
Clinical and genetic features of childhood-onset congenital combined pituitary hormone deficiency: a retrospective, single-center cohort study
Yoonha Lee, Young Ah Lee, Jung Min Ko, Choong Ho Shin, Yun Jeong Lee
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Dyslipidaemia and growth hormone deficiency – A comprehensive review
Matthias Hepprich, Fahim Ebrahimi, Emanuel Christ
Best Practice & Research Clinical Endocrinology & Metabolism.2023; 37(6): 101821. CrossRef

Special Article

Miscellaneous
COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society: Cheol Ryong Ku, Kyong Yeun Jung, Chang Ho Ahn, Jun Sung Moon, Ju Hee Lee, Eun Heui Kim, Hyemi Kwon, Hee Kyung Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Eun Roh, Jin Hwa Kim, Mi-kyung Kim, the Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2021;36(4):757-765. Published online August 17, 2021; DOI: https://doi.org/10.3803/EnM.2021.404

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Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

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Original Articles

Hypothalamus and Pituitary Gland Big Data Articles (National Health Insurance Service Database)
Descriptive Epidemiology and Survival Analysis of Prolactinomas and Cushing’s Disease in Korea: Jin Sun Park, Soo Jin Yun, Jung Kuk Lee, So Young Park, Sang Ouk Chin; Endocrinol Metab. 2021;36(3):688-696. Published online June 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1000

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Background
Only a few studies have established the epidemiology of prolactinoma and Cushing’s disease in Korea. Furthermore, the incidence of these disease are increasing than before associated with the development of technologies. This study was designed to evaluate the epidemiology of prolactinoma and Cushing’s disease and their survival analysis according to treatment.
Methods
The nationwide, population-based study evaluated incidence and prevalence of prolactinoma and Cushing’s disease using de-identified claims data in The Korean Health Insurance Review and Assessment Service database between 2013 and 2017. The survival analysis investigated regarding treatment over a period of 6 years. A log-rank test and Cox proportional hazard regression analysis were used.
Results
The 6,056 patients with newly diagnosed prolactinoma and 584 patients with Cushing’s disease were recorded between 2013 and 2017. The annual incidence of prolactinoma was 23.5 cases per million, and its prevalence was 82.5 cases per million, and 2.3 cases per million/year and 9.8 cases per million for Cushing’s disease. The survival benefit was insignificant in prolactinoma according to treatment, but treatment of Cushing’s disease ameliorated the survival rate significantly.
Conclusion
Overall, the incidence of prolactinoma and Cushing’s disease was similar with those found previously, but the prevalence of two diseases were inconsistent when compared with the early studies. The present study also proposed necessity of treatment in Cushing’s disease for improving the survival rate.

Citations

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The 24-Hour Urinary Cortisol/Urinary Creatinine Ratio Helps Differentiate Cushing's Syndrome From Simple Obesity
Meng Wang, Xueting Sun, Shiwei Li, Xin Li, Jingqiu Cui
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Sang Ouk Chin
Endocrinology and Metabolism.2024; 39(4): 573. CrossRef
Reframing the Paradigm: A Nuanced Approach to Prolactinoma Management
Jung Hee Kim
Endocrinology and Metabolism.2024; 39(6): 850. CrossRef
Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma
Min-Ho Lee, Jae Won Hong, Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee
Endocrinology and Metabolism.2024; 39(6): 819. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Cushing Syndrome
Martin Reincke, Maria Fleseriu
JAMA.2023; 330(2): 170. CrossRef
Clinical Biology of the Pituitary Adenoma
Shlomo Melmed, Ursula B Kaiser, M Beatriz Lopes, Jerome Bertherat, Luis V Syro, Gerald Raverot, Martin Reincke, Gudmundur Johannsson, Albert Beckers, Maria Fleseriu, Andrea Giustina, John A H Wass, Ken K Y Ho
Endocrine Reviews.2022; 43(6): 1003. CrossRef

Hypothalamus and Pituitary Gland
Heart Rate Variability in Postoperative Patients with Nonfunctioning Pituitary Adenoma: Jeonghoon Ha, Hansang Baek, Chaiho Jeong, Minsoo Yeo, Seung-Hwan Lee, Jae Hyoung Cho, Ki-Hyun Baek, Moo Il Kang, Dong-Jun Lim; Endocrinol Metab. 2021;36(3):678-687. Published online June 10, 2021; DOI: https://doi.org/10.3803/EnM.2021.978

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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.

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Vaccines.2023; 11(3): 567. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef
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Journal of Clinical Medicine.2022; 11(12): 3421. CrossRef

Review Article

Hypothalamus and Pituitary gland
Best Achievements in Pituitary and Adrenal Diseases in 2020: Chang Ho Ahn, Jung Hee Kim; Endocrinol Metab. 2021;36(1):51-56. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.108

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Significant progress in pituitary and adrenal diseases was made in 2020. This review presents major translational and clinical advances in research on pituitary and adrenal diseases, encompassing their epidemiology, pathogenesis, diagnosis, and clinical management. We address the controversy regarding the nomenclature of pituitary neuroendocrine tumors, omics-based molecular classification of pituitary adenomas, and novel drugs for Cushing’s disease in the field of pituitary diseases. In the field of adrenal diseases, we cover big data-driven epidemiology of adrenal tumors, steroid profiling as a new diagnostic tool, and the utility of scoring systems in the decision-making process of managing primary aldosteronism. This brief article will broaden readers’ understanding of pituitary and adrenal diseases.

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Surgical management and outcomes of spinal metastasis of malignant adrenal tumor: A retrospective study of six cases and literature review
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2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef

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