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.

Miscellaneous
Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility: Daham Kim, Yoon Hee Cho, Min Jeong Kang, So Jeong Lee, Soohyun Lee, Bo Hyon Yun, Hyunjin Chi, Jeongsuk An, Kyungsun Lee, Jaekyu Han, Susan Chi, Moo Young Song, Sang-Hoon Cha, Eun Jig Lee; Endocrinol Metab. 2025;40(1):146-155. Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2090

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Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function.
Methods
SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test.
Results
The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight.
Conclusion
These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

Review Article

Hypothalamus and pituitary gland
Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma: Min-Ho Lee, Jae Won Hong, Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2024;39(6):819-826. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.2057

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Prolactinomas are the most prevalent type of pituitary neuroendocrine adenomas, primarily affecting women of reproductive age. Unlike other pituitary tumors, the first-line management has traditionally been pharmacological rather than surgical. This preference is due to the effectiveness of dopamine agonists (DAs), which typically reduce tumor size and normalize prolactin levels in most patients. However, this does not imply that there is no room for improvement; the duration of treatment and medication side effects often lead to compliance issues among patients. Recent advances in surgical techniques and molecular biology have paved the way for the development of precision medicine, allowing for more flexible and personalized treatment strategies for prolactinomas. This review aims to enhance clinical decision-making and patient care for endocrinologists by focusing on several key factors: predictive markers of DA sensitivity, clinical characteristics and suitability for transsphenoidal adenomectomy as a potential first-line treatment, factors determining the successful withdrawal of DAs after prolonged use, safety concerns during pre/post-pregnancy and breastfeeding, and determinants of tumor aggressiveness. Through tailored therapy—a patient-focused, multidisciplinary approach— we aim to improve the management of prolactinoma patients.

Citations

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When to embark on surgery for prolactin-secreting pituitary adenoma?
Nazmin Ahmed, Subodh Gautam, Bipin Chaurasia
Annals of Medicine & Surgery.2025; 87(4): 1798. CrossRef

Original Article

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea: Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku; Endocrinol Metab. 2023;38(6):690-700. Published online October 30, 2023; DOI: https://doi.org/10.3803/EnM.2023.1782

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Background
Acromegaly leads to various skeletal complications, and fragility fractures are emerging as a new concern in patients with acromegaly. Therefore, this study investigated the risk of fractures in Korean patients with acromegaly.
Methods
We used the Korean nationwide claims database from 2009 to 2019. A total of 931 patients with acromegaly who had never used an osteoporosis drug before and were treated with surgery alone were selected as study participants, and a 1:29 ratio of 26,999 age- and sex-matched osteoporosis drug-naïve controls without acromegaly were randomly selected from the database.
Results
The mean age was 46.2 years, and 50.0% were male. During a median follow-up of 54.1 months, there was no difference in the risks of all, vertebral, and non-vertebral fractures between the acromegaly and control groups. However, hip fracture risk was significantly higher (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.32 to 5.65), and non-hip and non-vertebral fractures risk was significantly lower (HR, 0.40; 95% CI, 0.17 to 0.98) in patients with acromegaly than in controls; these results remained robust even after adjustment for socioeconomic status and baseline comorbidities. Age, type 2 diabetes mellitus, cardio-cerebrovascular disease, fracture history, recent use of acid-suppressant medication, psychotropic medication, and opioids were risk factors for all fractures in patients with acromegaly (all P<0.05).
Conclusion
Compared with controls, patients surgically treated for acromegaly had a higher risk of hip fractures. The risk factors for fracture in patients with acromegaly were consistent with widely accepted risk factors in the general population.

Citations

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Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data
Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2025; 40(1): 1. CrossRef
Musculoskeletal disease in acromegaly—a population-based registry study
Christian Rosendal, Mai Christiansen Arlien-Søborg, Eigil Husted Nielsen, Claus Larsen Feltoft, Åse Krogh Rasmussen, Marianne Skovsager Andersen, Jens Otto Lunde Jørgensen, Jakob Dal
European Journal of Endocrinology.2025; 192(3): 308. CrossRef
Novel approach to bone comorbidity in resistant acromegaly
Stefano Frara, Matteo Acanfora, Vincenzo Franzese, Maria Luisa Brandi, Marco Losa, Andrea Giustina
Pituitary.2024; 27(6): 813. 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

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
Clinical Nuclear Medicine.2024; 49(1): 27. CrossRef
Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study
Seung Shin Park, Chang Ho Ahn, Seunghoo Lee, Woochang Lee, Won Woong Kim, Yu‐Mi Lee, Su Jin Kim, Tae‐Yon Sung, Kyu Eun Lee, Jung Hee Kim, Seung Hun Lee, Jung‐Min Koh
Journal of Internal Medicine.2024; 296(1): 68. CrossRef
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
Annals of Laboratory Medicine.2024; 44(6): 591. CrossRef
Raccomandazioni della lista del GdS-Endocrinologia e Malattie del Metabolismo SIPMeL-Choosing wisely: tiroide, anticorpi anti-tiroide, cortisolo, surrene, vitamina D: aggiornamento 2024
Romolo M. DORIZZI, Vincenzo BRESCIA, Marina VITILLO, Ottavia PORZIO, Federica D’AURIZIO
La Rivista Italiana della Medicina di Laboratorio.2024;[Epub] CrossRef
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Seung Min Chung
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Clinical and epidemiological characteristics of patients with pheochromocytoma and retroperitoneal paraganglioma
D. V. Rebrova, N. V. Vorokhobina
Meditsinskiy sovet = Medical Council.2024; (16): 206. CrossRef
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association
A Ram Hong, Ho-Cheol Kang
Endocrinology and Metabolism.2023; 38(2): 175. CrossRef
Lesion-based indicators predict long-term outcomes of pheochromocytoma and paraganglioma– SIZEPASS
Helena Hanschell, Salvador Diaz-Cano, Alfredo Blanes, Nadia Talat, Gabriele Galatá, Simon Aylwin, Klaus Martin Schulte
Frontiers in Endocrinology.2023;[Epub] CrossRef
Interleukin-6-producing paraganglioma as a rare cause of systemic inflammatory response syndrome: a case report
Yin Young Lee, Seung Min Chung
Journal of Yeungnam Medical Science.2023; 40(4): 435. CrossRef
(Extremely rare intrapericardial location of paraganglioma)
Jaroslav Zajíc, Aleš Mokráček, Ladislav Pešl, Jiří Haniš, Dita Schaffelhoferová
Cor et Vasa.2023; 65(4): 692. CrossRef
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Naoki Okada, Akihiro Shioya, Sumihito Togi, Hiroki Ura, Yo Niida
Cureus.2023;[Epub] CrossRef
KSNM60 in Nuclear Endocrinology: from the Beginning to the Future
Chae Moon Hong, Young Jin Jeong, Hae Won Kim, Byeong-Cheol Ahn
Nuclear Medicine and Molecular Imaging.2022; 56(1): 17. CrossRef
Change of Computed Tomography-Based Body Composition after Adrenalectomy in Patients with Pheochromocytoma
Yousun Ko, Heeryoel Jeong, Seungwoo Khang, Jeongjin Lee, Kyung Won Kim, Beom-Jun Kim
Cancers.2022; 14(8): 1967. CrossRef
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: a Position Statement from the Korean Thyroid Association
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
International Journal of Thyroidology.2022; 15(1): 1. CrossRef
Pheochromocytoma with Retroperitoneal Metastasis: A Case Report
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Advances in Clinical Medicine.2021; 11(05): 2239. CrossRef

Original Articles

Clinical Study
Associations of GNAS Mutations with Surgical Outcomes in Patients with Growth Hormone-Secreting Pituitary Adenoma: Hyein Jung, Kyungwon Kim, Daham Kim, Ju Hyung Moon, Eui Hyun Kim, Se Hoon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2021;36(2):342-350. Published online March 23, 2021; DOI: https://doi.org/10.3803/EnM.2020.875

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Background
The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics.
Methods
We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor.
Results
GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively).
Conclusion
GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

Citations

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Contract to kill: GNAS mutation
Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy
Molecular Cancer.2025;[Epub] CrossRef
Genetic diagnosis in acromegaly and gigantism: From research to clinical practice
Claudia Ramírez-Rentería, Laura C. Hernández-Ramírez
Best Practice & Research Clinical Endocrinology & Metabolism.2024; 38(3): 101892. CrossRef
Unlocking the Genetic Secrets of Acromegaly: Exploring the Role of Genetics in a Rare Disorder
Ioana Balinisteanu, Lavinia Caba, Andreea Florea, Roxana Popescu, Laura Florea, Maria-Christina Ungureanu, Letitia Leustean, Eusebiu Vlad Gorduza, Cristina Preda
Current Issues in Molecular Biology.2024; 46(8): 9093. CrossRef
Advancements in Molecular Diagnosis and Pharmacotherapeutic Strategies for Invasive Pituitary Adenomas
Dingkai Xu, Ling Wang, Maohua Zheng
Immunity, Inflammation and Disease.2024;[Epub] CrossRef
GNAS mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma
CHAO TANG, CHUNYU ZHONG, JUNHAO ZHU, FENG YUAN, JIN YANG, YONG XU, CHIYUAN MA
Oncology Research.2024; 32(6): 1079. CrossRef
CD8/PD-L1 immunohistochemical reactivity and gene alterations in cutaneous squamous cell carcinoma
Haruto Nishida, Yoshihiko Kondo, Takahiro Kusaba, Kazuhiro Kawamura, Yuzo Oyama, Tsutomu Daa, Avaniyapuram Kannan Murugan
PLOS ONE.2023; 18(2): e0281647. CrossRef
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Xiya Ma, Kun Zhang, Jing Xu, Hongjun Gao, Shaoxing Yang, Haifeng Qin, Hong Wang, Fang Gao, Xiaoqing Liu
Thoracic Cancer.2023; 14(20): 1980. CrossRef
Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine
Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee
Endocrinology and Metabolism.2023; 38(5): 463. CrossRef
Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors
Mariana Torres-Morán, Alexa L. Franco-Álvarez, Rosa G. Rebollar-Vega, Laura C. Hernández-Ramírez
Cancers.2023; 15(23): 5685. CrossRef

Endocrine Research
Danshen Extracts Prevents Obesity and Activates Mitochondrial Function in Brown Adipose Tissue: Yoon Hee Cho, Cheol Ryong Ku, Young-Suk Choi, Hyeon Jeong Lee, Eun Jig Lee; Endocrinol Metab. 2021;36(1):185-195. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.835

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Background
Danshen has been widely used in oriental medicine to improve body function. The purpose of this study is to investigate the effect of water-soluble Danshen extract (DE) on weight loss and on activation proteins involved in mitochondrial biogenesis in brown adipose tissue (BAT) in obese mice.
Methods
BAT was isolated from 7-week-old male Sprague-Dawley rats, and expression of proteins related to mitochondrial biogenesis was confirmed in both brown preadipocytes and mature brown adipocytes treated with DE. For the in vivo study, low-density lipoprotein receptor knock out mice were divided into three groups and treated for 17 weeks with: standard diet; high fat diet (HFD); HFD+DE. Body weight was measured every week, and oral glucose tolerance test was performed after DE treatment in streptozotocin-induced diabetic mice. To observe the changes in markers related to thermogenesis and adipogenesis in the BAT, white adipose tissue (WAT) and liver of experimental animals, tissues were removed and immediately frozen in liquid nitrogen.
Results
DE increased the expression of uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in brown preadipocytes, and also promoted the brown adipocyte differentiation and mitochondrial function in the mature brown adipocytes. Reactive oxygen species production in brown preadipocytes was increased depending on the concentration of DE. DE activates thermogenesis in BAT and normalizes increased body weight and adipogenesis in the liver due to HFD. Browning of WAT was increased in WAT of DE treatment group.
Conclusion
DE protects against obesity and activates mitochondrial function in BAT.

Citations

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Pharmacological Benefits and Underlying Mechanisms of Salvia miltiorrhiza against Molecular Pathology of Various Liver Diseases: A Review
Cho Hyun Hwang, Eungyeong Jang, Jang-Hoon Lee
The American Journal of Chinese Medicine.2023; 51(07): 1675. CrossRef

Special Article

Miscellaneous
Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology: Jung Hee Kim, Hyun Wook Chae, Sang Ouk Chin, Cheol Ryong Ku, Kyeong Hye Park, Dong Jun Lim, Kwang Joon Kim, Jung Soo Lim, Gyuri Kim, Yun Mi Choi, Seong Hee Ahn, Min Ji Jeon, Yul Hwangbo, Ju Hee Lee, Bu Kyung Kim, Yong Jun Choi, Kyung Ae Lee, Seong-Su Moon, Hwa Young Ahn, Hoon Sung Choi, Sang Mo Hong, Dong Yeob Shin, Ji A Seo, Se Hwa Kim, Seungjoon Oh, Sung Hoon Yu, Byung Joon Kim, Choong Ho Shin, Sung-Woon Kim, Chong Hwa Kim, Eun Jig Lee; Endocrinol Metab. 2020;35(2):272-287. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.272

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Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

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Once-Weekly Somapacitan as an Alternative Management of Growth Hormone Deficiency in Prepubertal Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trial
Ghina Tsurayya, Cut Alifiya Nazhifah, Muhammad Rahmat Pirwanja, Putri Oktaviani Zulfa, Muhammad Raihan Ramadhan Tatroman, Fajar Fakri, Muhammad Iqhrammullah
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Hsa_circ_0002473 inhibits GH3 cell proliferation and GH secretion as a competitive endogenous RNA for has-miR-4645-3p
Kaiyu Pan, Xiaoguang Jiang, Xiaohong Hu, Jianhua Zhan, Chengyue Zhang
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Yun Jeong Lee, Chong Kun Cheon, Junghwan Suh, Jung-Eun Moon, Moon Bae Ahn, Seong Hwan Chang, Jieun Lee, Jin Ho Choi, Minsun Kim, Han Hyuk Lim, Jaehyun Kim, Shin-Hye Kim, Hae Sang Lee, Yena Lee, Eungu Kang, Se Young Kim, Yong Hee Hong, Seung Yang, Heon-Seo
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Review Article

Hypothalamus and Pituitary gland
Precision Therapy in Acromegaly Caused by Pituitary Tumors: How Close Is It to Reality?: Cheol Ryong Ku, Vladimir Melnikov, Zhaoyun Zhang, Eun Jig Lee; Endocrinol Metab. 2020;35(2):206-216. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.206

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Acromegaly presents with an enigmatic range of symptoms and comorbidities caused by chronic and progressive growth hormone elevations, commonly due to endocrinologic hypersecretion from a pituitary gland tumor. Comprehensive national acromegaly databases have been appearing over the years, allowing for international comparisons of data, although still presenting varying prevalence and incidence rates. Lack of large-scale analysis in geographical and ethnic differences in clinical presentation and management requires further research. Assessment of current and novel predictors of responsiveness to distinct therapy can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and reduction of increased morbidity and mortality associated with acromegaly. This review compares current data from epidemiological studies and assesses the present-day application of prognostic factors in medical practice, the reality of precision therapy, as well as its future prospects in acromegaly, with a special focus on its relevance to the South Korean population.

Citations

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Biomarkers of response to treatment in acromegaly
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Predictors of morphofunctional features of somatotrophic tumors and of the effectiveness of treatment with first-generation somatostatin receptor ligands
E. V. Pronin, V. S. Pronin, M. B. Antsiferov, A. V. Petryaykin, T. M. Alexeeva, A. M. Lapshina, L. S. Urusova, A. N. Khoruzhaya, S. M. Tamaeva
Meditsinskiy sovet = Medical Council.2024; (6): 98. 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
Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine
Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee
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Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study
Shinje Moon, Sangmo Hong, Kyungdo Han, Cheol-Young Park
European Journal of Endocrinology.2023; 189(3): 363. CrossRef
The Future of Somatostatin Receptor Ligands in Acromegaly
Monica R Gadelha, Luiz Eduardo Wildemberg, Leandro Kasuki
The Journal of Clinical Endocrinology & Metabolism.2022; 107(2): 297. CrossRef
Innovative therapeutics in acromegaly
Leandro Kasuki, Mônica R. Gadelha
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Risk of Neurodegenerative Diseases in Patients With Acromegaly
Sangmo Hong, Kyungdo Han, Kyung-Soo Kim, Cheol-Young Park
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Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands
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Original Articles

Endocrine Research
Therapeutic Effect of a Novel Chimeric Molecule Targeting Both Somatostatin and Dopamine Receptors on Growth Hormone-Secreting Pituitary Adenomas: Jean Kim, Ju Hun Oh, Heather Harlem, Michael D. Culler, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2020;35(1):177-187. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.177

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Background

Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs with improved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist.

Methods

The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigated with MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration of BIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changes in IGF-1 levels before and after treatment was further investigated.

Results

In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065 using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantly following treatment with BIM23B065 for 4 weeks.

Conclusion

The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeutic agent for acromegaly.

Citations

Citations to this article as recorded by

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Rodanthi Vamvoukaki, Maria Chrysoulaki, Grigoria Betsi, Paraskevi Xekouki
Medicina.2023; 59(4): 812. CrossRef
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Nicolas Sahakian, Frédéric Castinetti, Thierry Brue, Thomas Cuny
Journal of Clinical Medicine.2022; 11(4): 955. CrossRef
Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells
Thomas Cuny, Thomas Graillon, Célines Defilles, Rakesh Datta, Shengwen Zhang, Dominique Figarella-Branger, Henry Dufour, Grégory Mougel, Thierry Brue, Tanya Landsman, Heather A. Halem, Michael D. Culler, Anne Barlier, Alexandru Saveanu
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Efficacy of a Novel Second-Generation Somatostatin-Dopamine Chimera (TBR-065) in Human Medullary Thyroid Cancer: A Preclinical Study
Alessandra Dicitore, Maria Celeste Cantone, Germano Gaudenzi, Davide Saronni, Silvia Carra, Maria Orietta Borghi, Manuela Albertelli, Diego Ferone, Leo J. Hofland, Luca Persani, Giovanni Vitale
Neuroendocrinology.2021; 111(10): 937. CrossRef
Emerging drugs for the treatment of acromegaly
Claudia Campana, Giuliana Corica, Federica Nista, Francesco Cocchiara, Giulia Graziani, Keyvan Khorrami, Marta Franco, Mara Boschetti, Diego Ferone, Federico Gatto
Expert Opinion on Emerging Drugs.2020; 25(4): 409. CrossRef

Clinical and Sellar MR Findings in Central Diabets Inspidus.: Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Su Youn Nam, Eun Jig Lee, Sei Chang Oh, Byung Hee Lee, Dong Ik Kim; J Korean Endocr Soc. 1996;11(3):285-292. Published online November 7, 2019

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Abstract PDF: Background
s: Diabetes insipidus(DI) is a clinical syndrome characterized by excretion of copious volumes of dilute urine combined with persistent intake of abnormally large quantities of fluid. Central DI, caused by lack of antidiuretic hormone(ADH), most often results from lesions in the hypothalamic-neurohypophyseal axis. Magnetic resonance(MR) imaging is particularly useful in documenting the presence of a structural lesion, as opposed to assigning a diagnosis of idiopathic DI for which only symptomatic therapy is prescribed. Recently, several reports have described a specific MR finding in central DI, that is absence of normal posterior pituitary bright spot(PPBS). Methods: We retrospectivesly studied the clinical and MR findings in 25 patients with central DI, diagnosed by warter deprivation test. Results: 1) The subjects included 17 males and 8 females, between the ages of 2 and 58 years. 2) 24-hour urine volumes were 2,340~13,750 mL, and mean urine osmolarity was 147.7±65.8 mOsm/kg. The 23 subjects diagnosed complete central DI by warter deprivation test. 3) We found that the most common cause of cntral DI was infiltrative lesions of hypothalmic-neurohypophyseal axis(60%). Germ cell tumor was the single leading cause in present study, accounting for 36% of cases. The other causes were found, including pituitary apoplexy, meningitis, and trauma. Idiopathic central DI accounted for 20% of all cases. 4) Growth hormone deficiency was the most common accompanying anterior pituitary deficit, and panhypopituitarism was found in 7 cases, Hyperprolactinernia was seen in 6 cases. 5) In all patients, PPBS on Tl weighted MR images were not observed. A thickened pituitary stalk was seen in 15 cases(9 patients with germ cell tumor, 3 patients with histiocytosis X, 1 patient with tuberculosis, 2 patients with unknown origin). Conclusion: In our results, the most common causes of central DI was suprasellar infiltrative lesions. MR is currently the imaging methods of choice in the evaulation of dysfunction of the hypothalamic-neurohypophyseal system in patients with central DI. A specific MR finding, that is loss of normal PPBS allows a confirmative diagnosis of central DI.

Reduction of Central Dopamine Release in Hyperprolactinemia.: Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Su Youn Nam, Eun Jig Lee, Bong Chul Chung, Jung Han Kim, Sei Chang Oh; J Korean Endocr Soc. 1996;11(3):277-284. Published online November 7, 2019

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Abstract PDF: Background
Prolactin(PRL) secretion is tonically inhibited by doparnine that originates from the hypothalamic tuberoinfundibular tract and reaches the lactotroph via the hypophyseal portal vessel. Hyperprolactinemia associated with oligomenorrhea-amenorrhea, galactorrhea and/or infertility is mainly due to PRL-secreting pituitary adenoma(PA). The diagnosis of idiopathic hyperprolac- tinemia(IHP) is made, when hyperprolactinemia is sustained and all causes of hyperprolactinemia are excluded without radiological abnormality. It is not known, whether IHP and PA are two distinct entities or two subsequent phases of the same disease. The etiology of both disorders remains unresolved. We investigated that PRL hypersecretion in patients with IHP and PA may be the result of a defect in the central nervous system(CNS)-dopamine release, and that there may be some differences in pathogenesis of both diseases. Methods: We measured 24 hour-urinary dopamine, norepinephrine, epinephrine, and serum and 24 hour-urinary VMA(vanillyl rnandelic acid), HVA(homovanilic acid), DOPAC(3,4-dihydroxy phenylaceticacid), MHPG(3-methoxy 4-hydroxy phenylglycol) in 10 normal controls, 9 patients with IHP, and 17 patients with PA in the early follicular phase. Results: Urinary HVA and DOPAC concentrations, the major metabolites of CNS dopaminergic activity, were signficantly lower in both patients with IHP and PA compared with those in normal controls(p 0.05), whereas they were not different in both disease groups. Dopamine, norepine-phrine, epinephrine, MHPG concentrations were similar to those of the normal controls. Although VMA concentrations of both disease groups were significantly higher than those of normal controls, all of them were within normal range. Conelusion: Although our data are unable to establish the precise biochemical defect responsible for central dopamine deficiency in pathogensis of IHP and PA, we can support the presence of a pathological reduction of brain dopamine activity in IHP and PA.

Case Report

A Case of Anterior Cervical Lipoma Mimicking Diffuse Goiter.: Eun Jig Lee, Moon Suk Nam, Su Youn Nam, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Kyung Rae Kim, Jun Sik Na, Yee Hyun Nam, Jeon Hong Kang, Jung Ki Seo; J Korean Endocr Soc. 1995;10(4):418-423. Published online November 7, 2019

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Abstract PDF: Lipoma is a benign fatty tumor that can arise in any location of the body where fat is present. It is found most commonly in the upper half of the body, particularly the head and neck, shoulders, and back. A mass in the antero-inferior part of the neck may be initially thought to be thyroid masses and then other cervical masses should be considered. Ultrasongraphic examination of benign lipoma demonstrates solid and echogenic mass and may differentiate nonthyroid from thyroid masses. Although the location of tumors, its consistency, and its motion with deglutition, seperation from the thyroid on sonographic examination, all pointed to nonthyroidal origin, did not rule out a possible mass that isolated from the lobes of the thyroid. Fine needle aspiration and biopsy can provide clear answer.We herein report a case of anterior cervical mass in a 48-yr-old male patient presenting a non-tender, slightly hard and nodular mass slowly growing for several years and moved with swallowing, and diagnosed his case as benign lipoma using thyroid scan and ultrasonography. When we encounter patients with anterior neck mass, we should consider benign lipoma mimicking diffuse goiter.

Original Article

Clinical and Endocrinologic Differences between Prolactinoma and Pseudoprolactinoma Proven by Immunohistochemical Study.: Jae Wha Jo, Eun Jig Lee, Moon Suk Nam, Su Youn Nam, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Tae Seung Kim, Sun Ho Kim, Kyung Rae Kim, Bong Soo Cha, Ji Hyun Lee, Sung Kil Lim; J Korean Endocr Soc. 1995;10(4):362-369. Published online November 7, 2019

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Abstract PDF: Hyperprolactinemia is the most common hypothalamo-pituitary disorder encountered in clinical endocrinology. Excluding the drug-induced hyperprolactinemia, the most common cause of this disorder is a pituitary tumor. Prolactinoma is mainly made up of prolactin-secreting cells but pseudoprolactinoma is tumor that does not secrete prolactin itself. The pseudoprolactinoma interrupts the flow of prolactin inhibiting factor, dopamine, from the hypothalamus through the pituitary stalk to the normal pituitary. The differentiation prolactinoma from pseudoprolactinoma is vitally important since true prolactinomas are most commonly responded well in terms of tumor shrinkage to medical treatment using dopamine agonist therapy, whereas pseudoprolactinomas do not. Thus surgical treatment is clearly indicated as first-line treatment if we know that a lesion is a pseudoprolactinoma. We compared prolactinoma with pseudoprolactinoma in clinical and endocrinologic characteristics of 48 cases after immunohistochemical diagnosis. We could not find any differential point of both tumors in clinical and radiological characteristics although some differences were exist. But we had found the relationship between the mean level of pretreatment serum prolactin and the presence of positive immunohistochemical stain for prolactin. The pretreatment serum prolactin level was significantly higher in patients with tumors showing many prolactin immunohistochemical staining cells than in those with none(p<0.05). When the pretreatment serum prolactin exceeded 100ng/ml, the tumors contain 94% of prolactin positive cells in stain. So, if the pretreatment serum prolactin exceeds 100ng/ml, we primarily suspect prolactinoma and medical treatment should be considered. If the pretreatment level below 100ng/ml, we suspect pseudoprolactinoma and surgical treatment should be considered.

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