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Original Article
Adrenal gland
Effects of Chronic Restraint Stress on Body Weight, Food Intake, and Hypothalamic Gene Expressions in Mice
Joo Yeon Jeong, Dong Hoon Lee, Sang Soo Kang
Endocrinol Metab. 2013;28(4):288-296.   Published online December 12, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.4.288
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  • 147 Crossref
AbstractAbstract PDFPubReader   
Background

Stress affects body weight and food intake, but the underlying mechanisms are not well understood.

Methods

We evaluated the changes in body weight and food intake of ICR male mice subjected to daily 2 hours restraint stress for 15 days. Hypothalamic gene expression profiling was analyzed by cDNA microarray.

Results

Daily body weight and food intake measurements revealed that both parameters decreased rapidly after initiating daily restraint stress. Body weights of stressed mice then remained significantly lower than the control body weights, even though food intake slowly recovered to 90% of the control intake at the end of the experiment. cDNA microarray analysis revealed that chronic restraint stress affects the expression of hypothalamic genes possibly related to body weight control. Since decreases of daily food intake and body weight were remarkable in days 1 to 4 of restraint, we examined the expression of food intake-related genes in the hypothalamus. During these periods, the expressions of ghrelin and pro-opiomelanocortin mRNA were significantly changed in mice undergoing restraint stress. Moreover, daily serum corticosterone levels gradually increased, while leptin levels significantly decreased.

Conclusion

The present study demonstrates that restraint stress affects body weight and food intake by initially modifying canonical food intake-related genes and then later modifying other genes involved in energy metabolism. These genetic changes appear to be mediated, at least in part, by corticosterone.

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Close layer
Review Articles
Adrenal gland
How to Establish Clinical Prediction Models
Yong-ho Lee, Heejung Bang, Dae Jung Kim
Endocrinol Metab. 2016;31(1):38-44.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.38
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AbstractAbstract PDFPubReader   

A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice.

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Close layer
Adrenal gland
Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future
Soo-Hyun Kim
Endocrinol Metab. 2015;30(4):456-466.   Published online December 31, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.4.456
  • 9,984 View
  • 144 Download
  • 73 Web of Science
  • 72 Crossref
AbstractAbstract PDFPubReader   

The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime.

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Close layer
Adrenal gland
Diagnosis and Treatment of Hypopituitarism
Seong Yeon Kim
Endocrinol Metab. 2015;30(4):443-455.   Published online December 31, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.4.443
  • 18,300 View
  • 588 Download
  • 56 Web of Science
  • 64 Crossref
AbstractAbstract PDFPubReader   

Hypopituitarism is a chronic endocrine illness that caused by varied etiologies. Clinical manifestations of hypopituitarism are variable, often insidious in onset and dependent on the degree and severity of hormone deficiency. However, it is associated with increased mortality and morbidity. Therefore, early diagnosis and prompt treatment is necessary. Hypopituitarism can be easily diagnosed by measuring basal pituitary and target hormone levels except growth hormone (GH) and adrenocorticotropic hormone (ACTH) deficiency. Dynamic stimulation tests are indicated in equivocal basal hormone levels and GH/ACTH deficiency. Knowledge of the use and limitations of these stimulation tests is mandatory for proper interpretation. It is necessary for physicians to inform their patients that they may require lifetime treatment. Hormone replacement therapy should be individualized according to the specific needs of each patient, taking into account possible interactions. Long-term endocrinological follow-up of hypopituitary patients is important to monitor hormonal replacement regimes and avoid under- or overtreatment.

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Close layer
Adrenal gland
Recent Updates on the Diagnosis and Management of Cushing's Syndrome
Lynnette K. Nieman
Endocrinol Metab. 2018;33(2):139-146.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.139
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AbstractAbstract PDFPubReader   ePub   

Cushing's syndrome, a potentially lethal disorder characterized by endogenous hypercortisolism, may be difficult to recognize, especially when it is mild and the presenting features are common in the general population. However, there is a need to identify the condition at an early stage, as it tends to progress, accruing additional morbidity and increasing mortality rates. Once a clinical suspicion is raised, screening tests involve timed measurement of urine, serum or salivary cortisol at baseline or after administration of dexamethasone, 1 mg. Each test has caveats, so that the choice of tests must be individualized for each patient. Once the diagnosis is established, and the cause is determined, surgical resection of abnormal tumor/tissue is the optimal treatment. When this cannot be achieved, medical treatment (or bilateral adrenalectomy) must be used to normalize cortisol production. Recent updates in screening for and treating Cushing's syndrome are reviewed here.

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Close layer
Original Article
Adrenal gland
Clinical Characteristics for 348 Patients with Adrenal Incidentaloma
Jongho Kim, Kwi Hyun Bae, Yeon Kyung Choi, Ji Yun Jeong, Keun Gyu Park, Jung Guk Kim, In Kyu Lee
Endocrinol Metab. 2013;28(1):20-25.   Published online March 25, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.1.20
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AbstractAbstract PDFPubReader   
Background

Adrenal incidentaloma is an adrenal neoplasm frequently encountered in clinical practice for which detection rates have recently increased. We describe here the clinical characteristics of adrenal incidentalomas.

Methods

A retrospective study was performed examining the age, sex, location, size, function, and the histological findings for 348 patients with an adrenal mass discovered incidentally on computed tomography (CT) undertaken for health examination or nonadrenal disease from August 2005 to May 2012.

Results

Patients consisted of 156 males (44.8%) and 192 females (55.2%), aged between 20 and 86. Adrenal masses were most commonly found in patients in their sixth decade (32.5%). Regarding the location of the masses, 62.0% were found in the left adrenal gland, 30.2% were found in the right, and 7.8% were found bilaterally. Of all of the masses analyzed, 87.1% were 1 to 4 cm in size, and an adenoma-like appearance was the most common finding (75.3%) seen on CT scans. Hormonal analysis showed that 82.2% of the masses were nonfunctioning, 6.0% were diagnosed as subclinical Cushing's syndrome, 4.6% were aldosterone-producing adenomas, and 7.2% were pheochromocytomas. Adrenalectomy was performed in a total of 69 patients having adenoma (50.7%), pheochromocytoma (24.6%), and carcinoma (4.3%).

Conclusion

The characteristics of benign, malignant, nonfunctional, and functional adrenal masses that were incidentally found at our hospital were similar to those presented in other studies.

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Close layer
Review Article
Adrenal gland
The Molecular Pathogenesis of Pituitary Adenomas: An Update
Xiaobing Jiang, Xun Zhang
Endocrinol Metab. 2013;28(4):245-254.   Published online December 12, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.4.245
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AbstractAbstract PDFPubReader   

Pituitary tumors represent the most common intracranial neoplasms accompanying serious morbidity through mass effects and inappropriate secretion of pituitary hormones. Understanding the etiology of pituitary tumorigenesis will facilitate the development of satisfactory treatment for pituitary adenomas. Although the pathogenesis of pituitary adenomas is largely unknown, considerable evidence indicates that the pituitary tumorigenesis is a complex process involving multiple factors, including genetic and epigenetic changes. This review summarized the recent progress in the study of pituitary tumorigenesis, focusing on the role of tumor suppressor genes, oncogenes and microRNAs.

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Close layer
Original Article
Adrenal gland
Clinical Characteristics, Management, and Outcome of 22 Cases of Primary Hypophysitis
Sun Mi Park, Ji Cheol Bae, Ji Young Joung, Yoon Young Cho, Tae Hun Kim, Sang-Man Jin, Sunghwan Suh, Kyu Yeon Hur, Kwang-Won Kim
Endocrinol Metab. 2014;29(4):470-478.   Published online December 29, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.4.470
  • 5,250 View
  • 43 Download
  • 29 Web of Science
  • 27 Crossref
AbstractAbstract PDFPubReader   
Background

Primary hypophysitis causes varying degrees of endocrine dysfunction and mass effect. The natural course and best treatment have not been well established.

Methods

Medical records of 22 patients who had been diagnosed with primary hypophysitis between January 2001 and March 2013 were retrospectively reviewed. Based on the anatomical location, we classified the cases as adenohypophysitis (AH), infundibuloneurohypophysitis (INH), and panhypophysitis (PH). Clinical presentation, endocrine function, pathologic findings, magnetic resonance imaging findings, and treatment courses were reviewed.

Results

Among 22 patients with primary hypophysitis, 81.8% (18/22) had involvement of the posterior pituitary lobe. Two patients of the AH (2/3, 66.6%) and three patients of the PH (3/10, 30%) groups initially underwent surgical mass reduction. Five patients, including three of the PH (3/10, 33.3%) group and one from each of the AH (1/3, 33.3%) and INH (1/9, 11.1%) groups, initially received high-dose glucocorticoid treatment. Nearly all of the patients treated with surgery or high-dose steroid treatment (9/11, 82%) required continuous hormone replacement during the follow-up period. Twelve patients received no treatment for mass reduction due to the absence of acute symptoms and signs related to a compressive mass effect. Most of them (11/12, 92%) did not show disease progression, and three patients recovered partially from hormone deficiency.

Conclusion

Deficits of the posterior pituitary were the most common features in our cases of primary hypophysitis. Pituitary endocrine defects responded less favorably to glucocorticoid treatment and surgery. In the absence of symptoms related to mass effect and with the mild defect of endocrine function, it may not require treatment to reduce mass except hormone replacement.

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Close layer
Review Articles
Adrenal Gland
Clinical and Technical Aspects in Free Cortisol Measurement
Man Ho Choi
Endocrinol Metab. 2022;37(4):599-607.   Published online August 19, 2022
DOI: https://doi.org/10.3803/EnM.2022.1549
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  • 413 Download
  • 23 Web of Science
  • 26 Crossref
AbstractAbstract PDFPubReader   ePub   
Accurate measurement of cortisol is critical in adrenal insufficiency as it reduces the risk associated with misdiagnosis and supports the optimization of stress dose. Comprehensive assays have been developed to determine the levels of bioactive free cortisol and their clinical and analytical efficacies have been extensively discussed because the level of total cortisol is affected by changes in the structure or circulating levels of corticoid-binding globulin and albumin, which are the main reservoirs of cortisol in the human body. Antibody-based immunoassays are routinely used in clinical laboratories; however, the lack of molecular specificity in cortisol assessment limits their applicability to characterize adrenocortical function. Improved specificity and sensitivity can be achieved by mass spectrometry coupled with chromatographic separation methods, which is a cutting-edge technology to measure individual as well as a panel of steroids in a single analytical run. The purpose of this review is to introduce recent advances in free cortisol measurement from the perspectives of clinical specimens and issues associated with prospective analytical technologies.

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Close layer
Adrenal gland
Embryonic Development and Adult Regeneration of the Adrenal Gland
Ji-Hoon Kim, Man Ho Choi
Endocrinol Metab. 2020;35(4):765-773.   Published online December 23, 2020
DOI: https://doi.org/10.3803/EnM.2020.403
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  • 482 Download
  • 23 Web of Science
  • 21 Crossref
AbstractAbstract PDFPubReader   ePub   
The adrenal gland plays a pivotal role in an organism’s health span by controlling the endocrine system. Decades of research on the adrenal gland have provided multiscale insights into the development and maintenance of this essential organ. A particularly interesting finding is that founder stem/progenitor cells participate in adrenocortical development and enable the adult adrenal cortex to regenerate itself in response to hormonal stress and injury. Since major advances have been made in understanding the dynamics of the developmental process and the remarkable regenerative capacity of the adrenal gland, understanding the mechanisms underlying adrenal development, maintenance, and regeneration will be of interest to basic and clinical researchers. Here, we introduce the developmental processes of the adrenal gland and discuss current knowledge regarding stem/progenitor cells that regulate adrenal cortex remodeling and regeneration. This review will provide insights into the fascinating ongoing research on the development and regeneration of the adrenal cortex.

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Close layer
Adrenal gland
Primary Aldosteronism and Cerebrovascular Diseases
Zheng-Wei Chen, Chi-Sheng Hung, Vin-Cent Wu, Yen-Hung Lin
Endocrinol Metab. 2018;33(4):429-434.   Published online November 30, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.4.429
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AbstractAbstract PDFPubReader   ePub   

As diagnostic techniques have advanced, primary aldosteronism (PA) has emerged as the most common cause of secondary hypertension. The excess of aldosterone caused by PA resulted in not only cardiovascular complications, including coronary artery disease, myocardial infarction, arrhythmia, and heart failure, but also cerebrovascular complications, such as stroke and transient ischemic attack. Moreover, PA is associated more closely with these conditions than is essential hypertension. In this review, we present up-to-date findings on the association between PA and cerebrovascular diseases.

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Close layer
Original Article
Adrenal gland
Clinical Characteristics and Metabolic Features of Patients with Adrenal Incidentalomas with or without Subclinical Cushing's Syndrome
Bo-Yeon Kim, A-Reum Chun, Kyu-Jin Kim, Chan-Hee Jung, Sung Koo Kang, Ji-Oh Mok, Chul-Hee Kim
Endocrinol Metab. 2014;29(4):457-463.   Published online December 29, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.4.457
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AbstractAbstract PDFPubReader   
Background

The aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT) and to investigate metabolic features of subclinical Cushing's syndrome (SCS) in patients with adrenal incidentalomas in a tertiary hospital in Korea.

Methods

This retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing's syndrome, and aldosterone-secreting adenoma were performed.

Results

Most (n=218, 81.3%) cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%), 19 (7.1%) were diagnosed with SCS, nine (3.4%) with overt Cushing's syndrome, 12 (4.5%) with primary aldosteronism, and 10 (3.7%) with pheochromocytoma. Malignant tumors (both primary and metastatic) were rare (n=2, 0.7%). Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors.

Conclusion

Functioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.

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Close layer
Review Articles
Adrenal gland
Role of Reactive Oxygen Species in Hypothalamic Regulation of Energy Metabolism
Sabrina Diano
Endocrinol Metab. 2013;28(1):3-5.   Published online March 25, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.1.3
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AbstractAbstract PDFPubReader   

To understand the etiology of metabolic disorders, including obesity and type II diabetes, it is essential to gain better insight into how stored and available energy sources are monitored by the central nervous system. In particular, a comprehension of the fine cellular interplay and intracellular mechanisms that enable appropriate hypothalamic and consequent endocrine and behavioral responses to both circulating hormonal and nutrient signals remains elusive. Recent data, including those from our laboratories, raised the notion that reactive oxygen species (ROS) generation is not merely a by-product of substrate oxidation, but it plays a crucial role in modulating cellular responses involved in the regulation of energy metabolism. These review summarizes the published recent data on the effect of ROS levels in the regulation of neuronal function, including that of hypothalamic melanocortin neurons, pro-opiomelanocortin and neuropeptide Y-/agouti related peptide-neurons, in the modulation of food intake.

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    BMC Cardiovascular Disorders.2016;[Epub]     CrossRef
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Adrenal Gland
Long-Term Outcomes of Congenital Adrenal Hyperplasia
Anna Nordenström, Svetlana Lajic, Henrik Falhammar
Endocrinol Metab. 2022;37(4):587-598.   Published online July 8, 2022
DOI: https://doi.org/10.3803/EnM.2022.1528
  • 33,638 View
  • 364 Download
  • 17 Web of Science
  • 20 Crossref
AbstractAbstract PDFPubReader   ePub   
A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.

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Hypothalamus and Pituitary gland
Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations
Ahmed Al-Sharefi, Richard Quinton
Endocrinol Metab. 2020;35(3):526-540.   Published online September 22, 2020
DOI: https://doi.org/10.3803/EnM.2020.760
  • 12,288 View
  • 605 Download
  • 15 Web of Science
  • 19 Crossref
AbstractAbstract PDFPubReader   ePub   
Male hypogonadism—rebadged by some as testosterone deficiency syndrome—is a clinical and biochemical diagnosis of increasing worldwide interest. Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lower serum testosterone levels; principally due to burden of extra-gonadal comorbidities such as obesity, diabetes and metabolic syndrome, but with an underlying intact hypothalamo-pituitary-testicular (HPT) axis capable of springing back into operation once comorbidities are addressed. Despite encouraging observational data and plausible theoretical underpinning, evidence for efficacy and safety of testosterone in this “aging” group of men is lacking; addressing comorbid illnesses remains the key priority instead. Nevertheless, in recent years, accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Despite this, many men with organic hypogonadism remain undiagnosed or untreated; many more face a diagnostic odyssey before achieving care by the appropriate specialist. As testosterone therapy is not without risk several clinical practice guidelines have been published specialist societies to guide physicians on best practice. However, these are heterogeneous in key areas, reflecting divergent approaches to the same evidence basis. Herein, we navigate the major clinical practice guidelines on male hypogonadism and test their respective recommendations against current best evidence.

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