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Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells.
Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot.
OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells.
Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.
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The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.
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Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA.
Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins.
The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=−0.424,
Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.
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An adrenal incidentaloma is an adrenal mass found in an imaging study performed for other reasons unrelated to adrenal disease and often accompanied by obesity, diabetes, or hypertension. The prevalence and incidence of adrenal incidentaloma increase with age and are also expected to rise due to the rapid development of imaging technology and frequent imaging studies. The Korean Endocrine Society is promoting an appropriate practice guideline to meet the rising incidence of adrenal incidentaloma, in cooperation with the Korean Adrenal Gland and Endocrine Hypertension Study Group. In this paper, we discuss important core issues in managing the patients with adrenal incidentaloma. After evaluating core proposition, we propose the most critical 20 recommendations from the initially organized 47 recommendations by Delphi technique.
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Oxidative stress in primary aldosteronism (PA) is thought to worsen aldosterone-induced damage by activating proinflammatory processes. Therefore, we investigated whether inflammatory markers associated with oxidative stress is increased with negative impacts on heart function as evaluated by echocardiography in patients with PA.
Thirty-two subjects (mean age, 50.3±11.0 years; 14 males, 18 females) whose aldosterone-renin ratio was more than 30 among patients who visited Severance Hospital since 2010 were enrolled. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein 1, tumor necrosis factor α (TNF-α), and matrix metalloproteinase 2 (MMP-2), and MMP-9 were measured. All patients underwent adrenal venous sampling with complete access to both adrenal veins.
Only MMP-2 level was significantly higher in the aldosterone-producing adenoma (APA) group than in the bilateral adrenal hyperplasia (BAH). Patients with APA had significantly higher left ventricular (LV) mass and A velocity, compared to those with BAH. IL-1β was positively correlated with left atrial volume index. Both TNF-α and MMP-2 also had positive linear correlation with A velocity. Furthermore, MMP-9 showed a positive correlation with LV mass, whereas it was negatively correlated with LV end-systolic diameter.
These results suggest the possibility that some of inflammatory markers related to oxidative stress may be involved in developing diastolic dysfunction accompanied by LV hypertrophy in PA. Further investigations are needed to clarify the role of oxidative stress in the course of cardiac remodeling.
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Sitagliptin is a novel antidiabetic agent with a low risk for hypoglycemia. We investigated the efficacy and safety of sitagliptin when patients switched from a sulfonylurea to sitagliptin and identified good candidates for the switch.
Sixty-one patients with type 2 diabetes switched from glimepiride with metformin to sitagliptin with metformin due to clinical hypoglycemia. Serum glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour postprandial plasma glucose (2h-PPG) before and 12 and 24 weeks after the drug switch were checked.
HbA1c and FPG levels did not change 12 or 24 weeks after the switch; however, the 2h-PPG level decreased from 218.0±67.5 mg/dL at baseline to 197.1±69.9 mg/dL at 12 weeks and 192.3±67.4 mg/dL at 24 weeks after switching drugs (
Glycemic control was not aggravated in patients 24 weeks after the drug switch, and symptomatic hypoglycemia decreased significantly. Patients with dominant insulin resistance may be good candidates for switching from a sulfonylurea to sitagliptin to reduce hypoglycemia.
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