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CNS Neuroscience & Therapeutics Oct 2023Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign... (Review)
Review
Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign and stable, several tumors have malignant characteristics. The tumor microenvironment (TME) plays an important role in the process of tumorigenesis and is composed of several types of cells. Various cells in the TME are significantly affected by oxidative stress. It has been reported that immunotherapeutic strategies have good effects in several cancers. However, the clinical potential of immunotherapies in PitNETs has not yet been fully discussed. Oxidative stress can regulate PitNET cells and immune cells in the TME, thus affecting the immune status of the TME of PitNETs. Therefore, modulation of oxidative stress-regulated immune cells using a combination of several agents and the immune system to suppress PitNETs is a promising therapeutic direction. In this review, we systematically analyzed the oxidative stress process within PitNET cells and various immune cells to elucidate the potential value of immunotherapy.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Tumor Microenvironment
PubMed: 37341156
DOI: 10.1111/cns.14315 -
Journal of Medicine and Life Nov 2023Polycystic ovary syndrome (PCOS) is one of the most prevalent metabolic diseases during female reproductive life, often associated with insulin resistance and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of combined metformin and cabergoline versus metformin alone on ovarian and hormonal activities in Iraqi patients with PCOS and hyperprolactinemia: a randomized clinical trial.
Polycystic ovary syndrome (PCOS) is one of the most prevalent metabolic diseases during female reproductive life, often associated with insulin resistance and hyperprolactinemia. The efficacy of metformin and cabergoline for managing PCOS remains debated in the literature. This three-arm interventional study in Iraq assessed the effects of these drugs on body mass index (BMI), hormonal balance, and uterine artery blood flow in 75 women with PCOS and hyperprolactinemia. Participants were randomized into three groups: metformin (500 mg twice daily), cabergoline (0.5 mg weekly), and a combination of both, with 25 patients in each group. Baseline and 90-day follow-up characteristics included BMI, serum hormonal levels, and ultrasound features. Metformin resulted in significant weight reduction (p=0.038); however, the addition of cabergoline caused a more significant reduction in body mass index (p=0.001). The combined treatment significantly lowered testosterone levels (p=0.008). In addition, this combination significantly reduced the level of LH (p=0.043) and increased the level of FSH (p=0.047). The results suggest that metformin and cabergoline when used together, act synergistically and safely to reduce BMI, testosterone, and LH levels while increasing FSH levels. Furthermore, this combination improved endometrial blood flow and ovulation in women with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Metformin; Cabergoline; Luteinizing Hormone; Iraq; Hyperprolactinemia; Follicle Stimulating Hormone; Testosterone
PubMed: 38406771
DOI: 10.25122/jml-2023-0317 -
Proceedings of the National Academy of... Jul 2023The evolution of the extinct megatooth shark, , and its close phylogenetic relatives remains enigmatic. A central question persists regarding the thermophysiological...
The evolution of the extinct megatooth shark, , and its close phylogenetic relatives remains enigmatic. A central question persists regarding the thermophysiological origins of these large predatory sharks through geologic time, including whether was ectothermic or endothermic (including regional endothermy), and whether its thermophysiology could help to explain the iconic shark's gigantism and eventual demise during the Pliocene. To address these uncertainties, we present unique geochemical evidence for thermoregulation in from both clumped isotope paleothermometry and phosphate oxygen isotopes. Our results show that had an overall warmer body temperature compared with its ambient environment and other coexisting shark species, providing quantitative and experimental support for recent biophysical modeling studies that suggest endothermy was one of the key drivers for gigantism in and other lamniform sharks. The gigantic body size with high metabolic costs of having high body temperatures may have contributed to the vulnerability of species to extinction when compared to other sympatric sharks that survived the Pliocene epoch.
Topics: Animals; Sharks; Phylogeny; Gigantism; Body Temperature Regulation; Body Size
PubMed: 37364100
DOI: 10.1073/pnas.2218153120 -
Frontiers in Endocrinology 2023To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing's disease.
OBJECTIVE
To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing's disease.
METHODS
The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first. Study outcomes assessed in the extension included: mean urinary free cortisol (mUFC) response rates; changes in mUFC, serum cortisol and late-night salivary cortisol (LNSC); changes in cardiovascular and metabolic-related parameters; blood pressure, waist circumference and weight; changes in physical manifestations of Cushing's disease; changes in patient-reported outcomes for health-related quality of life; changes in tumor volume; and adverse events. Results were analyzed descriptively; no formal statistical testing was performed.
RESULTS
Of 60 patients who entered, 53 completed the extension, with 29 patients receiving osilodrostat for more than 96 weeks (median osilodrostat duration: 87.1 weeks). The proportion of patients with normalized mUFC observed in the core period was maintained throughout the extension. At their end-of-trial visit, 72.4% of patients had achieved normal mUFC. Substantial reductions in serum cortisol and LNSC were also observed. Improvements in most cardiovascular and metabolic-related parameters, as well as physical manifestations of Cushing's disease, observed in the core period were maintained or continued to improve in the extension. Osilodrostat was generally well tolerated; the safety profile was consistent with previous reports.
CONCLUSION
Osilodrostat provided long-term control of cortisol secretion that was associated with sustained improvements in clinical signs and physical manifestations of hypercortisolism. Osilodrostat is an effective long-term treatment for patients with Cushing's disease.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT02180217.
Topics: Humans; Pituitary ACTH Hypersecretion; Hydrocortisone; Quality of Life; Adrenocortical Hyperfunction
PubMed: 37680892
DOI: 10.3389/fendo.2023.1236465 -
Hormone and Metabolic Research =... Jul 2023The management of non-functioning pituitary tumors (NFPTs) relies on the risk of tumor growth and new endocrinopathies. The objective of this systematic review was to... (Meta-Analysis)
Meta-Analysis
The management of non-functioning pituitary tumors (NFPTs) relies on the risk of tumor growth and new endocrinopathies. The objective of this systematic review was to assess the risk of growth, new pituitary endocrinopathies, and surgery in patients with conservatively treated NFPTs. We conducted a bibliographical search identifying studies assessing NFPTs followed conservatively. Estimates were pooled using random-effects meta-analysis reporting events per 100 person years (PYs), in case of high heterogeneity (I2>75%) only the range of observed effects was reported. We identified 30 cohort studies including 1957 patients with a mean follow-up time of 4.0 (SD 1.5) years. The overall risk of tumor growth ranged from 0.0 to 14.2/100 PYs (I2=90%), while the overall risk of new endocrinopathies was 0.9/100 PYs (95% CI. 0.5 to 1.2; I2=: 35%) and risk of surgery ranged from 0.0 to 7.7/100 PYs (I2=: 80%). Compared to microadenomas, macroadenomas had higher risk of growth (p=: 0.002), higher risk of surgery (p=: 0.006), and non-significant differences in risk of new endocrinopathies (p=: 0.15). An analysis of microadenomas found the risk of growth to be 1.8/100 PYs (95% CI. 0.9 to 2.8; I2=: 58%), the risk of new endocrinopathies 0.7/100 PYs (95% CI. 0.0 to 1.6; I2=: 37%) and the risk of surgery 0.5/100 PYs (0.1 to 0.9; I2=: 37%). These data support individualized follow-up strategies of patients with NFPTs and particularly a less rigorous follow-up of patients with microadenomas.
Topics: Humans; Pituitary Neoplasms; Adenoma; Cohort Studies; Pituitary Gland
PubMed: 37494058
DOI: 10.1055/a-2096-1340 -
Cancer Imaging : the Official... Sep 2023Fluorine-Fluoro-deoxy-glucose (F-FDG) positron emission tomography (PET) is widely used for diagnosing various malignant tumors and evaluating metabolic activities....
BACKGROUND
Fluorine-Fluoro-deoxy-glucose (F-FDG) positron emission tomography (PET) is widely used for diagnosing various malignant tumors and evaluating metabolic activities. Although the usefulness of F-FDG PET has been reported in several endocrine diseases, studies on pituitary disease are extremely limited. To evaluate whether dexamethasone (DEX) suppression can improve F-FDG PET for the localization of adrenocorticotropic hormone-secreting adenomas in the pituitary gland in Cushing's disease (CD).
METHODS
We included 22 patients with CD who underwent PET imaging before and after DEX administration. We compared the success rates of PET before and after DEX suppression, magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus sampling (BIPSS). We determined the final locations of adenomas based on intraoperative multiple-staged resection and tumor tissue identification using frozen sections. Standardized uptake value (SUV) were analyzed to confirm the change of intensity of adenomas on PET.
RESULTS
Twenty-two patients were included (age at diagnosis: 37 [13-56] years), and most were women (90.91%). Pituitary adenomas compared to normal pituitaries showed increased maximum SUV after DEX suppression but without statistical significance (1.13 versus. 1.21, z=-0.765, P = 0.444). After DEX suppression, the mean and maximum SUV of adenomas showed a positive correlation with nadir cortisol levels in high-dose DEX suppression test (Rho = 0.554, P = 0.007 and Rho = 0.503, P = 0.017, respectively). In reference sites, mean SUV of cerebellum was significantly decreased (7.65 vs. 6.40, P = 0.006), but those of the thalamus and gray matter was increased after DEX suppression (thalamus, 8.70 vs. 11.20, P = 0.010; gray matter, 6.25 vs. 7.95, P = 0.010).
CONCLUSION
DEX suppression did not improve F-FDG PET/CT localization in patients with CD.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Male; Pituitary Neoplasms; Adrenocorticotropic Hormone; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Dexamethasone
PubMed: 37700359
DOI: 10.1186/s40644-023-00600-8 -
Journal of Clinical Medicine Jul 2023The pituitary gland is either directly or indirectly impacted by SARS-CoV-2 infection. As a consequence of SARS-CoV-2 infection, hypothalamic-pituitary dysfunction or...
The pituitary gland is either directly or indirectly impacted by SARS-CoV-2 infection. As a consequence of SARS-CoV-2 infection, hypothalamic-pituitary dysfunction or pituitary apoplexy can occur. This study aimed to investigate severe COVID-19 outcomes and COVID-19-related mortality in patients with underlying pituitary disease in Korea using a nationwide cohort database. The data required for this study were obtained from the Health Insurance Review and Assessment Service of Korea. Patients with SARS-CoV-2 infection between January 2020 and December 2021 were divided into the following three groups and analyzed: Group A, those who were hospitalized for SARS-CoV-2 infection without underlying pituitary disease (n = 725,170); Group B, those who were hospitalized for SARS-CoV-2 infection with underlying pituitary disease without exposure to systemic steroids (n = 1509); and Group C, patients with underlying pituitary disease and exposure to systemic steroids (n = 365). Differences in severe COVID-19, requirement for oxygen therapy, intensive care unit admission, application of invasive ventilation or use of extracorporeal membrane oxygenation, and COVID-19-related deaths between groups were then analyzed. Group C had the highest rates of hospitalization after COVID-19 infection (82.2%) and mortality within 30 days of infection (6.8%). Group B had a 1.3-fold increase in severe COVID-19 outcomes compared to Group A. Group C had 1.8-fold and 1.3-fold increases in severe COVID-19 outcomes compared to Group A and Group B, respectively. Group C also had 2.34 and 3.24 times higher mortality rates within 30 days of COVID-19 infection than Group A and Group B, respectively. In conclusion, patients with pituitary disease who are receiving systemic steroids have poorer outcomes and higher mortality associated with COVID-19. Therefore, thorough COVID-19 infection control is required in these patients.
PubMed: 37510914
DOI: 10.3390/jcm12144799 -
Drug Design, Development and Therapy 2024Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily... (Review)
Review
Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy.
Topics: Adult; Humans; Child; United States; Human Growth Hormone; Dwarfism, Pituitary; Growth Hormone; Treatment Outcome; Insulin-Like Growth Factor I; Histidine; Mannitol; Phenol
PubMed: 38333899
DOI: 10.2147/DDDT.S315172 -
The Journal of Clinical Endocrinology... Nov 2023Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I...
CONTEXT
Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control.
OBJECTIVE
As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed.
METHODS
A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008). The main outcome measures were safety and biochemical control (age-adjusted IGF-I ≤ upper limit of normal).
RESULTS
Patients (n = 50) entered 4 parental studies and 30 continued in the rollover; at data cutoff (June 2022), 27 were still receiving pasireotide. Overall, median (range) exposure was 58 (3-137) months. Normal IGF-I was achieved in 54%, and acromegaly symptoms and quality of life were improved with treatment. No predictors of pasireotide response were identified; however, controlled patients had smaller tumors and lower GH at baseline. Tumor volume reduction occurred in 63% of evaluable patients (n = 10/16). Most patients presented hyperglycemic events, including 63.2% of patients with normal glucose before treatment. Older patients and those with higher IGF-I, glucose, and HbA1c at baseline had higher glucose and HbA1c during pasireotide treatment.
CONCLUSION
Pasireotide provided clinical benefit and was well tolerated for more than 11 years of treatment in acromegaly patients, most of whom were resistant to first-generation SRLs.
Topics: Humans; Acromegaly; Insulin-Like Growth Factor I; Glycated Hemoglobin; Retrospective Studies; Quality of Life; Treatment Outcome; Human Growth Hormone; Growth Hormone; Glucose; Adenoma
PubMed: 37357993
DOI: 10.1210/clinem/dgad378 -
Frontiers in Endocrinology 2023Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of small-sized and medium (<30 mm) somatotropinoma removal and the incidence of postoperative complications in patients with acromegaly when using microscopic and endoscopic techniques.
METHODS
In this randomized controlled trial, a total of 83 patients with acromegaly underwent transspheroidal endoscopy or microscopic surgery. Somatotropinoma was the cause of acromegaly in all cases. Patients were randomly divided into two comparison groups depending on the applied surgical technique. Group 1 (n = 40) consisted of patients who underwent adenomectomy with transnasal transsphenoidal access by a microscope. Group 2 (n = 43) included patients who underwent the same surgical procedure with an endoscope. The following indicators were assessed: radicality of tumor removal, treatment effectiveness, postoperative complications, and remission rate.
RESULTS
The study has shown that removal of somatotropinoma in patients with acromegaly using endoscopic technique increases the radicality of tumor removal in comparison with microscopic technique. Total removal of somatotropinoma was successful in 88.4% of cases when using the endoscopic technique. Secondly, the segmentation of patients according to their tumor characteristics poses challenges, primarily owing to the rarity of acromegaly as a disease. The difference between groups was not statistically significant (p=1.02). There were no statistically significant differences in basal GH level and IGF-1 level between groups (p=0.546 and p=0.784, respectively).
DISCUSSION
Endonasal transsphenoidal endoscopic adenomectomy is proven efficacy, a less traumatic degree, and higher somatotropinoma removal radicality. Both surgical methods lead to disease remission.
Topics: Humans; Acromegaly; Endoscopy; Adenoma; Growth Hormone-Secreting Pituitary Adenoma; Postoperative Complications; Pituitary Neoplasms
PubMed: 37766690
DOI: 10.3389/fendo.2023.1128345