-
European Journal of Endocrinology Jul 2023Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are...
European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.
Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the Grading of Recommendations Assessment, Development and Evaluation system and updated systematic reviews on 4 predefined clinical questions crucial for the management of incidentalomas: (1) How to assess risk of malignancy?; (2) How to define and manage mild autonomous cortisol secretion?; (3) Who should have surgical treatment and how should it be performed?; and (4) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: (1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with Hounsfield unit (HU) ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. (2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/L [≤1.8 µg/dL]). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/L (>1.8 µg/dL) harbor increased risk of morbidity and mortality. For this condition, we propose the term "mild autonomous cortisol secretion" (MACS). (3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (eg, hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. (4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. (5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health, and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. (6) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of nonoperated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest 10 important research questions for the future.
Topics: Aged; Humans; Adrenal Gland Neoplasms; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone
PubMed: 37318239
DOI: 10.1093/ejendo/lvad066 -
Journal of the International Society of... Dec 2023Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and... (Review)
Review
Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Female athletes have unique and unpredictable hormone profiles, which influence their physiology and nutritional needs across their lifespan. To understand how perturbations in these hormones affect the individual, we recommend that female athletes of reproductive age should track their hormonal status (natural, hormone driven) against training and recovery to determine their individual patterns and needs and peri and post-menopausal athletes should track against training and recovery metrics to determine the individuals' unique patterns. 2. The primary nutritional consideration for all athletes, and in particular, female athletes, should be achieving adequate energy intake to meet their energy requirements and to achieve an optimal energy availability (EA); with a focus on the timing of meals in relation to exercise to improve training adaptations, performance, and athlete health. 3. Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent, therefore we recommend first ensuring athletes meet their carbohydrate needs across all phases of the menstrual cycle. Secondly, tailoring carbohydrate intake to hormonal status with an emphasis on greater carbohydrate intake and availability during the active pill weeks of oral contraceptive users and during the luteal phase of the menstrual cycle where there is a greater effect of sex hormone suppression on gluconogenesis output during exercise. 4. Based upon the limited research available, we recommend that pre-menopausal, eumenorrheic, and oral contraceptives using female athletes should aim to consume a source of high-quality protein as close to beginning and/or after completion of exercise as possible to reduce exercise-induced amino acid oxidative losses and initiate muscle protein remodeling and repair at a dose of 0.32-0.38 g·kg. For eumenorrheic women, ingestion during the luteal phase should aim for the upper end of the range due to the catabolic actions of progesterone and greater need for amino acids. 5. Close to the beginning and/or after completion of exercise, peri- and post-menopausal athletes should aim for a bolus of high EAA-containing (~10 g) intact protein sources or supplements to overcome anabolic resistance. 6. Daily protein intake should fall within the mid- to upper ranges of current sport nutrition guidelines (1.4-2.2 g·kg·day) for women at all stages of menstrual function (pre-, peri-, post-menopausal, and contraceptive users) with protein doses evenly distributed, every 3-4 h, across the day. Eumenorrheic athletes in the luteal phase and peri/post-menopausal athletes, regardless of sport, should aim for the upper end of the range. 7. Female sex hormones affect fluid dynamics and electrolyte handling. A greater predisposition to hyponatremia occurs in times of elevated progesterone, and in menopausal women, who are slower to excrete water. Additionally, females have less absolute and relative fluid available to lose via sweating than males, making the physiological consequences of fluid loss more severe, particularly in the luteal phase. 8. Evidence for sex-specific supplementation is lacking due to the paucity of female-specific research and any differential effects in females. Caffeine, iron, and creatine have the most evidence for use in females. Both iron and creatine are highly efficacious for female athletes. Creatine supplementation of 3 to 5 g per day is recommended for the mechanistic support of creatine supplementation with regard to muscle protein kinetics, growth factors, satellite cells, myogenic transcription factors, glycogen and calcium regulation, oxidative stress, and inflammation. Post-menopausal females benefit from bone health, mental health, and skeletal muscle size and function when consuming higher doses of creatine (0.3 g·kg·d). 9. To foster and promote high-quality research investigations involving female athletes, researchers are first encouraged to stop excluding females unless the primary endpoints are directly influenced by sex-specific mechanisms. In all investigative scenarios, researchers across the globe are encouraged to inquire and report upon more detailed information surrounding the athlete's hormonal status, including menstrual status (days since menses, length of period, duration of cycle, etc.) and/or hormonal contraceptive details and/or menopausal status.
Topics: Female; Humans; Male; Creatine; Progesterone; Athletes; Sports; Amino Acids
PubMed: 37221858
DOI: 10.1080/15502783.2023.2204066 -
Journal of Applied Physiology... Dec 2023Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher... (Meta-Analysis)
Meta-Analysis Review
Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.
Topics: Female; Humans; Contraceptives, Oral; Menstrual Cycle; Hormones; Progesterone; Hypertrophy
PubMed: 37823207
DOI: 10.1152/japplphysiol.00346.2023 -
JCI Insight Jul 2023The adrenal glands synthesize and release essential steroid hormones such as cortisol and aldosterone, but many aspects of human adrenal gland development are not well...
The adrenal glands synthesize and release essential steroid hormones such as cortisol and aldosterone, but many aspects of human adrenal gland development are not well understood. Here, we combined single-cell and bulk RNA sequencing, spatial transcriptomics, IHC, and micro-focus computed tomography to investigate key aspects of adrenal development in the first 20 weeks of gestation. We demonstrate rapid adrenal growth and vascularization, with more cell division in the outer definitive zone (DZ). Steroidogenic pathways favored androgen synthesis in the central fetal zone, but DZ capacity to synthesize cortisol and aldosterone developed with time. Core transcriptional regulators were identified, with localized expression of HOPX (also known as Hop homeobox/homeobox-only protein) in the DZ. Potential ligand-receptor interactions between mesenchyme and adrenal cortex were seen (e.g., RSPO3/LGR4). Growth-promoting imprinted genes were enriched in the developing cortex (e.g., IGF2, PEG3). These findings reveal aspects of human adrenal development and have clinical implications for understanding primary adrenal insufficiency and related postnatal adrenal disorders, such as adrenal tumor development, steroid disorders, and neonatal stress.
Topics: Infant, Newborn; Humans; Aldosterone; Hydrocortisone; Adrenal Glands; Adrenal Cortex; Steroids; Homeodomain Proteins
PubMed: 37440461
DOI: 10.1172/jci.insight.168177 -
Cells Nov 2023Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated... (Review)
Review
Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic-pituitary-adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer's and Parkinson's, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions.
Topics: Animals; Hydrocortisone; Depressive Disorder, Major; Neurodegenerative Diseases; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 38067154
DOI: 10.3390/cells12232726 -
Advances in Therapy Sep 2023Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide... (Review)
Review
INTRODUCTION
Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies.
METHODS
We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios.
RESULTS
A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence.
CONCLUSION
In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.
Topics: Humans; Budesonide; Drug Combinations; Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Fluticasone
PubMed: 37438554
DOI: 10.1007/s12325-023-02585-z -
Ugeskrift For Laeger May 2024This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality... (Review)
Review
This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.
Topics: Humans; Premature Birth; Pregnancy; Progesterone; Female; Progestins; Administration, Intravaginal; Risk Factors; Cervical Length Measurement; Cervix Uteri
PubMed: 38847312
DOI: 10.61409/V10230636 -
Microbiome Nov 2023Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with...
BACKGROUND
Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with neurological diseases; however, the mechanisms by which the microbiota regulates postoperative gastrointestinal and cognitive function are incompletely understood.
METHODS
Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, and immunofluorescence staining were employed to discern the impacts of surgery on microbial profiles, intestinal barriers, serum metabolism, and the brain. Interventions in mice included fecal microbiota transplantation, the anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid supplementation, and palmitic amide administration.
RESULTS
Surgery-induced cognitive impairment occurs predominantly in aged mice, and surgery-induced alterations in the microbiota composition profile exacerbate intestinal barrier disruption in aged mice. These adverse effects can be mitigated by transferring microbiota from young donors or by bolstering the intestinal barrier function using dexamethasone, Lactobacillus, or indole propionic acid. Moreover, microbiota composition profiles can be restored by transplanting feces from young mice to aged surgical mice, improving neuropathology and cognitive function, and these effects coincide with increased intestinal permeability. Metabolomic screening identified alterations in metabolites in mouse serum after surgery, especially the increase in palmitic amide. Palmitic amide levels in serum and brain can be decreased by transplanting feces from young mice to aged surgical mice. Oral palmitic amide exacerbates cognitive impairment and neuropathological changes in mice.
CONCLUSIONS
Gut microbial dysbiosis in mice after surgery is a key mechanism leading to cognition dysfunction, which disrupts the intestinal barrier and metabolic abnormalities, resulting in neuroinflammation and dendritic spine loss. Intestinal barrier damage and high level of palmitic amide in old mice may be the cause of high incidence of PND in the elderly. Preoperative microbiota regulation and intestinal barrier restoration may be of therapeutic benefit in preventing PND. Video Abstract.
Topics: Animals; Mice; Cognitive Dysfunction; Dexamethasone; Dysbiosis; Gastrointestinal Microbiome; Indoles; Mice, Inbred C57BL; RNA, Ribosomal, 16S
PubMed: 37936242
DOI: 10.1186/s40168-023-01689-6 -
Nutrients Dec 2023Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and... (Review)
Review
BACKGROUND
Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023.
METHODS
The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus.
RESULTS
Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects.
CONCLUSIONS
Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.
Topics: Humans; Plant Extracts; Withania; Hydrocortisone; Plants, Medicinal; Antioxidants
PubMed: 38140274
DOI: 10.3390/nu15245015 -
Dialogues in Clinical Neuroscience Dec 2023Postpartum depression has deleterious effects on childbearing persons globally. Existing treatments have been largely extrapolated from those for other forms of... (Review)
Review
Postpartum depression has deleterious effects on childbearing persons globally. Existing treatments have been largely extrapolated from those for other forms of depression and have included pharmacotherapy, psychotherapy, and neuromodulation. Hormonal treatments with oestrogen and progestogens, thought to be a rational approach to treatment in response to an emerging literature on the pathophysiology of postpartum depression, have only limited evidence for efficacy to date. Novel antidepressant development with allopregnanolone analogues, in contrast, has proven a promising avenue for the development of rationally designed and efficacious treatments. This state-of-the-art review presents the evidence for the current standard-of-care pharmacotherapy, hormonal treatment, and emerging allopregnanolone analogues for the treatment of postpartum depression along with a discussion of the current understanding of its neuroactive steroid-driven pathophysiology.
Topics: Female; Humans; Depression, Postpartum; Pregnanolone; Antidepressive Agents; Psychotherapy
PubMed: 37796239
DOI: 10.1080/19585969.2023.2262464