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Metabolites Jan 2024Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent... (Review)
Review
Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent hypoglycaemia. Here, we review the status quo of research related to the regulatory mechanisms of the adrenal medulla in its response to single and recurrent hypoglycaemia in both diabetic and non-diabetic subjects with particular focus given to catecholamine synthesis, enzymatic activity, and the impact of adrenal medullary peptides. Short-term post-transcriptional modifications, particularly phosphorylation at specific residues of tyrosine hydroxylase (TH), play a key role in the regulation of catecholamine synthesis. While the effects of recurrent hypoglycaemia on catecholamine synthetic enzymes remain inconsistent, long-term changes in TH protein expression suggest species-specific responses. Adrenomedullary peptides such as neuropeptide Y (NPY), galanin, and proenkephalin exhibit altered gene and protein expression in response to hypoglycaemia, suggesting a potential role in the modulation of catecholamine secretion. Of note is NPY, since its antagonism has been shown to prevent reductions in TH protein expression. This review highlights the need for further investigation into the molecular mechanisms involved in the adrenal medullary response to hypoglycaemia. Despite advancements in our understanding of HAAF in non-diabetic rodents, a reliable diabetic rodent model of HAAF remains a challenge.
PubMed: 38392992
DOI: 10.3390/metabo14020100 -
Journal of Kidney Cancer and VHL 2024This systematic review aims to investigate the clinical presentation, diagnostic methods, and management strategies for pheochromocytoma in patients with von...
This systematic review aims to investigate the clinical presentation, diagnostic methods, and management strategies for pheochromocytoma in patients with von Hippel-Lindau (VHL) disease, an autosomal dominant disorder that predisposes individuals to the development of various tumors, including pheochromocytomas. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla that occurs sporadically or as part of an inherited syndrome. The incidence of pheochromocytoma in VHL patients is estimated to be between 10-20%, making it the second most common tumor associated with VHL. Early detection and management of pheochromocytoma in VHL patients are critical for patient outcomes, as these tumors can cause severe hypertension, cardiovascular complications, and death. This review highlights the importance of screening for pheochromocytoma in VHL patients and discusses the current diagnostic and management strategies to optimize patient care.
PubMed: 38344311
DOI: 10.15586/jkcvhl.v11i1.275 -
International Journal of Molecular... Jan 2024Dichlorodiphenyltrichloroethane (DDT) is a wide-spread systemic pollutant with endocrine disrupting properties. Prenatal exposure to low doses of DDT has been shown to...
Postnatal Exposure to the Endocrine Disruptor Dichlorodiphenyltrichloroethane Affects Adrenomedullary Chromaffin Cell Physiology and Alters the Balance of Mechanisms Underlying Cell Renewal.
Dichlorodiphenyltrichloroethane (DDT) is a wide-spread systemic pollutant with endocrine disrupting properties. Prenatal exposure to low doses of DDT has been shown to affect adrenal medulla growth and function. The role of postnatal exposure to DDT in developmental disorders remains unclear. The aim of the present investigation is to assess growth parameters and the expression of factors mediating the function and renewal of chromaffin cells in the adult adrenal medulla of male Wistar rats exposed to the endocrine disruptor o,p'-DDT since birth until sexual maturation. The DDT-exposed rats exhibited normal growth of the adrenal medulla but significantly decreased tyrosine hydroxylase production by chromaffin cells during postnatal period. Unlike the control, the exposed rats showed enhanced proliferation and reduced expression of nuclear β-catenin, transcription factor Oct4, and ligand of Sonic hedgehog after termination of the adrenal growth period. No expression of pluripotency marker Sox2 and absence of Ascl 1-positive progenitors were found in the adrenal medulla during postnatal ontogeny of the exposed and the control rats. The present findings indicate that an increase in proliferative activity and inhibition of the formation of reserve for chromaffin cell renewal, two main mechanisms for cell maintenance in adrenal medulla, in the adult DDT-exposed rats may reflect a compensatory reaction aimed at the restoration of catecholamine production levels. The increased proliferation of chromaffin cells in adults suggests excessive growth of the adrenal medulla. Thus, postnatal exposure to DDT alters cell physiology and increases the risk of functional insufficiency and hyperplasia of the adrenal medulla.
Topics: Pregnancy; Female; Rats; Animals; Male; Rats, Wistar; Endocrine Disruptors; DDT; Hedgehog Proteins; Adrenal Medulla; Chromaffin Cells; Cell Physiological Phenomena
PubMed: 38338771
DOI: 10.3390/ijms25031494 -
Radiology Case Reports Apr 2024Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that originate from chromaffin cells in the adrenal medulla. They cause severe hypertension and...
Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that originate from chromaffin cells in the adrenal medulla. They cause severe hypertension and various clinical manifestations. While most arise in the adrenal medulla, some occur in extra-adrenal locations.We present a case report with clinical, laboratory and radiographic data, along with a brief literature review. We report a 33-year-old woman who presented with flushing and sharp lower abdominal pain. Abdominal ultrasound and urinary metanephrines suggested a pheochromocytoma. Subsequent Computed tomography (CT) and Ga-DOTATATE Positron emission tomography/Computed tomography (PET/CT) scans confirmed a pheochromocytoma in the organ of Zuckerkandl with distant bony metastasis. Extra-adrenal pheochromocytomas, or paragangliomas, are rare tumors found in specific anatomical locations. Their diagnostic challenges stem from variable clinical presentations and imaging findings. CT scans and Ga-DOTATATE PET/CT scans are crucial in diagnosis and prognosis. Surgical resection can cure localized cases, while metastatic disease requires palliative options, such as chemotherapy and I131-MIBG, due to a poorer prognosis.
PubMed: 38322234
DOI: 10.1016/j.radcr.2024.01.026 -
International Journal of Surgery Case... Feb 2024Phaeochromocytomas are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and are known as intra-adrenal paragangliomas. On the contrary,...
INTRODUCTION AND IMPORTANCE
Phaeochromocytomas are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and are known as intra-adrenal paragangliomas. On the contrary, paragangliomas are non-epithelial neuroendocrine neoplasms that produce other peptide hormones such as norepinephrine, epinephrine, and dopamine. In a setting with limited resources, such a condition may result in inaccurate diagnosis and treatment, which may lose a patient life if left untreated. In addition, PPGLs present a surgical challenge to many surgeons who are not thoroughly prepared.
CASE PRESENTATION
We describe a case of extra-adrenal paraganglioma in a 27-year-old female who presented with symptoms of heartbeat awareness for almost a year and abdominal swelling for three months. Physical examination revealed a palpable mass around the umbilicus. Abdominal pelvic CT scan revealed a well-circumscribed mass in the central retroperitoneum displacing the IVC laterally and abdominal aorta medially with no invasion of surrounding structures. Results for pheochromocytoma workup showed elevated levels of 24-h urine Vanillylmandelic acid (VMA), and 24-h metanephrine excretion. Laparotomy through extended midline incision was done with successful excision of the tumor. The blood pressure, which was initially high normalized after surgery.
DISCUSSION
The diagnosis of a malignant EAP is commonly made based on recurrence and the development of metastasis to lymph nodes or to other organs. Our patient presented with similar symptoms as pheochromocytoma. Compared to the commonly stated 10 % risk for pheochromocytomas, people with EAPs have been observed to have a 20 % to 50 % incidence of malignancy. EAPs account for at least 15 % of adult and 30 % of pediatric pheochromocytomas and are frequently found in the Zuckerkandl organ. Pheochromocytoma symptoms may manifest asymptomatically in patients with EAPs, or they may occur because of compression of nearby tissues. Surgical excision of the tumor is always the best option in managing EAP.
CONCLUSION
Extra-adrenal paragangliomas can be successfully managed surgically, provided there is a multidisciplinary team, and the tumor location is well recognized and can reduce the chance of tumor metastasis.
PubMed: 38306874
DOI: 10.1016/j.ijscr.2024.109315 -
Psychoneuroendocrinology Apr 2024Existing research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & OBJECTIVES
Existing research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to reliably induce physiological stress contagion based on direct face-to-face stress observation compared to an active placebo-stress observing control condition is lacking. Here, we tested a standardized randomized placebo-controlled experimental paradigm to investigate physiological reactivity to direct stress observation and characterized the stress contagion response of the major endocrine stress systems, including full reactivity kinetics.
METHODS
Healthy young male participants were randomly assigned to (1) undergo an adapted version of the Trier Social Stress Test ("TSST participants", n = 20), (2) observe it ("stress observers", n = 36), or (3) observe a corresponding placebo-stress control condition ("placebo-stress observers", n = 30). We repeatedly assessed heart rate, salivary alpha-amylase, salivary cortisol, and salivary aldosterone.
RESULTS
Stress observers exhibited greater physiological reactivity to stress observation as compared to placebo-stress observers to placebo-stress observation in heart rate, salivary alpha-amylase, and cortisol (p's ≤ .027), but not in aldosterone. We observed similar reactivity kinetics in TSST participants and stress observers but less pronounced in stress observers.
DISCUSSION
Extending previous literature, our findings indicate that independent of secondary effects of the observation setting, direct observation of stress in other individuals induces activation of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis. Moreover, the physiological stress contagion response resembles the physiological reactivity to first-hand stress but is less pronounced. Potential implications of physiological stress contagion regarding health, cognition, or behavior, as well as modulating factors need to be further elucidated.
Topics: Humans; Male; Aldosterone; Hydrocortisone; Adrenal Medulla; Cognition; Stress, Physiological
PubMed: 38301381
DOI: 10.1016/j.psyneuen.2024.106964 -
BioRxiv : the Preprint Server For... Jan 2024Chromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for...
Chromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for coupling cell stimulation to secretion are acetylcholine and pituitary adenylate activating polypeptide (PACAP). In contrast to acetylcholine, PACAP evokes a persistent secretory response from chromaffin cells. However, the mechanisms by which PACAP acts are poorly understood. Here, it is shown that PACAP induces sustained increases in cytosolic Ca which are disrupted when Ca influx through L-type channels is blocked or internal Ca stores are depleted. PACAP liberates stored Ca via inositol trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER), thereby functionally coupling Ca mobilization to Ca influx and supporting Ca -induced Ca -release. These Ca influx and mobilization pathways are unified by an absolute dependence on phospholipase C epsilon (PLCε) activity. Thus, the persistent secretory response that is a defining feature of PACAP activity, , is regulated by a signaling network that promotes sustained elevations in intracellular Ca through multiple pathways.
PubMed: 38260572
DOI: 10.1101/2024.01.03.574069 -
International Journal of Molecular... Dec 2023Hypertension is a global civilization disease and one of the most common causes of death in the world. Organ dysfunction is a serious health consequence of hypertension,...
Evaluation of the Expression and Localization of the Multifunctional Protein CacyBP/SIP and Elements of the MAPK Signaling Pathway in the Adrenal Glands of Rats with Primary and Secondary Hypertension.
Hypertension is a global civilization disease and one of the most common causes of death in the world. Organ dysfunction is a serious health consequence of hypertension, which involves damage to the heart, kidneys and adrenals. The interaction of recently discovered multifunctional protein-CacyBP/SIP with ERK1/2 and p38 kinases by regulating the activity and intracellular localization of these kinases may play an important role in the signaling pathways involved in the pathogenesis of hypertension. Due to the lack of data on this subject, we decided to investigate the localization, expression and possible relationship between the studied parameters in the adrenals under arterial hypertension. The study was conducted on the adrenals of rats with spontaneous and DOCA-salt hypertension. The expression of CacyBP/SIP, p-ERK1/2 and p-p38 was detected by immunohistochemistry and qRT-PCR. The results show a statistically significant decrease in CacyBP/SIP expression in the adrenal glands of hypertensive rats. With ERK1/2, there was a decrease in cortical immunoreactivity and an increase in the adrenal medulla of primary hypertensive rats. In contrast, in the adrenals of DOCA-salt rats, ERK1/2 immunoreactivity increased in the cortex and decreased in the medulla. In turn, p38 expression was higher in the adrenal glands of rats with primary and secondary hypertension. The obtained results may suggest the involvement of CacyBP/SIP in the regulation of signaling pathways in which MAP kinases play an important role and provide new insight into molecular events in hypertension. Moreover, they show the participation of CacyBP/SIP in response to oxidative stress.
Topics: Animals; Rats; MAP Kinase Signaling System; Desoxycorticosterone Acetate; Signal Transduction; Adrenal Glands; Hypertension; Sodium Chloride; Sodium Chloride, Dietary; Intracellular Signaling Peptides and Proteins
PubMed: 38203261
DOI: 10.3390/ijms25010084 -
Nutrients Dec 2023During the COVID-19 pandemic, an increase in the incidence of overweight and obesity in children was observed. It appears that unhealthy food choices, an unbalanced... (Review)
Review
During the COVID-19 pandemic, an increase in the incidence of overweight and obesity in children was observed. It appears that unhealthy food choices, an unbalanced diet, and a sedentary lifestyle, as well as experiencing stress related to the pandemic, may be contributing to this disturbing trend. Chronic stress is a significant factor contributing to eating disorders and obesity in youngsters, involving medical, molecular, and psychological elements. Individuals under chronic stress often focus on appearance and weight, leading to negative body image and disrupted relationships with food, resulting in unhealthy eating behaviors. Chronic stress also impacts hormonal balance, reducing the satiety hormone leptin and elevating the appetite-stimulating hormone ghrelin, fostering increased hunger and uncontrolled snacking. Two systems, the hypothalamic-pituitary-adrenal axis and the sympathetic system with the adrenal medulla, are activated in response to stress, causing impaired secretion of noradrenaline and cortisol. Stress-related obesity mechanisms encompass oxidative stress, neuroinflammation, insulin resistance, and neurohormonal and neurotransmission disorders. Stress induces insulin resistance, elevating obesity risk by disrupting blood sugar regulation and fat storage. Stress also affects the gut microbiome, potentially influencing chronic inflammation and metabolic processes linked to obesity. In conclusion, chronic stress is a multifaceted risk factor for eating disorders and obesity in children, necessitating a comprehensive understanding of effective preventive and intervention strategies amid the escalating prevalence of childhood overweight and obesity.
Topics: Child; Humans; Adolescent; Pediatric Obesity; Hypothalamo-Hypophyseal System; Insulin Resistance; Pandemics; COVID-19; Pituitary-Adrenal System; Feeding Behavior
PubMed: 38201884
DOI: 10.3390/nu16010054