Antidiuretic Hormone Secretion Research Articles

Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement.

The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.

Impact of Hyponatremia and ADH Secretion in MIS-C and COVID-19: An Integrative Approach of Prognostic and Diagnostic Markers

The COVID-19 pandemic has introduced challenges in pediatric care, especially due to the emergence of Multisystem Inflammatory Syndrome in Children (MIS-C), a severe condition associated with SARS-CoV-2 infection. This study investigated the impact of hyponatremia and antidiuretic hormone (ADH) secretion corelated to clinical outcomes in these patients. We conducted a retrospective cohort study, including 118 pediatric patients, with a detailed sub-cohort analysis of 53 patients for ADH secretion markers. Hyponatremia, defined by age-specific sodium thresholds, was present in 47.22% of MIS-C cases and 28.04% of COVID-19 cases. Ordinal logistic regression analysis revealed that severe hyponatremia significantly increased the likelihood of more severe clinical outcomes (β = 3.514, p < 0.001). A significant correlation was found between hyponatremia and prolonged hospitalization. For ADH secretion, a predictive model using ridge regression was analysed, which demonstrated that serum sodium level, U/P ratio, and hospitalization duration are key predictors of SIADH. This model fit was assessed using the ROC curve with an AUC of 0.96, indicating reliable model performance. Our findings underscore the significant role of hyponatremia on the clinical severity and hospitalization outcome of COVID-19 and MIS-C in pediatric patients.

The biology of water homeostasis.

Water homeostasis is controlled by a brain-kidney axis that consists of central osmoreceptors, synthesis and secretion of arginine vasopressin (AVP) and AVP-responsive aquaporin-2 (AQP2) water channels in kidney collecting duct principal cells that facilitate water reabsorption. In addition to AVP, thirst represents a second line of defense to maintain water balance. Water balance disorders arise because of deficiency, resistance or inappropriate secretion of AVP or disturbances in thirst sensation (hypodipsia, polydipsia). People with water balance disorders are prone to develop hyponatremia or hypernatremia, which expose cells to osmotic stress and activate cell volume regulation mechanisms. This review covers several recent insights that have expanded our understanding of central osmoregulation, AQP2 regulation and cell volume regulation. This includes the role of with-no-lysine kinase 1 (WNK1) as a putative central osmolality sensor and, more generally, as an intracellular crowding sensor that coordinates the cell volume rescue response by activating sodium and potassium cotransporters. Furthermore, several new regulators of AQP2 have been identified, including for AVP-dependent AQP2 regulation (yes-associated protein, nuclear factor of activated T-cells, microRNAs) and AVP-independent AQP2 regulation (epidermal growth factor receptor, fluconazole, prostaglandin E2). It is also becoming increasingly clear that long-term cell volume adaptation to chronic hypotonicity through release of organic osmolytes comes at the expense of compromised organ function. This potentially explains the complications of chronic hyponatremia, including cognitive impairment, bone loss and vascular calcification. This review will illustrate why these new insights derived from basic science are also relevant for developing new approaches to treat water balance disorders.

A Study of Hydroelectrolytic and Acid-Base Disturbances in MIS-C Patients: A Perspective on Antidiuretic Hormone Secretion.

COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) is a rare autoimmune disorder characterized by a range of polymorphic manifestations, similar to but distinct from other well-known inflammatory syndromes in children. We conducted a retrospective-descriptive study in which we summarized the clinical presentation of, biomarker variations in, and complications occurring in patients diagnosed with MIS-C, admitted to the Emergency Clinical Hospital for Children "Sf. Ioan", Galati, between July 2020 and June 2024. A total of 36 children met the MIS-C classification criteria according to the WHO-approved case definitions. A total of 41.7% (n = 15) were male and 58.3% (n = 21) were female. The median age of the study group was 4 years (IQR: 1.75-9.25 years). Surgical involvement was suspected in 16.7% (n = 6) of the patients, while 52.8% (n = 19) required intensive care. Clinically, fever was the most common symptom present in 89% (n = 32) of the cases. Gastrointestinal disorders were also common, with 50% (n = 18) presenting with inappetence, 42% (n = 15) with vomiting, and 39% (n = 14) with abdominal pain from admission, which worsened over time. Paraclinically, all patients exhibited signs of inflammation, and 86.1% (n = 31) had hydroelectrolytic and acid-base imbalances. The median hospital stay was 10 days (IQR: 7-12 days), with a stagnant clinical course in most cases. The inflammatory mechanisms in MIS-C, which can affect the secretion of antidiuretic hormone (ADH), were correlated with hydroelectrolytic disturbances and may lead to severe complications. For this reason, it is imperative to evaluate hydroelectrolytic disorders in the context of MIS-C and use diagnostic and prognostic biomarkers to develop effective therapeutic management strategies, ultimately improving the quality of life of affected children.

Frequency and severity of hyponatremia in healthy children with acute illness.

Hyponatremia can occur in the acute phase of any illness through various mechanisms. However, the frequency and severity of hyponatremia are not well known across a broad range of illnesses including medical and surgical diseases and trauma. The present, retrospective chart review was conducted at Tokyo Metropolitan Children's Medical Center from 2018 to 2019. Included were healthy children aged < 16years with an acute illness, who were urgently admitted, and had their serum sodium level measured on arrival. In total, 2717 patients were urgently admitted and had their serum sodium level measured. Of these, 1890 were included. Hyponatremia was found in 260 patients (13.8%). The most common hyponatremic disease was type 1 diabetes mellitus (69%) followed by acute infectious encephalopathy (60%), pyogenic arthritis (60%), and Kawasaki disease (51%). Kawasaki disease, seizure, urinary tract infection, acute appendicitis, lower respiratory tract infection, and acute gastroenteritis were associated with a significantly lower serum sodium value than cases of fracture comprising a control group. Conversely, acute bronchial asthma exacerbation (3%), anaphylaxis (0%), intussusception (0%), acute scrotal disease (0%), head injury (1%), and fracture (0%) were very infrequently associated with hyponatremia. The present study determined the frequency and severity of hyponatremia in various, acute, pediatric illnesses, including medical and surgical diseases and trauma. Despite reports of respiratory distress and pain inducing vasopressin secretion, hyponatremia was rarely observed on arrival in patients with acute bronchial asthma exacerbation, anaphylaxis, intussusception, acute scrotal diseases, head injury, or fracture.

7901 Clinical Challenges Of Paraneoplastic Endocrine Metabolic Syndromes: An Illustrative Example

Abstract Disclosure: S. Shankar: None. S.S. Sundar: None. M.S. Vaishnav: None. K. Thummala: None. L. Lekkala: None. S. Srikanta: None. K. Muniraj: None. T. Deepak: None. R.B. Vijay: None. V. Nath: None. C. Siddlingappa: None. P. Ravikumar: None. M.D. Chitra: None. Introduction: Paraneoplastic endocrine syndromes result from aberrant production by tumors of protein hormones, hormone precursors, or hormone like substances. In patients who are already receiving treatment for cancer, the onset of a paraneoplastic syndrome may be an indication of progression or relapse. Clinical Case: 2021: Age 81 female (hypertension). Carcinoma rectum; S/P surgery, colostomy, chemotherapy and radiotherapy. 2023: Palliative care, due to progressive metastatic (hepatic, pulmonary, bone) malignancy. 2023 Aug: Hospital admission for generalized weakness, not able to walk, severe pain and low-grade fever 10 days. A: Paraneoplastic Hyponatremia: Evaluation: S Sodium= 127, 129, 129, 137, 134 mmol/L (134-145); Spot urine sodium= 65 mmol; S Uric acid= 3.5 mg/dL (4.4-7.6); S Cortisol 8 am= 15.5 (6.7-22.6); T3 total= 0.34 ng/mL (0.97-1.69), T4 total= 6.87 mcg/dL (5.5-11), TSH= 1.87 mIU/mL (0.46-4.68); LH= 0.35 mIU/mL (16-54); FSH= 1.9 mIU/mL (23-116); S calcium= 8.9 mg/dL (8.4-10.2); S Phosphorus= 2.31mg/dL (2.5-4.5) Diagnosis: Possible paraneoplastic ADH secretion/ SIADH; pain/ narcotics-induced hypothalamic ADH secretion. Treatment: Fluid restriction, liberal salt intake, 3% saline; oral sodium bicarbonate and tolvaptan; tapentadol. B: Paraneoplastic Leukemoid reaction: Evaluation: Total leucocyte count= 29960, 36670, 44130, 58450 cells/mm3 (4000-11,000); Differential count: Neutrophils= 85-94%; Lymphocytes= 10-4%; CRP= 93.7, 24.0 mg/dL (&amp;lt;0.3); Procalcitonin= 0.097, 0.083 ng/mL (&amp;lt;0.1); Ruled out significant sepsis; no obvious laboratory or imaging evidence of any infectious or leukemic etiology. Diagnosis: Progressive leucocytosis due to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) secretion from various neoplasms has been reported in literature. Treatment: Empirical antibiotic coverage. C: Paraneoplastic Hypokalemia: Evaluation: S Potassium= 3.3, 3.4, 3.7, 2.9, 3.0 mmol/L (3.5-5.1). Diagnosis: Hypokalemia likely due to (in vivo and in vitro) intracellular potassium uptake by rapidly proliferating leukocytes (and neoplasm- primary and metastatic). (Ectopic ACTH secretion / ruled out). Therapy: IV and oral potassium supplements. D: Paraneoplastic Fever: Cytokines (e.g., tumor necrosis factor and interleukin-1) release from tumor cells or infiltrating mononuclear cells. Clinical Lessons: Endocrine paraneoplastic syndromes can complicate patient’s clinical course, response to treatment, impact prognosis and even be confused as metastatic spread or another “non-existent” clinical entity. They can precede, occur concomitantly or present at later stage of tumour development. Recognition of the diverse clinical manifestations improves clinical outcomes (earlier cancer diagnosis, better quality of life, optimal tumour-directed therapy or decision towards non-aggressive focussed palliative care). Presentation: 6/2/2024

8067 AVP Gene Mutation: A Rare Cause of Diabetes Insipidus

Abstract Disclosure: N. Navrange: None. M. Williams: None. P. Madhavan: None. Introduction: Arginine vasopressin deficiency (AVP-D), also known as neurohypophyseal or central diabetes insipidus (DI), is marked by a reduced secretion of arginine vasopressin (AVP), resulting in polyuria and polydipsia. AVP-D is a rare disorder, with a prevalence of 1 in 25,000. Typically, the disorder is acquired. However, in less than 5% of cases, it has a genetic etiology. The majority of mutations in the AVP gene are autosomal dominant. Normally, AVP encodes vasopressin, also known as antidiuretic hormone (ADH). It plays a key role in the reabsorption of water in the kidney, the regulation of blood pressure, and controlling the body’s osmotic balance. However, a mutation in this gene leads to a deficient release of ADH, leading to reduced reabsorption of water in the collecting duct and decreased ability to concentrate urine. This results in increased urine output and excessive thirst. The onset and severity of symptoms varies between individuals. Case Report: In this report, we discuss the case of a 40-year-old Caucasian female with familial neurohypophyseal diabetes insipidus. The patient presented to the clinic for follow-up care of DI and hyponatremia. She received her DI diagnosis before the age of 5 and has multiple family members with the condition including her maternal grandfather, mother, and 2 siblings. Additionally, she suspected one of her children was exhibiting excessive urination. Past medical history is also significant for seizure disorder, postpartum cardiomyopathy, Chiari malformation type I and remote history of substance abuse. Vitals were stable with blood pressure of 122/86 mmHg, heart rate of 93 bpm, body mass index of 31.8. Physical exam was unremarkable except for obesity. She is currently managed with DDAVP 0.05 mg twice daily. Previously, imaging was performed to rule out pituitary abnormalities. The patient was referred for genetic testing due to her family history and was found to have a previously described rare autosomal dominant mutation of the AVP protein. The single nucleotide polymorphism in exon 1 results in a missense mutation substituting an alanine nucleotide for threonine (c.55G&amp;gt;A). The patient was counseled to share these results with her children’s pediatrician, as they could benefit from testing for the mutation. Discussion: Our patient has a pathogenic variant in AVP, specifically a missense mutation from Alanine to Threonine at codon 19 of the AVP protein. This mutation is associated with autosomal dominant neurohypophyseal diabetes insipidus. This case provides an example of a rare cause of neurohypophyseal diabetes insipidus and emphasizes the necessity of obtaining detailed family history in patients who have DI and considering genetic testing for patients with suspicion for familial involvement. Presentation: 6/2/2024

8142 Endocrine Considerations Prior to Pituitary Tumor Resection

Abstract Disclosure: P. Einafshar: None. T. Delibasi: None. Endocrine Considerations in Pituitary Tumor Resection Introduction: Diabetes Insipidus (DI) is an endocrine condition involving a disturbance to the action of Anti-Diuretic Hormone (ADH) resulting in polyuria, and polydipsia with complications such as severe water and electrolyte disturbances. It can be classified into Central DI which affects the secretion of ADH or Nephrogenic DI which affects peripheral ADH receptors in Distal Convoluted Tubules (DCTs) in the renal system. Both subtypes however present similarly and are usually known to be transient. It is important to consider the most common etiologies contributing to both central and nephrogenic DI as severe complications may arise if not diagnosed and treated promptly. The most important step is to monitor and manage water and electrolytes and avoid excessive water loss which can lead to irreversible complications. This can be accomplished by introducing synthetic ADH called DDAVP or Desmopressin. Case Description: A 57-year-old female was admitted in preparation for a supra-orbital resection of a suprasellar mass. Two hours post-procedure, she was found to have an increase in urine output with her labs notable for a significant acute increase in serum sodium and a decrease in urine osmolality. Upon emergent Endocrinology evaluation, due to concerns of Acute Diabetes Insipidus in the setting of insult to the pituitary stalk, she was started on emergent treatment with IV DDAVP. Her course was complicated with persistent DI resulting in a case of permanent DI requiring out-patient daily treatments with DDAVP. Discussion: Injury to the pituitary stalk resulting in various endocrine abnormalities has been studied involving a trans-sphenoidal resection of pituitary tumors, but there is a paucity of cases reported when patients undergo a supra-orbital surgical approach. It is vital for Endocrinology and Neurosurgical services to be aware of this phenomenon, and a multi-disciplinary approach to patient management should be considered. Furthermore, close follow-up of pituitary hormones in the post-operative setting is imperative in order to avoid severe complications, such as brain damage or poor mental status. We hope to educate residents and fellows about this phenomenon that is rarely reported in the literature but can have profound effects on patient’s quality of life if not considered by the consulting Endocrinology team. References Christ-Crain, M., Winzeler, B., &amp; Refardt, J. (2021). Diagnosis and management of diabetes insipidus for the internist: an update. Journal of internal medicine, 290(1), 73-87. Mutter, C. M., Smith, T., Menze, O., Zakharia, M., &amp; Nguyen, H. (2021). Diabetes insipidus: pathogenesis, diagnosis, and clinical management. Cureus, 13(2). Presentation: 6/1/2024

Síndrome de secreción inadecuada de hormona antidiurética

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined as a disorder in renal free water excretion control due to the inability to suppress the secretion of antidiuretic hormone (ADH) or vasopressin. The most frequent causes are usually acquired, notable among which are central nervous system involvement, malignancy, pulmonary diseases, or drugs. Up to 35% of admitted patients have hyponatremia, of which up to 40% can be attributed to SIADH. It is considered acute when it occurs in less than 48hours. It can trigger vomiting, convulsions, coma, and death due to cerebral herniation resulting from increased intracranial pressure. Chronic forms are more common and entail symptoms such as nausea, confusion, weakness, or agitation. In order to diagnose it, it is necessary to identify the presence of a true hypoosmolar euvolemic hyponatremia, ruling out other hormonal abnormalities or drug use. Treatment of the acute form is based on the emergency use of hypertonic saline solution, avoiding excessively rapid sodium correction that would trigger an osmotic demyelination syndrome. In the case of chronic hyponatremia, water restriction, increased osmole intake, and tolvaptan can be used in addition to acting on the triggering causes.

Qingfei Zhisou oral liquid alleviates fever-induced inflammation by regulating arachidonic acid and lysophospholipids metabolism and inhibiting hypothalamus transient receptor potential ion channels expression.

To explore how Qingfei Zhisou oral liquid (, QFZS) adjusts body temperature bias and the interaction of inflammatory factors levels and metabolomic differences. Dry yeast was subcutaneously injected at 10 mL/kg to establish the pyrexia model. We randomly divided 60 Sprague-Dawley rats into five groups: control, model, positive, low dose of QFZS and high dose of QFZS. Inflammatory proteins were evaluated by Western blotting and immunohistochemistry. For the examination of the endogenous metabolites, enzyme linked immunosorbent assay and ultra-high-performance liquid chromatography high-resolution mass spectrometry were employed. QFZS significantly reduced rats' body temperature within 6 h after dry yeast injection and reduced the secretion of the arginine vasopressin, cyclic adenosine monophosphate, prostaglandin E-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β in serum. Meanwhile, we identified 41 metabolites between the model and QFZS groups, including arachidonic acid and lysophospholipids. QFZS restored normal arachidonic acid levels. Based on the differential metabolite enrichment analysis, QFZS's anti-inflammatory and anti-pyrexia effects might be related to the inflammatory pathway regulated by transient receptor potential. Additionally, QFZS treatment reduced transient receptor potential melastatin 2 ion channel expression and affected TNF-α, heat shock protein 70, and cyclooxygenase-2 expression in the hypothalamus. QFZS exerts its regulatory effects on fever by regulating the metabolism of lysophospholipids and arachidonic acid and the regulation of inflammation via transient receptor potential ion channels channels.

Intranasal Application of Diluted Saline Alleviates Ischemic Brain Injury in Association with Suppression of Vasopressin Neurons

Plain Language SummaryNeuroendocrine disorders during cerebral stroke are a major etiology of ischemic brain injury that occurs following the occlusion of the cerebral artery. A hypothalamic neuropeptide, antidiuretic hormone or vasopressin (VP), is a key neuroendocrine factor in ischemic brain injury. To identify the way to reduce the overly produced VP following the stroke, this study used a rat model of cerebral stroke and tested the effects of intranasal application/drops of low concentration saline-0.09% NaCl (IAL) on VP neuronal activity that determines VP secretion. The results revealed for the first time that IAL inhibition of stroke-evoked VP neuronal activation and its associated brain damage is related to IAL inhibition of ischemia-evoked astrocytic process retraction around VP neurons and increase in excitatory inputs on VP neurons from the mitral cells in the activated olfactory bulb in the ischemic side. Similar but weaker effects also occurred at oxytocin neurons that co-exist with VP neurons but exert neural protective effects. These findings highlight that IAL (or commercially available purified water?) inhibition of VP neuronal activity may provide a simply available protective strategy in the early stage of cerebral stroke after further clinical trials.

Oral Levodopa Stimulates Copeptin Secretion in Children and Adolescents with Intact Posterior Pituitary Function

BackgroundCopeptin stimulation tests can be used in the differential diagnosis of polyuria-polydipsia syndrome. Current stimulation methods rely on intravenous or subcutaneous administration. Oral stimulus can further simplify the diagnostic approach. The levodopa stimulation test is widely used in the evaluation of growth hormone deficiency, and the dopamine pathway was reported to be associated with arginine vasopressin secretion. This study aims to investigate the effect of oral levodopa on copeptin secretion. MethodsThis study was a prospective observational single-center cohort study. Patients <18 years old with short stature and no symptoms of polyuria or polydipsia undergoing the levodopa stimulation test for suspected growth hormone deficiency were recruited from May 2023 to Nov 2023. Copeptin and growth hormone were measured at 0, 30, 60, 90, and 120 min during the levodopa test. The insulin tolerance test with copeptin and growth hormone measured at the same time points was conducted in part of patients. ResultsForty-four participants were included in the final analysis. In the levodopa stimulation test, the median (interquartile range) copeptin concentration increased from 5.20 (3.51, 8.25) pmol/L to a maximum of 19.36 (8.97, 108.08) pmol/L (P < .001), 3.94 (1.41, 13.88) times that of the baseline (P < .001). Compared with the insulin tolerance test, peak copeptin in the levodopa test was significantly higher (34.61 [13.67, 98.96] vs 8.88 [7.14, 15.42] pmol/L, P = .009). Higher copeptin was associated with a larger dose of levodopa. ConclusionsOral levodopa could be used to stimulate copeptin.

Autoimmunity related to anti-Nax and anti-ZSCAN1 autoantibodies in adipsic hypernatremia.

"Adipsic hypernatremia" is clinically characterized by chronic elevation of plasma [Na+] with an inappropriate lack of thirst and upward resetting of the osmotic set point for arginine vasopressin (AVP) secretion, combined with a relative deficiency of AVP, thereby resulting in persistent hypernatremia. Many cases are accompanied by structural lesions in the hypothalamus, pituitary gland, and circumventricular organs (CVOs). On the other hand, cases without structural lesions have been reported since the 1970s, but the pathophysiology was unknown for a long time. In 2010, Hiyama et al. reported that an anti-Nax antibody response caused adipsic hypernatremia in a pediatric case with ganglioblastoma. In recent years, advances in clinical research have led researchers to recognize that an autoimmunological pathogenic mechanism might be associated with periventricular organs such as the subfornical organ (SFO). In addition, in pediatric cases diagnosed as ROHHAD (rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation) syndrome, it has been reported that half of the cases have abnormal serum Na levels, and some research findings indicated an autoimmune mechanism acting on the organs of the hypothalamus and CVOs. Then, anti-ZSCAN1 antibody response was detected in cases diagnosed as ROHHAD-NET in 2022. In this review, by summarizing a series of studies on Nax and ZSCAN1, which are expressed in the hypothalamus, pituitary gland, and SFO, I would like to describe the current findings of the autoimmune pathogenesis of adipsic hypernatremia.

Elucidating hematological profile and electrolyte balance in oral cancer patients.

Oral cancer is a serious health issue in both the developing and developed worlds, and it is one of the most common forms of cancer of the head and neck. In accordance with the 2017 World Health Organization classification, oral cancer can affect any part of the mouth, including the buccal mucosa, the front two-thirds of the tongue, the lip, the palate, the vestibule, the alveolus, the floor of the mouth, and the gingivae. Hematology and electrolyte balance have been proposed as tumor indicators and paths into cancer's genesis. Examining the patient's blood count and electrolyte levels in order to better understand their oral cancer. Electrolyte abnormalities are common in cancer patients and may be caused by the disease itself or by treatment. Hyponatremia is the most frequent electrolyte problem in cancer patients, and it is typically caused by the syndrome of improper ADH secretion. Although electrolyte problems are associated with a worse prognosis for cancer patients, timely and effective therapy has the potential to enhance both short- and long-term results and quality of life. Hematological tests on patients with oral cancer, including differential cell count, white blood cell count, and hemoglobin level. Compared to healthy controls, oral cancer patients show statistically significant differences in a number of biochemical parameters, including electrolytes (sodium, P<0.05; potassium, P=0.89; chloride, P<0.05); differential count (neutrophils, P<0.05; basophils, P<0.05). A significant risk factor for cancer patients is an electrolyte imbalance, which has been linked to inappropriate anti-diabetic hormone release. Clinicians will find these shifts in electrolytic level helpful in diagnosing and tracking oral cancer. Potentially malignant oral disorders and Oral squamous cell carcinoma may be better predicted using a combination of TLC, neutrophil, and lymphocyte counts, as shown in this study.

The Never-Ending Story of Hyponatremia: A Current Problem to Overcome.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt-wasting syndrome (CSWS) are in general associated to refractory hyponatremia especially in patients with neurologic disorders.Extracellular fluid (ECF) assessment is the key to distinguish between SIADH and CSWS.Nevertheless, measurement of the ECF volume is not sufficient to determine the correct etiology and more established diagnostic algorithms are required.

Sodium-Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction.

We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.

Maternal dehydration contributes to the development of salt sensitivity of blood pressure (SSBP) in offspring, with its influence likely tied to an elevation in vasopressin secretion.

Maternal dehydration contributes to the development of salt sensitivity of blood pressure (SSBP) in offspring, with its influence likely tied to an elevation in vasopressin secretion.

Cannabinoid receptor type 1 activation causes a water diuresis by inducing an acute central diabetes insipidus in mice.

Cannabis and synthetic cannabinoid consumption are increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G protein-coupled cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids, which are endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total body water and electrolyte homeostasis. As the kidney collecting duct (CD) regulates total body water, acid/base, and electrolyte balance through specific functions of principal cells (PCs) and intercalated cells (ICs), we examined the cell-specific immunolocalization of CB1R in the mouse CD. Antibodies against either the C-terminus or N-terminus of CB1R consistently labeled aquaporin 2 (AQP2)-negative cells in the cortical and medullary CD and thus presumably ICs. Given the well-established role of ICs in urinary acidification, we used a clearance approach in mice that were acid loaded with 280 mM NH4Cl for 7 days and nonacid-loaded mice treated with the cannabinoid receptor agonist WIN55,212-2 (WIN) or a vehicle control. Although WIN had no effect on urinary acidification, these WIN-treated mice had less apical + subapical AQP2 expression in PCs compared with controls and developed acute diabetes insipidus associated with the excretion of large volumes of dilute urine. Mice maximally concentrated their urine when WIN and 1-desamino-8-d-arginine vasopressin [desmopressin (DDAVP)] were coadministered, consistent with central rather than nephrogenic diabetes insipidus. Although ICs express CB1R, the physiological role of CB1R in this cell type remains to be determined.NEW & NOTEWORTHY The CB1R agonist WIN55,212-2 induces central diabetes insipidus in mice. This research integrates existing knowledge regarding the diuretic effects of cannabinoids and the influence of CB1R on vasopressin secretion while adding new mechanistic insights about total body water homeostasis. Our findings provide a deeper understanding about the potential clinical impact of cannabinoids on human physiology and may help identify targets for novel therapeutics to treat water and electrolyte disorders such as hyponatremia and volume overload.

Clinical and radiographic characteristics of patients with non-functioning pituitary adenomas categorized according to their serum prolactin concentration: novel predictors of postoperative transient diabetes insipidus following surgery.

Non-functioning pituitary adenomas (NFPAs) are often associated with hyperprolactinemia, which is known as the "stalk effect". However, the relationships between hyperprolactinemia and the radiographic characteristics of the tumor that affects the pituitary stalk have not been well characterized. We aimed to identify the differences in the clinical and radiographic characteristics of patients with NFPA, with and without hyperprolactinemia. We enrolled 107 patients with NFPA and allocated them to hyperprolactinemia and non-hyperprolactinemia groups using two different cut-off values: (1) the upper limit of the normal reference range, adjusted for sex and menopausal status, and (2) the upper quartile across the cohort, and compared their clinical and radiographic characteristics. These analyses were conducted to clarify the relationship between the "stalk effect" and the postoperative change in antidiuretic hormone secretion. The specific radiographic characteristics of the patients included the presence of a cystic or hemorrhagic tumor and the presence of pituitary stalk deviation, which were more frequent in the patients with hyperprolactinemia. Interestingly, the incidence of postoperative transient diabetes insipidus was statistically significantly higher in the hyperprolactinemia group (≥40 ng/mL) and in the group with radiologic evidence of stalk deviation, which were shown to be independent risk factors on multivariate analysis. The presence of a "stalk effect" was associated with a higher risk of postoperative transient diabetes insipidus, reflecting perioperative pituitary stalk dysfunction following NFPA surgery, especially in patients with serum prolactin concentrations ≥40 ng/mL and radiologic evidence of stalk deviation.

Dynamics of serum levels and reference ranges of copeptin in the 3rd trimester of pregnancy in healthy pregnant women with uncomplicated pregnancy and delivery.

Copeptin is a stable fragment of vasopressin. Copeptin levels have been found to reflect the degree of endothelial stress in various conditions, including acute coronary syndrome. Copeptin may be a bio marker for endothelial stress during pregnancy. However, there is still a lack of understanding of its dynamics and levels throughout pregnancy. This study aims to describe intra-individual and longitudinal changes in copeptin levels at 30th and 36th gestational weeks in healthy pregnant women with uncomplicated pregnancy and delivery and to establish specific reference ranges. A total of 125 pregnant women with uncomplicated pregnancy and delivery were included. These women were monitored throughout their pregnancy and gave birth at the Department of Obstetrics and Gynecology Olomouc University Hospital. The blood was taken at ~30 and ~36 gestational weeks. Serum copeptin levels were measured using a Kryptor Compact PLUS analyzer. For statistics, we used R software and the "referenceRanges" package. It was found that serum levels of copeptin were significantly higher in the 36th week group than in the 30th week group (P &lt; 0.05). Cook's distance was used to eliminate outliers. The 30th week median was 3.377 pmol/l, reference range = 1.343-7.829 pmol/l, and the 36 week was median 4.735 pmol/l and reference range = 2.06-13.2 pmol/l. In the 36th week reference range, the median was higher than in healthy, non-pregnant women (P &lt; 0.05). Copeptin values can exceed 10 pmol/l, particularly after the 36th week. In the 3rd trimester, this value may indicate cardiovascular and endothelial overload. Copeptin levels were found to vary significantly depending on gestational week. The proposed reference ranges take into account the increased secretion of vasopressin in pregnancy. The existence of specific upper reference limits represents a potential advantage in detecting pregnant women prone to hypertensive disease in the 3rd trimester.