Hypernatremia, defined as a plasma sodium concentration greater than 145 mmol/l, represents a deficit of water relative to sodium and is most commonly due to free water loss and/or inadequate free water intake, rather than sodium excess. The reported prevalence of hypernatremia varies depending on the clinical setting with retrospective analyses identifying a prevalence of 0.5-1 % in the community but up to 10 % in intensive care units. Patients with reduced cognition or consciousness have impaired access to free water making them particularly vulnerable to hypernatremia. Hypernatremia is associated with poorer outcomes including longer length of hospital stay, in-hospital mortality, and odds of discharge to hospice or nursing home. This review will describe the diagnosis and management of hypernatremia providing insight into physiological mechanisms underpinning salt and water homeostasis with particular focus on arginine vasopressin deficiency as an endocrine cause of hypernatremia.

Treatment of chronic hyponatremia requires careful diagnostic evaluation of the underlying etiology to adapt the treatment accordingly. Isotonic saline remains the cornerstone for hypovolemic hyponatremia, whereas fluid restriction and loop diuretics are preferred in hypervolemic states. Corticosteroid replacement is the first-line therapy in hyponatremia due to adrenal insufficiency. In the euvolemic syndrome of inappropriate antidiuresis, first-line treatment is fluid restriction, with additional oral urea or vasopressin receptor antagonists as second-line options. Novel strategies such as protein supplementation and SGLT2 inhibitors offer promising adjuncts. The most feared complication of hyponatremia treatment is osmotic demyelination syndrome, with highest risk in patients with severe hyponatremia (≤105 mmol/L), alcoholism, malnutrition, liver disease, or hypokalemia. Current guidelines recommend limiting sodium correction to ≤ 10-12 mmol/L per 24 h (≤8 mmol/L in high-risk patients). Ongoing research aims to investigate future treatment options and to foster evidence on correction limits to improve outcomes in patients with chronic hyponatremia.

Hyponatraemia is the most common electrolyte alteration in cancer patients and the main cause is the syndrome of inappropriate antidiuresis. In this context, arginine vasopressin secretion can be due to ectopic secretion by tumoral cells or to drugs, including chemotherapeutics. It is known that hyponatraemia is associated with a worse prognosis in cancer. Conversely, the correction of serum [Na] is associated with a favourable effect on the disease's outcome. Basic research provided evidence that reduced [Na] activates several intracellular pathways in cancer cells, which lead to an increased growth and invasiveness. Interestingly, vasopressin receptor antagonists, mainly used for the treatment of hyponatraemia secondary to the syndrome of inappropriate antidiuresis and in polycystic kidney disease, effectively reduced cancer cell proliferation in in vitro and in vivo experiments. Although this needs to be confirmed on clinical grounds, it is tempting to hypothesize that vasopressin receptor antagonists might have a possible role in future anti-cancer strategies.

Gestational diabetes mellitus (GDM), defined as hyperglycaemia first recognised during pregnancy, is an important clinical entity, especially with its impact on pregnancy outcomes and the increased risk of metabolic disease for both mother and child in their later lives. However, the definition and diagnosis of GDM have continued to evolve over the past 50 years, and this has sometimes caused confusion for clinicians. Currently, different countries adopt different strategies in diagnosing GDM, despite a previous attempt in 2008 to decide on a universally acceptable diagnostic algorithm. In this review, the biological principles that underpin dysglycaemia in pregnancy, the evolution of diagnostic standards for GDM over the years, reasons for the different diagnostic criteria and recognition of early versus late GDM will be discussed. The controversies and uncertainties, pitfalls and alternate ways to diagnose GDM will also be explored.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy, traditionally diagnosed using the oral glucose tolerance test (OGTT) and managed via self-monitoring of blood glucose (SMBG). However, both methods have limitations, including poor reproducibility, discomfort, and limited ability to detect glycaemic variability. Continuous glucose monitoring (CGM) offers a promising alternative by providing 24-hour glucose profiles and identifying glycaemic excursions missed by SMBG. CGM shows potential for early detection of subclinical dysglycaemia, improved diagnostic accuracy when combined with clinical risk scores, and improved patient satisfaction. Although randomised controlled trials (RCTs) have reported mixed results regarding perinatal outcomes, CGM is associated with improved glycaemic control, reduced gestational weight gain, and high user acceptability. Nocturnal hyperglycaemia identified by CGM may predict fetal overgrowth. Integration with telemedicine may further personalise care. Further large, robust, RCTs are needed to confirm CGM's clinical value and guide its broader implementation in GDM.

Diabetes is among the most prevalent chronic diseases worldwide, with incidence rising each year, shaped by social inequities which influence both vulnerability to disease and access to quality care. These inequities and their systemic drivers are collectively termed the Social Determinants of Health (SDOH). Pregnancy introduces additional physiological and social challenges that can intensify existing inequities. For individuals with diabetes, pregnancy can compound adverse SDOH, increasing both risks and disparities in perinatal outcomes. To effectively manage pregestational diabetes, healthcare professionals must expand their clinical knowledge to understand impact of SDOH, and systematically screen and refer to relevant social support programs. The root causes of SDOH lie in the systems and policies; engaging in advocacy is only way to enact systemic change and complements any individual-level efforts. This review aims to improve adverse perinatal outcomes by providing practical clinical tools to address SDOH in pregestational diabetes in European context.

Thiazide diuretics are widely used antihypertensive agents, but their use can be complicated by thiazide-induced hyponatremia (TIH), a more common adverse effect than previously recognized. TIH may present acutely or chronically, with neurological symptoms varying by onset. Acute cases may require hypertonic saline, while chronic TIH is managed by discontinuing the thiazide, fluid restriction, and solute repletion. TIH appears to be idiosyncratic and is more common in older adults, those with low-normal plasma sodium and potassium levels, poor solute intake, or concurrent use of other hyponatremia-inducing drugs. TIH likely results from combined sodium and potassium depletion, increased water intake, and impaired water excretion, possibly involving prostaglandin E or low solute intake. This review discusses new aspects of the epidemiology, clinical presentation, and mechanisms of TIH and offers guidance on its diagnosis and management. Emerging insights into renal and extra-renal thiazide targets may enhance the prediction of both therapeutic and adverse responses to these medications.

Hypernatremia is a disorder of water balance defined by a serum sodium concentration above 145 mEq/L. It reflects a relative deficiency of free water rather than sodium excess. Under physiological conditions, hypothalamic osmoreceptors maintain plasma osmolality through stimulation of arginine vasopressin release- which promotes renal water conservation- and stimulation of thirst, which drives fluid intake. Hypernatremia develops when these defences fail due to impaired vasopressin secretion or action, diminished thirst, or inability to access water. The resultant hyperosmolality causes osmotic efflux of water from brain cells, leading to cerebral shrinkage and neurological dysfunction. Hypernatremia is most often observed in hospitalized patients, particularly the elderly, the critically ill, and those with impaired consciousness, and is associated with substantial morbidity and mortality. Unreplaced water loss, renal or extrarenal, is the predominant cause, whereas sodium overload is a less frequent mechanism. Accurate diagnosis and carefully titrated correction of water deficit are essential to prevent neurological injury.

Hyponatremia is the most common electrolyte disturbance and is associated with increased morbidity and mortality. It is driven by an excess of free water relative to total body sodium. While determining the underlying cause(s) of hyponatremia can be challenging, this can be facilitated by an algorithmic approach. Hypotonic hyponatremia is diagnosed by excluding translocational and pseudohyponatremia and confirmed by measuring plasma osmolality. Measuring urine osmolality and urine sodium concentration together with clinical history and examination, especially assessment of volume status, can determine the underlying cause. The most common cause of hyponatremia is the syndrome of inappropriate diuresis, characterised by inappropriate arginine vasopressin activity resulting a high urine osmolality and high urine sodium concentration. Further investigation can determine the underlying cause(s) of the syndrome of inappropriate antidiuresis. This review provides a diagnostic algorithm for hyponatremia, with a focus on biochemical parameters supplemented by clinical fluid status examination.

The syndrome of inappropriate antidiuresis (SIAD) is caused by increased renal water retention due to excessive arginine vasopressin (AVP) release from the posterior pituitary, enhanced kidneys sensitivity to AVP, or ectopic secretion of AVP or AVP-like peptides. Consequently, augmenting water clearance is a key therapeutic strategy, achievable either through osmotic diuresis or aquaresis. Osmotic diuresis has traditionally been induced with oral urea powder, however, two randomized placebo-controlled trials have demonstrated that glucosuria, induced by the SGLT2 inhibitor empagliflozin, effectively raises plasma sodium levels in both inpatients and outpatients with SIAD. An indirect urea-driven osmotic diuresis has also been observed in a controlled open-label study evaluating high-protein supplementation in outpatients with chronic SIAD. Aquaresis can be achieved with AVP receptor antagonists (vaptans) and, to a lesser extent, with loop diuretics. Moreover, preclinical and preliminary clinical data suggest that apelin, an endogenous neuropeptide that counteracts AVP in salt and water homeostasis, is effective in increasing plasma sodium levels in SIAD.

Type 2 diabetes mellitus increasingly complicates pregnancy, amplifying risks for both mother and child. Despite well-established management strategies, most women enter pregnancy with suboptimal metabolic control, contributing to adverse outcomes including hypertensive disorders, fetal overgrowth, congenital anomalies and perinatal death. Early intervention is critical, including structured preconception counselling, discontinuation of teratogenic drugs, and folic acid supplementation. During pregnancy, dietary optimization, tight glucose monitoring and insulin therapy are essential, but the role of metformin remains debated due to concerns about fetal growth restriction. Diabetic complications such as nephropathy and retinopathy further increase maternal risk, while infants face heightened susceptibility to hypoglycemia and long-term metabolic disease. Emerging technologies are promising, but evidence in this population remains limited. Urgent efforts are needed to fill persistent gaps in medical care and improve outcomes in this growing and vulnerable cohort.

Although craniopharyngiomas (CPs) are typically histologically benign and can be cured by radical removal, they are associated with a high level of operative morbidity due to their deep-seated, highly functional location. During the previous decades, the surgical philosophy has changed from radical removal to more restrained strategies of subtotal resection followed by radiotherapy to preserve the integrity of the hypothalamus. However, with improved surgical techniques and the availability of novel molecular diagnostic and therapeutic tools, the concept of hypothalamus-sparing CP surgery should be revised. From an oncological point of view, gross total resection (GTR) should be attempted as it can provide lifelong freedom from disease. However, less than total resection is necessary in cases of hypothalamic infiltration, as hypothalamic damage is unacceptable. The extended transsphenoidal approach (eTSA) promises reduced hypothalamic manipulation compared to the traditional transcranial approach (TCA). There is strong consensus that hypothalamic morbidity is reduced if CP surgery is performed in specialized high-volume neurosurgical centers. Novel targeted therapies (TT) in PCP enables the possibility of biopsy only in selected patients with high-risk CP. This review aims to provide a practical approach to current strategies and concepts in hypothalamus-sparing surgery for CP, with special regard to oncological outcome, hypothalamic and endocrine morbidity, and quality of life.

Craniopharyngiomas (CPs) are rare embryonic malformational tumours of the sellar/parasellar region, classified by the World Health Organization (WHO) 5th edition as grade 1 tumours. They may arise anywhere on the path of embryonic cell migration between the midline sphenoid bone and the floor of the sella turcica. On rare occasions, they can be found remotely in areas like the nasopharynx, the orbit, the posterior fossa, the brain parenchyma and the spine. Such ectopic CPs may present as primary in an atypical location, or as secondary, which represent distant recurrence after initial surgical excision in an orthotopic location. The pathogenesis of primary and secondary ectopic CPs is considered distinct, reflecting differences in developmental biology versus tumour dissemination. Primary ectopic CPs are thought to arise either from embryologically misplaced tissue or from genetically driven tumourigenesis outside the sella. Pathogenesis of secondary ectopic CPs reflects tumour cell dissemination through surgical tract implantation, cerebrospinal fluid (CSF) seeding or meningeal seeding. Ectopic cases pose unique diagnostic and therapeutic challenges. In this review which encompasses 97 cases (42 primary and 55 secondary ectopic CPs) published during the period, 2000-2025, we discuss the pathogenesis, clinical presentation, diagnosis and management of these distinctive tumours.

Craniopharyngiomas are rare epithelial tumours arising along the path of the craniopharyngeal duct. They are histologically benign but potentially clinically aggressive tumours due to their invasive behaviour and high recurrence rates. Patients with craniopharyngioma have a high burden of comorbidities which could affect their long-term survival. Studies published in the last 20 years and reporting on standardized mortality ratios (SMR) have demonstrated high mortality (SMRs ranging between 2.45 and 12.2), as also proposed in older reports. Cardiovascular, respiratory diseases and infections are main causes of death. Apart from older age at diagnosis, data on other predictors of mortality are not consistent requiring further elucidation.

Hyponatremia is the most common electrolyte disorder, particularly in older adults. Its high prevalence in this population is driven by underlying conditions such as heart and kidney failure, as well as by factors like polypharmacy and malnutrition. Rising global temperatures have also been linked to increased hyponatremia rates. Chronic hyponatremia is associated with elevated risks of falls, osteoporosis, fractures, cognitive and muscular impairment, and mortality. Despite these adverse outcomes, the condition is often underdiagnosed and undertreated, partly due to the complexity of its evaluation. Simplified, step-by-step diagnostic algorithms in future guidelines may help address this gap. Evidence increasingly supports the clinical benefits of correcting hyponatremia, prompting investigation into novel therapies. Among these, SGLT2 inhibitors and protein supplementation are especially promising, offering efficacy not only in raising plasma sodium but also in providing broader health benefits. This review explores the impact of hyponatremia in the elderly, summarizes its leading causes, and evaluates diagnostic strategies alongside the advantages and limitations of current treatment options.

Obesity is rising among women of reproductive age and significantly contributes to subfertility. If conception occurs, maternal obesity is associated with increased risks for both maternal and neonatal complications, with potential long-term effects on the offspring's health. Current clinical guidelines emphasize the importance of preconception weight optimization in women with obesity to reduce maternal and fetal risks. Amid the rising use of incretin-based anti-obesity medications, particularly among young women, their potential role in preconception care is receiving growing clinical and research interest. With unplanned pregnancies remaining common, incidental exposure during early pregnancy is becoming more likely. In parallel, there is increasing interest in the potential of these agents to support preconception weight loss and enhance fertility outcomes in women with obesity. This narrative review examines the current human evidence on GLP-1 and dual GLP-1/GIP receptor agonists approved for obesity treatment, focusing on their potential role in preconception care and addressing key safety considerations and challenges related to their use during the preconception period, as well as inadvertent exposure in early pregnancy.

Research from the last 15 years has profoundly advanced our understanding of craniopharyngioma, a challenging tumour of the sella. Genetically and histologically distinct subtypes - adamantinomatous (ACP) and papillary (PCP) - have been decoded. ACP is primarily driven by CTNNB1 mutations, leading to β-catenin accumulation and WNT pathway activation, while PCP is characterized by BRAF-V600E mutations. Sophisticated ACP mouse models and human studies have proposed a mechanism of senescence-driven pathogenesis in which senescent epithelial cells secrete growth and inflammatory factors that orchestrate a tumour-promoting microenvironment through paracrine signalling. Single-cell RNA sequencing has confirmed this view and revealed intricate tumour ecosystems. These foundational insights are now directly informing novel therapies. Promising targeted approaches, including BRAF/MEK inhibitors for PCP and small molecules disrupting the senescence-associated secretory phenotype (SASP) in ACP are transitioning from bench to bedside, heralding a new biology-driven era for patients.

Patient-reported outcome measures (PROMs) are key to evaluating the real-life impact of care, particularly for individuals with differences/disorders of sex development (DSD). DSDs are congenital and life-long conditions, most often ascertained in infancy or adolescence, and are characterized by atypical chromosomal, gonadal, or phenotypic sex. PROMs capture vital aspects of health-related quality of life (HRQoL) and psychosocial well-being from the perspective of patients and caregivers, complementing traditional clinical outcomes. Despite their importance, there is a paucity of validated, DSD-specific PRO measures available across the lifespan, resulting in challenges for standardized assessment and clinical benchmarking. Recent developments have led to the creation and validation of shortened, condition-specific HRQoL questionnaires for young children with DSD and their parents, which demonstrate strong psychometric properties and good clinical acceptability. Integrating regular assessments with these PROMs, especially those tailored for DSD, into routine care and rare disease registries can support ongoing monitoring, facilitate timely psychosocial interventions, and enable robust evaluation of intervention effectiveness. However, several barriers to implementation remain, including respondent burden, variability in comprehension, cultural sensitivity, and the need for specialized personnel to interpret results and translate them into practical recommendations. Stigma associated with DSD can further hinder engagement, potentially resulting in under identification of those most in need. Future strategies should focus on the use of validated, culturally adapted PROMs across all age ranges, regular assessment intervals, and electronic integration within health records and registries. Incorporating PROMs enable a holistic, patient-centered approach to care for individuals with DSD, supporting improved outcomes and better informed shared decision making.