Best practice & research. Clinical endocrinology & metabolism最新文献

Pituitary adenomas are the most frequent cause of hypopituitarism in adults, due to the mass effect of the lesion on the pituitary gland, and/or their treatments (particularly surgery and/or radiotherapy). Prolactinomas represent the most frequent histotype of hormone-secreting pituitary adenomas. As is well known, high prolactin levels induce a suppression of the gonadotropic axis and subsequent hypogonadotropic hypogonadism. Overall, the reported prevalence of hypopituitarism is highly heterogeneous in the different studies, depending on the definition used and the cohort examined. Treatment of prolactinomas, whether medical or surgical, can lead to improvement or recovery of pituitary function in a substantial proportion of patients, particularly of the gonadal axis. Conversely, new pituitary deficits can also develop after surgical treatment or, more frequently, radiotherapy. In this review, we aim to summarize the currently available literature data on hypopituitarism in patients with prolactinoma, in order to better characterize patients requiring replacement therapy.

Prolactinoma is the most common subtype of pituitary tumor and a significant cause of infertility. Treatment with dopamine agonists, primarily cabergoline, can achieve normoprolactinemia and restoration of the gonadal axis within 6-12 months in most patients. In select cases with non-invasive micro- or macroprolactinomas, neurosurgery may be recommended as primary therapy. If the gonadal axis does not recover and fertility is desired, clomiphene citrate and other assisted reproductive techniques may be utilized. During pregnancy, the risk of symptomatic tumor growth is very low in microprolactinomas and intrasellar macroprolactinomas. Close follow-up throughout pregnancy is recommended, and cabergoline may need to be reintroduced or maintained in some patients. After delivery, prolactinoma status should be reassessed, as remission may occur. Breastfeeding is typically uneventful. This review addresses the principal mechanisms of infertility in hyperprolactinemia, in both women and men, as well as treatment approaches to achieving conception and recommendations for follow-up before, during, and after delivery.

Acute symptomatic hyponatraemia results in potentially fatal cerebral oedema, whereas overly rapid correction of hyponatraemia can cause osmotic demyelination syndrome (ODS) with permanent neurological damage. To balance these two risks, we recommend a limited rapid increase of serum sodium level by at least 5 mmol/l by administration of fixed bolus(es) of hypertonic saline (HTS) to reverse symptoms of cerebral oedema, while limiting total increase to 8-10 mmol/l in the first 24 h, and each subsequent 24 h period. Neurological status, urine output, and biochemistry should be carefully monitored. Desmopressin and/or intravenous dextrose are recommended to reverse or prevent overly rapid correction. Interventional trials focused on optimal HTS volume, best approaches for prevention and treatment of overly rapid correction, and their clinical outcomes are needed for strong evidence-based recommendations.

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.

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.

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.

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.

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 E₂ 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.

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.