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Best Practice & Research. Clinical... Sep 2020In primary polydipsia pathologically high levels of water intake physiologically lower arginine vasopressin (AVP) secretion, and in this way mirror the secondary... (Review)
Review
In primary polydipsia pathologically high levels of water intake physiologically lower arginine vasopressin (AVP) secretion, and in this way mirror the secondary polydipsia in diabetes insipidus in which pathologically low levels of AVP (or renal responsiveness to AVP) physiologically increase water intake. Primary polydipsia covers several disorders whose clinical features and significance, risk factors, pathophysiology and treatment are reviewed here. While groupings may appear somewhat arbitrary, they are associated with distinct alterations in physiologic parameters of water balance. The polydipsia is typically unrelated to homeostatic regulation of water intake, but instead reflects non-homeostatic influences. Recent technological advances, summarized here, have disentangled functional neurocircuits underlying both homeostatic and non-homeostatic physiologic influences, which provides an opportunity to better define the mechanisms of the disorders. We summarize this recent literature, highlighting hypothalamic circuitry that appears most clearly positioned to contribute to primary polydipsia. The life-threatening water imbalance in psychotic disorders is caused by an anterior hippocampal induced stress-diathesis that can be reproduced in animal models, and involves phylogenetically preserved pathways that appear likely to include one or more of these circuits. Ongoing translational neuroscience studies in these animal models may potentially localize reversible pathological changes which contribute to both the water imbalance and psychotic disorder.
Topics: Animals; Diabetes Insipidus; Drinking; Homeostasis; Humans; Hyponatremia; Polydipsia; Polydipsia, Psychogenic; Risk Factors; Water-Electrolyte Balance; Water-Electrolyte Imbalance
PubMed: 33222764
DOI: 10.1016/j.beem.2020.101469 -
Neuroendocrinology 2020Diabetes insipidus (DI), be it from central or from nephrogenic origin, has to be differentiated from primary polydipsia. This differentiation is crucial since wrong... (Review)
Review
Diabetes insipidus (DI), be it from central or from nephrogenic origin, has to be differentiated from primary polydipsia. This differentiation is crucial since wrong treatment can have dangerous consequences. For decades, the "gold standard" for differential diagnosis has been the standard water deprivation test. However, this test has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 h and is cumbersome for patients. Also clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. Direct measurement of arginine vasopressin (AVP) upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay. Copeptin is secreted in equimolar ratio to AVP, mirroring AVP concentrations in the circulation. We have shown that copeptin, without prior fluid deprivation, identifies patients with nephrogenic DI. For the more difficult differentiation between central DI and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these 2 entities with a high diagnostic accuracy and is superior to the water deprivation test. However, it is important to note that close and regular sodium monitoring every 30 min during the hypertonic saline test is a prerequisite, which is not possible in all hospitals. Furthermore, side effects are common. Therefore, a nonosmotic stimulation test would be advantageous. Arginine significantly stimulates copeptin and therefore is a novel, so far unknown stimulus of this peptide. Consequently, infusion of arginine with subsequent copeptin measurement was shown to be an even simpler and better tolerated test, but head to head comparison is still lacking.
Topics: Diabetes Insipidus, Nephrogenic; Diabetes Insipidus, Neurogenic; Glycopeptides; Humans; Polydipsia, Psychogenic
PubMed: 31986514
DOI: 10.1159/000505548 -
Brain and Behavior Aug 2021Bipolar disorder (BD) poses a significant public health concern, with roughly one-quarter of sufferers attempting suicide. BD is characterized by manic and depressive... (Review)
Review
Bipolar disorder (BD) poses a significant public health concern, with roughly one-quarter of sufferers attempting suicide. BD is characterized by manic and depressive mood cycles, the recurrence of which can be effectively curtailed through lithium therapy. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li CO ), is associated with a host of adverse health outcomes following chronic use: these unwanted effects range from relatively minor inconveniences (e.g., polydipsia and polyuria) to potentially major complications (e.g., hypothyroidism and/or renal impairment). As these undesirable effects can limit patient compliance, an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes. Lithium orotate (LiC H N O ; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. LiOr is proposed to cross the blood-brain barrier and enter cells more readily than Li CO , which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns. This review addresses the controversial history of LiOr, complete with discussions of experimental and clinical efficacy, putative mechanisms of action, adverse effects, and its potential future in therapy.
Topics: Antimanic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds; Organometallic Compounds
PubMed: 34196467
DOI: 10.1002/brb3.2262 -
Best Practice & Research. Clinical... Sep 2020Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a... (Review)
Review
Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of conditions (genetic, congenital, inflammatory, neoplastic, traumatic) that arise mainly from the hypothalamus. The differential diagnosis between diseases presenting with polyuria and polydipsia is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating the sellar-suprasellar region in CDI. Pituitary stalk size at presentation is variable and can change over time, depending on the underlying condition, and other brain areas or other organs - in specific diseases - may become involved during follow up. An early diagnosis and treatment are preferable in order to avoid central nervous system damage and the risk of dissemination of germ cell tumor, or progression of Langerhans Cell Histiocytosis, and in order to start treatment of additional pituitary defects without further delay. This review focuses on current diagnostic work-up and on the role of neuroimaging in the differential diagnosis of CDI in children and adolescents. It provides an update on the best approach for diagnosis - including novel biochemical markers such as copeptin - treatment and follow up of children and adolescents with CDI; it also describes the best approach to challenging situations such as post-surgical patients, adipsic patients, patients undergoing chemotherapy and/or in critical care.
Topics: Adolescent; Age of Onset; Biomarkers; Brain; Child; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Diagnostic Imaging; Diagnostic Techniques, Endocrine; Histiocytosis, Langerhans-Cell; Humans; Magnetic Resonance Imaging; Polydipsia; Polyuria
PubMed: 32646670
DOI: 10.1016/j.beem.2020.101440 -
Diagnostics (Basel, Switzerland) Aug 2023Diabetic ketoacidosis (DKA) represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM)... (Review)
Review
Diabetic ketoacidosis (DKA) represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, Type 2 Diabetes Mellitus (T2DM) in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia, and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline and Scopus databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, between DKA and hyperosmolar hyperglycaemic state (HHS), and between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen, and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration, restoration of shifting electrolyte disorders and addressing underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention, and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.
PubMed: 37568965
DOI: 10.3390/diagnostics13152602 -
Journal of Feline Medicine and Surgery Jul 2022Both hyperthyroidism and chronic kidney disease (CKD) are common long-term conditions in older cats, which might be diagnosed concurrently or develop at different times.... (Review)
Review
PRACTICAL RELEVANCE
Both hyperthyroidism and chronic kidney disease (CKD) are common long-term conditions in older cats, which might be diagnosed concurrently or develop at different times. Hyperthyroidism may mask the presence of CKD, and vice versa, by various mechanisms that are described in this review. Hyperthyroidism treatment options should be carefully considered when CKD has also been diagnosed.
CLINICAL CHALLENGES
Although it can be difficult to diagnose hyperthyroidism and CKD simultaneously, given that one condition may mask the other, it is important to consider the presence of both diseases when examining an older cat presenting with vomiting, weight loss, polyuria/ polydipsia, anorexia or sarcopenia. The concurrent presence of hyperthyroidism and CKD requires careful monitoring of glomerular filtration rate biomarkers, and adequate and prompt support of kidney function when normal thyroid function is re-established. Iatrogenic hypothyroidism is a recognised complication of all of the treatment options for hyperthyroidism, and increases the risk of azotaemia. Therapy with levothyroxine is recommended for cats that are hypothyroid and azotaemic.
EVIDENCE BASE
The information in this review draws on current literature and guidelines related to the pathophysiology, diagnosis and treatment recommendations for feline hyperthyroidism and CKD.
Topics: Animals; Cat Diseases; Cats; Glomerular Filtration Rate; Hyperthyroidism; Hypothyroidism; Renal Insufficiency, Chronic; Thyroxine
PubMed: 35481810
DOI: 10.1177/1098612X221090390 -
The New England Journal of Medicine Nov 2023Distinguishing between arginine vasopressin (AVP) deficiency and primary polydipsia is challenging. Hypertonic saline-stimulated copeptin has been used to diagnose AVP...
BACKGROUND
Distinguishing between arginine vasopressin (AVP) deficiency and primary polydipsia is challenging. Hypertonic saline-stimulated copeptin has been used to diagnose AVP deficiency with high accuracy but requires close sodium monitoring. Arginine-stimulated copeptin has shown similar diagnostic accuracy but with a simpler test protocol. However, data are lacking from a head-to-head comparison between arginine-stimulated copeptin and hypertonic saline-stimulated copeptin in the diagnosis of AVP deficiency.
METHODS
In this international, noninferiority trial, we assigned adult patients with polydipsia and hypotonic polyuria or a known diagnosis of AVP deficiency to undergo diagnostic evaluation with hypertonic-saline stimulation on one day and with arginine stimulation on another day. Two endocrinologists independently made the final diagnosis of AVP deficiency or primary polydipsia with use of clinical information, treatment response, and the hypertonic-saline test results. The primary outcome was the overall diagnostic accuracy according to prespecified copeptin cutoff values of 3.8 pmol per liter after 60 minutes for arginine and 4.9 pmol per liter once the sodium level was more than 149 mmol per liter for hypertonic saline.
RESULTS
Of the 158 patients who underwent the two tests, 69 (44%) received the diagnosis of AVP deficiency and 89 (56%) received the diagnosis of primary polydipsia. The diagnostic accuracy was 74.4% (95% confidence interval [CI], 67.0 to 80.6) for arginine-stimulated copeptin and 95.6% (95% CI, 91.1 to 97.8) for hypertonic saline-stimulated copeptin (estimated difference, -21.2 percentage points; 95% CI, -28.7 to -14.3). Adverse events were generally mild with the two tests. A total of 72% of the patients preferred testing with arginine as compared with hypertonic saline. Arginine-stimulated copeptin at a value of 3.0 pmol per liter or less led to a diagnosis of AVP deficiency with a specificity of 90.9% (95% CI, 81.7 to 95.7), whereas levels of more than 5.2 pmol per liter led to a diagnosis of primary polydipsia with a specificity of 91.4% (95% CI, 83.7 to 95.6).
CONCLUSIONS
Among adult patients with polyuria polydipsia syndrome, AVP deficiency was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. (Funded by the Swiss National Science Foundation; CARGOx ClinicalTrials.gov number, NCT03572166.).
Topics: Adult; Humans; Arginine; Arginine Vasopressin; Diagnosis, Differential; Glycopeptides; Polydipsia; Polydipsia, Psychogenic; Polyuria; Saline Solution, Hypertonic; Sodium; Deficiency Diseases
PubMed: 37966286
DOI: 10.1056/NEJMoa2306263 -
The Journal of Clinical Endocrinology... Apr 2022Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a...
Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of disorders affecting the hypothalamic-posterior pituitary network. The differential diagnosis is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies, and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating congenital or acquired cerebral and pituitary stalk lesions. Pituitary stalk size at presentation could be normal, but it may change over time, depending on the underlying condition, while other brain areas or organs may become involved during follow-up. Early diagnosis and treatment are crucial to avoid central nervous system damage and germ cell tumor dissemination and to minimize complications of multiple pituitary hormone defects. We provide a practical update on the diagnosis and management of patients with CDI and highlight several pitfalls that may complicate the differential diagnosis of conditions presenting with polyuria and polydipsia. The need for a careful and close follow-up of patients with apparently idiopathic CDI is particularly emphasized because the underlying condition may be recognized over time. The clinical scenario that we outline at the beginning of this article represents the basis for the discussion about how the etiological diagnosis of CDI can be overlooked and demonstrates how a water intake and urine output improvement can be a sign of progressive damage of both hypothalamus and anterior pituitary gland with associated pituitary hormonal deficiencies.
Topics: Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Female; Humans; Magnetic Resonance Imaging; Male; Pituitary Gland, Posterior; Polydipsia
PubMed: 34993537
DOI: 10.1210/clinem/dgab930