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Internal Medicine Journal Mar 2018The main determinants for the maintenance of water homeostasis are the hormone arginine vasopressin (AVP) and thirst. Disturbances in these regulatory mechanisms can... (Review)
Review
The main determinants for the maintenance of water homeostasis are the hormone arginine vasopressin (AVP) and thirst. Disturbances in these regulatory mechanisms can lead to polyuria-polydipsia syndrome, which comprises of three different conditions: central diabetes insipidus (DI) due to insufficient secretion of AVP, nephrogenic DI caused by renal insensitivity to AVP action and primary polydipsia due to excessive fluid intake and consequent physiological suppression of AVP. It is crucial to determine the exact diagnosis because treatment strategies vary substantially. To differentiate between the causes of the polyuria-polydipsia syndrome, a water deprivation test combined with desmopressin administration is the diagnostic 'gold standard'. Thereby, AVP activity is indirectly evaluated through the measurement of urine osmolality after prolonged dehydration. However, this test has several limitations and may fail to distinguish precisely between patients with primary polydipsia and mild forms of central and nephrogenic DI. The direct measurement of AVP during the water deprivation test, which was reported in the 1980s, has not been widely adopted due to availability, assay issues and diagnostic performance. Recently, copeptin, the c-terminal portion of the larger precursor peptide of AVP, has been evaluated in the setting of polyuria-polydipsia syndrome and appears to be a useful candidate biomarker for the differential diagnosis. A standardised method for the water deprivation test is presented as part of a joint initiative of the Endocrine Society of Australia, the Australasian Association of Clinical Biochemists and the Royal College of Pathologists of Australasia to harmonise dynamic endocrine tests across Australia.
Topics: Arginine Vasopressin; Diagnosis, Differential; Homeostasis; Humans; Polydipsia; Polyuria; Syndrome
PubMed: 28967192
DOI: 10.1111/imj.13627 -
Deutsches Arzteblatt International Mar 2018The incidence of type 1 diabetes mellitus in childhood and adolescence is steadily rising and now stands at 22.9 new cases per year per 100 000 persons up to age 15. (Review)
Review
BACKGROUND
The incidence of type 1 diabetes mellitus in childhood and adolescence is steadily rising and now stands at 22.9 new cases per year per 100 000 persons up to age 15.
METHODS
This review is based on pertinent publications retrieved by a selective literature search, with special attention to the current German S3 guideline on diabetes in childhood and adolescence.
RESULTS
Polydipsia, polyuria, and weight loss are the characteristic presenting symptoms of diabetes mellitus. The acutely presenting patient needs immediate stabilization because of the danger of rapid metabolic decompensation (risk of keto - acidosis, 21.1%). Long-term insulin therapy can be delivered either by subcutaneous injection or by an insulin pump. The goals of treatment are the near-normalization of glucose metabolism (HbA1c <7.5%), the avoidance of acute complications (hypoglycemia and ketoacidosis), the reduction of diabetes-specific sequelae (retinopathy, nephropathy, neuropathy, hypertension, and hyperlipidemia), unrestricted participation in age-appropriate everyday activities, and normal physical and psychosocial development. Children and adolescents with diabetes need individualized treatment with frequent adjustments and holistic overall care so that these goals can be effectively met.
CONCLUSION
Every physician must be able to diagnose the initial presentation of diabetes and to initiate the first steps in its management. The patient should be referred as soon as possible to a diabetes team that has experience in the treatment of children and adolescents.
Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disabled Children; Female; Germany; Humans; Hypoglycemic Agents; Infant; Insulin; Male; Polydipsia; Polyuria; Weight Loss
PubMed: 29563012
DOI: 10.3238/arztebl.2018.0146 -
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 -
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 -
Clinical Endocrinology Jul 2019Copeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for... (Review)
Review
Copeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for copeptin are similar to AVP, that is an increase in osmolality and a decrease in arterial blood volume and pressure. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation. Copeptin has, therefore, been evaluated as diagnostic biomarker in vasopressin-dependent disorders of body fluid homeostasis. Disorders of body fluid homeostasis are common and can be divided into hyper- and hypoosmolar circumstances: the classical hyperosmolar disorder is diabetes insipidus, while the most common hypoosmolar disorder is the syndrome of inappropriate antidiuresis (SIAD). Copeptin measurement has led to a "revival" of the direct test in the differential diagnosis of diabetes insipidus. Baseline copeptin levels, without prior thirsting, unequivocally identify patients with nephrogenic diabetes insipidus. In contrast, for the difficult differentiation between central diabetes insipidus and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is clearly superior to the classical water deprivation test. On the contrary, in the SIAD, copeptin measurement is of only little diagnostic value. Copeptin levels widely overlap in patients with hyponatraemia and emphasize the heterogeneity of the disease. Additionally, a variety of factors lead to unspecific copeptin elevations in the acute setting further complicating its interpretation. The broad use of copeptin as diagnostic marker in hyponatraemia and specifically to detect cancer-related disease in SIADH patients can, therefore, not be recommended.
Topics: Diabetes Insipidus; Glycopeptides; Humans; Hypernatremia; Hyponatremia; Polydipsia, Psychogenic
PubMed: 31004513
DOI: 10.1111/cen.13991 -
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