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Sultan Qaboos University Medical Journal Aug 2021Central diabetes insipidus (CDI) is a common complication after pituitary surgery. However, it is most frequently transient. It is defined by the excretion of an... (Review)
Review
Central diabetes insipidus (CDI) is a common complication after pituitary surgery. However, it is most frequently transient. It is defined by the excretion of an abnormally large volume of dilute urine with increasing serum osmolality. The reported incidence of CDI after pituitary surgery ranges from 0-90%. Large tumour size, gross total resection and intraoperative cerebrospinal fluid leak usually pose an increased risk of CDI as observed with craniopharyngioma and Rathke's cleft cysts. CDI can be associated with high morbidity and mortality if not promptly recognised and treated on time. It is also essential to rule out other causes of postoperative polyuria to avoid unnecessary pharmacotherapy and iatrogenic hyponatremia. Once the diagnosis of CDI is established, close monitoring is required to evaluate the response to treatment and to determine whether the CDI is transient or permanent. This review outlines the evaluation and management of patients with CDI following pituitary and suprasellar tumour surgery to help recognise the diagnosis, consider the differential diagnosis, initiate therapeutic interventions and guide monitoring and long-term management.
Topics: Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Humans; Neoplasms
PubMed: 34522399
DOI: 10.18295/squmj.4.2021.010 -
European Journal of Endocrinology May 2022The differential diagnosis of diabetes insipidus is challenging. The most reliable approaches are copeptin measurements after hypertonic saline infusion or arginine,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The differential diagnosis of diabetes insipidus is challenging. The most reliable approaches are copeptin measurements after hypertonic saline infusion or arginine, which is a known growth hormone secretagogue but has recently also been shown to stimulate the neurohypophysis. Similar to arginine, glucagon stimulates growth hormone release, but its effect on the neurohypophysis is poorly studied.
DESIGN
Double-blind, randomized, placebo-controlled trial including 22 healthy participants, 10 patients with central diabetes insipidus, and 10 patients with primary polydipsia at the University Hospital Basel, Switzerland.
METHODS
Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test. The primary objective was to determine whether glucagon stimulates copeptin and to explore whether the copeptin response differentiates between diabetes insipidus and primary polydipsia. Copeptin levels were measured at baseline, 30, 60, 90, 120, 150, and 180 min after injection.
RESULTS
In healthy participants, glucagon stimulated copeptin with a median increase of 7.56 (2.38; 28.03) pmol/L, while placebo had no effect (0.10 pmol/L (-0.70; 0.68); P < 0.001). In patients with diabetes insipidus, copeptin showed no relevant increase upon glucagon, with an increase of 0.55 (0.21; 1.65) pmol/L, whereas copeptin was stimulated in patients with primary polydipsia with an increase of 15.70 (5.99; 24.39) pmol/L. Using a copeptin cut-off level of 4.6pmol/L had a sensitivity of 100% (95% CI: 100-100) and a specificity of 90% (95% CI: 70-100) to discriminate between diabetes insipidus and primary polydipsia.
CONCLUSION
Glucagon stimulates the neurohypophysis, and glucagon-stimulated copeptin has the potential for a safe, novel, and precise test in the differential diagnosis of diabetes insipidus.
Topics: Arginine; Diabetes Insipidus; Diabetes Mellitus; Diagnosis, Differential; Glucagon; Glycopeptides; Growth Hormone; Humans; Polydipsia, Psychogenic
PubMed: 35521789
DOI: 10.1530/EJE-22-0033 -
The New England Journal of Medicine Aug 2018The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and...
BACKGROUND
The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.
METHODS
From 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked.
RESULTS
A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test.
CONCLUSIONS
The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .).
Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Glycopeptides; Humans; Hyponatremia; Male; Middle Aged; Osmolar Concentration; Polydipsia; Polyuria; ROC Curve; Saline Solution, Hypertonic; Sensitivity and Specificity; Urine; Water Deprivation
PubMed: 30067922
DOI: 10.1056/NEJMoa1803760 -
The Veterinary Clinics of North... Apr 2022Polyuria and polydipsia are rare, but significant, manifestations of several different diseases of horses. Causes can be endocrine, iatrogenic, psychogenic, infectious,... (Review)
Review
Polyuria and polydipsia are rare, but significant, manifestations of several different diseases of horses. Causes can be endocrine, iatrogenic, psychogenic, infectious, or toxic in nature and can also be due to primary renal disease or diseases of other organs, such as the liver. Although numerous causes of polyuria and polydipsia in horses exist, the most common conditions include chronic kidney disease, pituitary pars intermedia dysfunction, and psychogenic polydipsia with secondary polyuria. Additional testing is dictated by history, other clinical signs, and the results of blood work and/or urinalysis. Prognosis for horses with polyuria and/or polydipsia varies significantly based on the underlying cause.
Topics: Animals; Horse Diseases; Horses; Pituitary Diseases; Polydipsia; Polyuria; Urinalysis
PubMed: 35282965
DOI: 10.1016/j.cveq.2021.11.007 -
Lancet (London, England) Aug 2019Differential diagnosis of diabetes insipidus is challenging. The most reliable approach is hypertonic saline-stimulated copeptin measurements. However, this test is... (Clinical Trial)
Clinical Trial
BACKGROUND
Differential diagnosis of diabetes insipidus is challenging. The most reliable approach is hypertonic saline-stimulated copeptin measurements. However, this test is based on the induction of hypernatraemia and requires close monitoring of plasma sodium concentrations. Arginine-stimulated copeptin measurements might provide an alternative, simple, and safe test.
METHODS
In this prospective diagnostic study, we recruited a development cohort from University Hospital Basel, Basel, Switzerland, and a validation cohort from five centres in Basel, Aarau, Luzern, Bern, and St Gallen, Switzerland, and the University Hospital Würzburg, Würzburg, Germany. For both cohorts, patients were eligible for inclusion if they were aged 18 years or older, were newly referred with polyuria (>50 mL/kg bodyweight per day) or had a known diagnosis of central diabetes insipidus or primary polydipsia. We also recruited a comparator cohort of healthy controls in parallel to each cohort, comprising adults (aged 18 years and older, with normal drinking habits, and no history of polyuria) and children who underwent arginine stimulation to diagnose growth hormone deficiency (children were only included in the comparator cohort to the development cohort as proof of concept). Patients and healthy controls underwent arginine stimulation with measurement of plasma copeptin at baseline and 30, 45, 60, 90, and 120 min. The primary objective in the development cohort was to determine the diagnostic accuracy of plasma copeptin concentrations to discriminate between diabetes insipidus and primary polydipsia, and in the validation cohort was to confirm those results. Adverse effects of the test were monitored in all participants, with tolerability of the test rated using a visual analogue scale (VAS) that ranged from no (0) to maximum (10) discomfort. This trial is registered with ClinicalTrials.gov, number NCT00757276.
FINDINGS
Between May 24, 2013, and Jan 11, 2017, 52 patients were enrolled in the development cohort (12 [23%] with complete diabetes insipidus, nine [17%] with partial diabetes insipidus, and 31 [60%] with primary polydipsia) alongside 20 healthy adults and 42 child controls. Between Oct 24, 2017, and June 27, 2018, 46 patients were enrolled in the validation cohort (12 [26%] with complete diabetes insipidus, seven [15%] with partial diabetes insipidus, and 27 [59%] with primary polydipsia) alongside 30 healthy adult controls (two patients in this cohort were excluded from the main analysis because of early vomiting during the test). In the pooled patient and control datasets, median arginine-stimulated copeptin concentrations increased in healthy adult controls (from 5·2 pM [IQR 3·3-10·9] to a maximum of 9·8 pM [6·4-19·6]) and in participants with primary polydipsia (from 3·6 pM [IQR 2·4-5·7] to a maximum of 7·9 pM [5·1-11·8]), but only minimally in those with diabetes insipidus (2·1 pM [IQR 1·9-2·7] to a maximum of 2·5 pM [1·9-3·1]). In the development cohort, a cutoff of 3·5 pM at 60 min provided the highest diagnostic accuracy of 94% (95% CI 84-98). The accuracy of this cutoff in the validation cohort was 86% (95% CI 73-94). By pooling the data from both cohorts, an optimal accuracy of 93% (95% CI 86-97) was reached at a cutoff of 3·8 pM copeptin at 60 min (sensitivity 93%, 95% CI 86-98; specificity 92%, 95% CI 84-100). The test was safe and well tolerated, with median VAS scores of 3·5 (IQR 2-4) in patients with diabetes insipidus, 3 (2-4) in those with primary polydipsia, 1 (1-3) in healthy adults, and 1 (0-5) in healthy children in the pooled participant dataset.
INTERPRETATION
Arginine-stimulated copeptin measurements are an innovative test for diabetes insipidus with high diagnostic accuracy, and could be a simplified, novel, and safe diagnostic approach to diabetes insipidus in clinical practice.
FUNDING
Swiss National Science Foundation and University Hospital Basel.
Topics: Adult; Aged; Arginine; Case-Control Studies; Diabetes Insipidus, Nephrogenic; Diagnosis, Differential; Female; Glycopeptides; Humans; Male; Middle Aged; Prospective Studies; Sensitivity and Specificity; Young Adult
PubMed: 31303316
DOI: 10.1016/S0140-6736(19)31255-3 -
Annales D'endocrinologie Oct 2016Diabetes insipidus is a syndrome that associates both hypotonic polyuria and polydipsia, due to insufficient or ineffective arginine vasopressin (AVP) synthesis, or to... (Review)
Review
Diabetes insipidus is a syndrome that associates both hypotonic polyuria and polydipsia, due to insufficient or ineffective arginine vasopressin (AVP) synthesis, or to AVP resistance. The diagnosis between central/renal origin, or an abnormal thirst regulation (primary polydipsia) is required to organize an adapted management. Because water deprivation tests are not reliable, it's often based on medical history, response to treatment and MRI. Copeptin is an AVP precursor which could be very helpful for the diagnosis. Its basal dosage may identify nephrogenic DI whereas osmotic stimulated dosage would discriminate central DI and primary polydipsia. Central DI is quite frequent after pituitary surgeries or traumatic brain injuries, and often transient. In case of early diagnosis and familial history of DI, a mutation of AVP gene is suspected, most of the time autosomal dominant. MRI is required to identify the other causes, i.e. tumors and inflammatory diseases (sarcoidosis, histiocytosis, hypophysitis). An advanced evaluation is required before idiopathic DI be retained, especially if a thickening of pituitary stalk is observed. The treatment of central DI is mainly based on lyophilisate of desmopressin administration.
Topics: Arginine Vasopressin; Diabetes Insipidus; Humans; Postoperative Complications
PubMed: 28645353
DOI: 10.1016/S0003-4266(17)30073-2 -
Nagoya Journal of Medical Science Dec 2016Central diabetes insipidus (CDI), characterized by polyuria and polydipsia, is caused by deficiency of arginine vasopressin (AVP), an antidiuretic hormone which acts on... (Review)
Review
Central diabetes insipidus (CDI), characterized by polyuria and polydipsia, is caused by deficiency of arginine vasopressin (AVP), an antidiuretic hormone which acts on V2 receptors in kidney to promote reabsorption of free water. CDI is classified into three subtypes; idiopathic, secondary and familial. A previous study suggests that infundibulo-neurohypophysitis might be an underlying cause of idiopathic CDI. Among secondary CDI, the tumors in the central nervous system such as craniopharyngioma and germ cell tumors are the most frequent causes. Familial CDI is inherited mostly in an autosomal dominant mode, and the number of causal mutations in the AVP gene locus reported so far exceeds 80. CDI is treated with desmopressin, an analogue of vasopressin, and the tablet is preferred to the nasal form because it is easier to administer. It is also shown that the oral disintegrating tablet formula increases QOL and decreases the incidence of hyponatremia in CDI patients. In some CDI patients, the osmoreceptors in the hypothalamus do not function and patients do not sense thirst. These adipsic CDI patients are treated with desmopressin and adjusting the amount of daily water intake based on body weight measurement; but controlling the water balance is extremely difficult, and morbidity and mortality are shown to be high in these patients.
PubMed: 28008190
DOI: 10.18999/nagjms.78.4.349 -
Archives of Disease in Childhood.... Jun 2019Children can present with polydipsia and/or polyuria for a number of reasons. We will discuss polydipsia and polyuria, how a child may present and how to investigate... (Review)
Review
Children can present with polydipsia and/or polyuria for a number of reasons. We will discuss polydipsia and polyuria, how a child may present and how to investigate further in order to establish the cause. We highlight the important areas to cover in the history and examination of a child presenting with polydipsia and/or polyuria.
Topics: Child; Dehydration; Drug-Related Side Effects and Adverse Reactions; Humans; Medical History Taking; Physical Examination; Polydipsia; Polyuria
PubMed: 30131352
DOI: 10.1136/archdischild-2018-315486 -
Handbook of Clinical Neurology 2021The hormone arginine vasopressin (AVP) is a nonapeptide synthesized by hypothalamic magnocellular nuclei and secreted from the posterior pituitary into the bloodstream.... (Review)
Review
The hormone arginine vasopressin (AVP) is a nonapeptide synthesized by hypothalamic magnocellular nuclei and secreted from the posterior pituitary into the bloodstream. It binds to AVP receptor 2 in the kidney to promote the insertion of aquaporin channels (AQP2) and antidiuretic responses. AVP secretion deficits produce central diabetes insipidus (CDI), while renal insensitivity to the antidiuretic effect of AVP causes nephrogenic diabetes insipidus (NDI). Hereditary and acquired forms of CDI and NDI generate hypotonic polyuria, polydipsia, hyperosmolality, and hypernatremia. The AVP mutant (Brattleboro) rat is the principal animal model of hereditary CDI, while neurohypophysectomy, pituitary stalk compression, hypophysectomy, and mediobasal hypothalamic lesions produce acquired CDI. In animals, hereditary NDI is mainly caused by mutations in AVP2R or AQP2 genes, while acquired NDI is most frequently induced by lithium. We report here on the determinants of the intake and excretion of water and mineral salts and on the different types of DI in humans. We then describe the hydromineral characteristics of these animal models and the responses observed after administration of hypertonic NaCl or when they are fed with low-sodium diets. Finally, we report on the effects of drugs such as AVP analogues and/or oxytocin, another neuropeptide that increases sodium excretion in animal models and humans with CDI, and sildenafil, a compound that increases the expression and function of AQP2 channels in animal models and humans with NDI.
Topics: Animals; Aquaporin 2; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diabetes Mellitus; Humans; Models, Animal; Rats; Rats, Brattleboro
PubMed: 34238463
DOI: 10.1016/B978-0-12-820683-6.00020-8 -
BMJ (Clinical Research Ed.) Feb 2019
Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Diabetes Insipidus; Endocrinology; Humans; Male; Osmolar Concentration; Polydipsia; Polyuria; United Kingdom; Young Adult
PubMed: 30819684
DOI: 10.1136/bmj.l321