Concept: Diabetes insipidus
Background: The water deprivation test is the gold standard test to differentiate central or nephrogenic diabetes insipidus (DI) from primary polydipsia (PP) in patients with polyuria and polydipsia. Few studies have addressed the diagnostic performance of this test. Methods: The aim of this retrospective cohort study was to evaluate the diagnostic performance of the standard water deprivation test, including plasma arginine vasopressin (AVP) measurements, in 40 consecutive patients with polyuria. We compared initial test results to the final clinical diagnosis, i.e., no DI, central DI or nephrogenic DI. Median length of follow up was 8 years. In a subset of 10 patients, the novel marker copeptin (CP) was measured in plasma. Results: Using the final diagnosis as gold standard, a threshold for urine osmolality of > 800 mOsmol/kg after water deprivation yielded a sensitivity and specificity of 96% and 100% for diagnosing PP. Sensitivity increased to 100% if the cut off value for urine osmolalilty was set at 680 mOsmol/kg. Plasma AVP levels did not differ between patient groups and did not differentiate between central DI, nephrogenic DI or PP. In all three patients with central DI, plasma CP was <2.5 pmol/L with plasma osmolality > 290 mOsmol/kg, and >2.5 pmol/L in patients without DI. Conclusions: The optimal cut-off value for differentiating PP from DI during a water deprivation test was urine osmolality > 680 mOsmol/kg. Differentiating between central and nephrogenic DI should be based on clinical judgement since AVP levels did not discriminate.
Diabetes insipidus without perception of thirst, as may follow an anterior communicating artery aneurysm, requires prescription of fluid intake as well as desmopressin. The management goal of maintaining a normal serum sodium is rendered more challenging in a humid subtropical environment, where insensible losses are higher.
Primary polydipsia (PP) has been defined as excessive intake of fluids. However, the pathogenesis of PP remains unexplored. Different theories include a dysfunction in the thirst mechanism, involvement of the hippocampus, stress-reducing behaviour and lesion occurrences in specific areas of the brain. Most studies have been performed in the psychiatric setting, indicating that PP coincides with schizophrenia, anxiety disorder and depression. However, an increasing number of case reports emphasise the incidence of PP in non-psychiatric patients. As often recommended by healthcare professions and in life-style programmes, the phenomenon of excessive fluid intake appears to be growing, especially in health-conscious and active people. PP is part of the polyuria-polydipsia syndrome, so the differential diagnosis diabetes insipidus (central or nephrogenic) must be excluded. The gold standard when differentiating between these disorders has been the water deprivation test. However, new options for distinguishing between these entities have been proposed e.g., measurement of copeptin, a reliable surrogate marker of the hormone arginine vasopressin (AVP). The major risk of excessive drinking is the development of hyponatraemia and the ensuing complications. In patients with PP, factors reducing the renal excretory capacity of the kidney such as acute illness, medications or low solute intake may accumulate in hyponatraemia. Treatment options for PP remain scarce. Different medication and behavioural therapy have been investigated, but never on a large scale and rarely in non-psychiatric patients. This review provides an overview of the pathophysiology, characteristics, complications, and outcomes of patients with PP in the medical and psychiatric patient.
The combination of hyperosmolar hyperglycaemic state and central diabetes insipidus is unusual and poses unique diagnostic and therapeutic challenges for clinicians. In a patient with diabetes mellitus presenting with polyuria and polydipsia, poor glycaemic control is usually the first aetiology that is considered, and achieving glycaemic control remains the first course of action. However, severe hypernatraemia, hyperglycaemia and discordance between urine-specific gravity and urine osmolality suggest concurrent symptomatic diabetes insipidus. We report a rare case of concurrent manifestation of hyperosmolar hyperglycaemic state and central diabetes insipidus in a patient with a history of craniopharyngioma.
The World Anti-Doping Agency (WADA) has recently added desmopressin, a synthetic analogue of the endogenous peptide hormone arginine vasopressin, to the Prohibited List, owing to the potential masking effects of this drug on hematic parameters useful to detect blood doping. A qualitative method for detection of desmopressin in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated. Desmopressin purification from urine was achieved by means of delipidation with a 60:40 di-isopropyl ether/n-butanol and solid-phase extraction with WCX cartridges. The lower limit of detection was 25 pg/mL. Extraction recovery was determined as 59.3% (SD 29.4), and signal reduction owing to ion suppression was estimated to be 42.7% (SD 12.9). The applicability of the method was proven by the analysis of real urine samples obtained after intravenous, oral and intranasal administration of desmopressin, achieving unambiguous detection of the peptide in all the cases. Copyright © 2012 John Wiley & Sons, Ltd.
Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution’s experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7 %) and 14 cases of permanent DI (8.1 %). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80 % specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98 % specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.
- The Journal of clinical endocrinology and metabolism
- Published over 8 years ago
Context: The differential diagnosis of diabetes insipidus (DI) is often challenging but essential, because treatment may vary substantially. This article analyzes the database and performance of currently used differential diagnostic tests for DI and discusses future perspectives for diagnostic improvement. Evidence Acquisition: A review of electronic and print data comprising original and review articles retrieved from the PubMed or Cochrane Library database up to January 2012 was conducted. The search term “polyuria polydipsia syndrome” was cross-referenced with underlying forms of disease and associated clinical, diagnostic, and therapeutic MeSH terms. In addition, references from review articles and textbook chapters were screened for papers containing original data. Search results were narrowed to articles containing primary data with a description of criteria for the differential diagnosis of DI. Evidence Synthesis: Fifteen articles on differential diagnosis of DI were identified, mainly consisting of small series of patients, and mostly covering only part of the differential diagnostic spectrum of DI. Test protocols differed, and prospective validation of diagnostic criteria was consistently missing. Inconsistent data were reported on the diagnostic superiority of direct plasma arginine vasopressin determination over the indirect water deprivation test. Both test methods revealed limitations, especially in the differentiation of disorders with a milder phenotype. Conclusion: The available data demonstrate limitations of current biochemical tests for the differential diagnosis of DI, potentially leading to incorrect diagnosis and treatment. The newly available assay for copeptin, the C terminus of the vasopressin precursor, holds promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol in DI.
Novel AQP2 mutation causing congenital nephrogenic diabetes insipidus: challenges in management during infancy
- Journal of pediatric endocrinology & metabolism : JPEM
- Published over 7 years ago
Abstract Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, mostly caused by AVPR2 mutations. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene. Diagnosis and management of this condition remain challenging especially during infancy. Here, we report two unrelated patients, a 6-month-old Thai boy and a 5-year-old Emirati girl, with a history of failure to thrive, chronic fever, polydipsia, and polyuria presented in early infancy. The results of water deprivation test were compatible with a diagnosis of NDI. The entire coding regions of the AVPR2 and AQP2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a novel missense AQP2 mutation p.G96E, inherited from both parents. Patient 2 harbored a previously described homozygous p.T126M mutation in the AQP2 gene. Both patients were treated with a combination of thiazide diuretics and amiloride. Patient 1 developed paradoxical hyponatremia and severe dehydration 2 weeks after medical treatment began. In conclusion, we report a novel mutation of the AQP2 gene and highlight an important role of genetic testing for definite diagnosis. Vigilant monitoring of the fluid status and electrolytes after beginning the therapy is mandatory in infants with NDI.
Polyuria after kidney transplantation is a common, usually self-limiting disorder. However, persistent polyuria can cause not only patient discomfort, including polyuria and polydipsia, but also volume depletion that can produce allograft dysfunction. Herein, we have report a case of central diabetes insipidus newly diagnosed after kidney transplantation. A 45-year-old woman with end-stage kidney disease underwent deceased donor kidney transplantation. Two months after the transplantation, she was admitted for persistent polyuria, polydipsia, and nocturia with urine output of more than 4 L/d. Urine osmolarity was 100 mOsm/kg, which implied that the polyuria was due to water rather than solute diuresis. A water deprivation test was compatible with central diabetes insipidus; desmopressin treatment resulted in immediate symptomatic relief. Brain magnetic resonance imaging (MRI) demonstrated diffuse thickening of the pituitary stalk, which was considered to be nonspecific finding. MRI 12 months later showed no change in the pituitary stalk, although the patient has been in good health without polyuria or polydipsia on desmopressin treatment. The possibility of central diabetes insipidus should be considered in patients presenting with persistent polyuria after kidney transplantation.
Hypernatremia and polyuria are the main symptoms of diabetes insipidus. Polyuria is characterized by a 24-h urine volume in excess of 40-50 ml/kg in adults. Dexmedetomidine, a highly selective, short-acting intravenous alpha-2 agonist, is used as a component of anesthesia, and has been suspected to induce polyuric syndrome. We report a patient who presented with severe hypernatremia and polyuria after intravenous infusion of dexmedetomidine.