Establishment and validation of a predictive nomogram for polyuria during general anesthesia in thoracic surgery.

BACKGROUND: To develop and evaluate a predictive nomogram for polyuria during general anesthesia in thoracic surgery. METHODS: A retrospective study was designed and performed. The whole dataset was used to develop the predictive nomogram and used a stepwise algorithm to screen variables. The stepwise algorithm was based on Akaike's information criterion (AIC). Multivariable logistic regression analysis was used to develop the nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the model's discrimination ability. The Hosmer-Lemeshow (HL) test was performed to check if the model was well calibrated. Decision curve analysis (DCA) was performed to measure the nomogram's clinical usefulness and net benefits. P < 0.05 was considered to indicate statistical significance. RESULTS: The sample included 529 subjects who had undergone thoracic surgery. Fentanyl use, gender, the difference between mean arterial pressure at admission and before the operation, operation type, total amount of fluids and blood products transfused, blood loss, vasopressor, and cisatracurium use were identified as predictors and incorporated into the nomogram. The nomogram showed good discrimination ability on the receiver operating characteristic curve (0.6937) and is well calibrated using the Hosmer-Lemeshow test. Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: Individualized and precise prediction of intraoperative polyuria allows for better anesthesia management and early prevention optimization.

Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency.

Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific for AVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.

Biological Variation Estimates for Plasma Copeptin and Clinical Implications.

BACKGROUND: Plasma copeptin measurement is useful for the differential diagnoses of polyuria-polydipsia syndrome. It has also been proposed as a prognostic marker for cardiovascular diseases. However, limited information is available about the within- (CVI) and between-subject (CVG) biological variation (BV). This study presents BV estimates for copeptin in healthy individuals. METHODS: Samples were collected weekly from 41 healthy subjects over 5 weeks and analyzed using the BRAHMS Copeptin proAVP KRYPTOR assay after at least 8 h of food and fluid abstinence. Outlier detection, variance homogeneity, and trend analysis were performed followed by CV-ANOVA for BV and analytical variation (CVA) estimation with 95% confidence intervals. Reference change values (RCVs), index of individuality (II), and analytical performance specification (APS) were also calculated. RESULTS: The analysis included 178 results from 20 males and 202 values from 21 females. Copeptin concentrations were significantly higher in males than in females (mean 8.5 vs 5.2 pmol/L, P < 0.0001). CVI estimates were 18.0% (95% CI, 15.4%-21.6%) and 19.0% (95% CI, 16.4%-22.6%), for males and females, respectively; RCVs were -35% (decreasing value) and 54% (increasing value). There was marked individuality for copeptin. No result exceeded the diagnostic threshold (>21.4 pmol/L) for arginine vasopressin resistance. CONCLUSIONS: The availability of BV data allows for refined APS and associated II, and RCVs applicable as aids in the serial monitoring of patients with specific diseases such as heart failure. The BV estimates are only applicable in subjects who abstained from oral intake due to the rapid and marked effects of fluids on copeptin physiology.

Antidiuretic hormone deficiency secondary to inactive hydrocephalus: a case report.

BACKGROUND: Diabetes insipidus is a syndrome characterized by polyuria, which is almost always associated with polydipsia. The most frequent cause is central diabetes insipidus, which is the result of an inadequate secretion of the antidiuretic hormone, and diagnosis involves differentiating it from other causes of polyuria and polydipsia. CASE PRESENTATION: Here, we present a clinical case of a previously healthy 13-year-old Nepali boy, who, in December 2022, was found to have intense polydipsia accompanied by polyuria. He had bilateral lower limb weakness at the time of presentation. Biochemical evaluation demonstrated raised serum sodium (181 mEq/L), serum creatinine (78 µmol/L), and serum uric acid (560 µmol/L) with suppressed serum potassium (2.7 mEq/L), which was the major concern to the clinicians. Further laboratory workup revealed an increased serum osmolarity (393.6 mOsm/kg) with reduced urine osmolarity (222.7 mOsm/kg). On contrast magnetic resonance imaging of the brain, a thick-walled third ventricular cyst with bilateral foramen obstruction, thin membrane-like structure at top of aqueduct of Sylvius with gross obstructive hydrocephalus (inactive), and compressed and thinned pituitary gland with no bright spot was observed. The laboratory findings, radiological findings, and case presentation provided the provisional diagnosis of diabetes insipidus due to hydrocephalus and third ventricular cyst. CONCLUSIONS: Central diabetes insipidus due to hydrocephalus, though rare, can have serious complications including the predilection to develop a deficit of other pituitary hormones. Thus, even if hydrocephalus is dormant with normal intracranial pressure, it must be addressed during investigations of central diabetes insipidus.

The diagnostic performance of copeptin in clinical practice: A prospective study.

OBJECTIVE: Plasma copeptin is a relatively new biomarker for evaluation of arginine vasopressin (AVP) secretion. The aim of this study was to test the diagnostic performance of copeptin in patients with polyuria-polydipsia syndrome. DESIGN, PATIENTS AND MEASUREMENTS: This was a prospective study where 88 patients with polyuria-polydipsia syndrome were evaluated with a water deprivation test (WDT). Weight, urine osmolality, urine specific gravity, and plasma copeptin were collected at baseline, after 8 h, and at termination of the WDT when one of the following had been reached: (i) >3% weight reduction, (ii) urine specific gravity >1.017 or urine osmolality >600 mOsm/kg, or (iii) intolerable adverse symptoms. RESULTS: Of 88 patients (57 women), 21 (24%) were diagnosed with central diabetes insipidus (cDI), 5 (6%) with nephrogenic DI (nDI), and 62 (71%) with primary polydipsia (PP). Median (interquartile range) copeptin at baseline was 1.7 (1.4-2.5) pmol/L in cDI, 22 (18-65) pmol/L in nDI, and 2.7 (2-4) pmol/L in PP. After 8 h of WDT, the highest copeptin in patients with cDI was 4.0 pmol/L. In patients with PP: (i) 41 had urine osmolality <600 mOsm/kg, 7 (17%) of these had copeptin >4.0 pmol/L, (ii) 21 had urine osmolality ≥600 mOsm/kg, 14 (67%) of these had copeptin >4.0 pmol/L. CONCLUSIONS: Copeptin >4.0 pmol/L after an overnight WDT can be used to rule out cDI and copeptin ≥21 pmol/L at baseline to diagnose nDI. The diagnostic performance of copeptin in the context of the WDT is otherwise limited in the diagnostic work-up of patients with polyuria-polydipsia syndrome.

The diagnostic role of arginine-stimulated copeptin in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in pediatric age.

PURPOSE: In recent years, copeptin stimulation through arginine administration has been evaluated as a new potential tool in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in adults; to date very few data, all retrospective, exist in pediatric age. The aim of this prospective study is to evaluate the diagnostic performance of the arginine-stimulation test for copeptin in a cohort of pediatric patients affected by PPS. METHODS: All children (<18 years) referred to the Department of Pediatric Endocrinology of the Regina Margherita Children Hospital for polyuria-polydipsia in the period January 2021-June 2023 were enrolled. The Arginine-stimulation test for copeptin was performed in all patients presenting PPS after water deprivation test (WDT). Patients with polyuria-polydipsia were then classified as having primary polyuria (PP), complete and partial central diabetes insipidus (CDI), according to the standardized interpretation. Arginine-stimulation test for copeptin was also performed in a control cohort. RESULTS: A significant difference in arginine-stimulated copeptin values was observed at baseline (p = 0.005), at 60 min (p = 0.01), and at 90 min (p = 0.005) in 7 subjects presenting PP, 6 patients affected by CDI and 50 subjects of the control cohort. Plasma osmolality values remained stable at all measurements. The arginine-stimulated copeptin test demonstrated sensitivity and specificity of 100%, whereas the sensitivity of the WDT test was 83.3% and the specificity was 85.7%. CONCLUSION: Given the reliability and the minor adverse effects and costs, the copeptin level after arginine administration could replace the WDT in the diagnostic workup of these in pediatric age.

Poliuria en el adulto. Una aproximación diagnóstica basada en la fisiopatología / Polyuria in adults. A diagnostic approach based on pathophysiology

La poliuria es una condición clínica frecuente caracterizada por un volumen de orina inapropiadamente alto para los niveles de presión arterial y sodio plasmático del paciente (volumen de orina >3L/24h). Desde el punto de vista fisiopatológico se clasifica en 2 tipos: debido a una mayor excreción de solutos (osmolaridad urinaria >300mOsm/L) o debido a una incapacidad de aumentar la concentración de solutos (osmolaridad urinaria <150mOsm/L). En ocasiones pueden coexistir ambos mecanismos (osmolaridad urinaria 150-300mOsm/L). La poliuria supone un reto diagnóstico y su tratamiento correcto exige una evaluación de la historia clínica, la determinación de la osmolaridad urinaria, la estimación del aclaramiento de agua libre, el uso de pruebas de deprivación hídrica en la poliuria acuosa y la medición de electrólitos en sangre y orina en el caso de la poliuria osmótica (AU)

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 liters in 24 hours) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria (AU)

Importancia del seguimiento a largo plazo de la diabetes insípida; de hipofisitis linfocitaria a germinoma / Importance of long-term follow-up of diabetes insipidus; from lymphocytic hypophysitis to germinoma

Se describe el caso de un trastorno del eje hipotálamo hipofisario en un niño de 10 años que comenzó con diabetes insípida y evolucionó a un panhipopituitarismo. En estos casos siempre se debe sospechar una lesión hipotalámica oculta y realizar seguimiento. A los 3 años, se detectó la aparición de lesiones en el tallo hipofisario. Los marcadores tumorales fueron negativos pero la lesión creció y fue biopsiada. El resultado anatomopatológico fue de hipofisitis linfocitaria. En el seguimiento hubo un aumento de los marcadores tumorales, por lo que se realizó una nueva biopsia que fue diagnóstica de germinoma. La hipofisitis linfocitaria es muy rara en estas edades y algunos casos son diagnosticados finalmente de germinoma. El interés radica en resaltar la importancia del seguimiento de los casos de diabetes insípida central y en cuestionar un posible diagnóstico de hipofisitis linfocitaria, o mejor infundibuloneurohipofisitis linfocitaria, muy raro en estas edades y que puede enmascarar un germinoma, con muy pocos casos reportados

A case is presented of a 10-year old boy who had a hypothalamic-pituitary axis disorder. He initially presented with diabetes insipidus that progressed to panhypopituitarism. A hidden hypothalamic lesion should be suspected in all these cases, and should be followed up. New lesions were found in the pituitary stem three years later. Although tumor markers were negative, there was an increase in size, and a biopsy was performed. The histopathology reported a Lymphocytic Hypophysitis. There were increases in the tumor markers during the follow-up, thus a second biopsy was performed, with the diagnosis of Germinoma. Lymphocytic Hypophysitis is an uncommon diagnosis in children. Few cases have been reported, and in some cases, they were later diagnosed with Germinoma. We believe this case highlights the importance of the follow-up of children with Central Diabetes Insipidus with a normal MRI, as well as not taking the diagnosis of Lymphocytic Hypophysitis/ lymphocytic Infundibular neurohypophysitis as definitive, as it is a rare diagnosis at thisage, and could mask a Germinoma, as recorded in some cases

Enfoque práctico para el diagnóstico y tratamiento de los estados poliúricos en pacientes con injuria cerebral aguda / Diagnosis and therapy of polyuric states in patients with acute cerebral injury

In patients with acute cerebral injury, polyuric states can potentially trigger, maintain and aggravate the primary neurological damage, due to hypovolemia, arterial hypotension and alterations of osmolarity. The true incidence of the condition in this population is unknown. A widely validated definition of polyuric state is lacking and its etiology is multifactorial. There are two principal classes of polyuria: a) aqueous polyuria with diabetes insipidus as the main cause; and b) osmotic polyuria in which sodium, glucose or ureaplay the main role. Polyuric states are in close association with disorders of water and sodium metabolism and with alterations in acid-base balance. A detailed analysis of the history, clinical picture and simple laboratory determinations in blood and urine, are required for an adequate assessment of these polyuric states. The problem must be faced with pathophysiological reasoning and a systematic and sequential approach, because each disorder needs a specific therapy.

A Case of Transient Central Diabetes Insipidus after Aorto-Coronary Bypass Operation

Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB.

Un caso de diabetes insípida central en un paciente con trastorno bipolar consumidora de litio desde hace años / A case of central diabetes insipidus in a female patient with bipolar disorder, consumer of lithium over the last years

Litio es un fármaco que sigue siendo la primera indicación de varios trastornos psiquiátricos. Su manejo es pues imprescindible para el psiquiatra, que debe estar familiarizado con sus numerosos efectos secundarios, contraindicaciones, interacciones y precauciones. Diabetes insípida nefrógena es un efecto secundario de litio conocido. Presentamos un caso de diabetes insípida central en una paciente consumidora de litio desde hace muchos años, pero que concurrentemente presenta otras patologías. Se realiza diagnóstico diferencial y se discute patogénesis y tratamiento

Lithium is still the first prescribed drug for several psychiatric disorders. Its use is thus indispensable for every psychiatrist, who must be familiar with its numerous secondary effects, counterindications, interactions and precautions. Nephrogenic diabetes insipidus is a well-known secondary effect of lithium. We present a case of central diabetes insipidus in a female patient who has been consuming lithium for many years, but concurrently shows other pathologies. A differential diagnosis is carried out together with a discussion of pathogenesis and treatment

Guía para el diagnóstico y tratamiento de la enuresis nocturna monosintomática en Atención Primaria / Guide for the diagnosis and treatment of monosymptomatic nighttime enuresis in Primary Health Care

La enuresis nocturna monosintomática es una entidad nosológica benigna, muy frecuente en la infancia, que puede favorecer la aparición de importantes problemas psicológicos y de autoestima a medida que se va incrementando la edad de los niños que no corrigen su problema. En la presente Guía se repasan los criterios diagnósticos, los exámenes complementarios que se recomiendan inicialmente y los tratamientos disponibles en la actualidad. Al tratarse de un proceso benigno, el tratamiento de la enuresis debe realizarse con medios terapéuticos eficaces y con una baja tasa de efectos secundarios potenciales. Se recomienda iniciar el tratamiento con desmopresina o con alarmas sonoras. La ausencia de eficacia de uno de los dos remedios o de ambos debe ser criterio de remisión de los jóvenes pacientes a un centro especializado (AU)

The Monosyptomatic nocturnal enuresis is a benign entity very frequent in childhood that can trigger the appearance of important psychological problems and of selfesteem, especially, when the children do not correct this problem grow older. In the present paper we review the diagnostic criteria, the complementary exams initially recommended and the current available treatments. Being a benign process, the nocturnal enuresis treatment should be carried out with effective therapeutic means and with a low rate of potentials secondary effects. The treatment should begin with desmopressin or with sound alarms. The lack of effectiveness of either or both remedies should be a criterion for remission of the patient to a specialized Center (AU)

Síndrome poliúrico / Poliuric syndrome

Se sospecha Síndrome Poliúrico (SP) cuando el volumen urinario excede en 2 a 3 veces lo esperado para la edad o cuando a raíz de una deshidratación o restricción hídrica no se produce concentración urinaria adecuada. El volumen y la osmolaridad de los líquidos orgánicos se regulan con gran precisión gracias a la actividad de la hormona antidiurética (HAD), producida en el eje hipotálamo hipofisiario, que maneja la permeabilidad del agua de los túbulos distales y colectores renales. El SP se clasifica en dos grandes grupos: 1) con niveles plasmáticos bajos de HAD (diabetes insípida central DIC o neurogénica y polidipsia primaria) y 2) con niveles plasmáticos normales de HAD (diuresis osmótica y diabetes insípida nefrogénica DIN). El diagnóstico diferencial se hace con la prueba de deprivación acuosa y el tratamiento consiste en reemplazo hormonal con HAD en DIC y en la DIN reducción del aporte calórico proteico con la ingesta libre de agua, más diuréticos tiazídicos y antiinflamatorios. En el presente artículo se hace una revisión actualizada del SP.

Diabetes insípida central familiar: una enfermedad evolutiva / Familial central diabetes insipidus: an evolutive disease

La diabetes insípida (DI) central familiar constituye una enfermedad hereditaria, pero no congénita, de carácter evolutivo y que suele iniciar manifestaciones clínicas en la primera infancia. Se presenta el caso de dos hermanas gemelas univitelinas de 5 años de edad, con padre afecto de DI pitresín-sensible, remitidas para estudio de enuresis primaria y síndrome de polidipsiapoliuria. Son diagnosticadas inicialmente de polidipsia primaria por presentar una respuesta normal a dos tests de restricción hídrica. Debido a la progresión y empeoramiento de la sintomatología se inicia tratamiento con desmopresina nasal presentando oligoanuria y desaparición de la sed. Un nuevo test de restricción hídrica muestra una capacidad de concentración urinaria conservada (paciente 1: 745 mOsm/kg; paciente 2: 757 mOsm/kg). Tras la administración de desmopresina la osmolalidad urinaria se incrementa a 933 mOsm/kg y 864 mOms/kg respectivamente, siendo diagnosticadas de DI central parcial. La resonancia magnética nuclear (RMN) en T1 muestra ausencia de la señal hiperintensa de la neurohipófisis. El estudio genético del gen de la vasopresina en el padre y las dos hermanas pone de manifiesto la mutación R51C en heterozigosis en el exón 2 de la neurofisina, confirmando la existencia de una DI central parcial familiar. En conclusión, ante un paciente con síndrome poliuria-polidipsia en caso de obtener resultados compatibles con polidipsia primaria, estaría indicado el estudio genético si tenemos constancia de antecedentes familiares (AU)

Patología hipofisaria en la edad pediátrica: utilidad de la resonancia magnética / Pituitary disease in childhood: utility of magnetic resonance

Objetivos: Valorar la utilidad de la resonancia magnética (RM) en el estudio de pacientes pediátricos con sospecha clínica de patología hipofisaria.Material y métodos: Hemos estudiado 18 pacientes con edades entre 7-18 años. Quince de ellos presentaban trastornos hormonales, dos tenían amenorrea y una paciente presentaba cefalea, fiebre y cuadro de poliuria-polidipsia. Todos los pacientes fueron estudiados con un equipo 1 Tesla Siemens 42 SP. Se realizaron series EE T1 sagitales y coronales, en diez casos se realizó una serie EE T2 o FEE T2 y en nueve pacientes se administró gadolinio intravenoso.Resultados: Encontramos nueve pacientes con disgenesia hipotálamo-hipofisaria, dos germinomas, dos casos de hemosiderosis hipofisaria en pacientes con talasemia, dos microadenomas, un absceso, un caso de diabetes insípida central idiopática y un caso de histiocitosis de células de Langerhans.Conclusiones: La RM nos ha permitido valorar las alteraciones estructurales de la hipófisis en niños con deficiencias hormonales hipotálamo-hipofisarias. En nuestro estudio la disgenesia hipotálamo-hipofisaria ha sido la causa más frecuente de déficit adenohipofisario, y las masas en la región selar y supraselar han resultado las causas más frecuentes de diabetes insípida central. En pacientes con talasemia los estudios de RM con series potenciadas en T2 pueden ser útiles para valorar el grado de depósito de hierro en la adenohipófisis. Los estudios con gadolinio nos han resultado útiles en el estudio de las masas y en los casos de sospecha de microadenomas (AU)

La estrategia diagnóstica en poliuria / Diagnostic strategy in polyuria

Se entiende por poliuria, la presencia de una diuresis mayor de 80 ml/hr/m* de superficie corporal; habitualmente se trata de una diuresis de 2 a 10 litros por día, la orina presenta, en la mayoría de los casos, una densidad urinaria inferior a 1.005 con osmolaridad de 40 a 200 mOsm/l. Para entender la fisiopatogenia de este signo renal se tienen que conocer los mecanismos normales que intervienen en la concentración de la orina, entendiendo la relación existente entre excreción renal de solutos, concentración urinaria y volumen de orina. El ser humano no puede excretar solutos sin agua, por lo que tiene una pérdida obligatoria de agua a nivel renal, la cual es de aproximadamente 55 ml de agua por cada 100 calorías. En el adulto normal se excretan 600 mOsm por día, en un volumen aproximadamente 2.000 ml, lo que da una osmolaridad urinaria de 300 mOsm/litro. Si un adulto sano se encuentra en el desierto, requiere evitar pérdidas de agua, para lo cual sus riñones concentrarán la orina al máximo, al hacer esto la concentración urinaria aumenta 4 veces de 300 a 1.200 mOsm/l y su volumen urinario disminuye 4 veces de 2.000 a 500 ml, con lo que su organismo se ahorra la pérdida de 1.500 ml. Ahora bien, bajo otra situación, si la ingesta de líquidos ha sido cuantiosa, para evitar una intoxicación acuosa, sus riñones diluyen la orina a su máxima capacidad, con lo cual la osmolaridad urinaria disminuye 5 veces de 300 a 60 mOsm/l y el volumen urinario aumenta 5 veces de 2.000 ml a 10.000 ml