-
International Journal of Environmental... Feb 2022Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms that occur from childhood to adulthood. Usually, the first clinical sign is... (Review)
Review
Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms that occur from childhood to adulthood. Usually, the first clinical sign is non-autoimmune diabetes even if other clinical features (optic subatrophy, neurosensorial deafness, diabetes insipidus) may be present in an early state and may be diagnosed after diabetes' onset. Prognosis is poor, and the death occurs at the median age of 39 years as a consequence of progressive respiratory impairment, secondary to brain atrophy and neurological failure. The aim of this paper is the description of the metabolic treatment of the WS. We reported the experience of long treatment in patients with this syndrome diagnosed in pediatric age and followed also in adult age. It is known that there is a correlation between metabolic control of diabetes, the onset of other associated symptoms, and the progression of the neurodegenerative alterations. Therefore, a multidisciplinary approach is necessary in order to prevent, treat and carefully monitor all the comorbidities that may occur. An extensive understanding of WS from pathophysiology to novel possible therapy is fundamental and further studies are needed to better manage this devastating disease and to guarantee to patients a better quality of life and a longer life expectancy.
Topics: Adolescent; Adult; Child; Humans; Neurodegenerative Diseases; Quality of Life; Wolfram Syndrome; Young Adult
PubMed: 35270448
DOI: 10.3390/ijerph19052755 -
Pituitary Apr 2021Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt... (Review)
Review
PURPOSE
Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but can also reflect several physiological adaptive mechanisms in the postoperative phase. These may be difficult to distinguish from and might coincide with DI. The difficulty to distinguish DI from other causes of postoperative polyuria might explain the high variation in incidence rates. This limits interpretation of outcomes, in particular complication rates between centers, and may lead to unnecessary treatment. Aim of this review is to determine a pathophysiologically sound and practical definition of DI for uniform outcome evaluations and treatment recommendations.
METHODS
This study incorporates actual data and the experience of our center and combines this with a review of literature on pathophysiological mechanisms and definitions used in clinical studies reporting of postoperative DI.
RESULTS
The occurrence of excessive thirst and/or hyperosmolality or hypernatremia are the best indicators to discriminate between pathophysiological symptoms and signs of DI and other causes. Urine osmolality distinguishes DI from osmotic diuresis.
CONCLUSIONS
To improve reliability and comparability we propose the following definition for postoperative DI: polyuria (urine production > 300 ml/hour for 3 h) accompanied by a urine specific gravity (USG) < 1.005, and at least one of the following symptoms: excessive thirst, serum osmolality > 300 mosmol/kg, or serum sodium > 145 mmol/L. To prevent unnecessary treatment with desmopressin, we present an algorithm for the diagnosis and treatment of postoperative DI.
Topics: Diabetes Insipidus; Humans; Pituitary Neoplasms; Postoperative Period; Vasopressins
PubMed: 32990908
DOI: 10.1007/s11102-020-01083-7 -
Scars, Burns & Healing 2022Diabetes insipidus (DI) is characterized by polyuria and polydipsia. In most cases, the condition results from either an inadequate release or resistance to the activity...
UNLABELLED
Diabetes insipidus (DI) is characterized by polyuria and polydipsia. In most cases, the condition results from either an inadequate release or resistance to the activity of antidiuretic hormone in the renal collecting tubules. The underlying pathophysiology may be related to destruction the destruction or degeneration of neurons from inflammatory, autoimmune diseases, vascular diseases, Langerhans cell histiocytosis, sarcoidosis, or trauma. However, a large majority of diabetes insipidus cases (50%) are considered idiopathic. An exceedingly rare cause of idiopathic central DI occurs in burn injuries, which has only been reported in eight cases. We present an extremely rare case of idiopathic DI in a 15-year-old male with 76% total body surface area (TBSA) burns with the development of idiopathic central DI. An extensive literature review was accomplished to compare this case with the small number of previously reported case reports of idiopathic DI in burn patients.
LAY SUMMARY
Diabetes insipidus (DI) is a rare complication of burn injuries that results from the destruction of neurons involved in the secretion of antidiuretic hormone from the pituitary gland. Only eight cases of DI have been reported in the literature in association to burn injuries. The patient in this case report received immediate fluid resuscitation, burn treatment, and intensive observation after the initial burn injury. The rapid response was likely the main reason for the absence of neurological damage as reported in the CT image. Therefore, the treatment of burn injuries remains an important step for reducing neurological damage and hormonal dysregulation leading to diabetes insipidus.
PubMed: 36274672
DOI: 10.1177/20595131221122312 -
Seminars in Nephrology Jul 2023The tubular system of the kidneys is a complex series of morphologic and functional units orchestrating the content of tubular fluid as it flows along the nephron and... (Review)
Review
The tubular system of the kidneys is a complex series of morphologic and functional units orchestrating the content of tubular fluid as it flows along the nephron and collecting ducts. Renal tubules maintain body water, regulate electrolytes and acid-base balance, reabsorb precious organic solutes, and eliminate specific metabolites, toxins, and drugs. In addition, decisive mechanisms to adjust blood pressure are governed by the renal tubules. Genetic as well as acquired disorders of these tubular functions may cause serious diseases that manifest both in childhood and adulthood. This article addresses a selection of tubulopathies and the underlying pathomechanisms, while highlighting the important differences in pediatric and adult nephrology care. These range from rare monogenic conditions such as nephrogenic diabetes insipidus, cystinosis, and Bartter syndrome that present in childhood, to the genetic and acquired tubular pathologies causing hypertension or nephrolithiasis that are more prevalent in adults. Both pediatric and adult nephrologists must be aware of these conditions and the age-dependent manifestations that warrant close interaction between the two subspecialties.
Topics: Humans; Child; Nephrology; Kidney Tubules; Kidney; Diabetes Insipidus, Nephrogenic; Nephrons
PubMed: 37968178
DOI: 10.1016/j.semnephrol.2023.151437 -
Swiss Medical Weekly May 2020Polyuria-polydipsia syndrome consists of the three main entities: central or nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between these...
Polyuria-polydipsia syndrome consists of the three main entities: central or nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between these diagnoses is essential as treatment differs substantially, with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the classical water deprivation test had several pitfalls and clinicians were often left with uncertainity concerning the diagnosis. With the establishment of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of the polyuria-polydipsia syndrome has been newly evaluated. Whereas unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, two new tests using stimulated copeptin cutoff levels showed a high diagnostic accuracy in differentiating central diabetes insipidus from primary polydipsia. For the hypertonic saline infusion test, osmotic stimulation via the induction of hypernatraemia is used. This makes the test highly reliable and superior to the classical water deprivation test, but also requires close supervision and the availability of rapid sodium measurements to guarantee the safety of the test. Alternatively, arginine infusion can be used to stimulate copeptin release, opening the doors for an even shorter and safer diagnostic test. The test protocols of the two tests are provided and a new copeptin-based diagnostic algorithm is proposed to reliably differentiate between the different entities. Furthermore, the role of copeptin as a predictive marker for the development of diabetes insipidus following surgical procedures in the sellar region is described.
Topics: Diabetes Insipidus; Diabetes Mellitus; Diagnosis, Differential; Diagnostic Tests, Routine; Glycopeptides; Humans; Polyuria
PubMed: 32374887
DOI: 10.4414/smw.2020.20237 -
Diabetologia Jul 2023Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic...
AIMS/HYPOTHESIS
Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons.
METHODS
The effect of the GLP-1R agonists dulaglutide and exenatide was examined in Wfs1 knockout mice and in an array of human preclinical models of Wolfram syndrome, including WFS1-deficient human beta cells, human induced pluripotent stem cell (iPSC)-derived beta-like cells and neurons from control individuals and individuals affected by Wolfram syndrome, and humanised mice.
RESULTS
Our study shows that the long-lasting GLP-1R agonist dulaglutide reverses impaired glucose tolerance in WFS1-deficient mice, and that exenatide and dulaglutide improve beta cell function and prevent apoptosis in different human WFS1-deficient models including iPSC-derived beta cells from people with Wolfram syndrome. Exenatide improved mitochondrial function, reduced oxidative stress and prevented apoptosis in Wolfram syndrome iPSC-derived neural precursors and cerebellar neurons.
CONCLUSIONS/INTERPRETATION
Our study provides novel evidence for the beneficial effect of GLP-1R agonists on WFS1-deficient human pancreatic beta cells and neurons, suggesting that these drugs may be considered as a treatment for individuals with Wolfram syndrome.
Topics: Humans; Animals; Mice; Wolfram Syndrome; Exenatide; Induced Pluripotent Stem Cells; Optic Atrophy; Insulin-Secreting Cells; Mice, Knockout
PubMed: 36995380
DOI: 10.1007/s00125-023-05905-8 -
The New England Journal of Medicine Nov 2023
Topics: Humans; Arginine; Arginine Vasopressin; Diabetes Insipidus, Neurogenic
PubMed: 37966292
DOI: 10.1056/NEJMe2311293 -
The New England Journal of Medicine Mar 2018
Topics: Cysts; Diabetes Insipidus, Nephrogenic; Humans; Kidney; Kidney Diseases; Lithium; Male; Middle Aged; Osmolar Concentration; Tomography, X-Ray Computed; Urine
PubMed: 29539276
DOI: 10.1056/NEJMicm1709438 -
Journal of the American Society of... Jun 2016Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with... (Review)
Review
Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for >60 years. However, in a substantial number of patients with bipolar disorder, long-term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium-induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD.
Topics: Animals; Bipolar Disorder; Diabetes Insipidus, Nephrogenic; Disease Models, Animal; Humans; Kidney Diseases; Kidney Failure, Chronic; Lithium Compounds; Renal Insufficiency, Chronic
PubMed: 26577775
DOI: 10.1681/ASN.2015080907 -
Deutsches Arzteblatt International Oct 2021
Topics: Diabetes Insipidus; Diabetes Mellitus; Humans
PubMed: 34935610
DOI: 10.3238/arztebl.m2021.0312