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Annals of Clinical Biochemistry Jan 2024Diabetes insipidus (DI) is a group of disorders that lead to inappropriate production of large volumes of dilute urine. The three main forms are central DI (CDI),... (Review)
Review
Diabetes insipidus (DI) is a group of disorders that lead to inappropriate production of large volumes of dilute urine. The three main forms are central DI (CDI), nephrogenic DI (NDI) and primary polydipsia (PP). Differentiating CDI/NDI from PP is important as patients with true DI are at risk of severe dehydration without treatment. Biochemical testing is key in the diagnosis of DI. The indirect water deprivation test (WDT) is commonly used in the investigation of DI but has drawbacks including being cumbersome and sometimes producing equivocal results. Direct measurement of AVP has theoretical advantages but has generally only been used in specialist centres. Disadvantages include the requirement to measure AVP under hypertonic stimulation and pre-analytical/analytical challenges. Copeptin (CT-proAVP) is a proxy marker for AVP that is more stable, easier to measure and has been studied more widely in recent years. Historically, the evidence supporting the diagnostic performance of these tests has been relatively poor, being based on a few small, usually single-centre studies. However more recent, well-designed prospective studies are improving the evidence base for investigation of DI. These studies have focused on the utility of copeptin measurements during stimulation tests. There is evidence that measurement of copeptin under stimulation offers improved diagnostic performance compared to the WDT. There is currently a lack of systematic, evidence-based guidelines on the diagnosis of DI, but as the quality of the evidence defining the diagnostic performance of tests for DI continues to improve, a clearer consensus on the optimal approach should become achievable.
Topics: Humans; Prospective Studies; Polyuria; Glycopeptides; Diagnosis, Differential; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus
PubMed: 36650746
DOI: 10.1177/00045632231154391 -
British Journal of Neurosurgery Jun 2024We describe a rare case of histopathologic-proven necrotizing infundibulo-hypophysitis (NIH). (Review)
Review
PURPOSE
We describe a rare case of histopathologic-proven necrotizing infundibulo-hypophysitis (NIH).
CLINICAL HISTORY
A 40-year-old female presented with coexistence of central diabetes insipidus and hypopituitarism. Imaging disclosed a thickened infundibulum and a diffusely enlarged pituitary mass with gadolinium rim enhancement pattern. Microsurgical endonasal transsphenoidal resection was performed. The presence of extensive liquefactive necrosis, surrounded by lymphoplasmocytic inflammatory infiltrate, allowed for the diagnosis of NIH. Follow-up cranial imaging 10 months after surgery showed no evidence of reappearance of the lesion. There was no progression to panhypopituitarism.
CONCLUSION
Surgery and histopathological confirmation are the key diagnostic feature in NIH. The current case is the fifth report of NIH and the first one with an indolent course and without progression to panhypopituitarism so far.
Topics: Humans; Female; Adult; Hypopituitarism; Necrosis; Hypophysitis; Magnetic Resonance Imaging; Diabetes Insipidus, Neurogenic
PubMed: 34148487
DOI: 10.1080/02688697.2021.1940857 -
The Journal of Physiology Jul 2024Aquaporin-2 (AQP2) is a member of the aquaporin water channel family. In the kidney, AQP2 is expressed in collecting duct principal cells where it facilitates water... (Review)
Review
Aquaporin-2 (AQP2) is a member of the aquaporin water channel family. In the kidney, AQP2 is expressed in collecting duct principal cells where it facilitates water reabsorption in response to antidiuretic hormone (arginine vasopressin, AVP). AVP induces the redistribution of AQP2 from intracellular vesicles and its incorporation into the plasma membrane. The plasma membrane insertion of AQP2 represents the crucial step in AVP-mediated water reabsorption. Dysregulation of the system preventing the AQP2 plasma membrane insertion causes diabetes insipidus (DI), a disease characterised by an impaired urine concentrating ability and polydipsia. There is no satisfactory treatment of DI available. This review discusses kinases that control the localisation of AQP2 and points out potential kinase-directed targets for the treatment of DI.
Topics: Aquaporin 2; Animals; Humans; Protein Kinases; Diabetes Insipidus; Cell Membrane
PubMed: 37440212
DOI: 10.1113/JP284100 -
British Journal of Clinical Pharmacology Aug 2023Sevoflurane is an ether-based inhalational anaesthetic that induces and maintains general anaesthesia. Our study aimed to detect sevoflurane-induced nephrogenic diabetes...
AIMS
Sevoflurane is an ether-based inhalational anaesthetic that induces and maintains general anaesthesia. Our study aimed to detect sevoflurane-induced nephrogenic diabetes insipidus using data mining algorithms (DMAs) and molecular docking. The FAERS database was analysed using OpenVigil 2.1 for disproportionality analysis.
METHODS
We analysed FAERS data from 2004 to 2022 to determine the incidence of nephrogenic diabetes insipidus associated with sevoflurane. Reporting odds ratios (RORs) and proportional reporting ratios (PRRs) with 95% confidence intervals were calculated. We also used molecular docking with AutoDock Vina to examine sevoflurane's binding affinity to relevant receptors.
RESULTS
A total of 554 nephrogenic diabetes insipidus cases were reported in FAERS, of which 2.5% (14 cases) were associated with sevoflurane. Positive signals were observed for sevoflurane with ROR of 76.012 (95% CI: 44.67-129.35) and PRR of 75.72 (χ : 934.688). Of the 14 cases, 50% required hospitalization, 14% resulted in death, and the remaining cases were categorized as other outcomes. Molecular docking analysis showed that sevoflurane exhibited high binding affinity towards AQP2 (4NEF) and AVPR2 (6U1N) with docking scores of -4.9 and -5.3, respectively.
CONCLUSIONS
Sevoflurane use is significantly associated with the incidence of nephrogenic diabetes insipidus. Healthcare professionals should be cautious when using this medication and report any adverse events to regulatory agencies. Further research is needed to validate these findings and identify risk factors while performing statistical adjustments to prevent false-positives. Clinical monitoring is crucial to validate potential adverse effects of sevoflurane.
PubMed: 37536932
DOI: 10.1111/bcp.15869 -
Pediatric Nephrology (Berlin, Germany) Jun 2024An 11-year-old male child who presented with increased frequency of urination, thirst and feeling of incomplete void was initially diagnosed with diabetes mellitus (DM)...
An 11-year-old male child who presented with increased frequency of urination, thirst and feeling of incomplete void was initially diagnosed with diabetes mellitus (DM) based on elevated blood sugar. Polyuria and polydipsia were confirmed even after normalisation of blood sugar. A standardised water deprivation test showed presence of central diabetes insipidus (DI) and patient was started on desmopressin. Presence of DM and DI led to suspicion of DIDMOAD/Wolfram syndrome and ophthalmic examination confirmed bilateral optic atrophy. Despite treatment for DM and DI the urinary complaints persisted, and ultrasound showed persistent bilateral hydronephroureterosis. Bladder workup including voiding cystourethrography (VCUG) and urodynamic study reported thickened trabeculated bladder wall along with overactivity, poor compliance and high bladder pressure. Bladder dysfunction has been documented to be associated with Wolfram syndrome and often may lead to chronic kidney disease which can be prevented by early diagnosis and appropriate management. The case highlights the need for comprehensive evaluation of children with urinary symptoms.
PubMed: 38842721
DOI: 10.1007/s00467-024-06424-3 -
Neuro-oncology Dec 2023Childhood craniopharyngioma (cCP) has excellent survival, but quality of life may be severely hampered by hypothalamic dysfunction. We aimed to evaluate treatment and...
BACKGROUND
Childhood craniopharyngioma (cCP) has excellent survival, but quality of life may be severely hampered by hypothalamic dysfunction. We aimed to evaluate treatment and hypothalamic outcomes of a Dutch cCP cohort, and evaluate the effect of centralization of care.
METHODS
A retrospective cohort study was performed, including cCP patients diagnosed between 2004 and 2021. Treatment characteristics and hypothalamic outcomes were evaluated and compared before and since centralization of care in May 2018.
RESULTS
We included 87 cCP patients. Cyst drainage/fenestration was performed in 29.9%, limited resection in 27.6%, near-total resection in 16.1%, and gross total resection (GTR) in 25.4%. Radiotherapy was given in 46.0%. After a median follow-up of 6.5 years, hypothalamic obesity (HO) was present in 24.7% and panhypopituitarism with diabetes insipidus in 71.3%. Higher body mass index (BMI) SDS at diagnosis and Muller grade II at last magnetic resonance imaging of follow-up were associated with overweight/obesity. No association was found between extensiveness of resection and overweight/obesity at last follow-up. When comparing before and after centralization of care, rates of GTR remained similar, but BMI outcomes changed; mean ΔBMI SDS 1 year after diagnosis from 1.12 (SD 1.15) to 0.81 (SD 1.24), and HO after 1 year decreased from 33.3% to 12.0% (P = .067), and after 2 years from 28.6% to 6.7% (P = NS).
CONCLUSIONS
In our nationwide cohort, GTR was performed in a relatively low percentage of patients and extensiveness of resection was no longer associated with HO at follow-up. A trend toward improvement of BMI is observed since centralization of care, which needs further exploration.
Topics: Humans; Child; Craniopharyngioma; Cohort Studies; Retrospective Studies; Overweight; Quality of Life; Pituitary Neoplasms; Obesity; Treatment Outcome
PubMed: 37381692
DOI: 10.1093/neuonc/noad112 -
Scientific Reports Sep 2023Aquaporins are water channels found in the cell membrane, where they allow the passage of water molecules in and out of the cells. In the kidney collecting duct,...
Aquaporins are water channels found in the cell membrane, where they allow the passage of water molecules in and out of the cells. In the kidney collecting duct, arginine vasopressin-dependent trafficking of aquaporin-2 (AQP2) fine-tunes reabsorption of water from pre-urine, allowing precise regulation of the final urine volume. Point mutations in the gene for AQP2 may disturb this process and lead to nephrogenic diabetes insipidus (NDI), whereby patients void large volumes of highly hypo-osmotic urine. In recessive NDI, mutants of AQP2 are retained in the endoplasmic reticulum due to misfolding. Here we describe the structural and functional characterization of three AQP2 mutations associated with recessive NDI: T125M and T126M, situated close to a glycosylation site and A147T in the transmembrane region. Using a proteoliposome assay, we show that all three mutants permit the transport of water. The crystal structures of T125M and T126M together with biophysical characterization of all three mutants support that they retain the native structure, but that there is a significant destabilization of A147T. Our work provides unique molecular insights into the mechanisms behind recessive NDI as well as deepens our understanding of how misfolded proteins are recognized by the ER quality control system.
Topics: Humans; Aquaporin 2; Diabetes Insipidus, Nephrogenic; Arginine Vasopressin; Biological Assay; Biophysics; Diabetes Mellitus
PubMed: 37674034
DOI: 10.1038/s41598-023-41616-1 -
Pituitary Aug 2023Sleep disturbances are widespread and associated with pituitary diseases, even those under long-term therapeutic management. The aim of this study was to investigate...
PURPOSE
Sleep disturbances are widespread and associated with pituitary diseases, even those under long-term therapeutic management. The aim of this study was to investigate sleep quality in patients with non-functioning pituitary adenoma (NFPA) and determine the factors that might influence sleep quality, including the detailed features of replacement therapy.
METHODS
Eighty-two patients with NFPA and 82 age- and gender-matched control subjects were included. Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS) and International Physical Activity Questionnaire (IPAQ) were used.
RESULTS
In the NFPA group, 57.3% of patients had decreased sleep quality, compared to 35.4% in the control group (p=0.005). Although there was no relationship between the presence of hydrocortisone replacement and sleep quality (p>0.05), a strong positive correlation was observed between PSQI and morning hydrocortisone replacement time in patients with secondary adrenal insufficiency (r=0.834, p<0.001). Diabetes insipidus was found to be significantly higher in the group with decreased sleep quality (p=0.01). Moreover, there was a negative correlation between PSQI and IGF-1 in patients with NFPA (r=-0.259, p=0.01). A multivariate logistic regression model revealed that depression score and free T4 level in the upper half of the normal limit influence the sleep quality of patients with NFPA.
CONCLUSION
Our study indicated the presence of depression, and a free T4 level in the upper half of the normal range have an impact on the sleep quality of patients with NFPA. The time of hydrocortisone replacement might be important factor for improved sleep quality in patients with secondary adrenal insufficiency.
Topics: Humans; Pituitary Neoplasms; Hydrocortisone; Adenoma; Sleep Quality; Adrenal Insufficiency; Sleep
PubMed: 37261656
DOI: 10.1007/s11102-023-01328-1 -
Clinical Endocrinology Jan 2024The elucidation of the underlying cause of polyuria-polydipsia syndrome (PPS) is a challenging-especially in the differentiation of partial defects of arginine... (Review)
Review
The elucidation of the underlying cause of polyuria-polydipsia syndrome (PPS) is a challenging-especially in the differentiation of partial defects of arginine vasopressin (AVP) secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated-copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population-incorporating the differences in physiological regulation of water homeostasis, and safety requirements-before there is widespread adoption into clinical practice.
PubMed: 38164825
DOI: 10.1111/cen.15011 -
Clinical Nephrology Jun 2024The polyuria and polydipsia state in diabetes insipidus (DI) can be challenging to manage for patients and clinicians with significant impact on the patients'...
The polyuria and polydipsia state in diabetes insipidus (DI) can be challenging to manage for patients and clinicians with significant impact on the patients' well-being. A review of literature shows that nonsteroidal anti-inflammatory drugs (NSAIDs), thiazide and potassium-sparing diuretics, along with low dietary solute and protein, and high water intake remain the standard medical therapy. Although these therapeutic approaches improve symptoms, the urine-concentrating defect is still considerable, posing a serious risk to patient's life from hypovolemia if high fluid intake is not maintained. Our case describes the challenges faced with the medical management of a patient with nephrogenic DI that was only partially responsive to standard medical therapy, resulting in debilitating effects on the patient's quality of life.
PubMed: 38916496
DOI: 10.5414/CN111366