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Hormone Research in Paediatrics 2024Diagnosis of central diabetes insipidus (CDI) remains challenging. Water deprivation testing and hypertonic saline infusion, as established diagnostic tests, are...
INTRODUCTION
Diagnosis of central diabetes insipidus (CDI) remains challenging. Water deprivation testing and hypertonic saline infusion, as established diagnostic tests, are mentally and physically demanding for patients. Arginine-stimulated copeptin has been shown as a putative parameter for the differential diagnosis of CDI in adults.
METHODS
In this single-centre retrospective study, we identified paediatric patients with suspected pituitary disorders who underwent standard arginine testing. Patients with CDI, matched controls, and primary polydipsia (PP) were identified. Diagnoses were confirmed retrospectively using comprehensive clinical and diagnostic characteristics. Serum copeptin concentrations were measured using a commercially available automated immunofluorescence assay (B.R.A.H.M.S Copeptin-proAVP KRYPTOR®) in samples stored for a median of 4.6 years (1.3-10.84) and collected before and 60 min after arginine infusion. Cut-off analyses were performed using ROC curves.
RESULTS
Serum samples from 32 patients with CDI, 32 matched controls, and 5 patients with PP (n = 69; 51 males, 18 females) were available for analysis. Median copeptin concentrations increased from 4.47 pmol/L (interquartile range [IQR]: 3.47-8.36) to 6.96 pmol/L (IQR: 4.51-12.89; p < 0.001) in controls, from 1.46 pmol/L (IQR: 1.21-2.12) to 1.44 (IQR: 1.10-1.87; p = 0.645, ns) in CDI, and from 4.40 pmol/L (3.95-6.33) to 9.58 pmol/L (8.19-11.42; p < 0.001) in PP. The published cut-off value of 3.8 pmol/L revealed a sensitivity of 100% and a specificity of 86.5% in confirming CDI.
CONCLUSION
Our results suggest that arginine-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for CDI in paediatric patients, which may replace and simplify the conventional diagnostic pathway of water deprivation testing and hypertonic saline infusion.
Topics: Humans; Glycopeptides; Male; Female; Child; Arginine; Adolescent; Retrospective Studies; Diabetes Insipidus, Neurogenic; Child, Preschool
PubMed: 37607514
DOI: 10.1159/000532015 -
Zhonghua Fu Chan Ke Za Zhi Dec 2023To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). The clinical data of 86 AFLP...
To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m. There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Adult; Retrospective Studies; Premature Birth; Pregnancy Complications; Fatty Liver; Fetal Death; Stillbirth
PubMed: 38123195
DOI: 10.3760/cma.j.cn112141-20230814-00047 -
Hormone Research in Paediatrics May 2024Stimulated copeptin may provide an alternative to water deprivation testing (WDT) in the evaluation of polyuria-polydipsia syndrome (PPS). Though best studied, arginine...
INTRODUCTION
Stimulated copeptin may provide an alternative to water deprivation testing (WDT) in the evaluation of polyuria-polydipsia syndrome (PPS). Though best studied, arginine stimulation alone produces a modest copeptin response in children. We investigated the effectiveness of the arginine + LevoDopa/Carbidopa stimulation test (ALD-ST) for copeptin.
METHODS
47 healthy short children (controls), 10 children with primary polydipsia, and 10 children with AVP deficiency received arginine hydrochloride (500 mg/kg intravenously over 30 min) and Levodopa/carbidopa (10:1 ratio; 175 mg of
l -Dopa/m2 BSA) orally. Serum copeptin was measured at 0, 60, 90, and 120 min.RESULTS
In controls, ALD-ST increased copeptin from a median of 7.0 pmol/L (IQR 5.0-10.0) to a peak of 44.0 pmol/L (IQR 21.4-181.0) between 60 and 120 min (p < 0.001). Copeptin peak was higher in subjects who experienced nausea or vomiting (57%) than in those who did not (131.0 pmol/L [IQR 42.5-193.8] vs. 22.7 pmol/L [IQR 16.0-33.7], p < 0.001). While subjects with primary polydipsia had similar baseline (8.5 pmol/L [IQR 8.0-11.0]) and stimulated (125.2 pmol/L [IQR 87.6-174.0]) copeptin levels as controls, subjects with AVP deficiency had lower baseline (2.5 pmol/L [IQR 2.0-3.1]) and peak levels (4.6 pmol/L [IQR 2.4-6.0]). A peak copeptin of ≥9.3 pmol/L best predicted absence of complete or partial AVP deficiency with a sensitivity of 100% and specificity of 80%.
CONCLUSIONS
ALD-ST induced a robust peak copeptin in healthy short children and children with primary polydipsia. Nausea/vomiting, a side effect of ALD-ST, amplified the copeptin response. The ALD-ST may be a suitable initial screening test in children with PPS.
PubMed: 38705144
DOI: 10.1159/000539208 -
Behavioral and Brain Functions : BBF Nov 2023Compulsivity is considered a transdiagnostic dimension in obsessive-compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes...
Compulsivity is considered a transdiagnostic dimension in obsessive-compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes associated with abnormalities in cortico-striatal-thalamic-cortical circuitry. The present study investigated the structural morphology of white and gray matter in rats selected for low- (LD) and high- (HD) compulsive drinking behavior on a schedule-induced polydipsia (SIP) task. Regional brain morphology was assessed using ex-vivo high-resolution magnetic resonance imaging (MRI). Voxel-based morphometry of segmented MRI images revealed larger white matter volumes in anterior commissure and corpus callosum of HD rats compared with LD rats. HD rats also showed significantly larger regional volumes of dorsolateral orbitofrontal cortex, striatum, amygdala, hippocampus, midbrain, sub-thalamic nucleus, and cerebellum. By contrast, the medial prefrontal cortex was significantly smaller in HD rats compared with LD rats with no significant group differences in whole brain, ventricular, or cerebrospinal fluid volumes. These findings show that limbic cortico-basal ganglia structures implicated in impulse control disorders are distinct in rats that are vulnerable to develop compulsive behavior. Such abnormalities may be relevant to the etiology of compulsive disorders in humans.
Topics: Humans; Rats; Male; Animals; Brain; Compulsive Behavior; Amygdala; Basal Ganglia; Phenotype; Magnetic Resonance Imaging; Brain Mapping
PubMed: 37932782
DOI: 10.1186/s12993-023-00221-y -
Journal of Medical Case Reports Jul 2023Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as:...
BACKGROUND
Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease.
CASE PRESENTATION
A 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient's initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms.
CONCLUSION
This case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms.
Topics: Humans; Child; Female; Young Adult; Adult; Diabetes Mellitus, Type 1; Anemia, Iron-Deficiency; Celiac Disease; Gastritis; Autoimmune Diseases; Vitamin B 12 Deficiency; Vitamin B 12; Diarrhea; Pain; Insulins
PubMed: 37507704
DOI: 10.1186/s13256-023-04039-0 -
Problemy Endokrinologii Sep 2023Polydipsia is a pathologically increased thirst, satisfied by the intake of water in large quantities, which can manifest itself in various somatic or mental diseases...
Polydipsia is a pathologically increased thirst, satisfied by the intake of water in large quantities, which can manifest itself in various somatic or mental diseases and at first glance is similar to a true vasopressin deficiency. Central diabetes insipidus (CDI) is a disease of the hypothalamic-pituitary region characterized by the inability of the kidneys to reabsorb water and concentrate urine, which is based on a defect in the synthesis or secretion of vasopressin and is manifested by severe thirst and excretion of large amounts of hypotonic urine. The prevalence of the disease in the population is 1:25,000, which characterizes it as a fairly rare pathology of the hypothalamic-pituitary region. The peak incidence is between 30 and 40 years of age. According to various literary sources, the disease is not characterized by gender differences in prevalence, however, on the example of the Moscow population, women prevailed in the incidence structure of CND in a ratio of 2.2:1. Insidiousness, with apparent absences in the difficulty of diagnosing primary polydipsia, lies in the manifestations of water intoxication, thus this condition requires knowledge of clear diagnostic criteria by healthcare professionals and an interdisciplinary approach in the treatment of this condition. On the example of this clinical case, we will try to highlight the differential diagnostic criteria for psychogenic polydipsia in comparison with the true deficiency of arginine vasopressin (AVP) or central diabetes insipidus (CDI), which can be applied in real clinical practice.
Topics: Humans; Polydipsia, Psychogenic; Female; Adult; Diagnosis, Differential; Male; Thirst; Polydipsia; Water Intoxication
PubMed: 38796762
DOI: 10.14341/probl13359 -
Current Topics in Behavioral... Feb 2024The development of animal models that demonstrate excessive levels of alcohol consumption has played an important role in advancing our knowledge about neurobiological...
The development of animal models that demonstrate excessive levels of alcohol consumption has played an important role in advancing our knowledge about neurobiological underpinnings and environmental circumstances that engender such maladaptive behavior. The use of these preclinical models has also provided valuable opportunities for discovering new and novel therapeutic targets that may be useful in the treatment of alcohol use disorder (AUD). While no single model can fully capture the complexities of AUD, the goal is to develop animal models that closely approximate characteristics of heavy alcohol drinking in humans to enhance their translational value and utility. A variety of experimental approaches have been employed to produce the desired phenotype of interest-robust and reliable excessive levels of alcohol drinking. Here we provide an updated review of five animal models that are commonly used. The models entail procedural manipulations of scheduled access to alcohol (time of day, duration, frequency), periods of time when access to alcohol is withheld, and history of alcohol exposure. Specially, the models involve (a) scheduled access to alcohol, (b) scheduled periods of alcohol deprivation, (c) scheduled intermittent access to alcohol, (d) scheduled-induced polydipsia, and (e) chronic alcohol (dependence) and withdrawal experience. Each of the animal models possesses unique experimental features that engender excessive levels of alcohol consumption. Both advantages and disadvantages of each model are described along with discussion of future work to be considered in developing more optimal models. Ultimately, the validity and utility of these models will lie in their ability to aid in the discovery of new and novel potential therapeutic targets as well as serve as a platform to evaluate treatment strategies that effectively reduce excessive levels of alcohol consumption associated with AUD.
PubMed: 38340255
DOI: 10.1007/7854_2024_461 -
Endocrinology, Diabetes & Metabolism... Oct 2023A 20-year-old South Asian male presented with polyuria, polydipsia, HbA1c 81 mmol/mol, BMI 28.8 and family history of both type 1 and type 2 diabetes mellitus. As...
SUMMARY
A 20-year-old South Asian male presented with polyuria, polydipsia, HbA1c 81 mmol/mol, BMI 28.8 and family history of both type 1 and type 2 diabetes mellitus. As autoantibody testing was negative and c-peptide level demonstrated significant endogenous insulin secretion, type 1 diabetes was excluded. Given his age and family history, the differential diagnosis included maturity-onset diabetes of the young (MODY), a rare form of diabetes caused by a single-gene variant. A high probability of MODY was calculated and he was subsequently referred for genetic testing. Although a useful tool, the pre-test probability calculator for MODY is only validated in White Europeans. A heterogenous variant of unknown clinical significance of the NEUROD1 gene was detected, leading to gliclazide use with poor response. The patient responded well to metformin. Type 2 diabetes was considered the most likely diagnosis. This case highlights the diagnostic challenges in young patients of Asian ethnicity and the importance of interpreting genetic results of unknown significance within the clinical context. Ethnicity-specific BMI thresholds should be used when classifying patients as overweight or obese.
LEARNING POINTS
Variants of unknown significance detected by genetic sequencing should be interpreted within the context of the patient's other clinical parameters. It is important to use ethnicity-specific BMI thresholds for obesity. Diagnosis of type 2 diabetes mellitus at younger ages is becoming increasingly common. The pre-test probability calculator for MODY is only validated in White Europeans; although a useful guide, results should be interpreted with caution in patients of other ethnicities.
PubMed: 37855645
DOI: 10.1530/EDM-23-0024 -
JFMS Open Reports 2023A 3-year-old male neutered Sphynx cat was referred for history of chronically increased liver enzymes and lower urinary tract signs that were first reported when the cat...
CASE SUMMARY
A 3-year-old male neutered Sphynx cat was referred for history of chronically increased liver enzymes and lower urinary tract signs that were first reported when the cat was 5 months old. Urine metabolic profile revealed increased amino aciduria and glucosuria despite normoglycemia, suggesting Fanconi syndrome. Urine sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a banding pattern suggestive of primary tubular damage. Serial blood work showed non-regenerative normocytic normochromic anemia, persistently elevated liver enzymes, worsening azotemia and progressive hyperchloremic metabolic acidosis. Ultrasound revealed irregular kidneys and bilaterally hyperechoic cortices and medullae with a loss of normal corticomedullary distinction. Laparoscopic kidney biopsy revealed a moderate-to-severe chronic interstitial fibrosis with chronic lymphoplasmacytic inflammation, tubular degeneration and atrophy, mild glomerulosclerosis and mild large vascular amyloidosis. Tubular epithelial cell karyomegaly was multifocally evident throughout the kidney. The liver had moderate diffuse zone 1 hepatocellular atrophy, periportal fibrosis, biliary hyperplasia, mild perisinusoidal amyloidosis and hepatocyte karyomegaly in zones 2 and 3. The patient continued to decline and developed polyuria, polydipsia, lethargy and hyporexia irrespective of rigorous management, which failed to curtail the progressive anemia and azotemia. The patient was euthanized 8 months from the onset of clinical signs.
RELEVANCE AND NOVEL INFORMATION
Fanconi syndrome in cats is a rare condition, with most reports occurring secondary to chlorambucil treatment. This is the first known case of Fanconi syndrome occurring with concurrent hepatorenal epithelial karyomegaly in a young Sphynx cat.
PubMed: 37810577
DOI: 10.1177/20551169231190611 -
Cureus Sep 2023Patients with hyponatremia are at risk of severe complications including seizures, coma, and death. Psychiatric patients are particularly susceptible to death from...
Patients with hyponatremia are at risk of severe complications including seizures, coma, and death. Psychiatric patients are particularly susceptible to death from hyponatremia due to the association between psychiatric conditions and psychogenic polydipsia, characterized by water intoxication. We report a case of a schizophrenic patient who presented with altered mental status, leading to a differential diagnosis narrowed through clinical investigations to include hypovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and psychogenic polydipsia. This case underscores the need to inquire about schizophrenic patients' water intake, advocating for a standardized approach. The timely diagnosis of disorders causing electrolyte abnormalities can prevent severe complications and aid in the management of psychiatric patients.
PubMed: 37809219
DOI: 10.7759/cureus.44766