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BMC Veterinary Research Jul 2023Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting...
BACKGROUND
Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting level of < 5% and high level of comfort there may be complacency and underestimation of the impact side effects of corticosteroids may have on a pet and pet owner.
OBJECTIVE
The objective of this clinical study was to describe the experience and perception of an owner who administered anti-inflammatory doses of oral prednisolone and prednisone to their dog for up to 14 days. We hypothesized dogs receiving anti-inflammatory doses of prednisone and prednisolone would experience much greater rates of side effects by day 14 then reported in current literature.
ANIMALS
There were 45 dogs initially enrolled in the study.
RESULTS
At each study point, 31 owners provided results. On day 5, 74% (23/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, polypnea and/or increased vocalization, with 11 individuals (35%) reporting these changes greatly increased. On day 14, 90% of owners (28/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, and/or polypnea as the most common changes noted. Overall, 61% (19/31) of owners reported an increase in filling of the water bowl over baseline and one-third (11/31) of pet owners reported cleaning up urinary accidents for pets who had been continent prior to the start of the study. Pet owner steroid satisfaction remained high through day 14 at 4.5/5 (1 = very unsatisfied, 5 = very satisfied).
CONCLUSION
This study highlights the impact short term anti-inflammatory doses of prednisone or prednisolone have on dog behaviour and confirms our hypothesis that by day 14, 90% of dogs experienced one or more behaviour changes, with polyuria and polydipsia most commonly reported. Adverse events were noted regardless of starting dosage or regimen. Although most pet owners expressed satisfaction with steroid treatment due to its high efficacy, 70% would select a more costly treatment if that treatment had fewer side effects.
Topics: Dogs; Animals; Prednisolone; Prednisone; Polyuria; Drug-Related Side Effects and Adverse Reactions; Hyperphagia; Polydipsia; Perception; Dog Diseases
PubMed: 37488543
DOI: 10.1186/s12917-023-03644-x -
IScience Aug 2023Sodium glucose cotransporters (SGLTs) are transport proteins that are expressed throughout the body. Inhibition of SGLTs is a relatively novel therapeutic strategy to...
Sodium glucose cotransporters (SGLTs) are transport proteins that are expressed throughout the body. Inhibition of SGLTs is a relatively novel therapeutic strategy to improve glycemic control and has been shown to promote cardiorenal benefits. Dual SGLT1/2 inhibitors (SGLT1/2i) such as sotagliflozin target both SGLT1 and 2 proteins. Sotagliflozin or vehicle was administered to diabetic Akimba mice for 8 weeks at a dose of 25 mg/kg/day. Urine glucose levels, water consumption, and body weight were measured weekly. Serum, kidney, pancreas, and brain tissue were harvested under terminal anesthesia. Tissues were assessed using immunohistochemistry or ELISA techniques. Treatment with sotagliflozin promoted multiple metabolic benefits in diabetic Akimba mice resulting in decreased blood glucose and improved polydipsia. Sotagliflozin also prevented mortalities associated with diabetes. Our data suggests that there is the possibility that combined SGLT1/2i may be superior to SGLT2i in controlling glucose homeostasis and provides protection of multiple organs affected by diabetes.
PubMed: 37520739
DOI: 10.1016/j.isci.2023.107260 -
Cureus Oct 2023Diabetes mellitus (DM) is a complex endocrine disorder characterized by abnormally high levels of glucose, also called hyperglycemia. DM usually occurs when the body...
Diabetes mellitus (DM) is a complex endocrine disorder characterized by abnormally high levels of glucose, also called hyperglycemia. DM usually occurs when the body does not produce enough insulin or cannot respond to the insulin in the body. Type 1 diabetes mellitus (T1DM) or insulin-dependent diabetes is an autoimmune disease that affects around 8 million people in the world. Patients with T1DM experience an array of symptoms such as polyuria, polydipsia, and weight loss. These patients are prone to immediate life-threatening complications, including hypoglycemia and diabetic ketoacidosis. These patients are also at increased risk of ischemic heart disease, stroke, chronic kidney disease, vision loss, and even damage to nerve endings resulting in neuropathy. In this article, we will discuss type 1 diabetes mellitus and the different treatment options, focusing primarily on the Food and Drug Administration (FDA)-approved first cellular therapy for T1DM, donislecel.
PubMed: 37954726
DOI: 10.7759/cureus.46912 -
Orphanet Journal of Rare Diseases Mar 2022Craniopharyngioma (CP) and cranial fibrous dysplasia (CFD) are rare embryonic benign cranial diseases that most commonly present during childhood or adolescence. The... (Review)
Review
BACKGROUND
Craniopharyngioma (CP) and cranial fibrous dysplasia (CFD) are rare embryonic benign cranial diseases that most commonly present during childhood or adolescence. The coexistence of CP and CFD is extremely rare and has not yet been reported.
METHODS
We retrospectively reviewed the data of five patients with concomitant CP and CFD treated at Beijing Tiantan Hospital from January 2003 to January 2021 and summarized their clinicopathological features, treatment modalities, and outcomes. We also performed a comprehensive literature review, tested the patients for characteristic GNAS gene mutations related to CFD, and tested the CP specimens for corresponding Gsα protein to explore the potential connection leading to the coexistence of CP and CFD.
RESULTS
The cohort comprised four men and one woman (median age, 39 years). The symptoms mainly included headache, dizziness, fatigue, polyuria/polydipsia, hypogonadism, and blurred vision. CFD most commonly involved the sphenoid bone (n = 4). Four patients underwent surgery to remove the CP (one trans-sphenoidal and three transcranial resections); complete and subtotal resection were achieved in two patients, respectively. The tumor subtype was adamantinomatous in three patients and unknown in one. The common postoperative complications were panhypopituitarism, diabetes insipidus, and hypothyroidism. The mean follow-up duration was 57.2 months. Two patients required postoperative hormone replacement therapy. Three patients underwent genetic study of the tumor specimens; GNAS mutations were not detected, but these patients were positive for Gsα protein.
CONCLUSIONS
Although a definite causative relationship has not been proved, the coexistence of CP and CFD means that potential interplay or an atypical fibrous dysplasia course as uncommon manifestations of CP cannot be excluded. It is more challenging to initiate prompt diagnosis and appropriate treatment for concomitant CP and CFD than for solitary CP because of skull base deformations. Current management strategies are aimed at surgical treating the CP and regularly monitoring the CFD.
Topics: Adolescent; Adult; Craniopharyngioma; Female; Fibrous Dysplasia of Bone; Humans; Male; Pituitary Neoplasms; Retrospective Studies; Skull
PubMed: 35303908
DOI: 10.1186/s13023-022-02281-1 -
Endocrinology, Diabetes & Metabolism... Oct 2021Hyponatraemia is the most common electrolyte disturbance in hospitalised patients and is associated with numerous adverse outcomes. Patients with schizophrenia are...
SUMMARY
Hyponatraemia is the most common electrolyte disturbance in hospitalised patients and is associated with numerous adverse outcomes. Patients with schizophrenia are particularly susceptible to hyponatraemia, in part due to the close association between this condition and primary polydipsia. We report the case of a 57-year-old woman with schizophrenia and primary polydipsia who was receiving inpatient psychiatric care. She became increasingly confused, had multiple episodes of vomiting, and collapsed 1 week after being commenced on quetiapine 300 mg. On examination, she was hypertensive and her Glasgow coma scale was nine. She had a fixed gaze palsy and a rigid, flexed posture. Investigations revealed extreme hyponatraemia with a serum sodium of 97 mmol/L. A CT brain demonstrated diffused cerebral oedema with sulcal and ventricular effacement. A urine sodium and serum osmolality were consistent with SIAD, which was stimulated by the introduction of quetiapine. The antidiuretic effect of vasopressin limited the kidney's ability to excrete free water in response to the patients' excessive water intake, resulting in extreme, dilutional hyponatraemia. The patient was treated with two 100 mL boluses of hypertonic 3% saline but deteriorated further and required intubation. She had a complicated ICU course but went on to make a full neurological recovery. This is one of the lowest sodium levels attributed to primary polydipsia or second-generation antipsychotics reported in the literature.
LEARNING POINTS
The combination of primary polydipsia and SIAD can lead to a life-threatening, extreme hyponatraemia. SIAD is an uncommon side effect of second-generation anti-psychotics. Serum sodium should be monitored in patients with primary polydipsia when commencing or adjusting psychotropic medications. Symptomatic hyponatraemia is a medical emergency that requires treatment with boluses of hypertonic 3% saline. A serum sodium of less than 105 mmol/L is associated with an increased risk of osmotic demyelination syndrome, therefore the correction should not exceed 8 mmol/L over 24 h.
PubMed: 34653996
DOI: 10.1530/EDM-21-0028 -
European Journal of Endocrinology Jul 2019Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia.... (Review)
Review
Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since decades, the gold standard for differentiation has been the water deprivation test, which has limitations leading to an overall unsatisfying diagnostic accuracy. Furthermore, it is cumbersome for patients with a long test duration. Clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. The direct test including vasopressin (AVP) measurement upon osmotic stimulation was meant to overcome these limitations, but failed to enter clinical practice mainly due to technical constraints of the AVP assay. Copeptin is secreted in equimolar amount to AVP but can easily be measured with a sandwich immunoassay. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation and has led to a 'revival' of the direct test in the differential diagnosis of DI. We have shown that a baseline copeptin, without prior thirsting, unequivocally identifies patients with nephrogenic DI. In contrast, for the differentiation between central DI and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is superior to the water deprivation test. Close sodium monitoring during the test is a prerequisite. Further new test methods are currently evaluated and might provide an even simpler way of differential diagnosis in the future.
Topics: Awards and Prizes; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Glycopeptides; Humans; Polydipsia; Polyuria; Saline Solution, Hypertonic; Syndrome; Vasopressins
PubMed: 31067508
DOI: 10.1530/EJE-19-0163 -
Maedica Jun 2021Diabetic ketoacidosis is an acute major life-threatening complication of diabetes, characterized by hyperglycemia, ketoacidosis and ketonuria, which can be life...
Diabetic ketoacidosis is an acute major life-threatening complication of diabetes, characterized by hyperglycemia, ketoacidosis and ketonuria, which can be life threatening if it is not promptly recognized and treated. This occurs mainly in patients with type 1 diabetes, but stressors like trauma and infection can increase the risk of ketoacidosis in other forms of diabetes such as type 2 diabetes. Type 2 diabetes mellitus is a complex metabolic disorder of heterogeneous etiology with behavioral, social, and environmental risk factors that unmask the effects of genetic susceptibility. Recent studies indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities. C-peptide is a useful and widely used method of assessing pancreatic beta cell function given his structure: part of proinsulin which is cleaved prior to co-secretion with insulin from pancreatic beta cells. This is used as a tool in the differentiation of type 1 diabetes from type 2 but also other types of diabetes. We present a 12-year-old previously healthy male who was hospitalized in our clinic for polydipsia, polyuria, weight loss and emesis, with symptom onset 10 days prior to admission. On the admission day, he presented to the emergency room for progressively increasing somnolence, apathy, decreased muscle tone and urinary incontinence. Physical examination was significant for grade I obesity [height 168 cm and weight 90 kg, yielding a body index mass (BMI) of 31.78 kg/m2, percentile >97%], lethargy, slurred speech, high blood pressure (145/90 mmHg), tachycardia (145 beats per minute) and acanthosis nigricans. Considering his physical examination, laboratory tests and clinical evolution, he was diagnosed with type 2 diabetes mellitus complicated with hyperosmolar hyperglycemic state and diabetic ketoacidosis. Diabetic ketoacidosis should be considered in the differential diagnosis of metabolic decompensation in all types of diabetes. Although type 2 diabetes mellitus seems to be still rare in childhood and adolescence, prevention and treatment of type 2 diabetes mellitus should become public awareness and public health intervention programs. The particularity of this case was the unusual onset of diabetes mellitus type 2 in a male child with metabolic syndrome.
PubMed: 34621360
DOI: 10.26574/maedica.2020.16.2.320 -
Nutrients Jul 2019The detrimental effects of dehydration, to both mental and physical health, are well-described. The potential adverse consequences of overhydration, however, are less... (Review)
Review
The detrimental effects of dehydration, to both mental and physical health, are well-described. The potential adverse consequences of overhydration, however, are less understood. The difficulty for most humans to routinely ingest ≥2 liters (L)-or "eight glasses"-of water per day highlights the likely presence of an inhibitory neural circuit which limits the deleterious consequences of overdrinking in mammals but can be consciously overridden in humans. This review summarizes the existing data obtained from both animal (mostly rodent) and human studies regarding the physiology, psychology, and pathology of overhydration. The physiology section will highlight the molecular strength and significance of aquaporin-2 (AQP2) water channel downregulation, in response to chronic anti-diuretic hormone suppression. Absence of the anti-diuretic hormone, arginine vasopressin (AVP), facilitates copious free water urinary excretion (polyuria) in equal volumes to polydipsia to maintain plasma tonicity within normal physiological limits. The psychology section will highlight reasons why humans and rodents may volitionally overdrink, likely in response to anxiety or social isolation whereas polydipsia triggers mesolimbic reward pathways. Lastly, the potential acute (water intoxication) and chronic (urinary bladder distension, ureter dilation and hydronephrosis) pathologies associated with overhydration will be examined largely from the perspective of human case reports and early animal trials.
Topics: Animals; Aquaporin 2; Arginine Vasopressin; Brain; Cognition; Disease Models, Animal; Drinking; Female; Humans; Male; Mice; Organism Hydration Status; Polydipsia; Signal Transduction; Urination; Volition; Water Intoxication; Water-Electrolyte Balance
PubMed: 31284689
DOI: 10.3390/nu11071539 -
Acta Endocrinologica (Bucharest,... 2023Patients with chronic schizophrenia and psychosis are more prone to develop hyponatremia. Hyponatremia could be due to medications e.g. antidepressants/antipsychotics or...
Patients with chronic schizophrenia and psychosis are more prone to develop hyponatremia. Hyponatremia could be due to medications e.g. antidepressants/antipsychotics or secondary to psychogenic polydipsia. They often present with altered consciousness, seizures and falls. Rapid correction of hyponatremia in patients with psychogenic polydipsia has been associated to cause rhabdomyolysis, an under-recognized yet serious condition which if left untreated can result in various complications e.g. acute kidney injury, electrolyte abnormalities. We report a case of young patient who had background illness of schizophrenia and presented to department with severe hyponatremia secondary to psychogenic polydipsia and was eventually diagnosed as case of rhabdomyolysis due to rapid correction of hyponatremia. Objective of case report is to highlight the correct diagnosis of underlying cause of hyponatremia and challenges associated with managing rhabdomyolysis with IV fluids that can result in worsening of hyponatremia, hence emphasizing the importance of close monitoring of sodium levels and measurement of creatine kinase in any patient who presents with severe hyponatremia, particularly in the presence of other risk factors for rhabdomyolysis and consideration of careful fluid administration strategies in relation to the relative onset and risk of over-correcting hyponatremia.
PubMed: 38356977
DOI: 10.4183/aeb.2023.345 -
Frontiers in Immunology 2023Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can... (Review)
Review
BACKGROUND
Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient's immune system. Here, we report a rare case of a new onset of diabetes mellitus (DM), caused by nivolumab, and we discuss the feasible treatment options with a focus on TNF antagonism.
CASE PRESENTATION
A 50-year-old man was diagnosed with metastatic renal cell carcinoma. Due to systemic progression, a combined immunotherapy with ipilimumab and nivolumab was initiated, according to the current study protocol (SAKK 07/17). The administration of ipilimumab was stopped after 10 months, due to partial response as seen in the computer tomography (CT), and nivolumab was continued as monotherapy. Fourteen months after the start of the treatment, the patient was admitted to the emergency department with lethargy, vomiting, blurred vision, polydipsia, and polyuria. The diagnosis of DM with diabetic ketoacidosis was established, although autoantibodies to β-cells were not detectable. Intravenous fluids and insulin infusion treatment were immediately initiated with switching to a subcutaneous administration after 1 day. In addition, the patient received an infusion of the TNF inhibitor infliximab 4 days and 2 weeks after the initial diagnosis of DM. However, the C-peptide values remained low, indicating a sustained insulin deficiency, and the patient remained on basal bolus insulin treatment. Two months later, nivolumab treatment was restarted without destabilization of the diabetic situation.
CONCLUSIONS
In contrast to the treatment of other irAEs, the administration of corticosteroids is not recommended in ICI-induced DM. The options for further treatment are mainly based on the low numbers of case series and case reports. In our case, the administration of infliximab-in an attempt to salvage the function of β-cells-was not successful, and this is in contrast to some previous reports. This apparent discrepancy may be explained by the absence of insulin resistance in our case. There is so far no evidence for immunosuppressive treatment in this situation. Prompt recognition and immediate start of insulin treatment are most important in its management.
Topics: Male; Humans; Middle Aged; Nivolumab; Ipilimumab; Carcinoma, Renal Cell; Antineoplastic Agents, Immunological; Infliximab; Kidney Neoplasms; Diabetes Mellitus; Insulins
PubMed: 37965350
DOI: 10.3389/fimmu.2023.1248919