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Endocrinology, Diabetes & Metabolism... Jan 2019Thymic enlargement (TE) in Graves' disease (GD) is often diagnosed incidentally when chest imaging is done for unrelated reasons. This is becoming more common as the...
Thymic enlargement (TE) in Graves' disease (GD) is often diagnosed incidentally when chest imaging is done for unrelated reasons. This is becoming more common as the frequency of chest imaging increases. There are currently no clear guidelines for managing TE in GD. Subject 1 is a 36-year-old female who presented with weight loss, increased thirst and passage of urine and postural symptoms. Investigations confirmed GD, non-PTH-dependent hypercalcaemia and Addison's disease (AD). CT scans to exclude underlying malignancy showed TE but normal viscera. A diagnosis of hypercalcaemia due to GD and AD was made. Subject 2, a 52-year-old female, was investigated for recurrent chest infections, haemoptysis and weight loss. CT thorax to exclude chest malignancy, showed TE. Planned thoracotomy was postponed when investigations confirmed GD. Subject 3 is a 47-year-old female who presented with breathlessness, chest pain and shakiness. Investigations confirmed T3 toxicosis due to GD. A CT pulmonary angiogram to exclude pulmonary embolism showed TE. The CT appearances in all three subjects were consistent with benign TE. These subjects were given appropriate endocrine treatment only (without biopsy or thymectomy) as CT appearances showed the following appearances of benign TE - arrowhead shape, straight regular margins, absence of calcification and cyst formation and radiodensity equal to surrounding muscle. Furthermore, interval scans confirmed thymic regression of over 60% in 6 months after endocrine control. In subjects with CT appearances consistent with benign TE, a conservative policy with interval CT scans at 6 months after endocrine control will prevent inappropriate surgical intervention. Learning points: Chest imaging is common in modern clinical practice and incidental anterior mediastinal abnormalities are therefore diagnosed frequently. Thymic enlargement (TE) associated with Graves' disease (GD) is occasionally seen in view of the above. There is no validated strategy to manage TE in GD at present. However, CT (or MRI) scan features of the thymus may help characterise benign TE, and such subjects do not require thymic biopsy or surgery at presentation. In them, an expectant 'wait and see' policy is recommended with GD treatment only, as the thymus will show significant regression 6 months after endocrine control.
PubMed: 30703065
DOI: 10.1530/EDM-18-0119 -
Aging and Disease Oct 2018Loss-of-function mutations of progranulin are associated with frontotemporal dementia in humans, and its deficiency in mice is a model for this disease but with normal...
Loss-of-function mutations of progranulin are associated with frontotemporal dementia in humans, and its deficiency in mice is a model for this disease but with normal life expectancy and mild cognitive decline on aging. The present study shows that aging progranulin deficient mice develop progressive polydipsia and polyuria under standard housing conditions starting at middle age (6-9 months). They showed high water licking behavior and doubling of the normal daily drinking volume, associated with increased daily urine output and a decrease of urine osmolality, all maintained during water restriction. Creatinine clearance, urine urea, urine albumin and glucose were normal. Hence, there were no signs of osmotic diuresis or overt renal disease, other than a concentrating defect. In line, the kidney morphology and histology revealed a 50% increase of the kidney weight, kidney enlargement, mild infiltrations of the medulla with pro-inflammatory cells, widening of tubules but no overt signs of a glomerular or tubular pathology. Plasma vasopressin levels were on average about 3-fold higher than normal levels, suggesting that the water loss resulted from unresponsiveness of the collecting tubules towards vasopressin, and indeed aquaporin-2 immunofluorescence in collecting tubules was diminished, whereas renal and hypothalamic vasopressin were increased, the latter in spite of substantial astrogliosis in the hypothalamus. The data suggest that progranulin deficiency causes nephrogenic diabetes insipidus in mice during aging. Possibly, polydipsia in affected patients - eventually interpreted as psychogenic polydipsia - may point to a similar concentrating defect.
PubMed: 30271659
DOI: 10.14336/AD.2017.1127 -
International Journal of Environmental... Feb 2021The effects of microcystin-RR (MC-RR) on water metabolism were studied on Sprague-Dawley (SD) rats and KunMing (KM) mice. In the single dose toxicity test, polydipsia,...
The effects of microcystin-RR (MC-RR) on water metabolism were studied on Sprague-Dawley (SD) rats and KunMing (KM) mice. In the single dose toxicity test, polydipsia, polyuria, hematuria and proteinuria were found in group of rats receiving a MC-RR dose of 574.7 μg/kg, and could be relieved by dexamethasone (DXM). Gradient damage was observed in kidney and liver in rats with gradient MC-RR doses of 574.7, 287.3, and 143.7 μg/kg. No significant water metabolic changes or kidney injuries were observed in mice treated with MC-RR doses of 210.0, 105.0, and 52.5 μg/kg. In the continuous exposure test, in which mice were administrated with 140.0, 70.0, and 35.0 μg/kg MC-RR for 28 days, mice in the 140.0 μg/kg group presented increasing polydipsia, polyuria, and liver damage. However, no anatomic or histological changes, including related serological and urinary indices, were found in the kidney. In summary, abnormal water metabolism can be induced by MC-RR in rats through kidney injury in single dose exposure; the kidney of SD rats is more sensitive to MC-RR than that of KM mouse; and polydipsia and polyuria in mice exposed to MC-RR for 28 days occurred but could not be attributed to kidney damage.
Topics: Animals; Kidney; Liver; Mice; Microcystins; Rats; Rats, Sprague-Dawley; Water
PubMed: 33669356
DOI: 10.3390/ijerph18041900 -
PloS One 2016Pituitary-dependent hyperadrenocorticism (PDH) is mainly caused by pituitary corticotroph tumors in dogs. A characteristic feature of corticotroph tumors is their...
Pituitary-dependent hyperadrenocorticism (PDH) is mainly caused by pituitary corticotroph tumors in dogs. A characteristic feature of corticotroph tumors is their resistance to negative feedback by glucocorticoids. In some animal species, including dogs, the aberrant expression of 11β-hydroxysteroid dehydrogenase (11HSD), a cortisol metabolic enzyme, is observed in corticotroph tumors. We previously reported that carbenoxolone (CBX), an inhibitor of 11HSD, suppressed ACTH secretion from the pituitary gland, and decreased cortisol concentrations in healthy dogs. Therefore, the aim of this study was to investigate the therapeutic effects of CBX on dogs with PDH. Six dogs with PDH were treated with 60 to 80 mg/kg/day of CBX for 6 weeks, followed by trilostane, which is a commonly used agent for canine PDH. CBX treatment led to a gradual decrease in both basal and in corticotropic releasing hormone (CRH)-stimulated plasma ACTH concentrations and CRH-stimulated serum cortisol concentrations, without side effects. However, basal and stimulated ACTH and cortisol concentrations remained higher than those of healthy dogs, and clinical symptoms such as polydipsia and polyuria were not ameliorated. After a 2-week wash-out interval, trilostane was administered for 2 weeks. Although basal plasma ACTH concentrations were higher after trilostane treatment than CBX treatment, polydipsia and polyuria resolved in all six dogs. The reason for the lack of improvement in polydipsia and polyuria with CBX treatment is unclear. Other mechanisms, in addition to a partial decrease in ACTH secretion, are likely to be involved. In conclusion, this is the first study to report the in vivo effects of CBX in dogs with PDH. The findings suggest that CBX inhibits ACTH secretion from canine pituitary tumors, resulting in lower cortisol concentrations.
Topics: 11-beta-Hydroxysteroid Dehydrogenases; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Carbenoxolone; Dihydrotestosterone; Dog Diseases; Dogs; Female; Glucocorticoids; Hydrocortisone; Male; Pituitary ACTH Hypersecretion; Pituitary Gland
PubMed: 27824928
DOI: 10.1371/journal.pone.0166267 -
JPGN Reports Nov 2022Inflammatory bowel disease (IBD) is a lifelong, immune-mediated disorder that often occurs in childhood and is becoming increasingly common worldwide. Diagnosis of IBD...
Inflammatory bowel disease (IBD) is a lifelong, immune-mediated disorder that often occurs in childhood and is becoming increasingly common worldwide. Diagnosis of IBD in children remains difficult due to the spectrum of symptoms, including gastrointestinal and extraintestinal manifestations. Type 1 diabetes mellitus (T1D) is one of the most common autoimmune diseases in children and adolescents. Classic manifestations of T1D in young people include polyuria, polydipsia, abdominal pain, weight loss, and ketoacidosis. However, children with autoimmunity of pancreatic β-cells may remain euglycemic and asymptomatic for many years. An accurate and prompt diagnosis of IBD and T1D is particularly important in children because they can negatively affect growth, psychosocial function and overall well-being. We present a case in which a previously healthy child was co-diagnosed with Crohn disease and T1D during a routine pediatric evaluation in the outpatient clinic of a peripheral secondary hospital.
PubMed: 37168469
DOI: 10.1097/PG9.0000000000000265 -
BMJ Open Dec 2021Excessive water intake is rarely associated with life-threatening hyponatraemia. The aim of this study was to determine the clinical characteristics and outcomes of...
INTRODUCTION
Excessive water intake is rarely associated with life-threatening hyponatraemia. The aim of this study was to determine the clinical characteristics and outcomes of hyponatraemia associated with excess water intake.
METHODS
This review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies (case reports, observational or interventional studies) reporting excess water intake and hyponatraemia in adults (1946-2019) were included.
RESULTS
A total of 2970 articles were identified and 177 were included (88.7% case reports), consisting of 590 patients. The mean age was 46±16 years (95% CI 44 to 48 years), 47% female, 52% had a chronic psychiatric disorder and 31% had no underlying condition. The median volume of water consumed and serum sodium at presentation was 8 L/day (95% CI 8.9 to 12.2 L/day) and 118 mmol/L (95% CI 116 to 118 mmol/L), respectively. The motivator for increased water consumption was psychogenic polydipsia (55%); iatrogenic (13%); exercise (12%); habitual/dipsogenic polydipsia (7%) and other reasons (13%). The clinical features on presentation were severe in 53% (seizures, coma); moderate in 35% (confusion, vomiting, agitation) and mild in 5% (dizziness, lethargy, cognitive deficit) and not reported in 5% of studies. Treatment was supportive in 41% of studies (fluid restriction, treatment of the underlying cause, emergency care), and isotonic and hypertonic saline was used in 18% and 28% of cases, respectively. Treatment-related complications included osmotic demyelination (3%) and rhabdomyolysis (7%), and death occurred in 13% of cases.
CONCLUSION
Water intoxication is associated with significant morbidity and mortality and requires daily intake to substantially exceed population-based recommendations. The limitations of this analysis are the low quality and high risk of bias of the included studies.
PROSPERO REGISTRATION NUMBER
A pre-existing protocol in the international prospective register of systematic reviews was updated to incorporate any new amendments and reregistered at http://www.crd.york.ac.uk/PROSPERO (registration no. CRD42019129809).
Topics: Adult; Chronic Disease; Drinking; Female; Humans; Hyponatremia; Male; Middle Aged; Saline Solution, Hypertonic; Water
PubMed: 34887267
DOI: 10.1136/bmjopen-2020-046539 -
IET Nanobiotechnology Feb 2017The combination of the fields of software engineering, gadgets, and science has stood out among the most revolutionary future innovations. Health issues have been the...
The combination of the fields of software engineering, gadgets, and science has stood out among the most revolutionary future innovations. Health issues have been the focus of various engaging and explanatory studies. One such health-related dilemma is diabetes. Diabetes at its serious stage results in impaired vision. Increase in the glucose level is a critical parameter that could result in hyperglycaemia, hypoglycaemia, massive heart attack, strokes, and aneurysms. Monitoring the glucose level in blood is one of the control measures for diabetes in the affected population. A glucose monitoring framework interminably measures and screens the glucose level in blood. A novel framework for measuring the glucose level is proposed in this study. This study employs nanopellets that evaluate the glucose level. When the glucose level increases or decreases, it is continuously recorded and displayed using a microcontroller (mixed signal processor (MSP) 430). The data are then sent to the physician through global system for mobile communication. The typical blood glucose level of human being ranges from 70 to 110 mg/dl. When the insulin level builds up to certain point, hyperglycaemia occurs. When decreases, hypoglycaemia occurs. Hyperglycaemia leads to cataracts, oedema, hypertension, polyuria, and polydipsia. Hypoglycaemia causes perplexity, energy, insensateness, coma, and death.
Topics: Biosensing Techniques; Blood Glucose Self-Monitoring; Conductometry; Electrodes; Equipment Design; Equipment Failure Analysis; Glucose; Metal Nanoparticles; Reproducibility of Results; Semiconductors; Sensitivity and Specificity; Signal Processing, Computer-Assisted
PubMed: 28476968
DOI: 10.1049/iet-nbt.2016.0037 -
Endocrinology, Diabetes & Metabolism... Jan 2022Juxtaglomerular cell tumour (JGCT) is an unusually encountered clinical entity. A 33-year-old man with severe long-standing hypertension and hypokalaemia is described....
SUMMARY
Juxtaglomerular cell tumour (JGCT) is an unusually encountered clinical entity. A 33-year-old man with severe long-standing hypertension and hypokalaemia is described. The patient also suffered from polyuria, polydipsia, nocturia and severe headaches. On admission, laboratory investigation revealed hypokalaemia, kaliuresis, high aldosterone and renin levels, and the abdomen CT identified a mass of 4 cm at the right kidney. Kidney function was normal. Following nephrectomy, the histological investigation revealed the presence of a JGCT. Immunostaining was positive for CD34 as well as for smooth muscle actin and vimentin. Following surgery, a marked control of his hypertension with calcium channel blockers and normalization of the serum potassium, renin or aldosterone levels were reached. According to our findings, JGCT could be included in the differential diagnosis of secondary hypertension as it consists of a curable cause. The association of JGCT with hypertension and hypokalaemia focusing on the clinical presentation, diagnostic evaluation and management is herein discussed and a brief review of the existing literature is provided.
LEARNING POINTS
Juxtaglomerular cell tumours (JGCT), despite their rarity, should be included in the differential diagnosis of secondary hypertension as they consist of a curable cause of hypertension. JGCT could be presented with resistant hypertension along with hypokalaemia, kaliuresis and metabolic alkalosis. Early recognition and management can help to prevent cardiovascular complications. Imaging (enhanced CT scans) may be considered as the primary diagnostic tool for the detection of renal or JGCT. For the confirmation of the diagnosis, a histopathologic examination is needed.
PubMed: 35023474
DOI: 10.1530/EDM-21-0042 -
BMC Infectious Diseases Mar 2022Tuberculosis (TB) control is threatened by an increasing prevalence of diabetes mellitus (DM), particularly in endemic countries. Screening for DM is not routinely...
BACKGROUND
Tuberculosis (TB) control is threatened by an increasing prevalence of diabetes mellitus (DM), particularly in endemic countries. Screening for DM is not routinely implemented in Tanzania; therefore, we aimed to screen for DM at TB diagnosis using clinical-demographic markers.
METHODS
Our cross-sectional study recruited TB patients who received anti-TB treatment between October 2019 and September 2020 at health care facilities in three regions from Tanzania. Patients were screened for DM using DM symptoms (polydipsia, polyphagia and polyuria) and random blood glucose (RBG) testing. Patients with a history of DM and those with no history of DM but an RBG ≥ 7.8 mmol/L had point-of-care glycated haemoglobin (HbA1c) testing, and were considered to have DM if HbA1c was ≥ 48 mmol/mol.
RESULTS
Of 1344 TB patients, the mean age was 41.0 (± 17.0) years, and 64.7% were male. A total of 1011 (75.2%) had pulmonary TB, and 133 (10.4%) had at least one DM symptom. Overall, the prevalence of DM was 7.8%, of which 36 (2.8%) TB patients with no history of DM were newly diagnosed with DM by RBG testing. TB/DM patients were older than those with only TB (50.0 ± 14.0 years vs 40.0 ± 17.0 years, p < 0.001). Patients with RBG ≥ 7.8 mmol/L were more likely to have pulmonary TB (p = 0.003), age ≥ 35 years (p = 0.018), and have at least one DM symptom (p < 0.001). There was a substantial agreement (Kappa = 0.74) between the on-site glucometer and point-of-care HbA1c tests in detecting DM range of hyperglycemia.
CONCLUSION
The implementation of clinical-demographic markers and blood glucose screening identified the overall prevalence of DM and those at risk of DM in TB patients. Clinical-demographic markers are independent predictors for DM range hyperglycemia and highlight the importance of further diagnostic testing and early co-management of TB and DM.
Topics: Adult; Cross-Sectional Studies; Diabetes Mellitus; Humans; Male; Prevalence; Tanzania; Tuberculosis
PubMed: 35296241
DOI: 10.1186/s12879-022-07249-x -
Frontiers in Endocrinology 2021The aquaporin 2 (AQP2) plays a critical role in water reabsorption to maintain water homeostasis. AQP2 mutation leads to nephrogenic diabetes insipidus (NDI),...
The aquaporin 2 (AQP2) plays a critical role in water reabsorption to maintain water homeostasis. AQP2 mutation leads to nephrogenic diabetes insipidus (NDI), characterized by polyuria, polydipsia, and hypernatremia. We previously reported that a novel mutation (G215S) caused NDI in a boy. In this study, we aimed to elucidate the cell biological consequences of this mutation on AQP2 function and clarify the molecular pathogenic mechanism for NDI in this patient. First, we analyzed AQP2 expression in Madin-Darby canine kidney (MDCK) cells by AQP2-G215S or AQP2-WT plasmid transfection and found significantly decreased AQP2-G215S expression in cytoplasmic membrane compared with AQP2-WT, independent of forskolin treatment. Further, we found co-localization of endoplasmic reticulum (ER) marker (Calnexin) with AQP2-G215S rather than AQP2-WT in MDCK cells by immunocytochemistry. The functional analysis showed that MDCK cells transfected with AQP2-G215S displayed reduced water permeability compared with AQP2-WT. Visualization of AQP2 structure implied that AQP2-G215S mutation might interrupt the folding of the sixth transmembrane α-helix and/or the packing of α-helices, resulting in the misfolding of monomer and further impaired formation of tetramer. Taken together, these findings suggested that AQP2-G215S was misfolded and retained in the ER and could not be translocated to the apical membrane to function as a water channel, which revealed the molecular pathogenic mechanism of AQP2-G215S mutation and explained for the phenotype of NDI in this patient.
Topics: Animals; Aquaporin 2; Cell Membrane; Diabetes Insipidus, Nephrogenic; Dogs; Endoplasmic Reticulum; Madin Darby Canine Kidney Cells; Mutation; Phenotype; Protein Conformation; Protein Folding; Protein Transport
PubMed: 34512542
DOI: 10.3389/fendo.2021.665145