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Frontiers in Endocrinology 2023MIRAGE syndrome is a rare disease characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Herein, we...
Case report: a premature infant with severe intrauterine growth restriction, adrenal insufficiency, and inflammatory diarrhea: a genetically confirmed case of MIRAGE syndrome.
INTRODUCTION
MIRAGE syndrome is a rare disease characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Herein, we report the case of a girl with MIRAGE syndrome who presented with adrenal insufficiency and chronic diarrhea.
CASE PRESENTATION
The patient was born at 29 + 6 weeks of gestational age with a birth weight of 656 g (<3p). Her height and head circumference were also <3p. At birth, she presented with respiratory distress, meconium staining, and pneumomediastinum, which were managed with high-frequency ventilation and empirical antibiotics. Physical examination showed generalized hyperpigmentation and normal female genitalia. A few days after birth, polyuria and hypotension developed, and laboratory findings revealed hypoglycemia, hyponatremia, and hyperkalemia. Plasma adrenocorticotropic hormone levels were elevated with low serum cortisol levels and high plasma renin activity, which were suggestive of adrenal insufficiency. Hydrocortisone and fludrocortisone were introduced and maintained, and hyperpigmentation attenuated with time. Both kidneys looked dysplastic, and adrenal glands could not be traced on abdominal ultrasound. From the early days of life, thrombocytopenia and anemia were detected, but not to life-threatening level and slowly recovered up to the normal range. Despite aggressive nutritional support, weight gain and growth spurt were severely retarded during the hospital stay. Additionally, after introducing enteral feeding, she experienced severe diarrhea and subsequent perineal skin rashes and ulcerations. Fecal calprotectin level was highly elevated; however, a small bowel biopsy resulted in non-specific submucosal congestion. The patient was diagnosed with MIRAGE syndrome with SAMD9 gene mutation. She was discharged with tube feeding and elemental formula feeding continued, but chronic diarrhea persisted. By the time of the last follow-up at 15 months of corrected age, she was fortunately not subjected to severe invasive infection and myelodysplastic syndrome. However, she was dependent on tube feeding and demonstrated a severe developmental delay equivalent to approximately 5-6 months of age.
CONCLUSION
The early diagnosis of adrenal crisis and hormone replacement therapy can save the life of -patients with MIRAGE syndrome; however, chronic intractable diarrhea and growth and developmental delay continue to impede the patient's well-being.
Topics: Humans; Infant, Newborn; Infant; Female; Fetal Growth Retardation; Intracellular Signaling Peptides and Proteins; Adrenal Insufficiency; Infant, Premature; Diarrhea; Myelodysplastic Syndromes; Hyperpigmentation
PubMed: 37745698
DOI: 10.3389/fendo.2023.1242387 -
Endocrine Journal Jun 2023Arginine vasopressin (AVP) is an antidiuretic hormone synthesized principally in the hypothalamic supraoptic and paraventricular nuclei. The immunoglobulin heavy chain...
Arginine vasopressin (AVP) is an antidiuretic hormone synthesized principally in the hypothalamic supraoptic and paraventricular nuclei. The immunoglobulin heavy chain binding protein (BiP), one of the most abundant endoplasmic reticulum (ER) chaperones, is highly expressed in AVP neurons, even under basal conditions. Moreover, its expression is upregulated in proportion to the increase in AVP expression under dehydration. These data suggest that AVP neurons are constantly exposed to ER stress. BiP knockdown in AVP neurons induces ER stress and autophagy, resulting in AVP neuronal loss, indicating that BiP is pivotal in maintaining the AVP neuron system. Furthermore, inhibition of autophagy after BiP knockdown exacerbates AVP neuronal loss, suggesting that autophagy induced under ER stress is a protective cellular mechanism by which AVP neurons cope with ER stress. Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant disorder caused by mutations in the AVP gene. It is characterized by delayed-onset progressive polyuria and eventual AVP neuronal loss. In AVP neurons of FNDI model mice, mutant protein aggregates are confined to a specific compartment of the ER, called the ER-associated compartment (ERAC). The formation of ERACs contributes to maintaining the function of the remaining intact ER, and mutant protein aggregates in ERACs undergo autophagic-lysosomal degradation without isolation or translocation from the ER, representing a novel protein degradation system in the ER.
Topics: Mice; Animals; Arginine Vasopressin; Protein Aggregates; Vasopressins; Endoplasmic Reticulum Stress; Neurons; Diabetes Insipidus, Neurogenic
PubMed: 37211400
DOI: 10.1507/endocrj.EJ23-0193 -
Frontiers in Microbiology 2024Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease comprising five stages: fever, hypotension, oliguria, diuresis (polyuria), and convalescence....
INTRODUCTION
Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease comprising five stages: fever, hypotension, oliguria, diuresis (polyuria), and convalescence. Increased vascular permeability, coagulopathy, and renal injury are typical clinical features of HFRS, which has a case fatality rate of 1-15%. Despite this, a comprehensive meta-analyses of the clinical characteristics of patients who died from HFRS is lacking.
METHODS
Eleven Chinese- and English-language research databases were searched, including the China National Knowledge Infrastructure Database, Wanfang Database, SinoMed, VIP Database, PubMed, Embase, Scopus, Cochrane Library, Web of Science, Proquest, and Ovid, up to October 5, 2023. The search focused on clinical features of patients who died from HFRS. The extracted data were analyzed using STATA 14.0.
RESULTS
A total of 37 articles on 140,295 patients with laboratory-confirmed HFRS were included. Categorizing patients into those who died and those who survived, it was found that patients who died were older and more likely to smoke, have hypertension, and have diabetes. Significant differences were also observed in the clinical manifestations of multiple organ dysfunction syndrome, shock, occurrence of overlapping disease courses, cerebral edema, cerebral hemorrhage, toxic encephalopathy, convulsions, arrhythmias, heart failure, dyspnea, acute respiratory distress syndrome, pulmonary infection, liver damage, gastrointestinal bleeding, acute kidney injury, and urine protein levels. Compared to patients who survived, those who died were more likely to demonstrate elevated leukocyte count; decreased platelet count; increased lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels; prolonged activated partial thromboplastin time and prothrombin time; and low albumin and chloride levels and were more likely to use continuous renal therapy. Interestingly, patients who died received less dialysis and had shorter average length of hospital stay than those who survived.
CONCLUSION
Older patients and those with histories of smoking, hypertension, diabetes, central nervous system damage, heart damage, liver damage, kidney damage, or multiorgan dysfunction were at a high risk of death. The results can be used to assess patients' clinical presentations and assist with prognostication.https://www.crd.york.ac.uk/prospero/, (CRD42023454553).
PubMed: 38638893
DOI: 10.3389/fmicb.2024.1329683 -
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 -
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 -
Kidney International Reports Aug 2023Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic cause of kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the first...
INTRODUCTION
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic cause of kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the first drug with proven disease-modifying activity. Long-term treatment adherence is crucial, but a considerable fraction of patients discontinue treatment, because of aquaretic side effects.
METHODS
Twenty-four-hour urine was collected in 75 patients with ADPKD during up-titration of tolvaptan and, in combination with clinical characteristics, examined to identify factors influencing urine volume. Patient-reported outcomes were analyzed using the Short Form-12 (SF-12) and patient-reported outcomes questionnaires reporting micturition frequency and burden of urine volume.
RESULTS
Initiation of therapy led to a large increase in urine volume followed by only minor further increase during up-dosing. Younger patients and patients with better kidney function experienced a larger relative rise. Twenty-four-hour urine osmolality dropped by about 50% after therapy initiation independently of dose, with a considerable proportion of patients achieving adequate suppression. Sodium and potassium intake turned out to be the only significant modifiable factors for urine volume after multivariate linear regression models, whereas age and weight could be identified as non-modifiable factors. No change in quality of life (QoL) was detected in relation to treatment or urine volume using SF-12 questionnaires, a finding that was further supported by the results of the patient-reported outcomes assessment.
CONCLUSION
This study provides an in-detail analysis of factors associated with the degree of polyuria on tolvaptan and puts them into the context of QoL. These findings will contribute to optimized patient counseling regarding this treatment option in ADPKD.
PubMed: 37547529
DOI: 10.1016/j.ekir.2023.05.011 -
BMC Veterinary Research Aug 2023Chronic kidney disease (CKD) is a common cause of morbidity and mortality in captive wildlife species. However, CKD has been rarely documented in giant pandas.
BACKGROUND
Chronic kidney disease (CKD) is a common cause of morbidity and mortality in captive wildlife species. However, CKD has been rarely documented in giant pandas.
CASE PRESENTATION
The following report describes a case of an eight-year-old female giant panda showing clinical signs of epistaxis, bloody diarrhea, polyuria, azotemia and anemia. The animal died despite of supportive treatments. Necropsy was performed. Grossly, both kidneys were shrunken and scarred with pallor. Subcutis edema and petechia on the epicardium of the heart were observed. The tissue samples were made into paraffin sections and stained by H.E and special staining including Periodic Acid-Schiff (PAS), von Kossa, Masson's trichrome, Phosphotungstic acid-hematoxylin (PTAH), and Congo red. Histopathology examination revealed severe chronic tubulointerstitial nephritis with marked interstitial fibrosis, glomerulosclerosis, tubular atrophy and calcification in kidneys, and acute necrotizing hemorrhagic myocarditis with calcification in heart. Other lesions included intestinal hemorrhage, hepatic fatty degeneration and necrosis with hemosiderin, and splenic hemosiderin.
CONCLUSIONS
In summary, chronic kidney disease was finally diagnosed based on the association of clinical, gross, and histopathological findings. Heart failure secondary to CKD is the leading cause of death in this giant panda. The potential cause of CKD in this animal is possibly due to long term and uncontrolled hypertension. Blood pressure monitoring is essential in establishing the diagnosis and management of hypertension in giant panda.
Topics: Animals; Female; Ursidae; Hemosiderin; Renal Insufficiency, Chronic; Kidney; Hypertension
PubMed: 37612662
DOI: 10.1186/s12917-023-03663-8 -
Archivos Argentinos de Pediatria Dec 2023Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased...
Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.
Topics: Humans; Child; Hyponatremia; Diabetes Insipidus, Neurogenic; Polyuria; Ibuprofen; Research
PubMed: 37493586
DOI: 10.5546/aap.2023-10035.eng -
JFMS Open Reports 2024A 10-year-old neutered male domestic shorthair cat was presented with an abdominal mass, associated renal failure, chronic vomiting, anorexia and progressive...
CASE SUMMARY
A 10-year-old neutered male domestic shorthair cat was presented with an abdominal mass, associated renal failure, chronic vomiting, anorexia and progressive polyuria/polydipsia lasting for 3 weeks. Clinical examination and initial blood work revealed azotaemia, hypokalaemia and hypertension. Abdominal ultrasound showed an adrenal mass with a diameter of 3 cm near the right kidney. High serum aldosterone suggested primary hyperaldosteronism. Surgery enabled identification of the mass and its excision along with the right adrenal gland. Histologically, carcinoma of the adrenal cortex was diagnosed. Postoperatively, an increase in serum creatinine and potassium, along with a low serum aldosterone, led to a diagnosis of hypoaldosteronism. Mineralocorticoid therapy for 6 months was necessary, resulting in clinical and biological improvement.
RELEVANCE AND NOVEL INFORMATION
To our knowledge, this case describes the longest-lasting reported secondary hypoaldosteronism in a cat, after unilateral adrenalectomy for an adrenal carcinoma with hyperaldosteronism.
PubMed: 38746623
DOI: 10.1177/20551169241243012 -
Cureus Dec 2023This study aims to determine the frequency of urinary tract infection (UTI), identify the isolated bacteria, and assess antibiotic sensitivity in patients undergoing...
OBJECTIVE
This study aims to determine the frequency of urinary tract infection (UTI), identify the isolated bacteria, and assess antibiotic sensitivity in patients undergoing orthopedic implant fixation for hip fractures.
METHODOLOGY
After ethical approval from the institutional review board, this retrospective cross-sectional study was conducted at the Orthopedic Surgery Department of Dow University Hospital Karachi from June 2022 to June 2023. Through non-probability consecutive sampling, 186 patients above 16 years of age, of either gender, presenting with hip fractures such as intracapsular or extracapsular fractures, who underwent surgical fixation, were included in the study. A urine sample for urinalysis of these patients was sent on admission. Patients who presented with open fractures or those treated with conservative management were excluded from the study. The fracture diagnosis was confirmed on radiographs. All other relevant baseline investigations were also performed before surgery, per protocol, and urine-detailed and cultured reports were followed. In addition, each patient was asked about common symptoms of UTI before surgery and then diagnosed with UTI on positive urine culture and sensitivity (CS).
RESULTS
Out of 186 hip fracture patients, 98 (52.7%) were males and 88 (47.3%) were females, with a mean age of 61.03 ± 16.43 (16-96) years. Pre-operative UTI symptoms were reported by 79 patients, including dysuria (16; 20.3%), polyuria (19; 24.0%), and burning (44; 55.7%). UTI was diagnosed on culture and sensitivity report in 65 (34.9%) patients with as commonly diagnosed bacteria 35 (53.8%), followed by Enterococcus 8 (12.4%), Klebsiella 7 (10.9%), 3 (4.7%), and Acinetobacter 2 (3.1%) patients. was sensitive to amikacin, amoxicillin/clavulanic acid, ampicillin, cefixime, ceftriaxone, cefuroxime, ciprofloxacin, colistin, cotrimoxazole, fosfomycin, gentamycin, levofloxacin, meropenem, nitrofurantoin, polymyxin B, and piperacillin-tazobactam.
CONCLUSION
Urinary tract infection is common in patients undergoing orthopedic implant fixation for hip fractures, which can lead to potentially serious outcomes. Overall, hygiene, prompt treatment, and standard protocol should be utilized to treat those infected and minimize the spread.
PubMed: 38045632
DOI: 10.7759/cureus.49817