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Molecular Genetics and Metabolism... Mar 2024Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disorder caused by biallelic pathogenic variants in genes related to the flavoprotein...
BACKGROUND
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disorder caused by biallelic pathogenic variants in genes related to the flavoprotein complex. Dysfunction of the complex leads to impaired fatty acid oxidation and ketone body production which can cause hypoketotic hypoglycemia with prolonged fasting. Patients with fatty acid oxidation disorders (FAODs) such as MADD are treated primarily with a dietary regimen consisting of high-carbohydrate foods and avoidance of prolonged fasting. However, information on the long-term sequelae associated with this diet have not been accumulated. In general, high-carbohydrate diets can induce diseases such as type 2 diabetes mellitus (T2DM), although few patients with both MADD and T2DM have been reported.
CASE
We present the case of a 32-year-old man with MADD who was on a high-carbohydrate diet for >30 years and exhibited symptoms resembling diabetic ketoacidosis. He presented with polydipsia, polyuria, and weight loss with a decrease in body mass index from 31 to 25 kg/m over 2 months. Laboratory tests revealed a HbA1c level of 13.9%; however, the patient did not show metabolic acidosis but only mild ketosis.
DISCUSSION/CONCLUSION
This report emphasizes the potential association between long-term adherence to high-carbohydrate dietary therapy and T2DM development. Moreover, this case underscores the difficulty of detecting diabetic ketosis in patients with FAODs such as MADD due to their inability to produce ketone bodies. These findings warrant further research of the long-term complications associated with this diet as well as warning of the potential progression of diabetes in patients with FAODs such as MADD.
PubMed: 38469101
DOI: 10.1016/j.ymgmr.2024.101061 -
Wiener Klinische Wochenschrift Feb 2024Hyponatremia is a disorder of water homeostasis. Water balance is maintained by the collaboration of renal function and cerebral structures, which regulate thirst...
Hyponatremia is a disorder of water homeostasis. Water balance is maintained by the collaboration of renal function and cerebral structures, which regulate thirst mechanisms and secretion of the antidiuretic hormone. Measurement of serum-osmolality, urine osmolality and urine-sodium concentration help to diagnose the different reasons for hyponatremia. Hyponatremia induces cerebral edema and might lead to severe neurological symptoms, which need acute therapy. Also, mild forms of hyponatremia should be treated causally, or at least symptomatically. An inadequate fast increase of the serum sodium level should be avoided, because it raises the risk of cerebral osmotic demyelination. Basic pathophysiological knowledge is necessary to identify the different reasons for hyponatremia which need different therapeutic procedures.
Topics: Humans; Hyponatremia; Austria; Consensus; Nephrology; Water; Sodium
PubMed: 38421476
DOI: 10.1007/s00508-024-02325-5 -
Cureus Jan 2024Dupilumab is a fully humanized monoclonal antibody that binds to IL-4 receptors and blocks IL-4 and IL-13 mediated T-helper 2 (Th2) responses. Dupilumab is estimated to...
Dupilumab is a fully humanized monoclonal antibody that binds to IL-4 receptors and blocks IL-4 and IL-13 mediated T-helper 2 (Th2) responses. Dupilumab is estimated to be used by over 600,000 patients worldwide for the treatment of atopic dermatitis and other immunologic conditions. Recently, a 66-year-old male patient being treated for atopic dermatitis with dupilumab presented to the clinic with complaints of polyuria and polydipsia. Upon initial testing, the patient was found to have considerable hyperglycemia. Upon genetic testing, he showed no predisposition for autoimmune diabetes and was negative for type I diabetes mellitus-associated human leukocyte antigen (HLA) genes. After immediate cessation of dupilumab, and with subsequent insulin therapy, the patient was able to obtain glycemic control. Following taper and eventual cessation of insulin therapy and over the course of seven months, the patient was able to achieve a full resolution of symptoms and his glycosylated hemoglobin (HgBA1c) levels returned to normal ranges. This case represents only the second documented case of dupilumab-induced diabetes mellitus and is the first known documented case of dupilumab-induced diabetes mellitus in a non-genetically predisposed individual. This case also describes a previously unobserved spontaneous resolution of symptoms upon cessation of the drug. This case further illustrates the potential existence of immunogenic or immunomodulatory side effects of the monoclonal antibody dupilumab that can affect patients who are both genetically and non-genetically predisposed to autoimmune diabetes mellitus.
PubMed: 38414708
DOI: 10.7759/cureus.53080 -
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 Neuroscience 2024Vanishing white matter (VWM) is a devastating autosomal recessive leukodystrophy, resulting in neurological deterioration and premature death, and without curative...
Vanishing white matter (VWM) is a devastating autosomal recessive leukodystrophy, resulting in neurological deterioration and premature death, and without curative treatment. Pathogenic hypomorphic variants in subunits of the eukaryotic initiation factor 2B (eIF2B) cause VWM. eIF2B is required for regulating the integrated stress response (ISR), a physiological response to cellular stress. In patients' central nervous system, reduced eIF2B activity causes deregulation of the ISR. In VWM mouse models, the extent of ISR deregulation correlates with disease severity. One approach to restoring eIF2B activity is by inhibition of GSK3β, a kinase that phosphorylates eIF2B and reduces its activity. Lithium, an inhibitor of GSK3β, is thus expected to stimulate eIF2B activity and ameliorate VWM symptoms. The effects of lithium were tested in zebrafish and mouse VWM models. Lithium improved motor behavior in homozygous mutant zebrafish. In lithium-treated mutant mice, a paradoxical increase in some ISR transcripts was found. Furthermore, at the dosage tested, lithium induced significant polydipsia in both healthy controls and mutant mice and did not increase the expression of other markers of lithium efficacy. In conclusion, lithium is not a drug of choice for further development in VWM based on the limited or lack of efficacy and significant side-effect profile.
PubMed: 38352041
DOI: 10.3389/fnins.2024.1275744 -
AACE Clinical Case Reports 2024Olanzapine is a second-generation antipsychotic medication with increased side effects of weight gain, hyperglycemia, and insulin resistance. Here we describe a case of...
BACKGROUND/OBJECTIVE
Olanzapine is a second-generation antipsychotic medication with increased side effects of weight gain, hyperglycemia, and insulin resistance. Here we describe a case of diabetic ketoacidosis in a patient who started taking olanzapine 12 weeks before she presented.
CASE REPORT
A 73-year-old African-American female presented with a 1-week history of confusion, polyuria, and polydipsia. Her past medical history included type 2 diabetes mellitus, hyperlipidemia, and severe depression with psychotic features. Her medications were olanzapine 5 mg, duloxetine 90 mg, and rosuvastatin 5 mg daily. Three weeks prior, she was diagnosed with COVID-19 and treated for a urinary tract infection. Her physical exam upon admission included severely dry mucous membranes and labored respirations. The circulating glucose was 748 mg/dL (70-110), anion gap 39 mmol/L (7-16), and hemoglobin A1c (HgbA1c) 11.8% (105 mmol/mol). Three months prior, her HgbA1c was 6.7% (50 mmol/mol). She was treated with intravenous fluids and continuous insulin infusion followed by subcutaneous basal-bolus glargine and lispro after an anion gap of 13 mmol/L (7-16) was obtained. Two weeks into her hospitalization, olanzapine was discontinued. She was discharged on 10 units of glargine and metformin 500 mg twice daily. Five months after discharge, she indicated not taking any of the prescribed insulin or metformin. At this follow-up, her HgbA1c was 6.7%.
DISCUSSION
Olanzapine may impair insulin secretion by causing pancreatic beta-cell apoptosis.
CONCLUSION
Increased awareness of the generalized metabolic effects and risk of diabetic ketoacidosis associated with antipsychotic medications is needed to develop a safe treatment plan for patients.
PubMed: 38303763
DOI: 10.1016/j.aace.2023.10.006 -
Therapeutic Advances in Neurological... 2023Granulomatosis or eosinophilic granulomatosis with polyangiitis (GPA/EGPA) can affect multiple organs resulting in heterogeneous symptoms and phenotypes. Pituitary gland...
Granulomatosis or eosinophilic granulomatosis with polyangiitis (GPA/EGPA) can affect multiple organs resulting in heterogeneous symptoms and phenotypes. Pituitary gland dysfunction rarely occurs in GPA (1-3%) and even less in EGPA (two case reports). Here, we report a case of a 51-year-old female patient with a four-year history of EGPA who presented with new polydipsia and polyuria. Laboratory testing and magnetic resonance imaging (MRI) confirmed pituitary gland dysfunction caused by a hypophysitis. Therapeutic adjustment with a switch from dupilumab to mepolizumab resulted in a decrease in clinical symptoms, inflammation in MRI, and normalization of C-reactive protein in serum. This case underlines hypophysitis as a rare organ involvement also in EGPA. Moreover, this case demonstrates the responsiveness of neuroinflammatory manifestations to the recently approved anti-interleukin-5 monoclonal antibody mepolizumab as a new potential treatment option.
PubMed: 38274358
DOI: 10.1177/17562864231182519 -
Journal of Veterinary Internal Medicine 2024An 8-year-old male neutered Miniature Schnauzer was diagnosed with diabetes mellitus based on fasting hyperglycemia and glucosuria after a 2-week history of polydipsia...
An 8-year-old male neutered Miniature Schnauzer was diagnosed with diabetes mellitus based on fasting hyperglycemia and glucosuria after a 2-week history of polydipsia and periuria, in line with the Agreeing Language in Veterinary Endocrinology consensus definition. Treatment of insulin and dietary management was initiated. The insulin dose was gradually reduced and eventually discontinued over the next year based on spot blood glucose concentrations that revealed euglycemia or hypoglycemia. After discontinuation, the dog remained free of clinical signs for 1 year until it was again presented for polyuria/polydipsia with fasting hyperglycemia and glucosuria. Insulin therapy was resumed and continued for the remainder of the dog's life. Although diabetic remission often occurs in cats and humans, the presumed etiopathogenesis of pancreatic beta cell loss makes remission rare in dogs, except for cases occurring with diestrus or pregnancy. This case demonstrates that diabetic remission is possible in dogs, even in cases without an identifiable reversible trigger.
Topics: Humans; Pregnancy; Female; Male; Dogs; Cats; Animals; Remission, Spontaneous; Blood Glucose; Diabetes Mellitus; Insulin; Hyperglycemia; Recurrence; Polydipsia; Cat Diseases; Dog Diseases
PubMed: 38240130
DOI: 10.1111/jvim.16991 -
Cureus Jan 2024The patient is a one-year-old girl referred to the hospital for an enlarged head after a 1.5-month history of two falls, followed by polydipsia, polyuria, and slow...
Infantile Rosai-Dorfman Disease With Isolated Brain Lesions Disseminated to the Parenchyma and Intraventricular Ependyma, Alteration of Leukocytes as a Promotion Factor in Immune Defense, and New Proposals: A Case Report and Literature Review.
The patient is a one-year-old girl referred to the hospital for an enlarged head after a 1.5-month history of two falls, followed by polydipsia, polyuria, and slow movement and growth. Three subsequent magnetic resonance imaging (MRI) examinations of the brain revealed nodular lesions disseminated in the brain parenchyma and intraventricular ependyma, resulting in obstructive hydrocephalus. Thoracic and abdominopelvic sonography showed no additional lesions. The preliminary diagnosis was a primary or metastatic neoplasm or infection. A biopsy of a lesion in the right frontal lobe was taken. The histological examination revealed features of Rosai-Dorfman disease (RDD), consisting of limited perivascular lymphoplasma cell infiltration with intervening sheets of proliferated histiocytes, with some of the histiocytes showing endocytosis of a single intact lymphocyte (emperipolesis).
PubMed: 38234391
DOI: 10.7759/cureus.52453 -
Comparative Medicine Dec 2023Southern giant pouched rats () are a small muroid species native to the sub-Saharan Africa. Their exceptionally developed olfactory system, trainability, and relatively...
Southern giant pouched rats () are a small muroid species native to the sub-Saharan Africa. Their exceptionally developed olfactory system, trainability, and relatively small size makes them useful working animals for various applications in humanitarian work. At our institution, a breeding colony of Southern giant pouched rats is maintained to study their physiology and utility as scent detectors. This case report describes the occurrence of spontaneous pituitary neoplasms with distinct clinical presentations in 2 geriatric (approximately 7.5 y old) wild-caught female Southern giant pouched rats. The first pouched rat displayed vestibular deficits, including left-sided head tilt, ataxia, disorientation, and circling. MRI revealed a large, focal heterogeneous mass arising from the pituitary fossa. The second pouched rat presented with polyuria, polydipsia, and hyperglycemia but no neurologic signs. Examination after euthanasia revealed a prolactin (PRL)-expressing pituitary carcinoma and adenoma in the first and second pouched rat, respectively, associated with mammary hyperplasia in both animals. This is the first report of spontaneous PRL-producing pituitary tumors in Southern giant pouched rats.
Topics: Animals; Female; Rats; Pituitary Neoplasms; Rodent Diseases
PubMed: 38217070
DOI: 10.30802/AALAS-CM-23-000051