-
SAGE Open Medical Case Reports 2024Neonatal Graves disease is the most common cause of hyperthyroidism during the newborn period. Maternal Graves disease increases the risk of intrauterine growth...
Neonatal Graves disease is the most common cause of hyperthyroidism during the newborn period. Maternal Graves disease increases the risk of intrauterine growth restriction, small for gestational age, and neonatal Graves disease. Intrauterine growth restriction and small for gestational age are associated with hypoglycemia and transient neonatal hyperinsulinism. Neonatal Graves disease with severe persistent hypoglycemia has not been well described. We present the case of a female patient born at 34 weeks and 3 days with a birth weight of 1.6 kg (fifth percentile) to a mother with recent treatment for Graves disease. Prenatal ultrasounds were significant for intrauterine growth restriction and small for gestational age. The mother did not begin hyperthyroidism medical therapy until 23 weeks and 2 days of gestation. After the infant was born, the infant not only had symptoms of hyperthyroidism such as tachycardia and abnormal thyroid values but also had persistent hypoglycemia, which could be due to maternal propranolol usage, prematurity, IUGR, increased metabolism due to neonatal Graves, and transient stress-induced hyperinsulinism. The infant was started on methimazole for hyperthyroidism and propranolol for tachycardia. She was also started on diazoxide for persistent hypoglycemia. By 6 months of age, the hyperthyroidism and hypoglycemia had resolved. This is an interesting case of neonatal Graves disease with severe persistent hypoglycemia which we suspect is due to transient neonatal hyperinsulinism induced by multiple stress responses.
PubMed: 38463451
DOI: 10.1177/2050313X241237433 -
Problemy Endokrinologii Feb 2024Insulinoma is the most common hormonally active neuroendocrine tumor (NET) of the pancreas. In recent years, there has been a trend towards an increase in the incidence... (Review)
Review
RELEVANCE
Insulinoma is the most common hormonally active neuroendocrine tumor (NET) of the pancreas. In recent years, there has been a trend towards an increase in the incidence of NET especially insulinoma.
AIM
Summarizing and analyzing current data on various approaches to the treatment of insulinoma. Our review includes a comprehensive assessment of the advantages and disadvantages of currently available insulinoma treatment methods in comparison with past experience, as well as a review of promising methods that are not currently widely used.
MATERIALS AND METHODS
Analysis of literature from such databases as scientific electronic library elibrary.ru, Pubmed, Google Scholar, MedLine, Scopus and Web of Science.
RESULTS
The most common treatment for insulinoma is surgery. For patients with high operative risk, alternative methods such as alcohol ablation, radiofrequency ablation, and tumor embolization may be used. Medications include the use of somatostatin analogues, diazoxide. The literature describes the potential benefit of the use of beta-blockers, phenytoin, glucagon, however, in clinical trials, these drugs have not demonstrated a significant effect. For the treatment of malignant and metastatically advanced insulinoma, targeted therapy (primarily Everolimus), chemotherapy, as well as embolization (including chemoembolization, radioembolization), radiofrequency ablation (RFA), microwave ablation and cryoablation, ultrasound ablation (HIFU), laser ablation, brachytherapy, irreversible electroporation are used.
CONCLUSION
The study of new drugs is an important task for scientists, among medications the most promising are new generations of somatostatin analogues, targeted drugs and chemotherapy drugs. The rare frequency of insulinoma makes it difficult to conduct randomized controlled trials and prospective studies. That is why physicians and scientists need to maintain close contacts with each other and take into account the experience of treating each patient with such disease, which will help develop effective treatment algorithms in the future.
Topics: Humans; Insulinoma; Prospective Studies; Neuroendocrine Tumors; Apudoma; Pancreatic Neoplasms; Somatostatin
PubMed: 38433541
DOI: 10.14341/probl13281 -
Endocrinology, Diabetes & Metabolism... Jan 2024Dumping syndrome is a rare but potentially serious condition that causes inappropriate postprandial hyperinsulinemia leading to hypoglycemia in children following...
SUMMARY
Dumping syndrome is a rare but potentially serious condition that causes inappropriate postprandial hyperinsulinemia leading to hypoglycemia in children following gastrointestinal surgeries. While dietary modifications are often the first line of treatment, severe cases may require pharmacological intervention to prevent severe hypoglycemia. We present a case of successful treatment of dumping syndrome with diazoxide. A 2-month-old infant with left hypoplastic heart syndrome who underwent single ventricle palliation pathway and developed feeding intolerance that required Nissen fundoplication. Postprandial hypoglycemia was detected following the procedure, with glucose level down to 12 mg/dL, and the diagnosis of dumping syndrome was established. The patient was successfully managed with diazoxide, which effectively resolved postprandial hypoglycemia without any major adverse events. The patient was eventfully weaned off the medication at the age of 5 months. This case highlights the potential role of diazoxide in the management of pediatric patients with postprandial hyperinsulinemic hypoglycemia secondary to dumping syndrome.
LEARNING POINTS
Dumping syndrome is a possible complication of gastrointestinal surgeries and should be suspected in children with abnormal glucose levels. Postprandial hyperglycemia should be monitored closely for significant subsequent hypoglycemia. Diazoxide might be considered as part of the treatment plan for dumping syndrome.
PubMed: 38432066
DOI: 10.1530/EDM-23-0137 -
Endocrinology, Diabetes & Metabolism Mar 2024Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is... (Review)
Review
INTRODUCTION
Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication.
METHODS
Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16.
RESULTS
The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes.
CONCLUSION
This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates.
Topics: Male; Female; Humans; Insulin-Like Growth Factor II; Insulin-Like Peptides; Retrospective Studies; Hypoglycemia; Observational Studies as Topic
PubMed: 38411039
DOI: 10.1002/edm2.471 -
Genes Feb 2024Intellectual disability with speech delay and behavioural abnormalities, as well as hypotonia, seizures, feeding difficulties and craniofacial dysmorphism, are the main...
Intellectual disability with speech delay and behavioural abnormalities, as well as hypotonia, seizures, feeding difficulties and craniofacial dysmorphism, are the main symptoms associated with pathogenic variants of the gene. The range of clinical manifestations of the ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present two previously unreported paediatric patients with neurodevelopmental challenges, who were diagnosed with missense variants in the gene. It should be noted that one of the individuals manifested with hyperinsulinaemic hypoglycaemia (HH), a symptom that was not described before in published works. The reason for the occurrence of HH in our proband is not clear, so we try to explain the origin of this symptom in the context of the syndrome. Thus, this paper contributes to knowledge on the range of possible manifestations of the disease and provides further evidence supporting its association with neurodevelopmental challenges.
Topics: Child; Humans; Abnormalities, Multiple; Cell Cycle Proteins; Co-Repressor Proteins; DNA-Binding Proteins; Intellectual Disability; Mutation, Missense; Phenotype; Syndrome
PubMed: 38397245
DOI: 10.3390/genes15020256 -
Scientific Reports Feb 2024Alzheimer's disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential...
Alzheimer's disease (AD) is the major form of dementia prevalent in older adults and with a high incidence in females. Identification of early biomarkers is essential for preventive intervention to delay its progression. Furthermore, due to its multifactorial nature, a multi-target approach could be therapeutically beneficial. Our studies included 4- (pre-pathology) and 11-month (mild-pathology) TgF344-AD rats, a transgenic Alzheimer's model that exhibits age-dependent AD progression. We identified two potential early biomarker genes for AD, early growth response 2 (EGR2) and histone 1H2AA (HIST1H2AA), in the hippocampus of 4-month females. Out of 17,168 genes analyzed by RNA sequencing, expression of these two genes was significantly altered in 4-month TgF344-AD rats compared to wild-type littermates. We also evaluated co-treatment with diazoxide (DZ), a potassium channel activator, and dibenzoylmethane (DIB), which inhibits eIF2α-P activity, on TgF344-AD and wild-type rats. DZ/DIB-treatment mitigated spatial memory deficits and buildup of hippocampal Aβ plaques and tau PHF in 11-month TgF344-AD rats but had no effect on wild-type littermates. To our knowledge, this preclinical study is the first to report EGR2 and HIST1H2AA as potential AD biomarkers in females, and the benefits of DZ/DIB-treatment in AD. Evaluations across multiple AD-related models is warranted to corroborate our findings.
Topics: Female; Rats; Animals; Alzheimer Disease; Rats, Transgenic; Diazoxide; Rats, Inbred F344; Spatial Memory; Biomarkers; Disease Models, Animal; Amyloid beta-Peptides; Chalcones
PubMed: 38355687
DOI: 10.1038/s41598-024-54156-z -
JFMS Open Reports 2024The patient was a castrated male American Shorthair cat, approximately 14 years old, weighing 3.4 kg. The patient had chronic kidney disease (CKD) (International Renal...
CASE SUMMARY
The patient was a castrated male American Shorthair cat, approximately 14 years old, weighing 3.4 kg. The patient had chronic kidney disease (CKD) (International Renal Interest Society stages 3-4) as an underlying disease. The cat was examined at a hospital for intermittent lethargy and seizures. Hypoglycaemia was repeatedly observed, and the insulin level was 1.78 ng/ml (reference interval 0.27-0.69) when the blood glucose was 49 mg/dl. Although the cat was tentatively diagnosed with insulinoma, surgery was not recommended because of the severe CKD. Although frequent feeding and prednisolone treatment were initially attempted, blood glucose decreased to 24-42 mg/dl. Diazoxide was additionally prescribed at a dose of 5.2 mg/kg q12h. The cat's clinical signs improved, and the blood glucose was in the range of 75-103 mg/dl during the first 2 months. It was maintained at >50 mg/dl until the patient died of renal failure 161 days after the start of diazoxide treatment. With regard to adverse events, vomiting once every 2-3 days without weight loss and non-regenerative anaemia were observed, which might have been at least partially caused by diazoxide treatment. An insulinoma was definitively diagnosed via pathological autopsy.
RELEVANCE AND NOVEL INFORMATION
This is the first reported case of long-term treatment with diazoxide in a cat with insulinoma. Since it was effective in situations where conventional therapies were unsuccessful, diazoxide could be useful as a new therapeutic option for cats with insulinoma. Since adverse events, such as progression of vomiting frequency and non-regenerative anaemia, were observed, careful monitoring was required during administration.
PubMed: 38268764
DOI: 10.1177/20551169231220290 -
BMC Endocrine Disorders Jan 2024ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of...
BACKGROUND
ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH).
METHODS
We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations.
RESULTS
The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation.
CONCLUSIONS
Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.
Topics: Infant, Newborn; Child; Humans; Congenital Hyperinsulinism; Diazoxide; Octreotide; Mutation; China; Sulfonylurea Receptors
PubMed: 38212772
DOI: 10.1186/s12902-023-01527-8 -
Biomedicines Dec 2023Modulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of...
Modulation of mitochondrial K channels represents a pharmacological strategy to promote cardioprotective effects. Isothiocyanates emerge as molecules capable of releasing hydrogen sulfide (HS), an endogenous pleiotropic gasotransmitter responsible for anti-ischemic cardioprotective effects also through the involvement of mitoK channels. Erucin (ERU) is a natural isothiocyanate resulting from the enzymatic hydrolysis of glucosinolates (GSLs) present in Mill. seeds, an edible plant of the family. In this experimental work, the specific involvement of mitoK channels in the cardioprotective effect induced by ERU was evaluated in detail. An in vivo preclinical model of acute myocardial infarction was reproduced in rats to evaluate the cardioprotective effect of ERU. Diazoxide was used as a reference compound for the modulation of potassium fluxes and 5-hydroxydecanoic acid (5HD) as a selective blocker of K channels. Specific investigations on isolated cardiac mitochondria were carried out to evaluate the involvement of mitoK channels. The results obtained showed ERU cardioprotective effects against ischemia/reperfusion (I/R) damage through the involvement of mitoK channels and the consequent depolarizing effect, which in turn reduced calcium entry and preserved mitochondrial integrity.
PubMed: 38137502
DOI: 10.3390/biomedicines11123281 -
Neurobiology of Pain (Cambridge, Mass.) 2023Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective...
Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective therapeutic strategies in preclinical models of chronic pain, especially diabetic neuropathy. We tested whether a ketogenic diet is antinociceptive through ketone oxidation and related activation of ATP-gated potassium (K) channels in mice. We demonstrate that consumption of a ketogenic diet for one week reduced evoked nocifensive behaviors (licking, biting, lifting) following intraplantar injection of different noxious stimuli (methylglyoxal, cinnamaldehyde, capsaicin, or Yoda1) in mice. A ketogenic diet also decreased the expression of p-ERK, an indicator of neuronal activation in the spinal cord, following peripheral administration of these stimuli. Using a genetic mouse model with deficient ketone oxidation in peripheral sensory neurons, we demonstrate that protection against methylglyoxal-induced nociception by a ketogenic diet partially depends on ketone oxidation by peripheral neurons. Injection of tolbutamide, a K channel antagonist, prevented ketogenic diet-mediated antinociception following intraplantar capsaicin injection. Tolbutamide also restored the expression of spinal activation markers in ketogenic diet-fed, capsaicin-injected mice. Moreover, activation of K channels with the K channel agonist diazoxide reduced pain-like behaviors in capsaicin-injected, chow-fed mice, similar to the effects observed with a ketogenic diet. Diazoxide also reduced the number of p-ERK cells in capsaicin-injected mice. These data support a mechanism that includes neuronal ketone oxidation and activation of K channels to provide ketogenic diet-related analgesia. This study also identifies K channels as a new target to mimic the antinociceptive effects of a ketogenic diet.
PubMed: 38099277
DOI: 10.1016/j.ynpai.2023.100138