-
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 -
International Journal of Endocrinology 2023Insulin autoimmune syndrome (IAS) is a rare endocrine disorder characterized by recurrent episodes of severe hypoglycemia, markedly elevated serum insulin, and positive... (Review)
Review
Insulin autoimmune syndrome (IAS) is a rare endocrine disorder characterized by recurrent episodes of severe hypoglycemia, markedly elevated serum insulin, and positive insulin autoantibodies. In recent years, various countries have reported it one after another. It can be seen that we must pay attention to this disease. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. High levels of insulin autoantibodies are found in patients, and C-peptide is not parallel to insulin, which could be diagnostic. IAS is a self-limiting disease with a good prognosis. Its treatment mainly includes symptomatic supportive treatment, such as adjusting the diet and using acarbose and other drugs to delay the absorption of glucose to prevent hypoglycemia. For patients with severe symptoms, available treatments may include drugs that reduce pancreatic insulin secretion (such as somatostatin and diazoxide), immunosuppressants (glucocorticoids, zaprin, and rituximab), and even plasma exchange to remove autoantibodies from the body. This review provides a comprehensive analysis of the epidemiology, pathogenesis, clinical manifestations, diagnosis and identification, and monitoring and treatment management of IAS.
PubMed: 36844104
DOI: 10.1155/2023/1225676 -
Frontiers in Pharmacology 2022To evaluate the efficacy of different pharmacologic treatment for severe hypertension during pregnancy. Two reviewers searched Ovid MEDLINE, Ovid EMbase, and the...
To evaluate the efficacy of different pharmacologic treatment for severe hypertension during pregnancy. Two reviewers searched Ovid MEDLINE, Ovid EMbase, and the Cochrane Library for randomized clinical trials from the establishment of the database to 15 July 2021 that were eligible for inclusion and analyzed the pharmaceuticals used for severe hypertension in pregnancy. 29 relevant trials with 2,521 participants were involved. Compared with diazoxide in rate of achieving target blood pressure, other pharmaceuticals, including epoprostenol (RR:1.58, 95%CI:1.01-2.47), hydralazine\dihydralazine (RR:1.57, 95%CI:1.07-2.31), ketanserin (RR:1.67, 95%CI:1.09-2.55), labetalol (RR:1.54, 95%CI:1.04-2.28), nifedipine (RR:1.54, 95%CI:1.04-2.29), and urapidil (RR:1.57, 95%CI:1.00-2.47), were statistically significant in the rate of achieving target blood pressure. According to the SUCRA, diazoxide showed the best therapeutic effect, followed by nicardipine, nifedipine, labetalol, and nitroglycerine. The three pharmaceuticals with the worst therapeutic effect were ketanserin, hydralazine, and urapidil. It is worth noting that the high ranking of the top two pharmaceuticals, including diazoxide and nicardipine, comes from extremely low sample sizes. Other outcomes were reported in the main text. This comprehensive network meta-analysis demonstrated that the nifedipine should be recommended as a strategy for blood pressure management in pregnant women with severe hypertension. Moreover, the conventional pharmaceuticals, including labetalol and hydralazine, showed limited efficacy. However, it was important to note that the instability of hydralazine reducing blood pressure and the high benefit of labetalol with high dosages intakes should also be of concern to clinicians.
PubMed: 36699058
DOI: 10.3389/fphar.2022.1092501 -
Healthcare (Basel, Switzerland) Feb 2022Hypertension in pregnancy causes significant maternal and fetal mortality and morbidity. A comprehensive assessment of the effectiveness of antihypertensive drugs for... (Review)
Review
BACKGROUND
Hypertension in pregnancy causes significant maternal and fetal mortality and morbidity. A comprehensive assessment of the effectiveness of antihypertensive drugs for severe hypertension during pregnancy is needed to make informed decisions in clinical practice. This systematic review aimed to assess the efficacy and safety of antihypertensive drugs in severe hypertension during pregnancy.
METHODS
A systematic review using the electronic databases MEDLINE (PubMed) and Cochrane Library was performed until August 2021. The risk-of-bias 2 tool was used to assess the risk-of-bias in each study included. Meta-analysis was conducted to assess heterogeneity and to estimate the pooled effects size.
RESULTS
Seventeen studies fulfilled the inclusion criteria and 11 were included in the meta-analysis. Nifedipine was estimated to have a low risk in persistent hypertension compared to hydralazine (RR 0.40, 95% CI 0.23-0.71) and labetalol (RR 0.71, 95% CI 0.52-0.97). Dihydralazine was associated with a lower risk of persistent hypertension than ketanserin (RR 5.26, 95% CI 2.01-13.76). No difference was found in the risk of maternal hypotension, maternal and fetal outcomes, and adverse effects between antihypertensive drugs, except for dihydralazine, which was associated with more adverse effects than ketanserin.
CONCLUSIONS
Several drugs can be used to treat severe hypertension in pregnancy, including oral/sublingual nifedipine, IV/oral labetalol, oral methyldopa, IV hydralazine, IV dihydralazine, IV ketanserin, IV nicardipine, IV urapidil, and IV diazoxide. In addition, nifedipine may be preferred as the first-line agent. There was no difference in the risk of maternal hypotension, maternal and fetal outcomes, and adverse effects between the drugs, except for adverse effects in IV dihydralazine and IV ketanserin.
PubMed: 35206939
DOI: 10.3390/healthcare10020325 -
PloS One 2021Diazoxide is the first-line drug for treating hyperinsulinism and the only pharmacological agent approved for hyperinsulinism by the Federal Drug Administration. This... (Meta-Analysis)
Meta-Analysis
Diazoxide is the first-line drug for treating hyperinsulinism and the only pharmacological agent approved for hyperinsulinism by the Federal Drug Administration. This systemic review and meta-analysis aimed to investigate the efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia (HH). The meta-analysis of the efficacy and safety of diazoxide in treating HH was performed by searching relevant studies in the PubMed, Embase, and Cochrane databases. The findings were summarized, and the pooled effect size and its 95% confidence interval (CI) were calculated. A total of 6 cohort studies, involving 1142 participants, met the inclusion criteria. Among the cohort studies, the pooled estimate of the response rate of diazoxide therapy was 71% (95% CI 50%-93%, Pheterogeneity< 0.001, I2 = 98.3%, Peffect< 0.001). The common side effects were hypertrichosis (45%), fluid retention (20%), gastrointestinal reaction (13%), edema (11%), and neutropenia (9%). Other adverse events included pulmonary hypertension (2%) and thrombocytopenia (2%). This meta-analysis suggested that diazoxide was potentially useful in HH management; however, it had some side effects, which needed careful monitoring. Furthermore, well-designed large-scale studies, such as randomized controlled trials, might be necessary in the future to obtain more evidence.
Topics: Antihypertensive Agents; Diazoxide; Humans; Hyperinsulinism; Hypertrichosis; Hypoglycemia; Treatment Outcome; Vasodilator Agents
PubMed: 33571197
DOI: 10.1371/journal.pone.0246463 -
British Journal of Clinical Pharmacology Sep 2018Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and... (Meta-Analysis)
Meta-Analysis Review
AIMS
Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs.
METHODS
Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random-effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates.
RESULTS
Fifty-one studies were included in the systematic review and 46 in the meta-analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [-15 (-20.6, -9.4)], nicardipine [-11.8 (-22.3, -1.2)], nifedipine/celastrol [-19.3 (-27.4, -11.1)], nifedipine/vitamin D [-17.1 (-25.7, -9.7)], nifedipine/resveratrol [-13.9 (-22.6, -5.2)] and glyceryl trinitrate [-33.8 (-36.7, -31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons.
CONCLUSION
The present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs.
Topics: Antihypertensive Agents; Dose-Response Relationship, Drug; Female; Headache; Humans; Hydralazine; Hypertension; Hypotension; Incidence; Labetalol; Network Meta-Analysis; Nifedipine; Perinatal Death; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic; Stillbirth; Tachycardia; Treatment Outcome
PubMed: 29974489
DOI: 10.1111/bcp.13649 -
The Cochrane Database of Systematic... Jul 2013Very high blood pressure during pregnancy poses a serious threat to women and their babies. The aim of antihypertensive therapy is to lower blood pressure quickly but... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Very high blood pressure during pregnancy poses a serious threat to women and their babies. The aim of antihypertensive therapy is to lower blood pressure quickly but safety, to avoid complications. Antihypertensive drugs lower blood pressure but their comparative effectiveness and safety, and impact on other substantive outcomes is uncertain.
OBJECTIVES
To compare different antihypertensive drugs for very high blood pressure during pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (9 January 2013).
SELECTION CRITERIA
Studies were randomised trials. Participants were women with severe hypertension during pregnancy. Interventions were comparisons of one antihypertensive drug with another.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data and checked them for accuracy.
MAIN RESULTS
Thirty-five trials (3573 women) with 15 comparisons were included. Women allocated calcium channel blockers were less likely to have persistent high blood pressure compared to those allocated hydralazine (six trials, 313 women; 8% versus 22%; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.21 to 0.66). Ketanserin was associated with more persistent high blood pressure than hydralazine (three trials, 180 women; 27% versus 6%; RR 4.79, 95% CI 1.95 to 11.73), but fewer side-effects (three trials, 120 women; RR 0.32, 95% CI 0.19 to 0.53) and a lower risk of HELLP (haemolysis, elevated liver enzymes and lowered platelets) syndrome (one trial, 44 women; RR 0.20, 95% CI 0.05 to 0.81).Labetalol was associated with a lower risk of hypotension compared to diazoxide (one trial 90 women; RR 0.06, 95% CI 0.00 to 0.99) and a lower risk of caesarean section (RR 0.43, 95% CI 0.18 to 1.02), although both were borderline for statistical significance.Both nimodipine and magnesium sulphate were associated with a high incidence of persistent high blood pressure, but this risk was lower for nimodipine compared to magnesium sulphate (one trial, 1650 women; 47% versus 65%; RR 0.84, 95% CI 0.76 to 0.93). Nimodipine was associated with a lower risk of respiratory difficulties (RR 0.28, 95% CI 0.08 to 0.99), fewer side-effects (RR 0.68, 95% CI 0.55 to 0.85) and less postpartum haemorrhage (RR 0.41, 95% CI 0.18 to 0.92) than magnesium sulphate. Stillbirths and neonatal deaths were not reported.There are insufficient data for reliable conclusions about the comparative effects of any other drugs.
AUTHORS' CONCLUSIONS
Until better evidence is available the choice of antihypertensive should depend on the clinician's experience and familiarity with a particular drug; on what is known about adverse effects; and on women's preferences. Exceptions are nimodipine, magnesium sulphate (although this is indicated for women who require an anticonvulsant for prevention or treatment of eclampsia), diazoxide and ketanserin, which are probably best avoided.
Topics: Antihypertensive Agents; Calcium Channel Blockers; Female; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 23900968
DOI: 10.1002/14651858.CD001449.pub3