International Journal of Endocrinology and Metabolism
Volume:20 Issue: 3, Jul 2022

 Findings from studies evaluating adverse pregnancy outcomes in pregnant women with subclinical hyperthyroidism are conflicting and inconclusive.

In this systematic review and meta-analysis, our aim was to evaluatethe pooled odds ratio (OR) of adverse pregnancy outcomes in women with subclinical hyperthyroidism, compared to euthyroid women. Data Sources: Scopus, PubMed (including Medline), and Web of Science databases were systemically searched for regaining published studies to January 2022 examining adverse pregnancy outcomes in women with subclinical hyperthyroidism. Study Selection: Outcomes of interest were classified into seven composite outcomes, including hypertensive disorders, preterm delivery, macrosomia/large for gestational age (LGA), pregnancy loss, adverse maternal outcomes, adverse neonatal outcomes, and adverse fetal outcomes.

In this meta-analysis, both fixed and random effect models were used. Publication bias was also evaluated by Egger test and the funnel plot, and the trim and fill method was conducted in case of a significant result, to adjust the bias.

Of 202 records retrieved through searching databases, 11 studies were selected for the final analyses. There were no significant differences in pooled ORs of hypertensive disorders, preterm delivery, macrosomia/LGA, and pregnancy loss in pregnant women with subclinical hyperthyroidism, compared to the euthyroid controls. The pooled OR of adverse maternal, neonatal, and fetal outcomes in pregnant women with subclinical hyperthyroidism was not statistically significantly different from that of the euthyroid control group.

The current meta-analysis demonstrated that subclinical hyperthyroidism in pregnancy is not related with adverse maternal and fetal outcomes. Therefore, clinicians should be avoided unnecessary treatments for pregnant women with subclinical hyperthyroidism.

The model of obesity-induced insulin resistance has long been used to explain the development of type 2 diabetes mellitus (T2DM) in obese individuals (Body Mass Index (BMI) > 25 kg/m2), but this model fails to explain the development of the disease in lean individuals (BMI < 18.5 kg/m2). Defects in the insulin signaling pathway have been postulated to play a role in these patients, particularly in suppressors of cytokine signaling (SOCS) proteins, which are involved in the downregulation of insulin transduction. The expression of SOCS is also known to be induced by cytokines such as interferon gamma (IFN-γ). It is still not clear whether these pathways operate differently in lean versus obese patients with T2DM. Therefore, this pilot study was designed to study the expression of SOCS1, SOCS3, and IFN-γ in lean and obese patients of T2DM.

This pilot study was designed to study the expression of SOCS1, SOCS3, and IFN-γ in lean and obese patients with T2DM. Further, this study compared the levels of IFN-γ in serum and the expression of messenger RNA (mRNA) of regulators of SOCS (SOCS1 and SOCS3) and IFN-γ genes in whole blood in lean and obese patients with T2DM.

Sixty newly diagnosed T2DM patients (without any pharmacotherapy) were enrolled and divided into 2 groups of lean (BMI < 18.5 kg/m2) and obese (BMI > 25 kg/m2) patients (n = 30 per group). Serum IFN-γ was measured by enzyme-linked immunosorbent assay (ELISA), and mRNA expression of IFN-γ, SOCS1, and SOCS3 was measured by real-time polymerase chain reaction (PCR) using the ∆∆ Ct method.

Serum IFN-γ levels were 10.83 ± 5.81 pg/mL in the lean group and 9.35 ± 5.14 pg/mL in the obese group (P = 0.02). Fasting serum insulin levels were 16.07 ± 8.39 µIU/mL in the lean group and 27.11 ± 4 .91 µIU/mL in the obese group (P = 0.001). There was a 3.16-fold increase in mRNA expression of IFN-γ and a 1.3-fold increase in mRNA expression of SOCS1 in the lean group compared to the obese group. mRNA expression of SOCS3 was similar in both groups.

The level of IFN-γ increased at both transcriptional and translational levels, and mRNA expression of SOCS1 was higher in the lean group than in the obese group. The SOCS protein is a known negative regulator in insulin signaling pathways. Thus, our findings and available scientific literature suggest that IFN-γ might impair the insulin signaling pathway to a greater extent in lean patients than in obese patients via induction of SOCS1. This signaling pathway could be a major contributing factor to hyperglycemia in lean patients with T2DM compared with obese counterparts. This suggests that different therapeutic approaches to these groups might be of greater benefit in the treatment of T2DM.

Electrolyte imbalances are common in COVID-19 infection and are associated with poor outcomes in hospitalized patients.

This study examined whether serum phosphate imbalances at admission are associated with mortality in hospitalized COVID-19 patients.

In this registry-based single-center retrospective cohort study, 1349 inpatients with COVID-19 were included from March 2020 to March 2021 in an academic hospital in Ilam (southwest Iran). The Cox proportional hazard (PH) regression model was applied to the data set of COVID-19.

The in-hospital median survival time for patients with low, normal, and high serum phosphate levels was 14, 25, and 8 days, respectively. In a multivariate model, adjusted for the other variables, patients with hypophosphatemia (adjusted hazard ratio [HR], 2.53; 95% CI, 1.15 - 5.58; P = 0.02) and hyperphosphatemia (adjusted HR, 1.77; 95% CI, 1.00 - 3.14; P = 0.05) had an increased mortality hazard compared with those who had normal levels of serum phosphate.

Our results demonstrate a strong effect of hypophosphatemia and hyperphosphatemia with increased in-hospital mortality in COVID-19 patients. Intensive medical care and more attention must be paid to COVID-19 patients with serum phosphate imbalances at admission.

Type 2 diabetes mellitus (T2DM) is associated with cardiometabolic changes, and menopause exacerbates these conditions, leading to a greater risk of cardiovascular diseases (CVDs). The G protein-coupled estrogen receptor (GPER), which mediates the rapid effects of estrogen, has beneficial cardiac effects in both T2DM and menopause, but its mechanism of action is not well understood.

This study aimed to determine whether G1 as a selective GPER-agonist has beneficial effects on cardiac lipid metabolism in ovariectomized rats with T2DM.

Female Wistar rats were divided into 5 groups (n = 7 in each group): Sham-control (Sh-Ctl), T2DM, ovariectomized-T2DM (OVX-T2DM), OVX-T2DM-G1 (GPER-agonist), and OVX-T2DM-vehicle (OVX-T2DM-Veh). After stabilization of T2DM, G1 (200 μg/Kg) was administrated for 6 weeks. Then, the levels of free fatty acids (FFAs), CD36, peroxisome proliferator-activated receptor α (PPARα), and lipid accumulation in the cardiac tissue were determined.

Compared with the Sh-Ctl group, cardiac FFAs (P < 0.001), CD36 (P < 0.05), and lipid accumulation (P < 0.001) increased, and cardiac PPARα (P < 0.01) decreased in T2DM animals; ovariectomy intensified these changes. Also, cardiac FFAs, PPARα, and lipid accumulation (P < 0.05) significantly decreased in the OVX-T2DM-G1 group compared to the OVX-T2DM-Veh group. However, cardiac CD36 levels did not change.

G1 as a selective GPER-agonist affects lipid metabolism in T2DM animals. It also plays a vital role in improving cardiac metabolism during postmenopausal diabetic conditions.

Subcutaneous insulin resistance syndrome (SIRS) is a rare condition in which patients poorly respond to subcutaneous (SC) insulin but maintain a normal response to intravenous (IV) insulin. The underlying pathophysiology remains elusive. Several treatment regimens have been tested for the management of SIRS, none of which included a sodium-glucose cotransporter-2 inhibitor (SGLT-2).

Two cases of type 1 diabetes initially achieved adequate glycemic control with subcutaneous insulin. Both cases later progressed into recurrent diabetic ketoacidosis that would resolve following IV insulin administration. Further investigation revealed unresponsiveness to SC insulin, but not IV, and the clinical diagnosis of SIRS was established accordingly. HbA1c values for cases 1 and 2 were 11% on 400 units/day of SC insulin, and 12% on 350 - 400 units/day of SC insulin, respectively. The patients required very high doses of intramuscular (IM) insulin. Subsequently, dapagliflozin as adjunct therapy significantly reduced the patients’ IM insulin requirements beyond the anticipated dose reduction. Ultimately, case 1 achieved an HbA1c of 7 - 8% on 90 units/day of IM insulin and 10 mg/day of dapagliflozin, and case 2 achieved an HbA1c of 7 - 8% on 120 units/day of IM insulin and 10 mg/day of dapagliflozin.

These are the first reported cases of SIRS in which dapagliflozin, an SGLT-2 inhibitor, was used. The substantial reduction in the IM insulin dose following the addition of dapagliflozin in our reported cases of SIRS suggests a possible novel mechanism for dapagliflozin beyond its glucosuric effects. In this report, we present a hypothetical basis for this possible novel mechanism.

Surgery for pheochromocytoma and paraganglioma (PPGL) can lead to life-threatening complications, such as intraoperative hypertensive crises, even when adequate doses of preoperative α-receptor blockades are administered.

The aim of this study was to identify preoperative factors associated with intraoperative maximum arterial pressure (AP) in patients with PPGL.

We retrospectively reviewed the cases of 61 PPGL patients who underwent surgical resection in our hospital between 2006 and 2020. The primary outcome was intraoperative maximum AP as a single index for continuous variables. Simple and multiple linear regression model were used for statistical analysis.

The median maximum systolic AP during surgery was 165 mmHg (interquartile range: 150 - 180 mmHg). Log24-h urinary-fractionated MN and NMN was correlated with intraoperative maximum AP (R-squared = 0.218, P < 0.001). Multiple regression analyses showed that diabetes mellitus, one or more of the classic triad, and log24-h urinary-fractionated MN and NMN were independent factors associated with intraoperative maximum AP.

Patients with PPGL accompanied by diabetes mellitus, one or more of the classic triad, and high log 24-h urinary-fractionated MN and NMN values may be at risk for hypertensive crises during surgery regardless of whether preoperative α-receptor blockades are used. Clinicians should manage these patients more carefully and effectively.

Paragangliomas are rare neuroendocrine tumors that arise from chromaffin cells. Often termed extra-adrenal pheochromocytomas, these tumors vary with regards to their functionality, location, and malignant potential. Mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia syndrome type 2 (MEN-2) and paragangliomas. The phenotypes of the individual mutations are documented to help determine prognosis.

We report a case of a 64-year-old man with a history of parathyroid adenoma who developed a pancreatic retroperitoneal paraganglioma. Despite having laboratory evidence of excess circulating catecholamines, the patient’s only presenting symptom was hip pain. The patient underwent resection, and histologic findings were consistent with paraganglioma with lymph node metastasis. Genetic testing revealed a variant of uncertain significance within the RET gene [c.731C>T (p.T244I)].

Paragangliomas are rare extra-adrenal neuroendocrine tumors that can be associated with germline mutations. Our patient was diagnosed with a pancreatic paraganglioma associated with a RET T244I mutation. Identifying patients with germline mutations is important for documenting phenotypic presentations of RET gene variants of uncertain significance, which will allow physicians to provide proper management and surveillance of paragangliomas and other associated tumors.

The literature review is integral to the research process, from developing research ideas to disseminating findings. It involves explaining, interpreting, and summarizing published materials around a topic to elaborate a research hypothesis/question, synthesize new concepts, identify knowledge gaps, develop new theories, and identify new research directions. Compelling reading and processing of the literature (i.e., analyzing and synthesizing) and actual writing of the literature (verbal or non-verbal output, e.g., tables and figures) are essential stages of an effective literature review. This article provides a practical guide to conducting an effective literature review. In addition, literature search and evaluation are also briefly discussed.

Due to the worldwide spread of COVID-19, various countries have designed scientific studies on different aspects of the disease. Patients with diabetes mellitus (DM) have been proven to be at higher risk of COVID-19-related complications, hospitalization, and death.

The aim was to conduct a scientometric analysis of scholarly outputs on diabetes and COVID-19.

Web of Science was searched for scientific publications on diabetes and COVID-19 by Middle Eastern researchers until September 14, 2021. Collected data were analyzed for document type, subject area, countries, top journals, citation number, and authors’ collaboration network using VOS viewer 1.6.15 and bibliometrix R-package 4.1.1.

Overall, the characteristics of 603 documents on DM and COVID-19 were analyzed. The top three productive countries in the field were Iran, Turkey, and Saudi Arabia. The top affiliation was from Iran; “Tehran University of Medical Sciences” (n = 168), followed by "Shahid Beheshti University of Medical Sciences" (n = 82). The total citation number was 3704 times. The highest cited paper (348) was a systematic review from Iran, published in arch Acad Emerg Med. The top source was "Diabetes & Metabolic Syndrome: Clinical Research & Reviews," with 26 documents.

The current study provides an overview of the quantity and quality of published scholarly documents on the intersection of DM and COVID-19 in the region. Our findings help scientists find the existing gaps, manage the research budgets, identify active authors and scientific institutes to collaborate with, and use their experience to produce new knowledge in the future.