The latest medical research on Endocrinology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about endocrinology gathered by our medical AI research bot.

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Pathogenic copy number and sequence variants in children born SGA with short stature without imprinting disorders.

Clinical Endocrinology

Children born small-for-gestational-age with short stature (SGA-SS) is associated with (epi) genetic defects, including imprinting disorders (IDs), pathogenic copy number variants (PCNVs), and pathogenic variants of genes involved in growth. However, comprehensive studies evaluating these three factors are very limited.

To clarify the contribution of PCNVs and candidate pathogenic variants to SGA-SS.

We enrolled 140 patients referred to us for genetic testing for SGA-SS. Among them, we excluded 42 patients meeting Netchine-Harbison clinical scoring system criteria for Silver-Russell syndrome (SRS) and four patients with abnormal methylation levels of the IDs-related differentially methylated regions. Consequently, we conducted copy number analysis and multigene sequencing for 86 SGA-SS patients with sufficient sample volume. We also evaluated clinical phenotypes of patients with PCNVs or candidate pathogenic variants.

We identified eight (9.3%) and eleven (12.8%) patients with PCNVs and candidate pathogenic variants, respectively. According to the American College of Medical Genetics standards and guidelines, five variants were classified as pathogenic and the remaining six variants were classified as variants of unknown significance. Genetic diagnosis was made in twelve patients. All patients with PCNVs or candidate pathogenic variants did not correspond perfectly to characteristic clinical features of each specific genetic cause.

We clarified the contribution of PCNVs and pathogenic variants to SGA-SS without IDs. Comprehensive molecular analyses, including copy number analysis and multigene sequencing, should be considered for patients with unknown SGA-SS etiology.

Change in circulating levels of endothelial progenitor cells and sexual function in women with type 1 diabetes.

Clinical Endocrinology

Endothelial progenitor cells (EPCs), which are involved in the mechanisms of vascular repair, and sexual function are decreased in diabetic women as compared with general population.

To investigate the circulating levels of EPCs and the change in sexual function during the menstrual cycle in women with type 1 diabetes (T1DM) compared with healthy women.

Differences in EPCs levels and sexual function between patients and controls.

Compared with controls, women with diabetes showed significantly lower levels of both CD34+ (P < 0.001) and CD34+CD133+ cells (P < 0.001) in the ovulatory phase, and CD34+KDR+ cells in both the ovulatory phase and in the luteal phase (P < 0.001 for both). Diabetic women showed significantly lower total FSFI scores and higher FSDS score than control women in all the phases of the menstrual cycle. FSFI total score was predicted by both CD34+CD133+ and CD34+KDR+ cells in the follicular phase, CD34+ and CD34+KDR+CD133+ cells in the ovulatory phase, CD34+KDR+ and CD34+KDR+CD133+ cells in the luteal phase.

Women with T1DM show lower levels of EPCs during the menstrual cycle, compared with controls. EPCs count predict sexual function in this selected population.

Isocaloric-restricted Mediterranean diet and Chinese diets high or low in plants in adults with prediabetes.

Clinical Endocrinology

Calorie restriction plus dietary advice is suggested as a preventive strategy for individuals with obesity and prediabetes, however, optimal diet is still debatable. We aimed to compare the effects of Mediterranean diet (MD) and Chinese diets high or low in plants on body weight and glucose homeostasis among high risk Chinese.

In this parallel-arm randomized controlled trial, 253 Chinese adults aged 25-60 years with BMI ≥24.0 kg/m 2 and fasting blood glucose ≥5.6 mmol/L were randomly assigned to three isocaloric-restricted diets: MD (n = 84), a traditional Jiangnan Diet high in plants (TJD, n = 85), or a control diet low in plants (CD, n = 84). During the 6-month trial, a 5-weekday full feeding regimen was followed, along with mobile app-based monitoring. Abdominal fat measurement (magnetic resonance imaging), oral glucose tolerance test (OGTT), and continuous glucose monitoring (CGM) were conducted at baseline, 3- and 6-month.

With a 25% calorie-restriction for 6 months, weight deduction was 5.72 kg (95% CI: 5.03, 6.40) for MD, 5.05 kg (4.38, 5.73) for TJD and 5.38 kg (4.70, 6.06) for CD (Ptime < 0.0001). No between-group differences were found for fasting glucose, insulin, and the Matsuda index from OGTT. Notably, CD had significantly longer time below range (glucose < 3.9 mmol/L) than MD [0.81% ( 0.21, 1.40), P = 0.024] and marginally longer time than TJD [0.56% (-0.03,1.15), P = 0.065], as measured by CGM.

With the 6-month isocaloric-restricted feeding, TJD and MD achieved comparable weight deduction and improved glucose homeostasis, whereas CD showed a higher risk for hypoglycemia.

Sleep fragmentation and estradiol suppression decrease fat oxidation in pre-menopausal women.

Clinical Endocrinology

Body fat gain associated with menopause has been attributed to estradiol (E2) withdrawal. Hypoestrogenism is unlikely to be the only contributing factor, however.

Given the links between sleep and metabolic health, we examined the effects of an experimental menopausal model of sleep fragmentation on energy metabolism.

Indirect calorimetry was used to assess fasted resting energy expenditure (REE) and substrate oxidation.

Sleep fragmentation in the estrogenized state increased the respiratory exchange ratio (RER) and carbohydrate oxidation while decreasing fat oxidation (all p<0.01). Similarly, in the hypo-estrogenized state without sleep fragmentation, RER and carbohydrate oxidation increased and fat oxidation decreased (all p<0.01); addition of sleep fragmentation to the hypo-estrogenized state did not produce further effects beyond that observed for either intervention alone (p<0.05). There were no effects of either sleep fragmentation or E2 state on REE.

Sleep fragmentation and hypoestrogenism each independently alter fasting substrate oxidation in a manner that may contribute to body fat gain. These findings are important for understanding mechanisms underlying propensity to body fat gain in women across the menopause transition.

Long-term efficacy and safety of rifampin in the treatment of a patient carrying a CYP24A1 loss-of-function variant.

Clinical Endocrinology

Pharmacological therapy may be useful in the treatment of moderate to severe hypercalcemia in patients with infantile hypercalcemia-1 (HCINF1) due to pathogenic variants in the cytochrome P450 24 subfamily A member 1 (CYP24A1). Rifampin is an antituberculosis drug that is a potent inducer of cytochrome P450 3 subfamily A member 4 (CYP3A4), involved in an alternative catabolic pathway of vitamin D. The efficacy of rifampin in improving hypercalcemia was previously reported but many questions remain on the long-term efficacy and safety. Aim of the study is to test the long-term efficacy and safety of rifampin in a patient with HCINF1.

We report clinical, biochemical and imaging features of a 23-year-old man affected by HCINF1 with moderate hypercalcemia (12.9 mg/dL), symptomatic nephrolithiasis, nephrocalcinosis and impaired kidney function (eGFR 60 mL/min/1.73 m2) treated with rifampin for an overall period of 24 months. Kidney, liver and adrenal function were evaluated at every follow-up visit.

In 2 months, rifampin induced a normalization of serum calcium (9.6 mg/dL) associated with an improvement of kidney function (eGFR 92 mL/min/1.73 m2) stable during the treatment. After 15 months, rifampin was temporally withdrawn because of asthenia, unrelated to impairment of adrenal function. After three months, the timing of drug administration was shifted from the morning to the evening, obtaining the remission of asthenia. At the end of follow-up, the nephrolithiasis disappeared and the nephrocalcinosis was stable.

Rifampin could represent an effective choice to induce a stable reduction of calcium levels in patients with HCINF1, with a good safety profile.

Assessment and management of Primary Aldosteronism in pregnancy (AMPA): a case control study.

Clinical Endocrinology

Primary aldosteronism (PA) is a common secondary cause of hypertension. Literature regarding PA in pregnancy has demonstrated poor outcomes.

Compare the management and outcomes of PA in pregnancy to both high and low-risk matched controls.

Management outcomes included preeclampsia prophylaxis and antihypertensive medications required prenatally, antenatally and postnatally. Maternal outcomes included incidence of preeclampsia, gestational diabetes, hypokalaemia, mode of delivery and length of stay postpartum. Neonatal outcomes included gestation, birth weight, Intensive Care Unit admission and length of stay.

Fifty-nine women with sixty pregnancies were included (20 PA, 20 high-risk and 20 low-risk). Women with PA took a similar number of antihypertensive medications pre-pregnancy compared to the high-risk group. A similar proportion of women in the PA and high-risk groups were prescribed preeclampsia prophylaxis and developed preeclampsia. Even after adjustment for several factors, PA was not independently associated with preeclampsia development. Women with PA had higher antihypertensive requirements and a longer stay in hospital postpartum than the high-risk group (both p=0.02). There was no difference in neonatal adverse outcomes. Four women took epleronone during pregnancy without any adverse effects noted.

Women with PA required more anti-hypertensives and had a longer postpartum length of stay than matched high-risk women, but similar rates of preeclampsia. There was no difference in the rate of NICU admissions or adverse outcomes for neonates.

Prevalence and Phenotypic Effects of Copy Number Variants in Isolated Hypogonadotropic Hypogonadism.

Clinical Endocrinology

The genetic architecture of Isolated Hypogonadotropic Hypogonadism (IHH) has not been completely defined.

To determine the role of copy number variants (CNVs) in IHH pathogenicity and define their phenotypic spectrum.

IHH probands [n=1,394: Kallmann Syndrome (KS): IHH with anosmia (n=706); normosmic IHH (nIHH) (n=688] and their family members (n= 1092).

A total of 29 CNVs in 13 genes were detected (overall IHH cohort prevalence: ~2%). Almost all (28/29) CNVs occurred in unsolved IHH cases. While some genes (e.g., ANOS1 and FGFR1) frequently harbor both CNVs and SNVs/indels, the mutational spectrum of others (e.g., CHD7) was restricted to SNVs/indels. Syndromic phenotypes were seen in 83% and 63% of IHH subjects with multigenic and single gene CNVs, respectively.

CNVs in known genes contribute to ~2% of IHH pathogenesis. Predictably, multigenic contiguous CNVs resulted in syndromic phenotypes. Syndromic phenotypes resulting from single gene CNVs validate pleiotropy of some IHH genes. Genome sequencing approaches are now needed to identify novel genes and/or other elusive variants (e.g., non-coding/complex structural variants) that may explain the remaining missing etiology of IHH.

Role of weekday variation on glucose, insulin, and triglyceride: A cross-sectional analysis from The Maastricht Study.

Clinical Endocrinology

The timing of sleep, physical activity and dietary intake shows variation over the week, with different timings in the weekend compared to the weekdays, which may potentially lead to impaired glucose and lipid regulation on Mondays compared to other weekdays.

The aim of the study was to investigate differences in glucose metabolism and fasting triglyceride concentrations on Mondays compared to the rest of the week.

Confounder-adjusted linear regression analysis was applied to study the associations of day of the week of examination with glucose and insulin responses to an oral glucose tolerance test (OGTT) and fasting triglyceride concentrations.

In fully confounder-adjusted models, mean (95% CI) concentrations of fasting glucose, insulin, and triglycerides were slightly higher on Mondays compared with the other weekdays (glucose: 1% (0;2); insulin: 9% (1;18); triglycerides: 5% (2;8)). Interaction analyses revealed that the association of weekday with insulin was only pronounced in men (18% (3;35), but not in women (1% (-8;10)), whereas the associations with glucose and triglycerides were only apparent for individuals with known type 2 diabetes (glucose: 4% (0;7); triglycerides: 14% (6;23) compared to the background population (glucose: 0% (0;1); triglycerides: 3% (0;6)).

Being examined on a Monday was associated with higher fasting insulin concentrations among men but not women.

Lipid metabolic genes and maternal supraphysiological hypercholesterolemia: an analysis of maternal-fetal interaction.

Clinical Endocrinology

The joint associations of maternal and fetal single nucleotide polymorphisms (SNPs) of lipid metabolic genes with the risk of maternal supraphysiological hypercholesterolemia (MSPH) are unclear.

This study aims to investigate the associations of maternal/fetal SNPs of APOE, LPL, LDLR, PCSK9 and SCARB1 with the risk of MSPH, and explore whether the maternal-fetal pairing pattern of the risk alleles can affect MSPH risk.

A nested case-control study was conducted, including 182 pregnant women with MSPH and 182 with maternal physiological hypercholesterolemia. Maternal venous and umbilical venous blood were collected to detect the SNPs of genes. The primary outcome was MSPH. Logistic regression model was used to determine the associations of SNPs with risk of MSPH.

The C-allele in maternal APOE rs429358 T>C (adjusted OR=1.72, P=0.033), G-allele in fetal APOE rs440446 C>G (adjusted OR=1.62, P=0.012) and T-allele in fetal LPL rs263 C>T (adjusted OR=1.53, P=0.011) increased the risk of MSPH. The A-allele in maternal LDLR rs7258950 G>A decreased the risk of MSPH (adjusted OR=0.67, P=0.028). For maternal-fetal pairing analysis, the variant concordance of PCSK9 rs2149041, rs7523141, rs7523242, rs7525649 and LDLR rs7258950 were associated with the decreased risk of MSPH under the dominant model. The variant concordance of other SNPs of PCSK9, APOE, LDLR, LPL and SCARB1 were associated with the increased risk of MSPH.

This study supports the hypothesis that maternal and fetal genetic polymorphisms of lipid metabolic genes are associated with the risk of MSPH. The maternal-fetal variant concordance is also associated with this risk.

Suppression of pituitary hormone genes in subjects who died from COVID-19 independently of virus detection in the gland.

Clinical Endocrinology

Involvement of the pituitary gland in SARS-CoV-2 infection has been clinically suggested by pituitary hormone deficiency in severe COVID-19 cases, by altered serum ACTH levels in hospitalized patients, and by cases of pituitary apoplexy. However, the direct viral infection of the gland has not been investigated.

To evaluate whether the SARS-CoV-2 genome and antigens could be present in pituitary glands of lethal cases of COVID-19, and to assess possible changes in the expression of immune-related and pituitary-specific genes.

SARS-CoV-2 genome and antigens were searched in the pituitary gland of 23 patients who died from COVID-19 and, as controls, in 12 subjects who died from trauma or sudden cardiac death. Real-time RT-PCR, in situ hybridization, immunohistochemistry and transmission electron microscopy were utilized. Levels of mRNA transcripts of immune-related and pituitary-specific genes were measured by the nCounter assay.

The SARS-CoV-2 genome and antigens were detected in 14/23 (61%) pituitary glands of the COVID-19 group, not in controls. In SARS-CoV-2 positive pituitaries, the viral genome was consistently detected by PCR in the adeno- and the neurohypophysis. Immunohistochemistry, in situ hybridization and transmission electron microscopy confirmed the presence of SARS-CoV-2 in the pituitary. Activation of type I interferon signaling and enhanced levels of neutrophil and cytotoxic cell scores were found in virus-positive glands. mRNA transcripts of pituitary hormones and pituitary developmental/regulatory genes were suppressed in all COVID-19 cases irrespective of virus-positivity.

Our study supports the tropism of SARS-CoV-2 for human pituitary and encourage to explore pituitary dysfunction post-COVID-19.

Impact of polymorphism in the β₂-receptor gene on metabolic responses to repeated hypoglycaemia in healthy humans.

Clinical Endocrinology

The Arg 16 variant in the β₂-receptor gene is associated with increased risk of severe hypoglycaemia in subjects with type 1 diabetes mellitus.

We hypothesized that the Arg 16 variant is associated with decreased metabolic and symptomatic responses to recurrent hypoglycaemia.

Mean glucose infusion rate (GIR) during H1-H3.

During H1-H3, there was neither difference between AA or GG subjects in GIR, counterregulatory hormones (glucagon, epinephrine, cortisol, growth hormone) or substrate levels of lactate, glycerol, and free fatty acids (FFA), nor symptom response score nor cognitive performance (trail making test, Stroop test). At H3 lactate response was reduced in both genotype groups, but AA subjects had decreased response (mean ± SEM of area under the curve) of glycerol (-13.1 ± 3.8 μmol l -1 h; P = 0.0052), FFA (-30.2 ± 11.1 μmol l -1 h; P = 0.021), and ß-hydroxybutyrate (-0.008 ± 0.003 mmol l -1 h; P = 0.027), while in GG subjects alanine response was increased (negative response values)(-53.9 ± 20.6 μmol l -1 h; P = 0.024).

There was no difference in GIR between genotype groups, but secondary outcomes suggest, a down-regulation of the lipolytic and ß-hydroxybutyrate responses to recurrent hypoglycaemia in AA subjects, in contrast to the responses in GG subjects.

Effects of sustained hyperglycemia on skeletal muscle lipids in healthy subjects.

Clinical Endocrinology

Sustained increases in plasma glucose promote skeletal muscle insulin resistance independent from obesity and dyslipidemia (i.e. glucotoxicity). Skeletal muscle lipids are key molecular determinants of insulin action, yet their involvement in the development of glucotoxicity is unclear.

To explore the impact of mild physiologic hyperglycemia on skeletal muscle lipids.

Skeletal muscle lipids, insulin sensitivity, lipid oxidation.

Despite impairing insulin-mediated glucose disposal and suppressing fasting lipid oxidation, hyperglycemia did not alter either the content or composition of skeletal muscle triglycerides, diacylglycerides, or phospholipids. Skeletal muscle ceramides decreased after glucose infusion, likely in response to a reduction in free fatty acid concentrations.

Our results demonstrate that the major lipid pools in skeletal muscle are unperturbed by sustained increases in glucose availability and suggest that glucotoxicity and lipotoxicity drive insulin resistance through distinct mechanistic pathways.