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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Request AccessSignificance of QTc interval in chronic hypoparathyroidism and its correlates.
Clinical EndocrinologyHypocalcemia predisposes patients with chronic hypoparathyroidism (cHypoPT) to an increased risk of QTc prolongation and life-threatening arrhythmias. Information on clinical and biochemical correlates of QTc in cHypoPT is limited.
Eighty-eight non-surgical cHypoPT (mean age 44.1 ± 15.4 years, 45 males) were assessed for QTc interval and its possible correlates including arrhythmic symptoms (palpitation/giddiness/syncope), serum total-calcium, phosphate, 25(OH)D and iPTH.
The mean QTc in HypoPT cohort was 428 ± 34 ms with 13.6% having prolonged QTc. There was a significant inverse correlation between QTc interval and serum total-calcium measured on the same day (r = -0.43, p < 0.001). The mean serum total-calcium was significantly lower in patients with prolonged QTc (7.05 ± 1.94 vs. 8.49 ± 1.01 mg/dL, p = 0.02). 21.6% of cHypoPT patients had arrhythmic symptoms. They had significantly higher mean QTc (p = 0.02) and also tended to have lower mean serum total-calcium during follow-up (p = 0.06). In multivariable regression, female gender, higher current-age, higher BMI, and low serum total-calcium showed significant association with prolonged QTc. For every mg/dL decrease in serum total-calcium, QTc increased by 13 ms. Receiver-operating-characteristic analysis revealed serum total-calcium at cut-off of 8.3 mg/dL discriminated prolonged QTc with area-under-curve being 0.72 [95% CI: 0.51,0.93].
One-fifth of cHypoPT had arrhythmic symptoms and a significant proportion had prolonged QTc. This highlights the need for close monitoring of cHypoPT patients for arrhythmic symptoms and QTc prolongation. The serum total-calcium should be maintained to at least 8.3 mg/dL to minimize the risk of potentially life-threatening arrhythmia in cHypoPT.
Effects of Metreleptin in Patients with Generalized Lipodystrophy Before vs After the Onset of Severe Metabolic Disease.
Clinical EndocrinologyLeptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD).
Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health.
Retrospective analysis of patients ≥ 6 months old with congenital (n=47) or acquired (n=16) GLD treated with metreleptin at the National Institutes of Health since 2001. Least squares means (LSM) for HbA1c, insulin area under the curve (AUC) from oral glucose tolerance tests, triglycerides, urine protein excretion, platelets, transaminases, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) for early and late treatment groups, defined by baseline metabolic health, were analyzed during median 72 (24, 108) months follow-up.
Compared to late groups, early groups based on metabolic status had higher mean±SEM insulin AUC (20831±1 vs 11948±1), lower HbA1c (5.3±0.3 vs 6.8±0.3%), triglycerides (101±1 vs 193±1 mg/dL), urine protein excretion (85±1.5 vs 404±1.4 mg/24 hr), ALT (30±1 vs 53±1 U/L), AST (23±1 vs 40±1 U/L), and APRI (0.22±1.3 vs 0.78±1.3), and higher platelets (257±24 vs 152±28 K/µL) during follow-up (P<0.05). Compared to patients ≥6 years old at baseline, patients <6 years had lower HbA1c (4.5±0.5 vs 6.4±0.2%) and higher AST (40±1vs 23±1 U/L) during follow (P<0.05).
Patients with GLD who initiated metreleptin before the onset of severe metabolic complications had better long-term control of diabetes, proteinuria, and hypertriglyceridemia. Early treatment may also result is less severe progression of liver fibrosis, but further histological studies are needed to determine the effects of metreleptin therapy on liver disease.
Environmental Phenols and Growth in Infancy: The Infant Feeding and Early Development Study.
Clinical EndocrinologyHigher mean and rapid increases in body mass index (BMI) during infancy are associated with subsequent obesity and may be influenced by exposure to endocrine-disrupting chemicals such as phenols.
In a prospective US-based cohort conducted 2010-2014, we investigated associations between environmental phenol exposures and BMI in 199 infants.
We measured seven urinary phenols at ages 6-8 and 12 weeks and assessed BMI z-score at up to 12 study visits between birth and 36 weeks. We examined individual and joint associations of averaged early infancy phenols with level of BMI z-score using mean differences (β [95% confidence intervals (CI)]) and with BMI z-score trajectories using relative risk ratios (RR [95% CI]).
Benzophenone-3, methyl and propyl paraben, and all phenols jointly were positively associated with higher mean BMI z-score (0.07 [-0.05, 0.18], 0.10 [-0.08, 0.27], 0.08 [-0.09, 0.25], 0.17 [-0.08, 0.43], respectively). Relative to a Stable trajectory, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and all phenols jointly were positively associated with risk of a Rapid Increase trajectory (1.46 [0.89, 2.39], 1.33 [0.88, 2.01], 1.66 [1.03, 2.68], 1.41 [0.71, 2.84], respectively).
Early phenol exposure was associated with a higher mean and rapid increase in BMI z-score across infancy, signaling potential long-term cardiometabolic consequences of exposure.
Prostate Risk and Monitoring During Testosterone Replacement Therapy.
Clinical EndocrinologyMen with hypogonadism have reduced risk of prostate cancer mortality; whether testosterone treatment increases the risk of prostate safety events i...
Loading enhances glucose uptake in muscles, bones, and bone marrow of lower extremities in humans.
Clinical EndocrinologyIncreased standing time has been associated with improved health, but the underlying mechanism is unclear.
We herein investigate if increased weight loading increases energy demand and thereby glucose uptake (GU) locally in bone and/or muscle in the lower extremities.
In this single-center clinical trial with randomized crossover design (ClinicalTrials.gov ID, NCT05443620), we enrolled 10 men with body mass index (BMI) between 30 and 35 kg/m2. Participants were treated with both high load (standing with weight vest weighing 11% of body weight) and no load (sitting) on the lower extremities. GU was measured using whole-body quantitative positron emission tomography/computed tomography (PET/CT) imaging. The primary endpoint was the change in GU ratio between loaded bones (i.e. femur and tibia) and non-loaded bones (i.e. humerus).
High load increased the GU ratio between lower and upper extremities in cortical diaphyseal bone (e.g. femur/humerus ratio increased by 19%, p = 0.029), muscles (e.g. m. quadriceps femoris/m. triceps brachii ratio increased by 28%, p = 0.014) and in certain bone marrow regions (femur/humerus diaphyseal bone marrow region ratio increased by 17%, p = 0.041). Unexpectedly, we observed the highest GU in the bone marrow region of vertebral bodies, but its GU was not affected by high load.
Increased weight-bearing loading enhances GU in muscles, cortical bone, and bone marrow of the exposed lower extremities. This could be interpreted as increased local energy demand in bone and muscle caused by increased loading. The physiological importance of the increased local GU by static loading remains to be determined.
Clustering Identifies Subtypes With Different Phenotypic Characteristics in Women With Polycystic Ovary Syndrome.
Clinical EndocrinologyHierarchical clustering (HC) identifies subtypes of polycystic ovary syndrome (PCOS).
This work aimed to identify clinically significant subtypes in a PCOS cohort diagnosed with the Rotterdam criteria and to further characterize the distinct subtypes.
Clustering was performed using the variables body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose. Subtype characterization was performed by analyzing the variables estradiol, androstenedione, dehydroepiandrosterone, cortisol, anti-Müllerian hormone (AMH), total follicle count (TFC), lipid profile, and blood pressure. Study participants were girls and women who attended our university hospital for reproductive endocrinology screening between February 1993 and February 2021. In total, 2502 female participants of European ancestry, aged 13 to 45 years with PCOS (according to the Rotterdam criteria), were included. A subset of these (n = 1067) fulfilled the National Institutes of Health criteria (ovulatory dysfunction and hyperandrogenism). Main outcome measures included the identification of distinct PCOS subtypes using cluster analysis. Additional clinical variables associated with these subtypes were assessed.
Metabolic, reproductive, and background PCOS subtypes were identified. In addition to high LH and SHBG levels, the reproductive subtype had the highest TFC and levels of AMH (all P < .001). In addition to high BMI and insulin levels, the metabolic subtype had higher low-density lipoprotein levels and higher systolic and diastolic blood pressure (all P < .001). The background subtype had lower androstenedione levels and features of the other 2 subtypes.
Reproductive and metabolic traits not used for subtyping differed significantly in the subtypes. These findings suggest that the subtypes capture distinct PCOS causal pathways.
PAPP-A as a Potential Target in Thyroid Eye Disease.
Clinical EndocrinologyProptosis in Thyroid Eye Disease (TED) can result in facial disfigurement and visual dysfunction. Treatment with Insulin-like growth factor I receptor (IGF-IR) inhibitors has been shown to be effective in reducing proptosis but with side effects.
To test the hypothesis that inhibition of IGF-IR indirectly and more selectively with PAPP-A inhibitors attenuates IGF-IR signaling in TED.
PAPP-A expression and proteolytic activity, IGF-I stimulation of phosphatidylinositol 3 kinase/Akt pathway and inhibition by immuno-neutralizing antibodies against PAPP-A, CD34+ status and associated PAPP-A and IGF-IR expression.
Pro-inflammatory cytokines markedly increased PAPP-A expression in TED fibroblasts. IGF-IR expression was not affected by cytokine treatment. Inhibition of PAPP-A's proteolytic activity suppressed IGF-IR activation in orbital fibroblasts from TED patients. TED fibroblasts that were CD34+ represented ∼80% of the cells in culture and accounted for ∼70% of PAPP-A and IGF-IR expressing cells.
These results support a role for PAPP-A in TED pathogenesis and indicate the potential for novel therapeutic targeting of the IGF axis.
Synergy of nodal factors in predicting recurrence after treatment of N1b papillary thyroid carcinoma.
Clinical EndocrinologyNodal factors are important predictors of prognosis for papillary thyroid carcinoma (PTC), but their synergy effect is not well understood. We aimed to explore their synergy effect in predicting recurrence of clinical N1b PTC.
Patients who underwent surgery for cN1b PTC from 2013 to 2017 were enrolled. The association between nodal factors and recurrence was assessed using Cox proportional hazards regression models. Interaction and stratified analyses were conducted according to significant nodal factors.
Of 1067 cN1b PTC patients included, all nodal factors (bilateral metastasis, largest dimension>3cm, micro and gross extranodal extension (mENE, gENE), No. of metastatic lymph nodes (MLN), lymph node yield (LNY) and ratio (LNR)) were significantly associated with all site and nodal recurrence in the univariate analysis (all P<0.05). Multivariate analyses revealed largest dimension>3cm, gENE and LNR>0.21 were associated with elevated both all site (HR [95%CI], 2.58 [1.67-4.00], 1.87[1.26-3.01], 1.68[1.11-2.42], all P<0.01) and nodal recurrences (HR[95%CI], 2.63[1.67-4.13], 1.90[1.15-3.12], 1.76[1.17-2.66], all P<0.01). LNR and gENE had interactive effect (all site recurrence: P for interaction = 0.009; nodal recurrence: P for interaction = 0.02). LNR was significantly associated with recurrence in patients without gENE (HR[95% CI], all site recurrence: 2.41[1.50-3.87]; nodal recurrence: 2.51[1.52-4.14], all P< 0.001), while when gENE appeared, LNR was no longer associated with recurrence (HR [95% CI], all site recurrence: 0.81[0.43-1.54], P=0.53; nodal recurrence: 0.85[0.43-1.67], P=0.64).
Nodal factors have synergy effect in predicting recurrence in cN1b PTC patients. Increasing lymph nodes harvest may only decrease recurrence in patients without gENE, while not in gENE patients.
Normative data for insulin-like growth factor-1 (IGF-1) in healthy children and adolescents from India.
Clinical EndocrinologySerum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents.
A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models.
We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability.
This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.
Assessing Lateralization Index of Adrenal Venous Sampling for Surgical Indication in Primary Aldosteronism.
Clinical EndocrinologyClinical practice guidelines recommend the Lateralization Index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Our goal was to identify the optimal LI cut-offs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure.
We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1,550 patients with PA who underwent AVS, with and/or without ACTH stimulation. The establishment of optimal cut-offs was informed by a survey of 82 PA patients in Japan, aimed at determining the LI cut-off aligned with patient expectations for a surgical cure rate.
The survey revealed that a median cure rate expectation of 80% would motivate PA patients towards undergoing adrenalectomy. The optimal LI cut-offs achieving an adjusted positive predictive value (PPV) of 80% were identified as 3.8 for unstimulated AVS and 3.4 for ACTH-stimulated AVS. Furthermore, a contralateral ratio of less than 0.4 and the detection of an adrenal nodule on CT imaging were identified as independent predictors of surgically curable PA. Incorporating these factors with the optimal LI cut-offs, the adjusted PPV increased to 96.6% for unstimulated AVS and 89.6% for ACTH-stimulated AVS. No clear differences in predictive ability between unstimulated and ACTH-stimulated LI were found.
The present study clarified the optimal LI cut-offs for without and with ACTH stimulation. The presence of contralateral suppression and adrenal nodule on CT imaging seems to provide additional available information besides LI for surgical indication.
Associations of vegetable and potato intakes with markers of type 2 diabetes risk in the AusDiab cohort.
Clinical EndocrinologyThe associations of vegetable and potato intakes with type 2 diabetes (T2D) appear to be nuanced, depending on vegetable types and preparation method, respectively.
We investigated the associations of total vegetable, vegetable subgroup, and potato intakes with 1) markers of T2D at baseline and 2) incident T2D cumulative over a 12-year follow-up period in Australian adults.
Using data from the Australian Diabetes, Obesity and Lifestyle Study, intakes of vegetables and potatoes were assessed via a food frequency questionnaire at baseline. Associations between vegetable intake and 1) fasting plasma glucose (FPG), 2-hour post load plasma glucose (PLG), updated homeostasis model assessment of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) cumulative incident T2D at the end of 12-year follow-up were examined using generalized linear and Cox proportional hazards models, respectively.
In total, 8,009 participants were included having median age of 52 years, and vegetable intake of 132 g/day. Higher intake of total vegetable, green leafy, yellow/orange/red, and moderate intakes of cruciferous vegetables was associated with lower PLG. Additionally, higher green leafy vegetable intake was associated with lower HOMA2-%β and serum insulin. Conversely, higher potato fries/chips intakes were associated with higher FPG, HOMA2-%β, serum insulin, and lower HOMA2-%S. Participants with moderate cruciferous vegetables intake had a 25% lower risk of T2D at the end of 12 years follow-up.
A higher intake of vegetables, particularly green leafy vegetables, may improve while consuming potato fries/chips, but not potatoes prepared in a healthy way, may worsen glucose tolerance and insulin sensitivity. Our findings suggest a nuanced relationship between vegetable subgroups and their impact on glucose tolerance.
Defining Overweight and Obesity by Percent Body Fat instead of Body Mass Index.
Clinical EndocrinologyThresholds for overweight and obesity are currently defined by body mass index (BMI), a poor surrogate marker of actual adiposity (percent body fat, %BF). Practical modern technologies provide estimates of %BF but medical providers need outcome-based %BF thresholds to guide patients. This analysis determines %BF thresholds based on key obesity-related comorbidities, exhibited as metabolic syndrome (MetSyn). These limits were compared to existing BMI thresholds of overweight and obesity.
Correlational analysis of data from cross sectional sampling of 16,918 adults (8,734 men and 8,184 women) from the US population, accessed by the National Health and Nutrition Examination Survey (NHANES) public use datasets.
Individuals measured by BMI as overweight (BMI>25 kg/m2) and with obesity (BMI>30 kg/m2) included 5% and 35% of individuals with MetSyn, respectively. For men, there were no cases of MetSyn below 18%BF, %BF equivalence to "overweight" (i.e., 5% of MetSyn individuals) occurred at 25%BF, and "obesity" (i.e., 35% of MetSyn individuals) corresponded to 30%BF. For women, there were no cases of MetSyn below 30%BF, "overweight" occurred at 36%BF, and "obesity" corresponded to 42%BF. Comparison of BMI to %BF illustrates the wide range of variability in BMI prediction of %BF, highlighting the potential importance of using more direct measures of adiposity to manage obesity-related disease.
Practical methods of body composition estimation can now replace the indirect BMI assessment for obesity management, using threshold values provided from this study. Clinically relevant "overweight" can be defined as 25 and 36% BF for men and women, respectively, and "obesity" is defined as 30 and 42% BF for men and women.
