Journal of Endocrinological Investigation最新文献

Purpose: Long COVID is a multisystemic syndrome leading to significant morbidity. To date, a comprehensive characterization of underlying risk factors is still being defined. Osteoporosis and vertebral fractures (VFs) were associated with worse acute COVID-19 and impaired respiratory recovery after hospitalization. Therefore, we aimed to assess the potential relationship between VFs and the occurrence of the Long COVID syndrome.

Methods: Patients hospitalized for acute COVID-19 and subsequently seen in our outpatient follow-up clinic 6-months after discharge were evaluated. We retrospectively included patients with available lateral chest X-rays performed at admission suitable for VFs assessments. We excluded patients with active neoplasia, and those managed at home or those hospitalized in ICU. Long COVID was diagnosed with a multidisciplinary evaluation.

Results: One-hundred sixty-two patients were included in the study. At least one VF was found in 42 patients at presentation (25.9%). Patients with VFs were significantly older and predominantly males. Long COVID was diagnosed in 25 patients (15.4%). No differences were found between patients with and without Long COVID regarding demographics and comorbidities; however, those with Long COVID were characterized by a higher prevalence of VFs at time of hospitalization for acute COVID-19 (48% vs. 22%, p = 0.01). After matching patients with and without VFs in a 1:1 ratio for demographics, comorbidities, and COVID-19 severity, a total of 84 patients were analysed and those presenting VFs were characterized by a significant higher prevalence of Long COVID (28.6% vs. 9.5%, p = 0.04) and VFs resulted as the only significant independent risk factor for Long COVID occurrence.

Conclusions: We observed that prevalent VFs detected at hospital admission were distinctive clinical features of patients presenting with Long COVID 6-months after discharge, independently from acute disease severity and other confounding factors. This highlights a potential detrimental association between skeletal fragility and the development of Long COVID.

Purpose: Levothyroxine (LT4) is commonly prescribed, but there is evidence strongly suggesting that a significant proportion of these patients are on treatment without solid evidence of hypothyroidism. Small trials on treatment discontinuation, did not detect any predictors of success. Therefore, we conducted this study in an attempt to identify predicting factors for successful LT4 withdrawal.

Methods: In 802 consecutive patients (83% females, mean age 48 ± 16 years) on LT4 treatment for 8.8 ± 7.3 years without a solid diagnosis of hypothyroidism, therapy was abruptly discontinued. A total of 387 persons were followed up for up to 4 months (group A) and 415 individuals who were euthyroid at 4 months post LT4 discontinuation, were followed up for up to 60 months (group B). Recurrent hypothyroidism was defined if thyrotropin (TSH) level exceeded 4.5mIU/L.

Results: Among the entire cohort, 182 patients (23%) became hypothyroid, 40% of group A and 7% of group B (p < 0.001). The Τhyroid treatment Discrimination Index (T4RxDI), the product of TSH levels multiplied by the daily LT4 dose divided by BMI, was calculated. In group A, successful LT4 withdrawal was strongly indicated by a T4RxDI value < 2.78 (72% sensitivity, 66% specificity), while in group B, the corresponding value was 3.75 (100% sensitivity, 48% specificity).

Conclusions: Our findings reveal considerable overuse of LT4 and propose a T4RxDI product of < 3 as a valuable predictive factor of recurrent hypothyroidism, justifying a treatment discontinuation trial. If hypothyroidism does not resume within 4 months, the risk of developing long-term hypothyroidism is likely to be minimal.

Purpose: Given the established link between GH/insulin-like growth factor 1 (IGF-1) deficiency and severe COVID-19 outcomes, this research seeks to determine whether GH therapy can enhance vaccine efficacy in patients with adult-onset growth hormone deficiency (aGHD).

Methods: We conducted an observational retrospective study involving two groups: a cohort of 10 patients (8 females, 2 males) with obesity and aGHD who initiated recombinant GH replacement therapy at a standard dose of 0.1 mg/day six months to one year before their first vaccine dose, and a matched control group of 7 patients (5 females, 2 males) with aGHD who had not started GH treatment. Both groups were matched for age, gender, and body mass index (BMI) to ensure comparability. Blood samples were collected 3 to 6 months after the third booster dose of the COVID-19 vaccine (BNT162b2, Pfizer-BioNTech) and analyzed for anti-SARS-CoV-2 antibodies using a commercially available assay.

Results: The GH-treated group exhibited a significantly greater humoral response compared to the untreated group, with a mean antibody titer of 19,122.1 ± 7,736.84 U/mL versus 9,539.14 ± 5,408.90 U/mL in the control group (p = 0.01). Multivariate regression analysis revealed that GH replacement therapy was the only statistically significant predictor of vaccine response, while factors such as male sex, age, and visceral adipose tissue showed negative correlations that did not reach significance.

Conclusion: Our findings suggest that GH replacement therapy may enhance the immune response to COVID-19 vaccination in patients with aGHD, potentially improving their overall metabolic health and immune function.

Objective: This study was aimed to analyze the clinical and genetic characteristics of hypoparathyroidism in children.

Methods: We performed a retrospective analysis of 74 patients diagnosed with pediatric hypoparathyroidism from 2014 to 2023, recruited in five medical centers across China. Data of basic information and clinical tests were extracted from patients' records. Whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis (CMA) were utilized to identify the genetic causes.

Results: The results indicated a median onset age of 6.07 ± 4.82 years and a median diagnosis age of 6.91 ± 4.88 years. Of the 46 patients who underwent genetic tests, 35 were found to carry pathogenic variants related to hypoparathyroidism. Specifically, 19 cases (19/46, 41.30%) had 22q11.2 microdeletion, while other variations included AIRE (8/46, 17.39%), GATA3 (3/46, 6.52%), CaSR (2/46, 4.34%), and the rest 3 patients with mutations of TBCE, PTH and mitochondrial gene deletion respectively. Convulsions were the most common initial presentation, observed in 43 cases. The non-DGS group exhibited the lowest serum PTH levels compared to DiGeorge syndrome and gene-negative group. Among the 66 patients who underwent cranial CT or MR, 26 (26/66, 39.99%) presented with intracranial calcification.

Conclusions: We reported the largest cohort of childhood hypoparathyroidism with genetic diagnoses, reinforcing the view that genetic disorders account for the majority of pediatric hypoparathyroidism, with the 22q11.2 microdeletion being the most prevalent. Identifying the genetic causes of hypoparathyroidism is crucial for predicting patient outcomes, managing comorbidities, and, importantly, informing decisions regarding the potential use of emerging recombinant human PTH therapy.

Purpose: Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid. We investigated the dual health ability of DHA to modulate gut microbiota in children with obesity and to exert anti-inflammatory activity on human intestinal Caco-2 cells.

Methods: In a pilot study involving 18 obese children (8-14 years), participants received a daily DHA supplement (500 mg/day) and dietary intervention from baseline (T0) to 4 months (T1), followed by dietary intervention alone from 4 months (T1) to 8 months (T2). Fecal samples, anthropometry, biochemicals and dietary assessment were collected at each timepoint. At preclinical level, we evaluated DHA's antioxidant and anti-inflammatory effects on Caco-2 cells stimulated with Hydrogen peroxide (H₂O₂) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase (iNOS) levels and cytokines, respectively.

Results: Ten children were included in final analysis. No major changes were observed for anthropometric and biochemical parameters, and participants showed a low dietary compliance at T1 and T2. DHA supplementation restored the Firmicutes/Bacteroidetes ratio that was conserved also after the DHA discontinuation at T2. DHA supplementation drove a depletion in Ruminococcaceae and Dialisteraceae, and enrichment in Bacteroidaceae, Oscillospiraceae, and Akkermansiaceae. At genus level, Allisonella was the most decreased by DHA supplementation. In Caco-2 cells, DHA decreased H₂O₂-induced reactive oxygen species (ROS) and nitric oxide (NO) production via iNOS pathway modulation. Additionally, DHA modulated proinflammatory (IL-1β, IL-6, IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokine production in LPS-stimulated Caco-2 cells.

Conclusion: An improvement in gut dysbiosis of children with obesity seems to be triggered by DHA and to continue after discontinuation. The ability to modulate gut microbiota, matches also with an anti-inflammatory effect of DHA on Caco-2 cells.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to manage type 2 diabetes (T2D) and obesity. Despite their recognized benefits in glycemic control and weight management, their impact on broader systemic has been less explored.

Objective: This study aimed to evaluate the impact of GLP-1RAs on a variety of systemic diseases in people with T2D or obesity.

Methods: We conducted a retrospective cohort study using data from the Global Collaborative Network, accessed through the TriNetX analytics platform. The study comprised two primary groups: individuals with T2D and those with obesity. Each group was further divided into subgroups based on whether they received GLP-1RA treatment or not. Data were analyzed over more than a 5-year follow-up period, comparing incidences of systemic diseases; systemic lupus erythematosus (SLE), systemic sclerosis (SS), rheumatoid arthritis (RA), ulcerative colitis (UC), crohn's disease (CD), alzheimer's disease (AD), parkinson's disease (PD), dementia, bronchial asthma (BA), osteoporosis, and several cancers.

Results: In the T2D cohorts, GLP-1RA treatment was associated with significantly lower incidences of several systemic and metabolic conditions as compared to those without GLP-1RA, specifically, dementia (Risk Difference (RD): -0.010, p < 0.001), AD (RD: -0.003, p < 0.001), PD (RD: -0.002, p < 0.001), and pancreatic cancer (RD: -0.003, p < 0.001). SLE and SS also saw statistically significant reductions, though the differences were minor in magnitude (RD: -0.001 and - 0.000 respectively, p < 0.001 for both). Conversely, BA a showed a slight increase in risk (RD: 0.002, p < 0.001).

Conclusions: GLP-1RAs demonstrate potential benefits in reducing the risk of several systemic conditions in people with T2D or obesity. Further prospective studies are needed to confirm these effects fully and understand the mechanisms.

Purpose: Neuroendocrine neoplasms (NENs) represent heterogeneous tumors arising from neuroendocrine cells in different organs. Despite growing interest in the nutritional aspects of NEN management, research in this area is limited. Aim of this review is to summarize the current state of knowledge, highlight research gaps, and underscore the significance of nutrition in the comprehensive care of NEN patients.

Methods: We conducted an extensive bibliographic search focusing on studies (including retrospective and prospective studies, systematic reviews, case series, and guidelines) exploring the relationship between nutritional assessments, dietary interventions, micronutrient deficiencies, and their impact on NEN outcomes.

Results: Significant gaps exist in current research, particularly in understanding the specific nutritional needs of NEN patients and how tailored nutritional interventions can improve clinical outcomes. Evidence suggests that a high-fat Western diet may promote the growth of NEN, while a Mediterranean diet may help lower insulin levels and strengthen the immune system, potentially preventing tumor development. The ketogenic diet and intermittent fasting may also have positive impacts. Addressing common micronutrient deficiencies, such as vitamin D and niacin, is crucial to mitigate disease progression. There's a crucial need for future studies to include a comprehensive nutritional assessment incorporating patient-reported outcomes, to fully capture the impact of nutritional strategies.

Conclusion: Nutritional management, an important but under-researched facet of NEN treatment, significantly improves patients' quality of life and survival. Integrating nutrition into personalized cancer care is essential, highlighting the role of nutritional strategies in optimizing patient outcomes.