Journal of Endocrinological Investigation最新文献

Purpose: The screening test to suspect infantile hypercalcemia-1 (HCINF1) is the measure of 25(OH)D₃/24,25(OH)₂D₃ ratio at mass spectroscopy (MS). When the ratio is > 80, the gold standard for the diagnosis is genetic analysis. Given its limited availability, MS may not represent a screening test and most cases of HCINF1 remain undiagnosed. Aim of the study is to identify cut-offs of serum calcium and PTH useful to suspect patients with HCINF1.

Methods: We compared the levels of total serum calcium and PTH of 6 patients with HCINF1 harboring biallelic CYP24A1 pathogenic variants with 3 different control groups: (1) 12 subjects wild type for CYP24A1; (2) 12 subjects matched for age and sex; (3) 12 subjects matched for vitamin D levels. We validated the cut-offs, testing the number of adult patients affected by HCINF1 reported in the literature that could be identified using these cut-offs.

Results: A serum calcium level > 9.6 mg/dL showed the highest sensitivity (100%) and specificity (91%) in the comparison between homozygous and wild-type subjects. A serum PTH index < 0.315 showed the highest sensitivity (100%) and specificity (83.3%). A serum calcium level > 9.6 mg/dL was able to identify all adult HCINF1 patients whereas a PTH ratio < 0.315 identified 89.8% of the cases. Superimposable results were obtained using the other control groups.

Conclusion: Patients with serum calcium levels higher than 9.6 mg/dL and a PTH index lower than 0.315 are likely to be affected by HCINF1. Their diagnosis may be confirmed using MS and genetic analysis.

Purpose: Peritoneal metastases (PM) of neuroendocrine neoplasm (NEN) origin are identified with increasing frequency and exert a significant effect on quality of life and clinical status of the patients. The aim of this study was to identify the characteristics and the prognostic significance of PM in patients with NENs.

Methods: A retrospective analysis of the data of patients from two tertiary referral centers was performed. We defined a control group of age- and gender-matched NEN patients with comparable stage IV disease but no PM.

Results: We analysed 70 patients (41 females) with PM. Small intestine was the most common primary NEN site (87.1%). PM prevalence was 10.3%. Forty-four patients presented with synchronous PM, whereas 26 developed metachronous PM. The majority of patients had other concomitant metastases (50 hepatic, 6 lung and 12 bone metastases). Twelve patients developed intestinal obstruction. After PM diagnosis, 76% of patients received treatment with somatostatin analogues while six patients (8.6%) were treated with peptide receptor radionuclide therapy (PRRT). The median progression-free survival (PFS) in the PRRT-treated group was 15 months (95% CI 2-28). Median overall survival (OS) in the PM group was 142 months [95% CI 71-213] while it was not reached in the control group.

Conclusion: Peritoneal metastases show low prevalence among NEN patients and are most likely to develop in patients with small intestinal NENs and advanced metastatic disease. The presence of PM does seem to be associated with a negative prognostic impact on OS of NEN patients and their identification and prompt treatment is of major importance.

Purpose: We aimed to determine the frequency of transient congenital hypothyroidism (TCH) in 17 participating centers in Türkiye, evaluate the etiological distribution in permanent congenital hypothyroidism (PCH) cases, and investigate the role of laboratory and clinical findings in predicting TCH.

Methods: This retrospective observational multicenter study included patients from 17 pediatric endocrinology centers identified by "National Newborn Screening Program" (NNSP) who were born in 2015 and followed for 6 years. Demographic, clinical, and laboratory information of the cases were compiled through the database http://cedd.saglik-network.org (CEDD-NET).

Results: Of the 239 cases initially treated for CH, 128 (53.6%) were determined as transient in whom a trial of levothyroxine (LT4) withdrawal was performed at a median age of 36 (34-38) months. Among the patients with PCH (n = 111), thyroid dysgenesis was diagnosed in 39.6% (n = 44). The predictive factors for TCH were: LT4 dose at the withdrawal of treatment, and initial newborn blood screening (NBS)-TSH level. Based on the receiver operating characteristic (ROC) curve analysis to predict optimal cut-offs for TCH predictors, LT4 dose < 2.0 µg/kg/day at treatment discontinuation was predictive for TCH and was associated with 94.5% specificity and 55.7% sensitivity, with an area under the curve (AUC) of 0.802. The initial NBS-TSH level value < 45 µIU/mL was predictive for TCH with 93.1% specificity and 45.5% sensitivity, with an AUC of 0.641. In patients with eutopic thyroid gland only LT4 dose < 1.1 µg/kg/day at withdrawal time was predictive for TCH with 84.7% sensitivity and 40.4% specificity, with an AUC of 0.750.

Conclusion: According to our national follow-up data, the frequency of TCH was 53.6%. We determined the LT4 dose < 2.0 µg/kg/day at discontinuation of treatment and the initial NBS-TSH level < 45 µIU/mL as the best cut-off limits to predict TCH.

Purpose: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC).

Methods: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated.

Results: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance.

Conclusion: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.

Purpose: Graves' ophthalmopathy (GO) is an autoimmune disease that affects orbital soft tissues and represents the most common extrathyroidal manifestation of Graves' disease (GD). The European Group of Graves' Ophthalmopathy (EUGOGO) has attempted to shed light on the European epidemiological picture of GO, suggesting that GO in newly diagnosed patients in recent years has a trend towards a less severe clinical presentation. There are no studies that focus this issue on the population of our area; we aimed to evaluate the trend of GO clinical presentation in our outpatient clinic through an observation period of 10 years.

Methods: We compared 55 consecutive patients, 11 males (F) and 44 females (M), who came to our observation from January 2005 to December 2006 [Group 1 (G1)], with 56 patients, 15 males, and 41 females, who were referred to us from 2015 to 2016 [Group 2 (G2)]. We studied the following putative predictors of GO presentation and severity: thyroid function, smoking, diabetes, hypercholesterolemia, time from GO diagnosis to referral to our thyroid centre (TGOD), sex and age.

Results: GO severity was significantly reduced in G2 vs. G1 (p = 0.04). TGOD ≥ 3 months was related to clinical characteristics of GO (severity and Clinical Activity Score ≥ 4) and was an independent predictor of GO severity (p = 0.01). The other variables evaluated had no independent effects.

Conclusions: We found that GO severity at presentation was significantly reduced over a ten-year observation period (2005-2006 vs. 2015-2016) in GO patients referred to our tertiary thyroid centre. TGOD ≥ 3 months was an independent predictor of GO severity.

Background: Gestational diabetes mellitus (GDM) is a serious health concern that affects pregnant women worldwide and can lead to adverse pregnancy outcomes. Early detection of high-risk individuals and the implementation of appropriate treatment can enhance these outcomes.

Methods: We conducted a study on a cohort of 3467 pregnant women during their pregnancy, with a total of 5649 clinical and biochemical records collected. We utilized this dataset as our training dataset to develop a web server called GDMPredictor. The GDMPredictor utilizes advanced machine learning techniques to predict the risk of GDM in pregnant women. We also personalize treatment recommendations based on essential biochemical indicators, such as A1MG, BMG, CysC, CO2, TBA, FPG, and CREA. Our assessment of GDMPredictor's effectiveness involved training it on the dataset of 3467 pregnant women and measuring its ability to predict GDM risk using an AUC and auPRC.

Results: GDMPredictor demonstrated an impressive level of precision by achieving an AUC score of 0.967. To tailor our treatment recommendations, we use the GDM risk level to identify higher risk candidates who require more intensive care. The GDMPredictor can accept biochemical indicators for predicting the risk of GDM at any period from 1 to 24 weeks, providing healthcare professionals with an intuitive interface to identify high-risk patients and give optimal treatment recommendations.

Conclusions: The GDMPredictor presents a valuable asset for clinical practice, with the potential to change the management of GDM in pregnant women. Its high accuracy and efficiency make it a reliable tool for doctors to improve patient outcomes. Early identification of high-risk individuals and tailored treatment can improve maternal and fetal health outcomes http://www.bioinfogenetics.info/GDM/ .

Purpose: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by persistent fatigue and decreased daily activity following physical and/or cognitive exertion. While ME/CFS affects both sexes, there is a higher prevalence in women. However, studies evaluating this sex-related bias are limited.

Methods: Circulating steroid hormones, including mineralocorticoids (aldosterone), glucocorticoids (cortisol, corticosterone, 11-deoxycortisol, cortisone), androgens (androstenedione, testosterone), and progestins (progesterone, 17α-hydroxyprogesterone), were measured in plasma samples using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Samples were obtained from mild/moderate (ME/CFSmm; females, n=20; males, n=8), severely affected patients (ME/CFSsa; females, n=24; males, n=6), and healthy controls (HC, females, n=12; males, n=17).

Results: After correction for multiple testing, we observed that circulating levels of 11-deoxycortisol, 17α-hydroxyprogesterone in females, and progesterone in males were significantly different between HC, ME/CFSmm, and ME/CFSsa. Comparing two independent groups, we found that female ME/CFSsa had higher levels of 11-deoxycortisol (vs. HC and ME/CFSmm) and 17α-hydroxyprogesterone (vs. HC). In addition, female ME/CFSmm showed a significant increase in progesterone levels compared to HC. In contrast, our study found that male ME/CFSmm had lower circulating levels of cortisol and corticosterone, while progesterone levels were elevated compared to HC. In addition to these univariate analyses, our correlational and multivariate approaches identified differential associations between our study groups. Also, using two-component partial least squares discriminant analysis (PLS-DA), we were able to discriminate ME/CFS from HC with an accuracy of 0.712 and 0.846 for females and males, respectively.

Conclusion: Our findings suggest the potential value of including steroid hormones in future studies aimed at improving stratification in ME/CFS. Additionally, our results provide new perspectives to explore the clinical relevance of these differences within specific patient subgroups.

Purpose: Although the thyroid isthmus seems like a rudimentary structure that connects bilateral lobes, it is an undiscovered area that needs to be explored. Currently, the data is evolving that the increase in the risk of malignancy is higher in the isthmic nodules, and extrathyroidal extensions and lymph node metastases are more common in isthmic-derived malignant thyroid nodules. Therefore, we aimed to compare the malignancy rate of isthmic and lobar nodules, the ultrasonographic features of isthmic and lobar nodules, and presence of lymph node metastases, distant metastases, and extrathyroidal invasions in malignant isthmic nodules.

Methods: In this retrospective study, we enrolled patients between the ages of 18-80 years, who had thyroid nodule/nodules cytology and/or pathology results from January 2009 to November 2022. 9504 nodules were selected for the analysis of US findings, cytopathology results, and malignancy rates.

Results: A mean ± SD age of 55.3 ± 13.0 years with a female to male ratio of [7618 (80.2%)/1886(19.8%)] were included in the study. 962 of the nodules were at isthmic localization; whereas 8542 nodules were at lobar localization. 1188 nodules were resulted as malignant from histopathological evaluation. Of the 1188 malignant nodules, 986 nodules were (83.0%) PTC, 114 nodules (9.6%) were FTC, 55 nodules were (4.6%) MTC, 16 nodules 1.3% were Hurtle cell carcinoma, 8 nodules (0.7%) were anaplastic thyroid carcinoma, and 9 nodules (0.8%) were thyroid tumors of uncertain malignant potential (TT-UMP). 156 of the malignant nodules (13.1%) were located in the isthmus, whereas the majority of the malignant nodules (n = 1032, 86.9%) were located at the lobar parts (right or left) of the thyroid. When the metastasis patterns of isthmic and lobar thyroid cancers were examined, no significant relationship was found between isthmic and lobar cancers in terms of capsule invasion (p = 0.435), muscle invasion (p = 0.294), and lymph node metastasis (p = 0.633). A significant relation was found between nodule localization (isthmus-upper-middle and lower lobes) and malignancy (p < 0.001). In our logistic regression analysis, isthmic and upper pole nodule localizations, age and TI-RADS were evaluated as independent risk factors for malignancy (p < 0.001 for all factors).

Conclusion: We recommend nodule localization has to be considered an additional risk factor when performing a Fine Needle Aspiration Biopsy for the increased malignancy risk in this localization.

Background: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of DN, but the mechanism is still indistinct. In this work, we explored the roles of hsa_circ_0008360 in DN.

Methods: The levels of hsa_circ_0008360, microRNA-346 (miR-346) and Winglesstype family member 2B (WNT2B) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in DN tissues and HK2 cells. Meanwhile, the protein level of WNT2B was quantified by Western blot analysis. Besides, the function of cells was examined by Cell Counting Kit-8 (CCK8) assay, flow cytometry assay, western blot, and ELISA kit. Furthermore, the interplay between miR-346 and hsa_circ_0008360 or WNT2B was detected by dual-luciferase reporter assay.

Results: The levels of hsa_circ_0008360 and WNT2B were increased, and the miR-346 level was decreased in the serum of DN patients and HG-treated HK2 cells. For functional analysis, hsa_circ_0008360 deficiency promoted cell viability, inhibits cell apoptosis, inflammatory response, and the synthesis of related fibrotic proteins in HG-treated HK2 cells. Moreover, overexpression of miR-346 induced the proliferation and inhibit apoptosis of HG-induced HK2 cells by inhibiting WNT2B expression. In mechanism, hsa_circ_0008360 acted as a miR-346 sponge to regulate the level of WNT2B.

Conclusion: Hsa_circ_0008360 can regulate miR-346/WNT2B axis in HG-induced HK2 cells, providing an underlying targeted therapy for DN patients.