The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17β-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17β-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17β-HSD1-positive group in Kaplan–Meier analysis (P = 0.028), and 17β-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24–0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17β-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17β-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.
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17β-hydroxysteroid dehydrogenase type 1 improves survival in serous epithelial ovarian tumors
Enrique Pedernera, Flavia Morales-Vásquez, María J Gómora, Miguel A Almaraz, Esteban Mena, Delia Pérez-Montiel, Elizabeth Rendon, Horacio López-Basave, Juan Maldonado-Cubas, and Carmen Méndez
Challenges past, present and future for Endocrine Connections
Adrian J L Clark
Characteristics of cardiac arrhythmia and heart rate variability in Chinese patients with primary aldosteronism
Shuang Wan, Chengcheng Zheng, Tao Chen, Lu Tan, Jia Tang, Haoming Tian, and Yan Ren
We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.
The effect of radioactive iodine treatment for differentiated thyroid cancer on male gonadal function: a meta-analysis
Yanling Cai, Yan Yang, Xiao Pang, and Suping Li
The aim was to investigate the effect of radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) on male gonadal function.
PubMed, Embase, Web of Science, OVID, Scopus, and Wanfang databases were searched up to June 10, 2022, to identify published studies related to RAI and male gonadal function. ReviewManager version 5.4.1 software was used to calculate mean differences (MDs) with 95% CIs.
Initially, 1958 articles were retrieved from the databases, and 6 articles were included in the quantitative analysis. The meta-analysis results showed that follicle-stimulating hormone (FSH) increased when the follow-up duration was ≥12 months after RAI, but the difference was not statistically significant (MD = −2.64, 95% CI = (−5.61, 0.33), P = 0.08). But the results of the subgroup analysis showed that when the follow-up time was ≤6 months, FSH levels were significantly higher after RAI (MD = −7.65, 95% CI = (−13.95, −1.34), P = 0.02). The level of inhibin B was significantly lower at ≥12 months and ≤6 months after RAI (MD = 66.38, 95% CI = (8.39, 124.37), P = 0.02) and (MD = 116.27, 95% CI = (43.56, 188.98), P = 0.002). Additionally, luteinizing hormone (LH) and testosterone have similar results – that is, LH and testosterone levels were higher after RAI, but the difference was not statistically significant (MD = –0.87, 95% CI = (−2.04, 0.30), P = 0.15) and (MD = −1.69, 95% CI (−7.29, 3.90), P = 0.55).
Male gonadal function may be temporarily impaired within 6 months after RAI but may return to normal levels afterward.
Electronic reporting of rare endocrine conditions within a clinical network: results from the EuRRECa project
S R Ali, J Bryce, A L Priego-Zurita, M Cherenko, C Smythe, T M de Rooij, M Cools, T Danne, H Katugampola, O M Dekkers, O Hiort, A Linglart, I Netchine, A Nordenstrom, P Attila, L Persani, N Reisch, A Smyth, Z Sumnik, D Taruscio, W E Visser, A M Pereira, N M Appelman-Dijkstra, and S F Ahmed
The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb.eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018.
Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021.
The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33).
e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network.
Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions within a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.
Epidemiologic trends of and factors associated with overall survival in patients with neuroendocrine tumors over the last two decades in the USA
Peiwen Wu, Dongjie He, Hao Chang, and Xiaozhi Zhang
Updated epidemiological data of neuroendocrine tumors are currently lacking. Thus, we performed epidemiological and survival analyses on a large cohort of patients with neuroendocrine tumors and developed a new nomogram to predict survival.
This population-based study examined 112,256 patients with neuroendocrine tumors between 2000 and 2018 using data from the Surveillance, Epidemiology, and End Results program.
The age-adjusted incidence per 100,000 persons of neuroendocrine tumors increased from 4.90 in 2000 to 8.19 in 2018 (annual percentage change, 3.40; 95% confidence interval, 3.13–3.67), with the most significant increases in grade 1, localized stage, and appendix neuroendocrine tumors. The age-adjusted mortality rate increased 3.1-fold from 2000 to 2018 (annual percentage change, 4.14; 95% confidence interval, 3.14–5.15). The 1-, 5-, and 10-year relative survival rates for all neuroendocrine tumors were 80.5%, 68.4%, and 63.5%, respectively. Multivariate analyses showed that male sex; older age; Black, American Indian, and Alaska Native populations; earlier year of diagnosis; lung neuroendocrine tumors; higher grades; and later stage were associated with a worse prognosis and that disease stage and grade were the most important risk factors for prognosis. Furthermore, we established a nomogram to predict the 3-, 5-, and 10-year survival rates, and its discrimination ability was better than that of the TNM classification.
The incidence, prevalence, and mortality rate of neuroendocrine tumors continued to increase over the last two decades. Additionally, the nomogram could accurately quantify the risk of death in patients with neuroendocrine tumors and had good clinical practicability.
Evaluation of the correlation between fetuin-B levels and essential hypertension: a cross-sectional study
Tao Gao, Rui Liu, Chunli Li, Xinglin Chu, Qiao Guo, and Dazhi Ke
Fetuin-B, a cytokine that regulates lipid metabolism, has recently been linked to cardiovascular diseases such as coronary heart disease. In this study, we discussed the relationship between fetuin-B and essential hypertension.
A bioinformatics analysis of fetuin-B was performed. A total of 206 with essential hypertension and 180 age- and-sex-matched healthy subjects were enrolled. Plasma fetuin-B, endothelin 1 (ET-1), nitric oxide (NO), and adiponectin (ADI) levels were measured using ELISA kits.
Bioinformatics analysis has revealed that fetuin-B plays an important role in pathways such as lipid metabolism. Compared with healthy subjects, serum fetuin-B levels in patients with essential hypertension were significantly increased. Correlation analysis showed that the serum fetuin-B level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure, body mass index, fat percentage in vivo, waist–hip ratio, intima–media thickness, low-density lipoprotein cholesterol (LDL-C), glutamyltranspeptidase, alanine transaminase, albumin, fasting blood glucose (FBG), glycated hemoglobin, and ET-1 in the overall study subjects (all P < 0.05) and negatively correlated with HDL-C, ADI, and NO (all P < 0.05). Multivariate linear regression analysis showed that SBP, FBG, LDL-C, ADI, and ET-1 were independent factors affecting serum fetuin-B. A binary logistic regression analysis showed that fetuin-B was an independent risk factor for primary hypertension (odds ratio: 1.060, 95% CI: 1.034–1.086, P < 0.001). Receiver operating characteristic curve analysis was used to evaluate the predictive value of fetuin-B for primary hypertension, and the optimal cutoff point was 83.14 μg/mL (sensitivity 77.4%, specificity 63.3%) (area under the curve) = 0.7738, 95% CI 0.7276–0.8200, P < 0.001).
Elevated fetuin-B levels are associated with an increased risk of essential hypertension.
Hyperthyroidism incidence in a large population-based study in northeastern Italy
Simona Censi, Laura Salmaso, Filippo Ceccato, Jacopo Manso, Ugo Fedeli, Mario Saia, and Caterina Mian
An improvement in iodine status in Veneto Region has been documented in the last decade. We aimed at estimating the incidence of hyperthyroidism in the Veneto Region (Italy) over the period 2013–2022.
Retrospective population-based study conducted in Veneto (4.9 million people) using the population registry, an administrative health database. Between 2012 and 2022, hyperthyroidism incidence was defined thank to a health-care co-payment exemption for hyperthyroidism or any hospital diagnosis of hyperthyroidism. Incident hyperthyroidism was defined from 2013 to 2022 to exclude prevalent cases. Standardized incidence rates (IRs) were reported by age, sex, and etiology of thyroid hyperfunction too.
We identified 26,602 incident cases (IR of 54.38 per 100,000 person-years, 2.47-fold higher in females than in males). IR decreased from 69.87 (95% CI: 67.49, 72.25) in 2013 to 42.83 (95% CI: 40.99, 44.66) in 2022. In 2020, an out-of-trend decrease in hyperthyroidism incidence was documented, corresponding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic outbreak, with a realignment to the trend in the subsequent years. The annual percentage change according to the cause of hyperthyroidism was as follows: −6.62% (95% CI: 8.47, 4.73) (P < 0.0001) in toxic multinodular goiter, −7.56% in toxic uninodular goiter (95% CI: 10.54, 4.48) (P < 0.001) and −4.70% (95% CI: 6.33, 3.04) in toxic diffuse goiter (Graves’ disease) (P < 0.001).
We documented a decline in the incidence of hyperthyroidism in Veneto Region, paralleling the improvement of the iodine status, thanks to a long and sustained iodine prophylaxis campaign. SARS-CoV-2 pandemic and vaccination campaign did not change the declining trend of hyperthyroidism incidence in our study region.
An improvement in iodine status in the population residing in the Veneto region has been documented in the last decade, thanks to a nationwide voluntary iodine prophylaxis program running since 2005, but its impact on the epidemiology of thyroid disease has never been documented. This is the largest study on the incidence rates of hyperthyroidism carried out in Italy and covers the longest observation period among all regionwide population-based studies of hyperthyroidism in our country. We documented a reduction in the incidence of hyperthyroidism, which was more pronounced in nodular goiter diagnosis but involved also toxic diffuse goiter. The decline in the incidence of hyperthyroidism in Veneto Region shows the efficacy and safety of the iodine prophylaxis campaign.
Hypothyroidism, comorbidity and health-related quality of life: a population-based study
Hanneke J C M Wouters, Bruce H R Wolffenbuttel, Anneke C Muller Kobold, Thera P Links, Gerwin Huls, and Melanie M van der Klauw
Hypothyroidism is associated with a decreased health-related quality of life (HRQoL). We hypothesized that individuals with hypothyroidism (defined as use of thyroid hormone (TH)) and especially those having an impaired HRQoL are characterized by a high prevalence of comorbid disorders and that the impact of hypothyroidism and comorbidity on HRQoL is synergistic. Presence of comorbidity was based on data obtained using structured questionnaires, physical examination, biochemical measurements and verified medication use. Single morbidities were clustered into 14 different disease domains. HRQoL was measured using the RAND-36. Logistic regression analyses were used to determine the effect of TH use on the odds of having an affected disease domain and a lower score than an age- and sex-specific reference value for HRQoL. TH was used by 4537/14,7201 participants of the population-based Lifelines cohort with a mean (± s.d.) age of 51.0 ± 12.8 years (88% females). Eighty-five percent of the TH users had ≥1 affected disease domain in contrast to 71% of nonusers. TH use was associated with a higher odds of 13 out of 14 affected disease domains independent of age and sex. In a multivariable model, TH use was associated with a decreased HRQoL across six out of eight dimensions. No significant interactions between TH use and affected disease domains were observed. TH users with an impaired HRQoL had significantly more comorbidity than those not having an impaired HRQoL. In this large, population-based study, we demonstrated that TH users had more comorbidity than individuals not using TH. The coexistence of other chronic medical conditions in subjects with TH use led to further lowering of HRQoL in an additive manner.
The impact of neonatal 17-hydroxyprogesterone cutoff determination in a public newborn screening program for congenital adrenal hyperplasia in Southern Brazil: 3 years’ experience
Simone Martins de Castro, Paloma Wiest, Poli Mara Spritzer, and Cristiane Kopacek
Congenital adrenal hyperplasia (CAH) occurs due to enzyme defects in adrenal steroidogenesis. The 21-hydroxylase deficiency accounts for 90–95% of cases, triggering accumulation of 17-hydroxyprogesterone (17-OHP). Early diagnosis through neonatal screening allows adequate treatment and reduced mortality. The purpose of the study was to determine 17-OHP cutoffs for the diagnosis of CAH in a public newborn screening program in Southern Brazil. A retrospective, descriptive, cross-sectional study was conducted to analyze 17-OHP levels in dried blood samples collected on filter paper of 317,745 newborns screened at a public newborn screening center from May 2014 to April 2017. Neonatal 17-OHP was measured in DBS samples using a time-resolved fluoroimmunoassay (GSP® kit 3305-0010; PerkinElmer). Different cutoffs were determined and stratified by birth weight. The incidence of CAH was 1:15,887 live births in the state of Rio Grande do Sul, with 20 cases of classical CAH diagnosed during the study period. Most newborns (80.73%) were white, and the prematurity rate was 9.8% in the study population. The combination of different percentiles, 98.5th for birth weight 2001–2500 g and 99.8th for the other birth weight groups, decreased false-positive results and increased specificity compared with current reference values to identify classical CAH cases. The local 17-OHP cutoffs determined were higher than those currently used by this screening program for all birth weight groups. The calculation of reference values from local population data and the combination of percentiles proved to be a valuable tool for proper diagnosis of CAH and reduction in the number of false positives.