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International Journal of Endocrinology publishes original research articles, review articles, and clinical studies that provide insights into the endocrine system and its associated diseases at a genomic, molecular, biochemical and cellular level.
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Analysis of the Relationships between Multiple Endocrine Hormones and Return of Spontaneous Circulation (ROSC) in Cardiac Arrest Patients: Possible Association of the Serum Free T4 Level with ROSC
Background. Endocrine hormones are closely associated with homeostasis, so it is important to clarify hormone secretion dynamics in shock. Few reports, however, have examined the dynamics of endogenous hormone secretion relative to prognosis in cardiac arrest patients. Therefore, to clarify the roles of endocrine hormones in out-of-hospital cardiac arrest (OHCA) patients, the concentrations of anterior pituitary, thyroid, and adrenocortical hormones were measured, and their associations with return of spontaneous circulation (ROSC) were examined. Methods. The subjects were OHCA patients transported to our Emergency Department. In addition to conventional clinical laboratory tests, the following were measured: serum TSH, serum free T3, serum free T4 (F-T4), plasma ACTH, serum cortisol, serum GH, serum IGF-1, plasma aldosterone concentration (PAC), and plasma renin activity. The primary endpoint was the presence or absence of ROSC, and the secondary endpoint was 24-hour survival. Results. A total of 29 patients, 17 in the ROSC group and 12 in the non-ROSC group, were studied. There were associations between ROSC and low serum potassium, high F-T4, low cortisol, and low PAC on bivariate analyses. There were associations between ROSC and serum potassium, F-T4, and GH using the step-wise method. On multiple logistic regression analysis, a relationship between ROSC and high serum F-T4 level was identified by both methods. There were also associations between 24-hour survival and both low serum potassium and elevated blood glucose levels. Conclusions. The present findings suggest a possible relationship between the serum F-T4 level and ROSC in OHCA patients. A higher serum F-T4 level might cause an increase in the β-adrenergic response in cardiomyocytes and increased responsiveness to catecholamines and was possibly associated with ROSC.
Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria
Background. Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. Methods. Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39–91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). Results. PFS after 24 months was 71% (95% CI: 56–87), and overall survival (OS) was 74% (95% CI: 60–88), respectively. OS was significantly shorter () in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39–86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66–98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). Conclusion. Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.
DPP4 Activities Are Associated with Osteopenia/Osteoporosis and Fracture Risk in Newly Diagnosed Type 2 Diabetes
Background. Recent studies have shown the beneficial effect of dipeptidyl peptidase-4 (DPP4) inhibitor on bone turnover in diabetes mellitus. However, little clinical evidence for DPP4 activity in newly diagnosed type 2 diabetes is available. This study was designed to investigate the relationship between plasma DPP4 activity and osteoporosis/osteopenia and fracture risk in newly diagnosed type 2 diabetes. Methods. A total of 147 subjects with newly diagnosed type 2 diabetes were enrolled for this cross-sectional study. The bone mineral density (BMD) at the lumbar spine (L1-4) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) was assessed by a modified fracture risk algorithm (FRAX) tool. The plasma DPP4 activity and clinical variables were measured. Correlation analyses between DPP4 activity and osteoporosis/osteopenia and fracture risk were performed. Results. Elevated plasma DPP activities were significantly associated with a higher proportion of osteoporosis/osteopenia (50% for quartile-1, 56.4% for quartile-2, 65.8% for quartile-3 and 72.2% for quartile-4). With increasing plasma DPP activities, the incidence rate of osteoporosis/osteopenia is gradually increasing ( for the trend between quartiles = 0.04). Of note, a statistically significant linear correlation was found between plasma DPP4 activities and modified FRAX MOF (r = 0.20, ). Moreover, plasma DPP4 activities were also positively related to modified FRAX HF in newly diagnosed type 2 diabetic patients (r = 0.21, ). Conclusions. Elevated plasma DPP4 activity tended to be associated with a higher proportion of osteoporosis/osteopenia and increased the fracture risk in newly diagnosed type 2 diabetes.
Clinical Characteristics and Spermatogenesis in Patients with Congenital Hypogonadotropic Hypogonadism Caused by FGFR1 Mutations
Objective. The aim of this study was to investigate the clinical characteristics of patients diagnosed with congenital hypogonadotropic hypogonadism (CHH) caused by FGFR1 (fibroblast growth factor receptor 1) gene mutations and to evaluate the effect of gonadotropin or pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis. Methods. A retrospective study was conducted on CHH patients admitted to Peking Union Medical College Hospital from January 2012 to March 2020. Clinical features and laboratory results were recorded. Testicular volume and sperm count responding to gonadotropin and pulsatile GnRH therapy were compared between the FGFR1 mutation group and the mutation-negative group. Results. (1) FGFR1 mutation group included 14 patients who received sperm-induction therapy, and the mutation-negative group enrolled 25 CHH patients. (2) The incidence of cryptorchidism was 50.0% (7/14) and 12.0% (3/25) in the FGFR1 group and the mutation-negative group, respectively (). The baseline testicular volume of the FGFR1 mutation group was smaller than that of the mutation-negative group, 1.6 (0.5–2.0) mL vs. 2 (1.75–4) mL (). The baseline luteinizing hormone (LH), Follicle-stimulating hormone (FSH), and testosterone levels were similar between the two groups. (3) Using the Kaplan–Meier and log-rank tests for the analysis of spermatogenesis, it was found that there was no significant difference in the first sperm appearance between the FGFR1 mutation group and the mutation-negative group (χ2 = 1.974, ). The median time of spermatogenesis in the FGFR1 mutation group was longer than that in the mutation-negative group, 16 months vs. 10 months, respectively. The cumulative spermatogenesis success rate at 12 months in the FGFR1 mutation group (35.71%) was lower than that in the mutation-negative group (68.75%) (). The sperm concentration in the mutation-negative group was more easily achieved for different thresholds compared with that in the FGFR1 mutation group, but no significant difference was observed () between the two groups. The last follow-up examination showed that the testicular volume was 7.00 (4.75–12.00) mL and 10.56 ± 4.82 mL (), the ejaculate volume of sperm was 2.20 (1.40–2.26) mL and 3.06 ± 1.42 mL (), and the sperm concentration was 7.19 (1.00–9.91) million/mL and 18.80 (4.58–53.62) million/mL () in the FGFR1 mutation and mutation-negative groups, respectively, while the sperm motility (A%, A + B%, and A + B + C%) was similar for the two groups (, 0.909, and 0.759, respectively). The testosterone level during treatment was 366.02 ± 167.03 ng/dL and 362.27 ± 212.86 ng/dL in the FGFR1 mutation and mutation-negative groups, respectively (). Conclusion. Patients with FGFR1 mutations have a higher prevalence of cryptorchidism and smaller testicular volume. Although patients with FGFR1 mutations have a similar rate of success for spermatogenesis compared to that of the mutation-negative patients, a longer treatment period was required and a lower sperm concentration was achieved.
Recovery of Prenatal Baicalein Exposure Perturbed Reproduction by Postnatal Exposure of Testosterone in Male Mice
Baicalein (BC), a flavonoid, which lacks the qualities of reproductive health and shows adverse effects, is tested in this study. Inseminated mice were injected with 30, 60, and 90 mg BC/Kg body weight on gestation days 11, 13, 15, and 17. The F1 BC-exposed males of each dosage were divided into six groups. First three groups (n = 6 from each BC dosage) were used for assessment of reproductive performance, the others (n = 4 from each BC dosage) were administered with testosterone 4.16 mg/kg body weight on postnatal days 21, 31, and 41. The reproductive health of adult F1 males at the age of 55 and 60 was tested. Prenatal BC exposure showed reduced fertility after cohabitation with control females. The BC exposure significantly reduced the body weight, tissue indices, and sperm parameters (motility, count, viability, and daily sperm count) and altered the sperm membrane in a hypoosmotic swelling test. A downward trend was observed in testicular steroidogenic marker enzymes (3β- and 17β-steroid dehydrogenases) and serum testosterone, whereas increase in serum titers of FSH and LH along with altered the testicular histology. Conversely, testosterone (4.16 mg/kg body weight) partially recovered reduced male reproductive health by BC. BC impaired male reproductive health due to low levels of testosterone is reverted by external testosterone is evidenced in this study.
Prevalence of Diabetes, Prediabetes, and Associated Factors in an Adult Chinese Population: Baseline of a Prediabetes Cohort Study
Purpose. To report baseline information of a prediabetes mellitus (PDM) cohort with the aim of exploring related factors for the progression of PDM and its complications. Methods. This study is an exploratory and cross-sectional analysis of the baseline data from a cohort study. Residents aged 18 to 70 years from Houtang Village, Nanyue Town, Yueqing City, Zhejiang Province, China, were invited to participate between October 1, 2018 and July 1, 2019. Blood samples were collected for analysis, and questionnaire interviews were conducted to assess behavioral characteristics. The study participants were divided into DM, PDM, and normal groups for comparisons based on their blood work, and multiple multinomial logistic regression analyses were used to assess the risk factors for DM and PDM. Results. Data from 406 participants were used in the baseline analysis, with a mean age of 51.2 ± 11.0 years and 160 (33.0%) males. The number of participants in the DM, PDM, and normal group was 58 (14.3%), 166 (40.9%), and 182 (44.8%), respectively. The prevalence of DM was 14.3%, and the prevalence of PDM was 40.9%. The regression analysis showed that older age (relative risk ratio (RRR) = 1.06; 95% CI, 1.01–1.11, ), higher systolic blood pressure (RRR = 1.04; 95% CI, 1.004–1.08, ), higher BMI (RRR = 1.20; 95% CI, 1.06–3.06, ), higher TG (RRR = 1.80; 95% CI, 1.06–3.06, ), and higher WBC count (RRR = 1.32; 95% CI, 1.07–1.64, ) were significantly associated with a higher risk of DM. Meanwhile, higher systolic blood pressure (RRR = 1.03; 95% CI, 1.004–1.06, ) was the only factor significantly associated with a higher risk of PDM. Conclusion. The prevalence of DM and PDM is relatively high in this wealthy East China village population. Many modifiable risk factors exist for DM and PDM, which will be closely monitored during our longitudinal observation.