Intrauterine growth restriction combined with postnatal accelerated growth (CG-IUGR) could lead to long-term detrimental metabolic outcomes characterized by insulin resistance. As an indispensable co-receptor of Wnt signaling, LRP6 plays a critical role in the susceptibility of metabolic disorders. However, whether LRP6 is involved in the metabolic programing is still unknown. We hypothesized that CG-IUGR programed impaired insulin sensitivity through the impaired LRP6-mediated Wnt signaling in skeletal muscle. A CG-IUGR rat model was employed. The transcriptional and translational alterations of the components of the Wnt and the insulin signaling in the skeletal muscle of the male CG-IUGR rats were determined. The role of LRP6 on the insulin signaling was evaluated by shRNA knockdown or Wnt3a stimulation of LRP6. Compared with controls, the male CG-IUGR rats showed an insulin-resistant phenotype, with impaired insulin signaling and decreased expression of LRP6/β-catenin in skeletal muscle. LRP6 knockdown led to reduced expression of the IR-β/IRS-1 in C2C12 cell line, while Wnt3a-mediated LRP6 expression increased the expression of IRS-1 and IGF-1R but not IR-β in the primary muscle cells of male CG-IUGR rats. The impaired LRP6/β-catenin/IGF-1R/IRS-1 signaling is probably one of the critical mechanisms underlying the programed impaired insulin sensitivity in male CG-IUGR.
Wenjun Long, Tuo Zhou, Xiuping Xuan, Qiuli Cao, Zuojie Luo, Yingfen Qin, Qin Ning, Xiaoping Luo, and Xuemei Xie
Georgios Kontogeorgos, Zoi Mamasoula, Emily Krantz, Penelope Trimpou, Kerstin Landin-Wilhelmsen, and Christine M Laine
Hypoparathyroidism (HypoPT) is a rare endocrine disorder in which insufficient levels of parathyroid hormone (PTH) lead to low serum calcium (S-Ca) levels and muscular cramps. The aim was to study the health-related quality of life (HRQoL) and comorbidities in patients with HypoPT compared with the general population and to estimate the need of treatment with PTH analog.
Patients with HypoPT were identified and compared with a population sample. Short Form-36 (SF-36) and EuroQol-5 Dimensions Visual Analogue Scale questionnaires were used. All patients were followed up at the Sahlgrenska University Hospital outpatient clinic.
From the medical records between 2007 and 2020, 203 patients with HypoPT were identified and compared with a population sample (n = 414) from the World Health Organization’s (WHO) MONICA project, Gothenburg, Sweden. Of the 203 patients who met the diagnostic criteria, 164 were alive and 65% answered the HRQoL questionnaires.
Patients with HypoPT, 80% postsurgical, and controls had similar age (60 years) and sex distribution (80% women). Patients had lower SF-36 summary component scores for physical (40.0 (interquartile range (IQR): 21) vs 51.2 (IQR: 14.6); P < 0.001) and mental (43.1 (IQR:17.4) vs 56.1(IQR:13.3); P < 0.001) well-being, irrespective of etiology or calcium levels. Individuals with HypoPT had more medications and lower renal function but not higher mortality than controls. Low HRQoL together with low calcium was present in 23% of individuals with HypoPT.
HRQoL was markedly lower in patients with HypoPT than in controls and independent of S-Ca levels. Treatment with PTH analog could be considered at least among patients with both low HRQoL and low calcium levels.
Josi Vidart, Paula Jaskulski, Ana Laura Kunzler, Rafael Aguiar Marschner, André Ferreira de Azeredo da Silva, and Simone Magagnin Wajner
We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of nonthyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients in 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2-63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% confidence interval (CI), 0.41–1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31–0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in TSH levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (OR = 2.21, 95% CI 1.64.- 2.97, I2 = 65% p < 0.01) The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.
Lauren R. Cirrincione, Bridgit O. Crews, Jane A. Dickerson, Matthew D. Krasowski, Jessica Rongitsch, Katherine L. Imborek, Zil Goldstein, and Dina N. Greene
Objectives: Recently, an estradiol immunoassay manufacturer (Beckman Coulter, USA) issued an “Important Product Notice” alerting clinical laboratories their assay (Access Sensitive Estradiol) was not indicated for patients undergoing exogenous estradiol treatment. The objective of this analysis was to evaluate immunoassay bias relative to liquid chromatography tandem mass spectrometry (LC-MS/MS) in transgender women and to examine the influence of unconjugated estrone on measurements.
Design: Cross sectional secondary analysis.
Methods: Estradiol concentrations from 89 transgender women were determined by three immunoassays (Access Sensitive Estradiol [‘New BC’] and Access Estradiol assays [‘Old BC’], Beckman Coulter; Estradiol III assay [‘Roche’], Roche Diagnostics) and LC-MS/MS. Bias was evaluated with and without adjustment for estrone concentrations. The number of participants who shifted between three estradiol concentration ranges for each immunoassay versus LC-MS/MS (>300 pg/mL, 70-300 pg/mL, and <70 pg/mL) was calculated.
Results: The New BC assay had the largest magnitude overall bias (median: -34%) and was -40%, -22%, and -10%, among participants receiving tablet, patch, or injection preparations, respectively. Overall bias was -12% and +17% for the Roche and Old BC assays, respectively. When measured with the New BC assay, 18 participants shifted to a lower estradiol concentration range (versus 9 and 10 participants based on Roche or Old BC assays, respectively). Adjustment for estrone did not minimize bias.
Conclusions: Immunoassay measurement of estradiol in transgender women may lead to falsely decreased concentrations that have the potential to affect management. A multi-disciplinary health care approach is needed to ensure appropriate analytical methods are available.
Ja Hye Kim, Yunha Choi, Soojin Hwang, Gu-Hwan Kim, Han-Wook Yoo, and Jin-Ho Choi
Objective: Heterozygous CHD7 mutations cause a broad spectrum of clinical phenotypes ranging from typical CHARGE syndrome to self-limited delayed puberty. This study aimed to investigate the clinical characteristics of endocrine dysfunction in patients with CHD7 mutations.
Methods: The clinical features and endocrine findings from 30 patients with CHD7 variants were retrospectively reviewed. A diagnosis of CHARGE syndrome was based on the Verloes diagnostic criteria.
Results: Seventeen patients fulfilled the criteria for typical CHARGE syndrome, one patient for partial/incomplete CHARGE, and the remaining 11 patients had atypical CHARGE syndrome. One patient was diagnosed with Kallmann syndrome and unilateral deafness. The most frequently observed features were inner ear anomalies (80.0%), intellectual disability (76.7%), and external ear anomalies (73.3%). The mean height and weight SDSs at diagnosis were -2.6 ± 1.3 and -2.2 ± 1.8, respectively. Short stature was apparent in 18 patients (60%), and one patient was diagnosed with growth hormone deficiency. Seventeen males showed genital hypoplasia, including micropenis, cryptorchidism, or both. Seven patients after pubertal age had hypogonadotropic hypogonadism with hyposmia/anosmia and olfactory bulb hypoplasia. Truncating CHD7 mutations were the most common (n = 22), followed by missense variants (n = 3), splice-site variants (n = 2), and large deletion (n = 2).
Conclusions: A diverse phenotypic spectrum was observed in patients with CHD7 variants, and endocrine defects such as short stature and delayed puberty occurred in most patients. Endocrine evaluation, especially for growth and pubertal impairment, should be performed during diagnosis and follow-up to improve the patient’s quality of life.
Jean-Philippe Bertocchio, Natalie Grosset, Lionel Groussin, Peter Kamenicky, Fabrice Larceneux, Anne Lienhardt-Roussie, Agnès Linglart, Gérard Maruani, Eric Mirallie, François Pattou, Riyad N.H. Seervai, Coralie Sido, Caroline Silve, Aurélie Vilfaillot, Antoine Tabarin, Marie-Christine Vantyghem, and Pascal Houillier
Context: Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians’ practices or their adherence to such guidelines.
Objective: To describe the practice patterns and their compliance with international guidelines.
Design: Cohort studies: Épi-Hypo (118 Physicians and 107 patients, from 09/2016 to 12/2019) and ePatients (110 patients, November 2019).
Methods: Internet-based cohorts involving all settings at a nationwide level (France). Participants were i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the ii) Épi-Hypo study (Épi-Hypo 2019 patients) or iii) Hypoparathyroidism France, the national representative association (ePatients).
Results: The physicians’ specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%) or miscellaneous (4%). Forty-five percent were practicing in public universities. The median number of pharmaceutical drug classes prescribed was 3 per patient. The combination of active vitamin D and calcium salt was given to 59% and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32% and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion.
Conclusions: The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target not only endocrinologists. Full adherence to the guidelines is low in France.
Kunzhe Lin, Lingling Lu, Zhijie Pei, Shuwen Mu, Shaokuan Huang, and Shousen Wang
The aim of this study was to evaluate the incidence and duration of delayed hyponatremia and to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) in pituitary adenomas.
We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of delayed hyponatremia.
Of the 285 patients with pituitary adenoma who underwent microscopic TSS, 44 (15.4%) developed postoperative-delayed hyponatremia and 241 (84.6%) did not. The onset of delayed hyponatremia occurred an average of 5.84 days post-surgery and persisted for an average of 5.36 days. Logistic regression analysis showed the highest risk of delayed hyponatremia in patients with significant change in tumor cavity height (odds ratio (OR), 1.158; 95% CI, 1.062, 1.262; P = 0.001), preoperative hypothalamus–pituitary–thyroid axis hypofunction (OR, 3.112; 95% CI, 1.481, 6.539; P = 0.003), and significant difference in blood sodium levels before and 2 days after TSS (OR, 1.101; 95% CI, 1.005, 1.206; P = 0.039).
Preoperative hypothyroidism, difference in blood sodium levels before and 2 days after TSS, and the change in tumor cavity height after TSS played important roles in predicting postoperative-delayed hyponatremia onset in patients with pituitary adenomas.
Laura Chioma, Carla Bizzarri, Martina Verzani, Daniela Fava, Mariacarolina Salerno, Donatella Capalbo, Chiara Guzzetti, Laura Penta, Luigi Di Luigi, Natascia Di Iorgi, Mohamad Maghnie, Sandro Loche, and Marco Cappa
Objective: This retrospective study aimed to evaluate children observed for suspected precocious puberty in 5 Italian centers of Pediatric Endocrinology during the first wave of COVID-19 pandemic (March- September 2020), compared to subjects observed in the same period of the previous year.
Design: The study population (490 children) was divided according to year of observation and final diagnosis: transient thelarche (TT), non-progressive precocious puberty (NPP), central precocious puberty (CPP), or early puberty (EP).
Results: Between March and September 2020, 338 subjects were referred for suspected precocious puberty, compared to 152 subjects in the same period of 2019 (+222%). The increase was observed in girls (328 subjects in 2020 versus 140 in 2019, p<0.05), especially during the second half of the period considered (92 girls from March to May versus 236 girls from June to September); while no difference was observed in boys (10 subjects in 2020 versus 12 in 2019). The percentage of girls with confirmed CPP was higher in 2020, compared to 2019 (135/328 girls [41%] versus 37/140 [26%], p<0.01). Anthropometric and hormonal parameters in 2019 and 2020 CPP girls were not different; 2020 CPP girls showed a more prolonged use of electronic devices and a more sedentary lifestyle both before and during the pandemic, compared to the rest of the 2020 population.
Conclusions: The present findings corroborate the recently reported association between the complex lifestyle changes related to the lockdown and a higher incidence of central precocious puberty in Italian girls.
Anna Liori, Damaskini Polychroni, Georgios K Markantes, Maria Stamou, Sarantis Livadas, George Mastorakos, and Neoklis Georgopoulos
Adequate vitamin D levels are particularly important in pregnant women for both maternal and neonatal health. Prior studies have shown a significantly high prevalence of vitamin D deficiency (VDD) among refugees. However, no study has addressed the prevalence of VDD in pregnant refugees and its effects on neonatal health. In this study, we examined the prevalence of VDD in refugee pregnant women living in Greece and compared our results with Greek pregnant inhabitants. VDD was frequent in both groups but was significantly more common in refugees (92.2 vs 67.3% of Greek women, P = 0.003) with 70.6% of refugees having severe hypovitaminosis D (<10 ng/mL). As a result, most newborns had VDD, which affected refugee newborns to a greater extent. Our results suggest a need to screen newcomer children and pregnant women for VDD in all host countries around the world. Such a screen will appropriately guide early and effective interventions with the goal to prevent adverse neonatal and maternal outcomes.
Huixing Liu and Daoquan Peng
Hypothyroidism is often associated with elevated serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides. Thyroid hormone (TH) affects the production, clearance and transformation of cholesterol, but current research shows that thyroid-stimulating hormone (TSH) also participates in lipid metabolism independently of TH. Therefore, the mechanism of hypothyroidism-related dyslipidemia is associated with the decrease of TH and the increase of TSH levels. Some newly identified regulatory factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiogenin-like proteins (ANGPTL), and fibroblast growth factors (FGF) are the underlying causes of dyslipidemia in hypothyroidism. High-density lipoprotein (HDL) serum concentration changes were not consistent, and its function was reportedly impaired. The current review focuses on the updated understanding of the mechanism of hypothyroidism-related dyslipidemia.