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Structural and Functional Biology Program, Universidade Federal de São Paulo, São Paulo, Brazil
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Structural and Functional Biology Program, Universidade Federal de São Paulo, São Paulo, Brazil
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Post-graduate Program in Interactive Processes of Organs and Systems, Health & Science Institute, Federal University of Bahia, Salvador, Brazil
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Post-graduate Program in Interactive Processes of Organs and Systems, Health & Science Institute, Federal University of Bahia, Salvador, Brazil
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Post-graduate Program in Interactive Processes of Organs and Systems, Health & Science Institute, Federal University of Bahia, Salvador, Brazil
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Department of Anatomic Pathology & Legal Medicine, Bahia Federal Medical School, Federal University of Bahia, Salvador, Brazil
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Division of Genetics, Department of Morphology and Genetics, Genetic Basis of Thyroid Tumors Laboratory, Paulista School of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil
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Post-graduate Program in Interactive Processes of Organs and Systems, Health & Science Institute, Federal University of Bahia, Salvador, Brazil
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Background
The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC).
Patients and methods
Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-β mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected.
Results
HOPX-β mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age.
Conclusion
A moderate coupling of downregulation of HOPX-β mRNA expression in DTC followed by high HOPX-β promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients.
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Dysregulation of thyroid function has known impact on body metabolism, however, data regarding metabolic outcome after restoration of thyroid function is limited. Therefore, the aim of the study was to investigate the effect of restoration of euthyroidism on serum visfatin, and its associations with insulin resistance and body composition. This is an observational study with consecutive enrollment. Forty-nine hyperthyroid (median age of 34 years) and 44 hypothyroid women (median age of 46 years) completed the study. Laboratory parameters and body composition analysis were assessed before and after the therapy. In the hyperthyroid group, visfatin concentrations increased (P < 0.0001), while glucose concentrations decreased (P < 0.0001). Total body mass and fat mass in the trunk and limbs significantly increased during the treatment. In the hypothyroid group, significant weight loss resulted from decrease of fat and muscle masses in trunk and limbs. Visfatin serum concentrations positively correlated with total fat mass (r = 0.19, P = 0.01) and insulin concentrations (r = 0.17, P = 0.018). In conclusion, restoration of thyroid function is not associated with beneficial changes in body composition, especially among hyperthyroid females.
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Objective
To define the optimized inter-injection interval of injectable testosterone undecanoate (TU) treatment for hypogonadal and transmen based on individual dose titration in routine clinical practice.
Design and methods
A prolective observational study of consecutive TU injections in men undergoing testosterone replacement therapy for pathological hypogonadism or masculinization of female-to-male transgender (transmen) subject to individual dosing titration to achieve a stable replacement regimen.
Results
From 2006 to 2019, 6899 injections were given to 325 consecutive patients. After excluding the 6-week loading dose, 6300 injections were given to 297 patients who had at least three and a median of 14 injections. The optimal injection interval (mean of last three injection intervals) had a median of 12.0 weeks (interquartile range 10.4–12.7 weeks). The interval was significantly influenced by age and body size (body surface area, BSA) but not by diagnosis or trough serum LH, FSH, and SHBG. Longer (≥14 weeks; 68/297, 23%), but not shorter (≤10 weeks; 22/297, 7.4%), intervals were weakly correlated with age but not diagnosis or other covariables. Low blood hemoglobin increased with trough serum testosterone to reach plateau once testosterone was about 10 nmol/L or higher.
Conclusion
Optimal intervals between TU injection after individual titration resulted in the approved 12-week interval in 70% of patients with only minor influence for clinical application of BSA and not of trough serum LH, FSH, and SHBG. Individually optimized inter-injection interval did not differ between men with primary or secondary hypogonadism or transmen.
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Background
Saliva is a useful sample as a source of hormones for the diagnosis of different diseases, particularly in pediatric patients and aged individuals, because saliva offers a noninvasive and stress-free alternative to serum collection. The aim of this study was to validate a salivary insulin method and to check its clinical application in pediatric patients.
Methods
Saliva samples were collected from 130 boys and 147 girls aged 6–14 years. Salivary and serum insulin levels were measured with the chemiluminescent automated method Access (Beckman Coulter, Brea, CA, USA). Serum blood glucose levels were measured with the glucose oxidase method in an autoanalyzer.
Results
The precision profile of the method was determined for six aliquots of different concentrations from pools of saliva, and the coefficients of variation (CV) were 2.4% for 1 μUI/ml, 4% for 0.5, 8.9% for 0.25, 19% for 0.12, 28% for 0.06, and 38% for 0.03 μUI/ml, being the functional sensibility (concentration corresponding to a 20% CV) 0.12 μUI/ml. Insulin recovery was 100.13%. Salivary insulin levels diminished 29.8% in samples stored during 7 days at 2–8 °C. Differences in insulin values were not observed when samples were stored at −20 °C during 7 days. The methods used to measure salivary and serum insulin correlated significantly (r=0.92, P<0.001). However, at levels of serum insulin >20 μUI/ml, this correlation declined (r=0.57, P=0.083).
Conclusion
The proposed method for salivary insulin measurement showed convenient analytical characteristics.
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Objective
A small thigh circumference is associated with an increased risk of diabetes, cardiovascular diseases, and total mortality. The purpose of this study was to evaluate the association between thigh circumference and hypertension in the middle-aged and elderly population.
Methods
A total of 9520 individuals aged 40 years and older with measurement of thigh circumference were available for analysis. The measurement of thigh circumference was performed directly below the gluteal fold of the thigh. The association of thigh circumference with hypertension was tested in logistic regression analyses and reported as odds ratio (OR) with 95% CI.
Results
Thigh circumference was negatively correlated with systolic blood pressure, diastolic blood pressure, fasting glucose, and total cholesterol. Compared with the lowest thigh circumference tertile group, the risk of hypertension was significantly lower in the highest tertile group, both in overweight individuals (OR 0.68; 95% CI 0.59–0.79, P < 0.001) and obese individuals (OR 0.51; 95% CI 0.38–0.70, P < 0.001).
Conclusion
In the present study, large thigh circumference is associated with lower risk of hypertension in overweight and obese Chinese individuals.
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Department of Medicine, National University Hospital, Singapore
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Department of Medicine, National University Hospital, Singapore
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Purpose:
Primary hyperparathyroidism (PHPT) is a common condition affecting people of all ages and is mainly treated with parathyroidectomy. Cinacalcet has been widely used in secondary or tertiary hyperparathyroidism, but the use of cinacalcet in PHPT is less clear.
Methods:
Searches were conducted in Medline and Embase for cinacalcet use in PHPT from induction to 10 April 2020. Articles and conferences abstracts describing the use of cinacalcet for PHPT in prospective or retrospective cohorts and randomized controlled trials restricted to English language only. We initially identified 1301 abstracts. Each article went extraction by two blinded authors on a structured proforma. Continuous outcomes were pooled with weight mean difference (WMD). Quality of included articles was assessed with Newcastle Ottwa Scale and Cochrane Risk of Bias 2.0.
Results:
Twenty-eight articles were included. Normalization rate of serum Ca levels was reported at 90% (CI: 0.82 to 0.96). Serum levels of Ca and PTH levels were significantly reduced (Ca, WMD: 1.647, CI: −1.922 to −1.371; PTH, WMD: −31.218, CI: −41.671 to −20.765) and phosphate levels significantly increased (WMD: 0.498, CI: 0.400 to 0.596) after cinacalcet therapy. The higher the baseline Ca levels, the greater Ca reduction with cinacalcet treatment. Age and gender did not modify the effect of cinacalcet on serum Ca levels.
Conclusion:
The results from the meta-analysis support the use of cinacalcet as an alternative or bridging therapy to treat hypercalcemia in people with PHPT.
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Background:
Glycoprotein non-metastatic protein B (Gpnmb) has been identified as a new cytokine secreted by hepatocyte that plays an important role in balancing lipid homeostasis and development of obesity and metabolic disorders. However, information is not available regarding the association between circulating Gpnmb and hyperthyroid in humans.
Methods:
We measured serum Gpnmb in 180 hyperthyroid patients and 82 healthy subjects that were recruited from the clinic. Of them, 46 hyperthyroid patients received thionamide treatment for 3 months.
Results:
Hyperthyroid subjects had higher levels of circulating Gpnmb than healthy controls (47.8 ± 10.1 ng/mL vs 31.0 ± 4.9 ng/mL, P < 0.001). Subjects with higher levels of serum free triiodothyronine (T3) and free thyroxine (T4) had higher levels of circulating Gpnmb. After thionamide treatment, levels of circulating Gpnmb in hyperthyroid subjects remarkably declined with significant improvement of thyroid function (P < 0.001). Furthermore, the change of circulating Gpnmb levels was significantly associated with basal metabolic rate (BMR) and thyroid hormones, including free T3 and free T4, adjusting for age, gender, smoking and BMI before thionamide treatment. In multivariable logistic regression analyses, circulating Gpnmb was significantly associated with risks of hyperthyroidism (OR (95% CI): 1.44 (1.20–1.74), P < 0.001), adjusted for age, gender, BMI, fasting glucose, HOMA-IR, LDL-cholesterol, ALT and AST.
Conclusions:
These findings indicate that circulating Gpnmb concentrations are independently associated with hyperthyroid, suggesting that circulating Gpnmb may be a predictor of risk for hyperthyroidism and can be used for therapeutic monitoring.
Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain
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Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain
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Departament de Cirurgia, Universitat Autònoma de Barcelona, Barcelona, Spain
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Objective:
Permanent hypoparathyroidism is an uncommon disease resulting most frequently from neck surgery. It has been associated with visceral calcifications but few studies have specifically this in patients with post-surgical hypoparathyroidism. The aim of the present study was to assess the prevalence of basal ganglia and carotid artery calcifications in patients with long-term post-thyroidectomy hypoparathyroidism compared with a control population.
Design:
Case–control study.
Methods:
A cross-sectional review comparing 29 consecutive patients with permanent postoperative hypoparathyroidism followed-up in a tertiary reference unit for Endocrine Surgery with a contemporary control group of 501 patients who had an emergency brain CT scan. Clinical variables and prevalence of basal ganglia and carotid artery calcifications were recorded.
Results:
From a cohort of 46 patients diagnosed with permanent hypoparathyroidism, 29 were included in the study. The mean duration of disease was 9.2 ± 7 years. Age, diabetes, hypertension, smoking and dyslipidemia were similarly distributed in case and control groups. The prevalence of carotid artery and basal ganglia calcifications was 4 and 20 times more frequent in patients with permanent hypoparathyroidism, respectively. After propensity score matching of the 28 the female patients, 68 controls were matched for age and presence of cardiovascular factors. Cases showed a four-fold prevalence of basal ganglia calcifications, whereas that of carotid calcifications was similar between cases and controls.
Conclusion:
A high prevalence of basal ganglia calcifications was observed in patients with post-surgical permanent hypoparathyroidism. It remains unclear whether carotid artery calcification may also be increased.
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Background
Excessive glucocorticoid secretion has been associated with type 2 diabetes mellitus (T2DM) and other features of the metabolic syndrome. We aimed to evaluate whether basal or evening salivary cortisol may predict the occurrence of incident insulin resistance (IR) or T2DM.
Method
This was a prospective, population-based study derived from the CoLaus/PsyCoLaus study including 1525 participants (aged 57.7 ± 10.3 years; 725 women). A total of 1149 individuals were free from T2DM at baseline. Fasting plasma glucose and insulin were measured after a follow-up of 5.3 years. Basal and evening salivary cortisol were measured at baseline. The association between basal or evening salivary cortisol level and incidence of IR or T2DM were analyzed by logistic regression, and the results were expressed for each independent variable as ORs and 95% CI.
Results
After a median follow-up of 5.3 years, a total of 376 subjects (24.7%) developed IR and 32 subjects (2.1%) developed T2DM. Basal and evening salivary cortisol divided in quartiles were not associated with incidence of IR or T2DM. Multivariable analysis for age, gender, body mass index, physical activity and smoking status showed no association between basal or evening salivary cortisol and incidence of IR or T2DM.
Conclusion
In the CoLaus/PsyCoLaus study of healthy adults, neither basal nor evening salivary cortisol was associated with incident IR or T2DM.
Faculty of Medicine, Department of Physiology, University of Helsinki, Helsinki, Finland
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Department of Pediatric Surgery, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Faculty of Medicine, Department of Physiology, University of Helsinki, Helsinki, Finland
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Faculty of Medicine, Department of Physiology, University of Helsinki, Helsinki, Finland
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Background
We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center.
Methods
DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts.
Results
Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 ± 5.5 years), Klinefelter syndrome (14.5%, 6.8 ± 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P < 0.001).
Conclusions
Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients’ adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.
