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Open access

Melinda Kertész, Szilárd Kun, Eszter Sélley, Zsuzsanna Nagy, Tamás Kőszegi, and István Wittmann


Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as well.


In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newly diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructosamine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulatory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphorylation among normal (5 mM) and high (25 mM) glucose levels with or without metformin treatment in a human embryonal kidney cell line.


Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweight, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect.


Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.

Open access

Chenjia Tang, Yanting Dong, Lusi Lu, and Nan Zhang

Objective: This study was designed to explore the relationships between the clinical characteristics and outcomes of patients with subacute thyroiditis (SAT).

Design: This is a single-center retrospective study.

Patients: Eighty-nine patients with SAT who were hospitalized in the Sir Run Run Shaw Hospital in Zhejiang, China, from October 2014 to September 2020 were included.

Methods: The Mann–Whitney U-test, chi-square test, and Cox regression analysis were conducted to identify the relationships between clinical characteristics and outcomes. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff levels of C-reactive protein (CRP) and thyroid-stimulating hormone (TSH).

Results: The hypothyroidism and recurrence rates were 15.7% and 16.9%, respectively. CRP (≥72.0 mg/L), TSH (<0.02 mIU/L), and free triiodothyronine (fT3) (≥4.10 pg/mL) were associated with hypothyroidism. The cutoff level was 97.80 mg/L for CRP (area under the curve (AUC), 0.717, p= 0.014; sensitivity, 57.1%; specificity, 84.0%) and 0.10 mIU/L for TSH (AUC, 0.752, p = 0.004; sensitivity, 100%; specificity, 46.0%) by ROC curve analysis for hypothyroidism. The factors under study were not associated with recurrence.

Conclusion: CRP and TSH were risk factors for hypothyroidism in SAT. Thyroid functions should be monitored closely to detect hypothyroidism early, especially in patients with CRP levels of more than 97.80 mg/L and TSH levels of less than 0.10 mIU/L.

Open access

Valeria Hirschler, Claudia Molinari, Silvia Lapertosa, Gustavo Maccallini, and Claudio D Gonzalez

Background: The association between central obesity and cardiometabolic complications justifies exploring its association in normal-weight and overweight/obese (OW/OB) schoolchildren.

Objective: To describe cardiometabolic markers in four groups according to BMI/WC categories: 1) normal weight with central OB; 2) normal weight without central OB; 3) OW/OB with central OB; and 4) OW/OB without central OB, in a sample of Argentinean schoolchildren.

Methods: A cross-sectional study of 1264 Argentinean schoolchildren (624 F), aged 9.5±2.2 years was performed between November 2013 and 2015. Children’s anthropometric measures, blood pressure (BP), glucose, lipids, and insulin were measured. Children were divided into four groups: 1) normal weight with and with central OB; 2) normal weight without central OB; 3) OW/OB with central OB; and 4) OW/OB without central OB.

Results: The prevalence of normal weight children without central OB was 64.3% (796), normal weight with central 5% (66), OW/OB without central OB 11% (137), and OW/OB with central OB 21% (265). Normal weight with central OB had significantly higher triglycerides than normal weight children without central OB (86 vs 70 mg/dL, respectively) and OW/OB children without central OB (81vs 77 mg/dL). Multiple linear regression analyses showed that age, systolic BP, HDL-C, triglycerides, and maternal WC were significantly associated with children’s WC; R2=0.50 as well as children’s BMI; R2=0.37.

Conclusion: This study found that children with central OB might be at future higher cardiometabolic risk than those without central OB independently of the presence of OW/OB. However, future longitudinal studies should be performed to confirm these findings.

Open access

Elena V Varlamov, Dan Alexandru Niculescu, Swechya Banskota, Simona Andreea Galoiu, Catalina Poiana, and Maria Fleseriu


The number of international acromegaly related registries is increasing; however, heterogeneity of acromegaly symptoms and signs across countries is not well described. We compared clinical disease manifestations at diagnosis between two large University referral centers from two continents.


Retrospective, comparative epidemiological study of acromegaly patients at two centers: (i) C. I. Parhon National Institute of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy Bucharest, Romania (Parhon), and (ii) Pituitary Center, Oregon Health & Science University, Portland, Oregon, United States (OHSU) from approved data repositories was undertaken. Data were extracted from medical charts and questionnaires. Binary logistic regression analysis was undertaken for the most frequently noted symptoms and clinical signs.


The study included 216 patients (87 Parhon, 129 OHSU). Age, sex, and median delay in diagnosis were similar between centers. IGF-1 index was higher in patients at Parhon (3.3 vs 2.1, P < 0.001). The top five symptoms at both centers were enlarged hands/feet, headache, arthralgia, fatigue, and irregular menses in women. A significant difference was noted for multiple signs and symptoms frequency, often > 20 percentage points between centers. Center was a predictor of many signs and symptoms, independent of acromegaly biochemical severity or disease duration.


We show in the first comparative study that differences in medical practice, documentation, and likely cultural differences can influence patients’ symptom(s) reporting and screening patterns in geographically different populations. Pooling data into large multicenter international registry databases may lead to loss of regional characteristics and thus a mixed overall picture of combined cohorts.

Open access

Jingci Chen, Yan Wu, Pengyan Wang, Huanwen Wu, Anli Tong, and Xiaoyan Chang

Introduction: Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm with most cases presented as single reports. Little is known about its pathogenesis and relationship with ordinary pheochromocytoma (PCC) or paraganglioma (PGL). Our study is aimed at analyzing the status of SDH and ATRX and identifying novel genetic changes in CP.

Methods: 18 CP cases were collected. SDH and ATRX status was screened by immunohistochemistry. Targeted region sequencing (TRS) was successfully performed on formalin-fixed paraffin-embedded tissues in 2 cases within 3 years. Based on the TRS result, Sanger sequencing of BRAF and HRAS was performed in 15 cases (including the 2 cases with TRS performed), with 3 cases excluded due to the limited amount of tissue.

Results: Histopathologically, all the cases were composite PCC/PGL-ganglioneuroma (GN). The GN components were either closely admixed or juxtaposed with the PCC/PGL component, with highly variable percentage (10-80%). All cases stained positive for SDHB and ATRX. HRAS and BRAF mutations were identified during TRS. In the subsequent Sanger sequencing, 20.0% (3/15) harbored BRAF mutations (K601E and K601N) and 46.7% (7/15) harbored HRAS mutations (Q61R, Q61L, G13R). The mutation rates were both significantly higher than reported in ordinary PCC/PGL.

Conclusions: We demonstrated that composite PCC/PGL-GN might be a unique entity with frequent HRAS and BRAF mutations rather than genetic changes of SDH and ATRX. Our findings revealed the possible pathogenesis of composite PCC/PGL-GN and provided clues for potential treatment targets.

Open access

Anna Sjöström, Susanne Rysz, Henrik Sjöström, and Charlotte Höybye

Acute systemic diseases, such as severe infections, can lead to electrolyte and acid-base alterations. To study the presence of electrolyte imbalance in severe COVID-19, we investigated the frequency and consequences of changes in electrolyte and acid-base patterns over time. We performed a retrospective cohort study including 406 patients with severe COVID-19. Levels of electrolytes, base excess, pH, serum osmolality, and hematocrit, the first 2 weeks of hospitalization, were collected daily from the laboratory database and clinical data from patients’ medical records. We found that hyponatremia was present in 57% of the patients at admission and 2% in hypernatremia. However, within 2 weeks of hospitalization 42% of the patients developed hypernatremia, more frequently in critically ill patients. Lower levels of sodium and potassium during admission were associated with the need for mechanical ventilation. Decreased pH at admission was associated with both death and the need for mechanical ventilation. Hypernatremia in the ICU was combined with rising base excess and a higher pH. In the group without intensive care, potassium levels were significantly lower in the patients with severe hypernatremia. Presence of hypernatremia during the first 2 weeks of hospitalization was associated with 3.942 (95% CI 2.269–6.851) times higher odds of death. In summary, hypernatremia was common and associated with longer hospital stay and a higher risk of death, suggesting that the dynamics of sodium are an important indicator of severity in COVID-19.

Open access

Unni Syversen, Mats Peder Mosti, Ida Maria Mynarek, Trude Seselie Jahr Vedal, Kristin Aasarød, Trude Basso, Janne E Reseland, Per Medb�e Thorsby, Bjorn O Asvold, Erik Fink Eriksen, and Astrid Kamilla Stunes

Objective: Type 1 diabetes (T1D) is associated with a substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have, however, not been uncovered. Men with TID seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D.

Design and Methods: In this cross-sectional study, men with T1D and healthy, male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body), and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) by in vivo impact microindentation. HbA1c and bone turnover markers were analyzed.

Results: Altogether, 33 men with T1D (43 ± 12 yrs) and 28 healthy male controls (42 ± 12 yrs) were included. Subjects with T1D exhibited lower whole body BMD than controls (p=0.04). TBS and BMSi were attenuated in men with T1D vs. controls (p=0.016 and p=0.004, respectively), and T1D subjects also had lower bone turnover. vs. controls. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD, but not with TBS or BMSi.

Conclusions: This study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, we confirm previous studies showing a modest decrease in BMD and low bone turnover in subjects with T1D, underscoring that bone should be recognized as a target of diabetic complications.

Open access

Siphiwe N Dlamini, Zané Lombard, Lisa K. Micklesfield, Nigel Crowther, Shane A. Norris, Tracy Snyman, Andrew A Crawford, Brian R Walker, and Julia H. Goedecke

Circulating glucocorticoids are associated with the metabolic syndrome and related cardiometabolic risk factors in non-Africans. This study investigated these associations in Africans, whose metabolic phenotype reportedly differs from Europeans. Measures of adiposity, blood pressure, glycaemia, insulin resistance, and lipid profile, were measured in 316 African men and 788 African women living in Soweto, Johannesburg. The 2009 harmonized criteria were used to define the metabolic syndrome. Serum glucocorticoids were measured using liquid chromatography-mass spectrometry. Cortisol was associated with greater odds of presenting with the metabolic syndrome (odds ratio (95% confidence interval, 95%CI) =1.50 [1.04, 2.17] and higher systolic (beta coefficient, β (95%CI) =0.04 [0.01, 0.08]) and diastolic (0.05 [0.02, 0.09]) blood pressure, but higher HDL (0.10 [0.02, 0.19]) and lower LDL (-0.14 [-0.24, -0.03]) cholesterol concentrations, in the combined sample of men and women. In contrast, corticosterone was only associated with higher insulin sensitivity (Matsuda index; 0.22 [0.03, 0.41]), but this was not independent of BMI. Sex-specific associations were observed, such that both cortisol and corticosterone were associated with higher fasting glucose (standardized β (95%CI): 0.24 [0.12, 0.36] for cortisol; and 0.12 [0.01, 0.23] for corticosterone) and HbA1c (0.13 [0.01, 0.25] for cortisol; and 0.12 [0.01, 0.24] for corticosterone) in men only, but lower HbA1c (0.10 [ -0.20, -0.01] for cortisol; and -0.09 [-0.18, -0.03] for corticosterone) in women only. Our study reports for the first time that associations between circulating glucocorticoid concentrations and key cardiometabolic risk factors exhibit both glucocorticoid- and sex-specificity in Africans.

Open access

Christine Rode Andreasen, Andreas Andersen, Filip Krag Knop, and Tina Vilsbøll

In recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of action, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

Open access

Luchuan Li, Baoyuan Li, Bin Lv, Weili Liang, Binbin Zhang, Qingdong Zeng, Andrew G. Turner, and Lei Sheng

Background: Multiple studies have reported increased incidence of thyroid cancer in patients with primary hyperparathyroidism (PHPT). However, the underlying risk factors of concomitant thyroid cancer in patients with PHPT remain unknown. The primary aim of this study was to examine the records of patients with PHPT to identify characteristics that correlated with the presence of coexisting thyroid nodules, and which may have an implication for the prediction of thyroid cancer.

Methods: Medical records of consecutive patients with PHPT (n=318) were reviewed from Jan 2010 to Sep 2020 in two tertiary medical centers in China. Patient clinicopathological and biological data were collected and analyzed.

Results: Of a total of 318 patients with PHPT, 105 (33.0%) patients had thyroid nodules and 26 (8.2%) patients were concomitant with thyroid cancer. A total of 38 thyroid nodules taken from 26 patients were pathologically assessed to be well-differentiated papillary thyroid carcinoma (PTC), with 81% being papillary thyroid microcarcinoma (PTMC). In 79% (30/38) of these cancers, thyroid nodules were considered suspicious following preoperative ultrasound. Multinomial logistic regression analysis revealed that female gender was associated with increased risk of thyroid nodules (OR=2.13, 95%CI: 1.13-3.99, p = 0.019), while lower log-transformed parathyroid hormone levels were an independent predictor of thyroid cancer in patients with PHPT (OR=0.50, 95%CI: 0.26-0.93, p = 0.028).

Conclusion: In conclusion, we observed a relatively high prevalence of thyroid cancer in our cohort of Chinese patients with PHPT. Evaluation of thyroid nodules by preoperative ultrasound may be advisable in patients with PHPT, particularly for females and patients with modestly elevated serum parathyroid hormone levels.