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Open access

Rossella Cannarella, Andrea Crafa, Sandro La Vignera, Rosita A Condorelli, and Aldo E Calogero

Background

Animal studies suggest that insulin-like growth factor 1 (IGF1) may influence the function of the hypothalamus–pituitary–testicular axis, especially in childhood, but the evidence in humans is scanty. Laron syndrome, a human model of IGF1 deficiency, may help to solve this issue.

Purpose

This systematic review aims to analyze puberty onset and progression, testicular volume, gonadotropin, and total testosterone serum levels, sperm parameters and fertility, and penile length in patients with Laron syndrome.

Methods

Specific keywords were used. All data on male patients with Laron syndrome were included.

Results

Seventeen articles matched the inclusion criteria and were entered in the analysis, for a total of 125 male patients. Puberty was absent in 8.9% and delayed in 35.6% of untreated patients of pubertal age. After onset, the duration of the pubertal process was prolonged in 76.9% of untreated patients. The growth spurt was absent in 52.6% and delayed in 31.6% of untreated patients. The testicular volume was small in the two patients who did not receive any treatment. Treatment with IGF1 increased gonadotropin and testosterone serum levels in five out of five patients of pubertal age. No effect was found in four out of four patients younger than 5 years. No study reported data on sperm parameters and fertility. Micropenis occurred in 67.2% of patients.

Conclusion and future perspectives

Delayed puberty is common in patients with Laron syndrome. The growth hormone–IGF1 axis may influence the time of puberty onset. Serum levels of IGF1 should be investigated in children with delayed puberty, scarce progression of testicular growth, and/or micropenis. IGF1 levels might be measured in children with delayed puberty, poor testicular growth, and/or micropenis.

Open access

C Chiapponi, H Alakus, M Faust, A M Schultheis, J Rosenbrock, and M Schmidt

Purpose

Five percent of patients with differentiated thyroid cancer are diagnosed with radioiodine refractory relapse in the course of the disease. For isolated or oligometastatic cervical recurrence, resection or another local treatment is recommended. In this study, the impact of surgical treatment of cervical radioiodine refractory 18F-FDG-PET positive relapse of papillary thyroid cancer (PTC) was evaluated.

Methods

Patients receiving radioiodine therapy between 2005 and 2015 at the University Hospital of Cologne, Germany, for PTC were screened. The subgroup of patients undergoing surgery during the course of disease after recommendation by a multidisciplinary endocrine team for cervical radioiodine refractory 18F-FDG-PET positive recurrence was identified. Demographics, clinic-pathologic characteristics, oncologic treatment, and outcome were analyzed.

Results

Thirty (3%) of 969 patients with PTC treated with radioiodine therapy at our institution underwent surgery for radioiodine refractory 18F-FDG-PET positive cervical recurrence during the course of the disease. In eight (26.6%) patients, more than one operation was performed. Sixteen (53%) patients received external beam radiation therapy (EBRT) after surgery. Follow-up was on average, 79.2 ± 61.6 months after the last surgical treatment. Biochemical and radiological cure was seen in 12 (40%) patients. Remission was significantly more frequent in younger patients (P = 0.0001) with lymph node rather than soft tissue tumor recurrence (P = 0.004).

Conclusions

Surgical treatment of radioiodine refractory 18F-FDG-PET positive cervical recurrence led to biochemical and radiological cure in about 40% of patients in this study. Further data are needed concerning risk stratification of potential subgroups benefitting of surgical approach and the possible role of EBRT after repetitive surgery.

Open access

Chun-feng Lu, Wang-shu Liu, Xiao-qin Ge, and Feng Xu

The aim of the present study was to evaluate the association between adenosine deaminase (ADA) levels and diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). In this study, patients with T2D who had been screened for DKD were recruited. Patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months were identified as having DKD. The prevalence of DKD was 13.3%, and the range of serum ADA levels was 4–37 U/L. Serum ADA levels were positively associated with cystatin C levels and UACR (r = 0.295 and r = 0.302, respectively, both P < 0.05) and negatively associated with eGFR (r = −0.342, P < 0.05). The proportion of participants with DKD increased significantly from 3.8% in the first tertile (T1) to 13.6% in the second tertile (T2) and 25.9% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for clinical risk factors for DKD via multiple logistic regression, the corresponding odds ratios (ORs) of DKD for the participants in T2 and T3 vs those in T1 of ADA were 5.123 (1.282–20.474) and 10.098 (1.660–61.431), respectively. Receiver operating characteristic (ROC) analysis revealed that the optimal cutoff value of ADA to indicate DKD was 10 U/L. Its corresponding sensitivity and specificity were 75.5 and 56.4%, respectively. Our results demonstrated that serum ADA levels were closely associated with DKD and partly reflect the risk of DKD in patients with T2D.

Open access

Dorte Glintborg, Katrine Hass Rubin, Simon Bang Mohr Kristensen, Øjvind Lidegaard, Guy T’Sjoen, Aisa Burgwal, Malene Hilden, and Marianne Skovsager Andersen

Background

Gender dysphoria could be associated with low socioeconomic status (SES). SES could be modified by age, ethnic background, and medical morbidity.

Aim

To determine SES in a national study population including transgender persons in Denmark.

Methods

National register-based cohort study in Danish transgender persons and age-matched controls. The transgender study cohort included persons with ICD-10 diagnosis code of 'gender identity disorder' and/or persons with legal sex change and persons who fulfiled the inclusion criteria during 2000–2018. The main outcome measure was SES including personal income, occupational status, and education.

Results

The cohort included 2770 transgender persons and 27,700 controls. In the transgender study cohort, 1437 were assigned male at birth (AMAB), median age (interquartile range, IQR) 26.0 (17.3) years, and 1333 were assigned female at birth (AFAB), median age 22.5 (10.3) years. Adjusting for age and sex, the relative risk ratio (RRR) of low vs high personal income was 5.6 (95% CI: 4.9; 6.3) in transgender persons compared to controls. The RRR of low vs high income was 6.9 (5.8; 8.3) in persons AMAB compared to control males and 4.7 (3.9; 5.6) in persons AFAB compared to control females. The RRR of low vs high income was 3.7 (3.2; 4.3) in transgender persons of Danish origin compared to controls. The Charlson comorbidity index was comparable in transgender persons vs controls.

Conclusions

Being transgender was negatively associated with SES. In transgender persons, the risk of low vs high income could be more pronounced in transgender persons of foreign origin.

Open access

Navid Tabriz, Kilian Gloy, Astrid Schantzen, Dennis Fried, Dirk Weyhe, and Verena Uslar

Objectives

Validation of a German version of the ThyPRO-39 questionnaire for quality of life (QoL) in patients with benign thyroid diseases.

Design

Internal consistency, retest reliability, and validity were to be assessed in a test-retest study.

Methods

The ThyPRO-39 was translated based on standard methodology. A sample of 98 patients with benign thyroid diseases was tested with the ThyPRO-39de and the generic EuroQol 5D-5L. Forty-four patients with stable symptoms after 2 weeks formed the repeated measures sample. Cronbach’s alpha was calculated for the ThyPRO-39de composite score and for each disease-specific scale. Intraclass correlations between the original and the repeated measures sample were calculated for each scale as well as Pearson correlations between various ThyPRO scales and the EuroQol. T-tests were used to test for differences in the goiter and hyperthyroid symptom scales between relevant patient groups and other patients.

Results

Internal consistency was between satisfactory and good, except for two scales (tiredness and cosmetic complaints/appearance). The test-retest correlation was between 0.62 and 0.8 for most scales, but below 0.5 for two scales (tiredness and impaired social life). There were significant correlations between the EuroQol index score and most aspects of the ThyPRO-39de. Only the hyperthyroid symptoms scale was specific for the relevant patient group (Graves’ disease).

Conclusion

The ThyPRO-39de may be recommended for use in clinical and research settings, especially with regards to the composite score. However, the underlying thyroid disease should always be kept in mind when interpreting the test results. A larger sample would be needed to implement further improvements.

Open access

Sandra Pereira, Jessy Moore, Jia-Xu Li, Wen Qin Yu, Husam Ghanim, Filip Vlavcheski, Yemisi Deborah Joseph, Paresh Dandona, Allen Volchuk, Carolyn L Cummins, Evangelia Tsiani, and Adria Giacca

Plasma free fatty acids (FFAs) are elevated in obesity and can induce insulin resistance via endoplasmic reticulum (ER) stress. However, it is unknown whether hepatic insulin resistance caused by the elevation of plasma FFAs is alleviated by chemical chaperones. Rats received one of the following i.v. treatments for 48 h: saline, intralipid plus heparin (IH), IH plus the chemical chaperone 4-phenylbutyric acid (PBA), or PBA alone and a hyperinsulinemic-euglycemic clamp was performed during the last 2 h. PBA co-infusion normalized IH-induced peripheral insulin resistance, similar to our previous findings with an antioxidant and an IκBα kinase β (IKKβ) inhibitor. Different from our previous results with the antioxidant and IKKβ inhibitor, PBA also improved IH-induced hepatic insulin resistance in parallel with activation of Akt. Unexpectedly, IH did not induce markers of ER stress in the liver, but PBA prevented IH-induced elevation of phosphorylated eukaryotic initiation factor-2α protein in adipose tissue. PBA tended to decrease circulating fetuin-A and significantly increased circulating fibroblast growth factor 21 (FGF21) without affecting markers of activation of hepatic protein kinase C-δ or p38 mitogen-activated protein kinase that we have previously involved in hepatic insulin resistance in this model. In conclusion: (i) PBA prevented hepatic insulin resistance caused by prolonged plasma FFA elevation without affecting hepatic ER stress markers; (ii) the PBA effect is likely due to increased FGF21 and/or decreased fetuin-A, which directly signal to upregulate Akt activation.

Open access

Jing Hong, Wen-Yue Liu, Xiang Hu, Fei-Fei Jiang, Ze-Ru Xu, Fang Li, Fei-Xia Shen, and Hong Zhu

Background

A prolonged heart rate-corrected QT interval (QTc) has been associated with peripheral artery disease (PAD) in the general population. However, no study to date has identified a link between prolonged QTc and the severity of PAD in patients with diabetes mellitus and foot ulcers (DFUs). This study aimed to investigate this relationship.

Methods

This multicenter study enrolled 281 patients with DFUs. The severity of PAD was classified into no severe PAD group (without stenosis or occlusion) and severe PAD group (with stenosis or occlusion) based on duplex ultrasonography. The association of prolonged QTc with severe PAD was evaluated in a multivariable mixed-effect logistic regression model, with the hospital as a random effect. Directed acyclic graphs were used to drive the selection of variables to fit the regression model.

Results

Patients with severe PAD had longer QTc than those without. Based on the multivariable mixed-effect logistic regression model, a prolonged QTc was positively associated with severe PAD (odds ratio (OR) = 2.61; 95% CI: 1.07–6.35) and severe DFUs (Wagner grade score ≥ 3) (OR = 2.87; 95% CI: 1.42–5.81).

Conclusions

A prolonged QTc was associated with severe PAD in patients with DFUs. Further research is required to ascertain whether the association is causal.

Open access

Reshma Aziz Merchant, Michael Wong Wai Kit, Jia Yi Lim, and John E Morley

Objective

To investigate the association of normal BMI with central obesity (CO), high BMI with CO, high BMI without CO, and normal BMI without CO, with function and cognition in older adults.

Methods

Cross-sectional study involving 754 participants ≥ 65 years. Data collected include demographics, cognition, and physical measurements.

Results

Females had a higher prevalence of high BMI with CO and a lower prevalence of high BMI without CO than males (61.0% vs 44.6% and 4.6% vs 15.0%, respectively). Within gender, CO groups, regardless of BMI, had lower mini-mental state examination (MMSE), handgrip strength (HGS), and longer timed-up-and-go (TUG) scores. Overall, the high BMI without CO group had the highest MMSE scores, HGS, and shortest TUG. Amongst males, HGS was significantly lower in the normal BMI with CO group (B −3.28, 95% CI −6.32 to −0.23, P = 0.04). CO, regardless of normal/high BMI, had significantly longer TUG time (B 2.65, 95% CI 0.45 to 4.84, P = 0.02; B 1.07, 95% CI 0.25 to 1.88, P = 0.01, respectively) than normal BMI without CO group. CO was associated with lower MMSE scores in both genders but significant only in males with normal BMI and CO (B −1.60, 95% CI −3.15 to −0.06, P = 0.04).

Conclusion

CO may be a better predictor of obesity and adverse outcomes in older adults. High BMI without CO was associated with better outcomes especially in males but require further validation. Prospective longitudinal studies are needed to ascertain the impact of BMI and/or CO on function, cognition, mortality, and gender differences.

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 for the early detection of hypothyroidism, 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: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) 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: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB.

Results

The prevalence of normal-weight children without central OB was 64.3% (796), normal weight with central OB 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 (81 vs 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.