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Open access

Xi Cao, Ming Lu, Rong-Rong Xie, Li-Ni Song, Wei-Li Yang, Zhong Xin, Guang-Ran Yang, and Jin-Kui Yang

Aims

In this study, we determined the association between thyroid-stimulating hormone (TSH) and diabetic macular edema (DME) by assessing the prevalence and risk factors for DME in type 2 diabetes mellitus (T2DM) patients with different thyroid dysfunctions.

Methods

This was a retrospective cross-sectional study including 1003 euthyroid and 92 subclinical hypothyroidism (SCH) T2DM patients. DME status was detected by optical coherence tomography (OCT). The association between TSH and DME and the impact of TSH on DME were analyzed.

Results

The DME prevalence was 28.3% in the SCH patients and 14.0% in the euthyroid population. The serum FT4 (P = 0.001) and FT3 (P < 0.001) levels were significantly higher in the non-DME group than in the DME group, and the TSH level (P < 0.001) was significantly lower. Four subgroups (G1–G4) were divided by TSH level, and the chi-square test indicated that even in the normal range, the TSH level was positively related to DME prevalence (P = 0.001). Subgroup data indicated that the association between TSH and DME detected by OCT (P = 0.001) was stronger than the correlation between TSH and diabetic retinopathy detected by digital retinal photographs (P = 0.027). The logistic regression model confirmed that elevated TSH was an independent risk factor for DME. The odds ratio was 1.53 (P = 0.02).

Conclusions

A high TSH level was an independent risk factor for DME. More attention should be given to the TSH level in T2DM patients due to its relationship with diabetic complications.

Open access

Sebastian Franik, Kathrin Fleischer, Barbara Kortmann, Nike M Stikkelbroeck, Kathleen D’Hauwers, Claire Bouvattier, Jolanta Slowikowska-Hilczer, Solange Grunenwald, Tim van de Grift, Audrey Cartault, Annette Richter-Unruh, Nicole Reisch, Ute Thyen, Joanna IntHout, Hedi L Claahsen-van der Grinten, and

Klinefelter syndrome (KS) is associated with an increased risk of neuropsychological morbidity, such as learning disabilities, which may have a significant impact on socioeconomic status (SES). The objective of this study was to investigate the SES in men with KS and to associate this outcome with social participation, age at diagnosis, testosterone therapy and physical and mental health status. Men with KS were recruited in 14 clinical study centers in six European countries which participated in the European dsd-LIFE study. Two hundred five men with KS were eligible for inclusion. Male normative data from the European Social Surveys (ESS) were used for comparison. Data related to education, occupation, satisfaction with income and householding were collected. Compared to the ESS reference population, fewer men with KS achieved a high level of education (13% vs 25%, P < 0.001). There was a significant difference in having a paid job (55% vs 66%, P < 0.001), and the percentage of absence by sickness or disability was higher among men with KS (10% vs 3%, P < 0.001). Furthermore, satisfaction with current household’s income was lower (32% vs 42%, P < 0.01). Lower scores for subjective general health were associated with lower scores for these outcomes. Men with KS achieve on average lower levels of education, occupation and report less satisfaction with income compared to the ESS reference population. The presence of health problems and lower scores of subjective general health was related to lower levels of occupation and lower satisfaction with income in men with KS.

Open access

Ramjan Sanas Mohamed, Biyaser Abuelgasim, Sally Barker, Hemanth Prabhudev, Niamh M Martin, Karim Meeran, Emma L Williams, Sarah Darch, Whitlock Matthew, Tricia Tan, and Florian Wernig

Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late-night salivary cortisol (LNSC) is recommended as a first-line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low-dose dexamethasone suppression test and 24-h urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients). LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/L the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home. We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS.

Open access

Keiko Ohkuwa, Kiminori Sugino, Ryohei Katoh, Mitsuji Nagahama, Wataru Kitagawa, Kenichi Matsuzu, Akifumi Suzuki, Chisato Tomoda, Kiyomi Hames, Junko Akaishi, Chie Masaki, Kana Yoshioka, and Koichi Ito

Objective

Parathyroid carcinoma is a rare tumor among parathyroid tumors. Aspiration cytology and needle biopsy are generally not recommended for diagnostic purposes because they cause dissemination. Therefore, it is commonly diagnosed by postoperative histopathological examination. In this study, we investigated whether preoperative inflammatory markers can be used as predictors of cancer in patients with primary hyperparathyroidism.

Design

This was a retrospective study.

Methods

Thirty-six cases of parathyroid carcinoma and 50 cases of parathyroid adenoma (PA) operated with the diagnosis of primary hyperparathyroidism and confirmed histopathologically at Ito Hospital were included in this study. Preoperative clinical characteristics and inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR)) were compared and their values in preoperative prediction were evaluated and analyzed.

Results

Preoperative intact-parathyroid hormone (P  = 0.0003), serum calcium (P  = 0.0048), and tumor diameter (P  = 0.0002) were significantly higher in parathyroid carcinoma than in PA. LMR showed a significant decrease in parathyroid carcinoma (P  = 0.0062). In multivariate analysis, LMR and tumor length diameter were independent predictors. In the receiver operating characteristics analysis, the cut-off values for LMR and tumor length diameter were 4.85 and 28.0 mm, respectively, for parathyroid cancer prediction. When the two extracted factors were stratified by the number of factors held, the predictive ability improved as the number of factors increased.

Conclusion

In the preoperative evaluation, a combination of tumor length diameter of more than 28 mm and LMR of less than 4.85 was considered to have a high probability of cancer.

Open access

Martijn J J Finken, Aleid J G Wirix, Ines A von Rosenstiel-Jadoul, Bibian van der Voorn, Mai J M Chinapaw, Michaela F Hartmann, Joana E Kist-van Holthe, Stefan A Wudy, and Joost Rotteveel

Objective

Childhood obesity is associated with alterations in hypothalamus–pituitary–adrenal axis activity. We tested the hypothesis that multiple alterations in the metabolism of glucocorticoids are required for the development of hypertension in children who become overweight.

Methods

Spot urine for targeted gas chromatography-mass spectrometry steroid metabolome analysis was collected from (1) overweight/hypertensive children (n  = 38), (2) overweight/non-hypertensive children (n  = 83), and (3) non-overweight/non-hypertensive children (n  = 56).

Results

The mean (± s.d.) age of participants was 10.4 ± 3.4 years, and 53% of them were male. Group 1 and group 2 had higher excretion rates of cortisol and corticosterone metabolites than group 3 (869 (interquartile range: 631–1352) vs 839 (609–1123) vs 608 (439–834) μg/mmol creatinine × m2 body surface area, P < 0.01, for the sum of cortisol metabolites), and group 1 had a higher excretion rate of naive cortisol than group 3. Furthermore, groups differed in cortisol metabolism, in particular in the activities of 11β-hydroxysteroid dehydrogenases, as assessed from the ratio of cortisol:cortisone metabolites (group 2 < group 3), 5α-reductase (group 1 > group 2 or 3), and CYP3A4 activity (group 1 < group 2 or 3).

Discussion

The sequence of events leading to obesity-associated hypertension in children may involve an increase in the production of glucocorticoids, downregulation of 11β-hydroxysteroid dehydrogenase type 1 activity, and upregulation of 5α-reductase activity, along with a decrease in CYP3A4 activity and an increase in bioavailable cortisol.

Open access

Malgorzata Fuksiewicz, Maria Kowalska, Agnieska D Kolasinska-Cwikla, and Beata Kotowicz

The aim of this study was to assess the usefulness of NSE concentrations as a prognostic factor in patients with neuroendocrine neoplasms and in determining the relationship between NSE and clinicopathological features. Serum NSE levels were assayed in 179 NENs patients before treatment. It was found that NSE levels in patients with a primary pancreatic location were higher compared in patients with a small intestine lesion (p=0.015). It was found that in patients with only primary location in the pancreas, NSE levels were significantly higher in the group with histological grade G2 compared with the group with low grade G1 (P=0.047). Patients with initial liver involvement showed significantly higher NSE levels in patients with tumour location in the pancreas (P=0.009). Statistical analysis confirmed that higher NSE levels were associated with disease progression (p=0.001) in both the overall study group and in patients with tumours in the pancreas and small intestine. During treatment monitoring, an increase in median NSE concentrations was observed in patients with persistent progression with subsequent blood draws, and a decrease in NSE concentrations was observed in patients with disease stabilisation. We showed that NSE concentrations have prognostic value for progression free survival in addition to primary liver involvement. In conclusion, the most important results of the study include the demonstration of an association between NSE concentrations and clinical status, which confirms its usefulness in patient monitoring and as a potential predictive indicator for progression free survival in patients with NENs.

Open access

Mohamed Asrih, Flore Sinturel, Richard Dubos, Idris Guessous, Zoltan Pataky, Charna Dibner, François R Jornayvaz, and Karim Gariani

Objective

Growth differentiation factor-15 (GDF15), a key metabolic regulator, is associated with obesity and diabetes in which sex-specific differences have been reported. Thus, we assessed whether GDF15 could be dependent on sex in diabetes and/or obesity groups.

Methods

We measured serum GDF15 levels by ELISA in eight lean women and men (n = 16), eight women and eight men having obesity (n = 16), eight women and eight men with type 2 diabetes (T2D, n = 16), and seven women and nine men with both diabetes and obesity (n = 16). Estimation of the difference in the means of each group was performed by two-way ANOVA. The interdependence of the different variates was addressed by multivariate analysis. Correlations between GDF15 levels and HOMA-IR, HbA1c, triglycerides, HDL, and LDL were explored by linear regression.

Results

Being a woman and having obesity alone or in combination with diabetes decreased GDF15 serum levels (β = −0.47, CI = −0.95, 0.00, P = 0.052; β = −0.45, CI = −0.94, 0.05, P= 0.075). Diabetes independently of metformin treatment and obesity were not predictive of low GDF15 levels (β = 0.10, CI = −0.36, 0.57, P = 0.7). Correlation analysis showed that HOMA-IR (r = 0.45, P = 0.008) and triglycerides (r = 0.41, P = 0.017) were positively correlated and HDL (r = −0.48, P = 0.005) was negatively correlated with GDF15 levels in men.

Conclusions/interpretation

GDF15 level was significantly different between men and women, as well as between the groups. Sex and group interaction revealed that being a woman and having obesity alone or in combination with diabetes decreased GDF15 levels.

Open access

Elena Valassi, Iacopo Chiodini, Richard A Feelders, Cornelie D Andela, Margueritta Abou-Hanna, Sarah Idres, and Antoine Tabarin

Background

Cushing’s syndrome (CS) is a rare condition of chronically elevated cortisol levels resulting in diverse comorbidities, many of which endure beyond successful treatment affecting the quality of life. Few data are available concerning patients’ experiences of diagnosis, care and persistent comorbidities.

Objective

To assess CS patients’ perspectives on the diagnostic and care journey to identify unmet therapeutic needs.

Methods

A 12-item questionnaire was circulated in 2019 by the World Association for Pituitary Organisations. A parallel, 13-item questionnaire assessing physician perceptions on CS patient experiences was performed.

Results

Three hundred twenty CS patients from 30 countries completed the questionnaire; 54% were aged 35–54 and 88% were female; 41% were in disease remission. The most burdensome symptom was obesity/weight gain (75%). For 49% of patients, time to diagnosis was over 2 years. Following treatment, 88.4% of patients reported ongoing symptoms including, fatigue (66.3%), muscle weakness (48.8%) and obesity/weight gain (41.9%). Comparisons with delay in diagnosis were significant for weight gain (P = 0.008) and decreased libido (P = 0.03). Forty physicians completed the parallel questionnaire which showed that generally, physicians poorly estimated the prevalence of comorbidities, particularly initial and persistent cognitive impairment. Only a minority of persistent comorbidities (occurrence in 1.3–66.3%; specialist treatment in 1.3–29.4%) were managed by specialists other than endocrinologists. 63% of patients were satisfied with treatment.

Conclusion

This study confirms the delay in diagnosing CS. The high prevalence of persistent comorbidities following remission and differences in perceptions of health between patients and physicians highlight a probable deficiency in effective multidisciplinary management for CS comorbidities.

Open access

Rongpeng Gong, Yuanyuan Liu, Gang Luo, Jiahui Yin, Zuomiao Xiao, and Tianyang Hu

Background

In recent decades, with the development of the global economy and the improvement of living standards, insulin resistance (IR) has become a common phenomenon. Current studies have shown that IR varies between races. Therefore, it is necessary to develop individual prediction models for each country. The purpose of this study was to develop a predictive model of IR applicable to the US population.

Method

In total, 11 cycles of data from the NHANES database were selected for this study. Of these, participants from 1999 to 2010 (n  =  14931) were used to establish the model, and participants from 2011 to 2020 (n  =  13,646) were used to validate the model. Univariate and multivariable logistic regression was used to analyze the factors associated with IR. Optimal subset regression was used to filter the best modeling variables. ROC curves, calibration curves, and decision curve analysis were used to determine the strengths and weaknesses of the model.

Results

After screening the variables by optimal subset regression, variables with covariance were excluded, and a total of seven factors (including HDL, LDL, ALB, GLB, GLU, BMI, and waist) were finally included to establish the prediction model. The AUCs were 0.851 and 0.857 in the training and validation sets, respectively, and the Brier value of the calibration curve was 0.153.

Conclusion

The optimal subset predictive model proposed in this study has a great performance in predicting IR, and the decision curve analysis shows that it has a high net clinical benefit, which can help clinicians and epidemiologists easily detect IR and take appropriate interventions as early as possible.

Open access

Ditte Sofie Dahl Sørensen, Jesper Krogh, Åse Krogh Rasmussen, and Mikkel Andreassen

Background

There is no consensus regarding markers of optimal treatment or timing between glucocorticoid intake and assessment of hormone levels in the follow-up of female 21-hydroxylase deficient patients.

Objective

To examine visit-to-visit repeatability in levels of adrenal hormones in adult female patients, to identify predictors of repeatability in hormone levels and to examine concordance between levels of different adrenal hormones.

Method

All patients with confirmed 21-hydroxylase deficiency treated with glucocorticoids, were included. The two most recent blood samples collected on a stable dose of glucocorticoid replacement were compared. Complete concordance was defined as all measured adrenal hormones either within, below or above normal range evaluated in a single-day measurement.

Results

Sixty-two patients, median age of 35 (range 18–74) years were included. All hormone levels showed moderate to excellent repeatability with an intraclass correlation coefficient between 0.80 and 0.99. Repeatability of hormone levels was not affected by the use of long-acting glucocorticoids or time of day for blood sample collection. The median difference in time between the two sample collections was 1.5 (range 0–7.5) h. Complete concordance between 17-hydroxyprogesterone, androstenedione, and testosterone was found in 21% of cases.

Conclusion

During everyday, clinical practice hormone levels in adult female patients with 21-hydroxylase deficiency showed a moderate to excellent repeatability, despite considerable variation in time of day for blood sample collection. We found no major predictors of hormone level variation. Future studies are needed to address the relationship between the timing of glucocorticoid intake vs adrenal hormone levels and clinical outcome in both adults and children.