Potential biomarkers for diagnosis of sarcoidosis using proteomics in serum

SummaryBackgroundSarcoidosis is a multi-systemic inflammatory disorder, which affects the lungs in 90% of the cases. The main pathologic feature is chronic inflammation resulting in non-caseating granuloma formation. Until now there is no satisfying biomarker for diagnosis or prognosis of sarcoidosis. This study is focused on the detection of potential biomarkers in serum for the diagnosis of sarcoidosis using surface-enhanced laser desorption ionization-time of flight-mass spectrometry (SELDI-TOF-MS).MethodsFor detection of potential biomarkers, protein profiles of anion exchange fractionated serum of 35 sarcoidosis patients and 35 healthy controls were compared using SELDI-TOF-MS. Sensitivities and specificities of the potential biomarkers obtained with SELDI-TOF-MS, generated with decision tree algorithm, were compared to the conventional markers angiotensin converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R).ResultsOptimal classification was achieved with metal affinity binding arrays. A single marker with a mass-to-charge (m/z) value of 11,955 resulted in a sensitivity and specificity of 86% and 63%, respectively. A multimarker approach of two peaks, m/z values of 11,734 and 17,377, resulted in a sensitivity and specificity of 74% and 71%, respectively. These sensitivities and specificities were higher compared to measurements of ACE and sIL-2R. Identification of the peak at m/z 17,377 resulted in the α-2chain of haptoglobin.ConclusionsThis study acts as a proof-of-principle for the use of SELDI-TOF-MS in the detection of new biomarkers for sarcoidosis. The peak of the multimarker at m/z 17,377 was identified as the α-2chain of haptoglobin

Low-Iodine Diet of 4 Days Is Sufficient Preparation for I-131 Therapy in Differentiated Thyroid Cancer Patients

CONTEXT: No consensus exists about the optimal duration of the low-iodine diet (LID) in the preparation of (131)I therapy in differentiated thyroid cancer (DTC) patients. OBJECTIVE: This work aimed to investigate if a LID of 4 days is enough to achieve adequate iodine depletion in preparation for (131)I therapy. In addition, the nutritional status of the LID was evaluated. METHODS: In this prospective study, 65 DTC patients treated at 2 university medical centers were included between 2018 and 2021. The patients collected 24-hour urine on days 4 and 7 of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-hour urinary iodine excretion (UIE) on both days. RESULTS: The median 24-hour UIE on days 4 and 7 of the LID were not significantly different (36.1 mcg [interquartile range, 25.4-51.2 mcg] and 36.5 mcg [interquartile range, 23.9-47.7 mcg], respectively, P = .43). On day 4 of the LID, 72.1% of the DTC patients were adequately prepared (24-hour UIE < 50 mcg), and 82.0% of the DTC patients on day 7 (P = .18). Compared to the self-reported regular diet, DTC patients showed a significantly (P < .01) lower percentage of nutrient intake (calories, protein, calcium, iodine, and water) during the LID. CONCLUSION: The 24-hour UIE on day 4 of the LID did not differ from day 7, and therefore shortening the LID from 7 to 4 days seems justified to prepare DTC patients for (131)I therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment

Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans

Objective Obesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans. Design A cross-sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex. Participants Healthy men (n = 34) and women (n = 21) were combined from two cross-sectional studies. Forty-two per cent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%). Results DNL was inversely associated with SHBG in women (beta: -0.015, 95% CI: -0.030; 0.000), but not in men (beta: 0.007, 95% CI: -0.005; 0.019) (p for interaction = .068). Adjustment for study population, age and body mass index did not materially change these results, although statistical significance was lost after adjustment for serum insulin. Conclusions An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.Peer reviewe

Abnormal Aortic Wall Properties in Women with Turner Syndrome

Background Turner syndrome (TS) is associated with aortic dilatation and dissection, but the underlying process is unclear. The aim of this study was to investigate the elastic properties and composition of the aortic wall in women with TS. Methods In this cross-sectional study, 52 women with TS aged 35 ± 13 years (50% monosomy, 12 with bicuspid aortic valve [BAV] and 4 with coarctation) were investigated using carotid-femoral pulse wave velocity (CF-PWV) by echocardiography and ascending aortic distensibility (AAD) and aortic arch pulse wave velocity (AA-PWV) by magnetic resonance imaging (MRI). As control group, 13 women with BAV without TS and 48 healthy patients were included. Results Women with TS showed a higher AA-PWV (β = 1.08, confidence interval [CI]: 0.54-1.62) after correcting for age and comorbidities compared with controls. We found no significant difference in AAD and CF-PWV. In women with TS, the presence of BAV, coarctation of the aorta, or monosomy (45, X) was not associated with aortic stiffness. In addition, aortic tissue samples were investigated with routine and immunohistochemical stains in five additional women with TS who were operated. The tissue showed more compact smooth muscle cell layers with abnormal deposition and structure of ela

The relationships of sex hormone-binding globulin, total testosterone, androstenedione and free testosterone with metabolic and reproductive features of polycystic ovary syndrome

Objective A recent Mendelian randomization study has suggested a causal role for sex hormone-binding globulin (SHBG), total testosterone and free testosterone in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to assess the relationships of SHBG, androstenedione, total and free testosterone with the individual metabolic and reproductive features of PCOS. Design Cross-sectional data in PCOS patients (n=96) prospectively collected in a secondary/tertiary clinic for menstrual cycle disorders. Methods Multivariable regression analyses were conducted to study the associations between SHBG, androstenedione, total and free testosterone with metabolic (BMI, waist circumference, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homeostatic model assessment for insulin resistance [HOMA2-IR]) and reproductive features (menstrual cycle length, antral follicle count, anti-Mullerian hormone, luteinizing hormone, follicle-stimulating hormone and Ferriman-Gallwey score) of PCOS. Results Serum SHBG and free testosterone, but not total testosterone or androstenedione, were significantly associated with BMI, waist circumference, serum triglycerides, HDL cholesterol, LDL cholesterol and HOMA2-IR. The strength of the associations with serum lipids was reduced after adjustment for BMI, but not for HOMA2-IR. Total testosterone was significantly associated with antral follicle count. SHBG, total testosterone and androstenedione were significantly associated with serum AMH. Only the strength of the association for SHBG was reduced after adjustment for BMI. Conclusions Serum SHBG is associated with primarily metabolic features, whereas total testosterone and androstenedione are associated with reproductive features of PCOS. These results suggest a differential underlying pathophysiology for the metabolic and reproductive features of PCOS

The relationships of sex hormone-binding globulin, total testosterone, androstenedione and free testosterone with metabolic and reproductive features of polycystic ovary syndrome

OBJECTIVE: A recent Mendelian randomization study has suggested a causal role for sex hormone‐binding globulin (SHBG), total testosterone and free testosterone in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to assess the relationships of SHBG, androstenedione, total and free testosterone with the individual metabolic and reproductive features of PCOS. DESIGN: Cross‐sectional data in PCOS patients (n=96) prospectively collected in a secondary/tertiary clinic for menstrual cycle disorders. METHODS: Multivariable regression analyses were conducted to study the associations between SHBG, androstenedione, total and free testosterone with metabolic (BMI, waist circumference, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homeostatic model assessment for insulin resistance [HOMA2‐IR]) and reproductive features (menstrual cycle length, antral follicle count, anti‐Müllerian hormone, luteinizing hormone, follicle‐stimulating hormone and Ferriman‐Gallwey score) of PCOS. RESULTS: Serum SHBG and free testosterone, but not total testosterone or androstenedione, were significantly associated with BMI, waist circumference, serum triglycerides, HDL cholesterol, LDL cholesterol and HOMA2‐IR. The strength of the associations with serum lipids was reduced after adjustment for BMI, but not for HOMA2‐IR. Total testosterone was significantly associated with antral follicle count. SHBG, total testosterone and androstenedione were significantly associated with serum AMH. Only the strength of the association for SHBG was reduced after adjustment for BMI. CONCLUSIONS: Serum SHBG is associated with primarily metabolic features, whereas total testosterone and androstenedione are associated with reproductive features of PCOS. These results suggest a differential underlying pathophysiology for the metabolic and reproductive features of PCOS