Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL.

The use of 18F-PSMA-1007 and the role of PET/MR in the diagnosis of prostate cancer are not conclusively confirmed. There are reports indicating the potential pros and cons of using 18F-PSMA-1007 as well as the PET/MR technique in prostate cancer recurrence, but they are not yet included in the EAU guidelines. The aim of the study was to assess the effectiveness of 18F-PSMA-1007 PET/MR in detecting BCR lesions at very low PSA levels <0.5 ng/mL. METHODS: Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1-0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. RESULTS: Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. CONCLUSIONS: 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR.

Clinical significance of oxidative stress markers as angioinvasion and metastasis indicators in papillary thyroid cancer.

Angioinvasion remains the important prognostic feature in papillary thyroid cancer (PTC) patients. Literature data indicates several markers that may be associated with oxidative stress and/or angioinvasion. Therefore, we assessed the utility of selected parameters in angioinvasion and metastasis screening in serum of PTC patients. Serum antioxidant capacity (TAC) and sirtuin 3 (SIRT3) levels were decreased (all p < 0.05) and both DNA/RNA oxidative stress damage products (DNA/RNA OSDP) and malondialdehyde (MDA) levels were increased in PTC patients with angioinvasion and metastasis (study group) when compared with PTC patients without these features (all p < 0.01). The highest screening utility in differentiation between angioinvasion and metastasis presence and absence in PTC patients was presented for DNA/RNA OSDP (AUC = 0.71), SIRT3 (AUC = 0.70), and TAC (AUC = 0.67) (all p < 0.05). Our study suggests that peripheral concentration of oxidative stress markers could be useful as angioinvasion and metastasis indicator in PTC patients.

The Relationship between Oxidative Status and Radioiodine Treatment Qualification among Papillary Thyroid Cancer Patients.

Total oxidative status (TOS), total antioxidant capacity (TAC), tumor protein 53 (p53), nuclear factor kappa B (NF-κB), forkhead box protein O1 (FOXO), and sirtuin 1 (SIRT1) play crucial roles in oxidative homeostasis and the progression of papillary thyroid cancer (PTC), as previously demonstrated in the literature. Therefore, profiling these markers among PTC patients may be useful in determining their eligibility for radioiodine (RAI) treatment. Since treatment indications are based on multiple and dynamic recommendations, additional criteria for adjuvant RAI therapy are still needed. In our study, we evaluated the TOS, TAC, and serum concentrations of p53, NF-κB, FOXO, and SIRT1 to analyze the relationship between oxidative status and qualification for RAI treatment. For the purpose of this study, we enrolled 60 patients with PTC allocated for RAI treatment as the study group and 25 very low-risk PTC patients not allocated for RAI treatment as a reference group. The serum TOS and SIRT1 concentrations were significantly higher in the study group compared to the reference group (both p < 0.001), whereas the TAC and p53, NK-κB, and FOXO concentrations were significantly lower (all p < 0.05). We also demonstrated the diagnostic utility of TAC (AUC = 0.987), FOXO (AUC = 0.648), TOS (AUC = 0.664), SIRT1 (AUC = 0.709), p53 (AUC = 0.664), and NF-κB (AUC = 0.651) measurements as indications for RAI treatment based on American Thyroid Association recommendations. Our study revealed that oxidative status-related markers may become additional criteria for RAI treatment in PTC patients.

The impact of specific pulmonary arterial hypertension therapy on cardiac fluorodeoxyglucose distribution in PET/MRI hybrid imaging-follow-up study.

BACKGROUND: PET/MRI hybrid imaging in pulmonary arterial hypertension (PAH) provides important prognostic information identifying patients who might benefit from early therapy escalation, as right ventricle (RV) metabolic alterations are linked with hemodynamics and might precede clinical deterioration. Now, we hypothesize that adequate PAH therapy escalation may result in reversal of unfavourable increased glucose uptake of RV, which is associated with improved prognosis. METHODS: Out of twenty-six initially clinically stable PAH patients who had baseline PET/MRI scans, twenty (49.9 ± 14.9 years) had second PET/MRI after 24 months. SUVRV/SUVLV ratio was used to estimate and compare cardiac glucose uptake. Occurrences of clinical endpoints (CEP), defined as death or clinical deterioration, were assessed during 48-month follow-up from baseline. RESULTS: In first 24 months of observation, sixteen patients had CEP and needed PAH therapy escalation. At follow-up visits, we observed significant improvement of RV ejection fraction (45.1 ± 9.6% to 52.4 ± 12.9%, p = 0.01), mean pulmonary artery pressure (50.5 ± 18.3 to 42.8 ± 18.6 mmHg, p = 0.03), and SUVRV/SUVLV, which tended to decrease (mean change -0.20 ± 0.74). Patients with baseline SUVRV/SUVLV value higher than 0.54 had worse prognosis in 48 months observation (log-rank test, p = 0.0007); follow up SUVRV/SUVLV > 1 predicted CEP in the following 24 months, regardless of previously escalated treatment. CONCLUSIONS: PAH therapy escalation may influence RV glucose metabolism, what seems to be related with patients' prognosis. PET/MRI assessment may predict clinical deterioration regardless of previous clinical course, however its clinical significance in PAH requires further studies. Importantly, even mild alterations of RV glucose metabolism predict clinical deterioration in long follow-up. Clinical Trial Registration ClinicalTrials.gov, NCT03688698, 05/01/2016, https://clinicaltrials.gov/ct2/show/study/NCT03688698?term=NCT03688698&draw=2&rank=1.

Platelet sTWEAK and plasma IL-6 are associated with 18F-fluorodeoxyglucose uptake in right ventricles of patients with pulmonary arterial hypertension: A pilot study.

BACKGROUND: Cytokines soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and interleukin 6 (IL-6) are involved in immune response, proliferation, apoptosis, and cardiovascular pathologies. We have previously confirmed that changes of their platelet or plasma contents are associated with pulmonary arterial hypertension (PAH). The positron emission tomography/magnetic resonance imaging (PET/MRI) hybrid imaging provides detailed insight into right ventricle (RV) hemodynamic and metabolic function. OBJECTIVES: To evaluate the relationship between RV parameters obtained using PET/MRI and concentrations of plasma and platelet sTWEAK and IL-6 in stable PAH patients. MATERIAL AND METHODS: Eighteen stable PAH patients (48.44 ±16.7 years) had simultaneous PET/MRI scans with 18F-fluorodeoxyglucose (18F-FDG) performed. Its uptake was presented as a standardized uptake value (SUV) for RV and left ventricle (LV). Cytokines concentrations were measured in platelet-poor plasma and platelet lysate. Follow-up time of this study was 58 months; the combined endpoint (CEP) was defined as death or clinical deterioration. RESULTS: We observed significant correlations between platelet sTWEAK levels, plasma IL-6 and PET parameter SUVRV/LV (r = -0.57, p = 0.011; r = 0.50, p = 0.032, respectively). In logistic regression, platelet sTWEAK and IL-6 were both prognostic factors for unfavorable ratio of SUVRV/LV higher than 1 (hazard ratio (HR) = 0.44, 95% confidence interval (95% CI): [0.23; 0.84], p = 0.017; and HR = 3.62, 95% CI: [1.21; 10.17], p = 0.011, respectively). Furthermore, their concentrations were related with prognostically important higher late gadolinium enhancement mass index (LGEMI) and RV global longitudinal strain/systolic pulmonary artery pressure (RV GLS/sPAP) values. Patients who had CEP in follow-up (n = 13) had significantly lower platelet sTWEAK content and higher plasma IL-6 at baseline than stable patients. Lower platelet sTWEAK was related to a worse prognosis in log-rank test (p = 0.006). Platelet sTWEAK and plasma IL-6 together with RV GLS/sPAP, RV ejection fraction (RVEF), mean pulmonary arterial pressure (mPAP), and SUVRV/LV were significantly associated with time to CEP in univariate Cox analysis. CONCLUSIONS: The sTWEAK and IL-6 concentrations in PAH patients are linked with metabolic and functional changes of RV visualized in PET/MRI, and both sTWEAK and IL-6 predict clinical deterioration.

Hypercalcaemic crisis due to parathyroid adenoma of atypical location.

Not required for Clinical Vignette.

Assessment of different markers of ovarian reserve in women with papillary thyroid cancer treated with radioactive iodine.

Treatment with radioactive iodine (RAI) in women with differentiated thyroid cancer is associated with decreased serum concentrations of anti-Müllerian hormone (AMH); however, other markers have not been investigated. Therefore, this study aimed to evaluate the effect of RAI treatment on antral follicle count (AFC) and the serum concentration of inhibin B, follicle-stimulating hormone (FSH), and AMH in women with papillary thyroid cancer (PTC) treated with RAI. We examined 25 women at a median age of 33 years treated with a single dose of RAI. We divided the participants into women over (n = 11) and under 35 years of age (n = 14). Serum concentrations of inhibin B, FSH, AMH, and AFC were assessed at baseline and 1 year after RAI treatment. We found decreased AFC (P = 0.03), serum levels of AMH (P < 0.01), inhibin B (P = 0.03), but not FSH (P = 0.23), 1 year after RAI treatment in comparison to baseline in the whole group. When we compared serum levels of AMH in younger vs older women separately, we observed a significant reduction of this hormone's serum level after RAI treatment in both groups (P < 0.01; P = 0.04, respectively). We concluded that RAI treatment significantly impacts the functional ovarian reserve in premenopausal women with PTC.

Oxidative stress and radioiodine treatment of differentiated thyroid cancer.

It is hypothesized that the oxidative stress level in thyroid cancer patients is additionally upregulated by radioactive iodine (RAI) treatment, that may exert an important impact on future health concerns. In our study, we evaluated the oxidative stress level changes using the measurement of malondialdehyde (MDA) concentration in patients with differentiated thyroid cancer (DTC) undergoing RAI treatment. Considering the results obtained in the study group, the serum levels of MDA in DTC patients were significantly higher compared to the healthy subjects (p < 0.05). The MDA concentration was significantly higher on the third day after RAI (p < 0.001) and significantly lower one year after RAI (p < 0.05) in DTC patients compared to the baseline concentration. Moreover, the redox stabilization after RAI treatment in patients with DTC during a year-long observation was demonstrated. Accordingly, an increased oxidative stress impact on the related biochemical parameters reflecting the health conditions of the DTC patients was determined. Our study showed that increased oxidative stress reflected by MDA measurements in DTC patients is further enhanced by RAI, but this effect is no longer observed one year after the therapy.

Assessment of Clinical Utility of Assaying FGF-23, Klotho Protein, Osteocalcin, NTX, and Sclerostin in Patients with Primary Hyperparathyroidism.

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium-phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed.

Dosimetry during adjuvant 131I therapy in patients with differentiated thyroid cancer-clinical implications.

The activity of radioiodine (131I) used in adjuvant therapy for thyroid cancer ranges between 30 mCi (1.1 GBq) and 150 mCi (5.5 GBq). Dosimetry based on Marinelli's formula, taking into consideration the absorbed dose in the postoperative tumour bed (D) should systematise the determination of 131I activity. Retrospective analysis of 57 patients with differentiated thyroid cancer (DTC) after thyreidectomy and adjuvant 131I therapy with the fixed activity of 3.7 GBq. In order to calculate D from Marinelli's formula, the authors took into account, among other things, repeated dosimetry measurements (after 6, 24, and 72 h) made during scintigraphy and after administration of the therapeutic activity or radioiodine. In 75% of the patients, the values of D were > 300 Gy (i.e. above the value recommended by current guidelines). In just 16% of the patients, the obtained values fell between 250 and 300 Gy, whereas in 9% of the patients, the value of D was < 250 Gy. The therapy was successful for all the patients (stimulated Tg < 1 ng/ml and 131I uptake < 0.1% in the thyroid bed in follow-up examination). Dosimetry during adjuvant 131I therapy makes it possible to diversify the therapeutic activities of 131I in order to obtain a uniform value of D.

Clinical relevance of estimating circulating interleukin-17 and interleukin-23 during methylprednisolone therapy in Graves' orbitopathy: A preliminary study.

PURPOSE: Graves' orbitopathy (GO) is an important problem in endocrinology. Currently used methods of assessing the degree of activity of the autoimmune process are not satisfactory. Therefore, there is a need to establish indicators of greater utility. PATIENTS AND METHODS: The study included 35 patients: 15 with GO, 10 with Graves' disease (GD) without GO and 10 controls. Patients with GO received methylprednisolone (MP) for 12 weeks. Concentrations of thyrotropin receptor antibodies (TSHRab), interleukin 17 (IL-17) and 23 (IL-23) were obtained before administering the first dose of MP, after 6 and 12 weeks of therapy, and 3 months after treatment cessation. Patients were classified as responders (n â€‹= â€‹11) if a reduction of ≥2 points in the Clinical Activity Score (CAS) was observed. RESULTS: A significant decrease in exophthalmos, muscles' thickness and CAS value was demonstrated after MP treatment in responders group. Significantly higher concentrations were found in baseline IL-23 between the GD and GO groups compared to controls. No statistically significant differences in serum concentrations of IL-17 and IL-23 were observed during treatment with MP and 3 months after treatment cessation. A statistically significant reduction in TSHRab concentration was demonstrated 3 months after treatment cessation compared to baseline values in responders group. CONCLUSIONS: Low baseline IL-17 concentration, in addition to high TSHRab titre, serves as marker of disease activity. Although, we expect that low IL-23 concentration, in addition to high TSHRab titre, could be used as predictors of disease activity and a prognostic factor of response to immunosuppressive therapy in GO.

Multimodal assessment of right ventricle overload-metabolic and clinical consequences in pulmonary arterial hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH) increased afterload leads to adaptive processes of the right ventricle (RV) that help to maintain arterio-ventricular coupling of RV and preserve cardiac output, but with time the adaptive mechanisms fail. In this study, we propose a multimodal approach which allows to estimate prognostic value of RV coupling parameters in PAH patients. METHODS: Twenty-seven stable PAH patients (49.5 ± 15.5 years) and 12 controls underwent cardiovascular magnetic resonance (CMR). CMR feature tracking analysis was performed for RV global longitudinal strain assessment (RV GLS). RV-arterial coupling was evaluated by combination of RV GLS and three proposed surrogates of RV afterload-pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC). 18-FDG positron emission tomography (PET) analysis was used to assess RV glucose uptake presented as SUVRV/LV. Follow-up time of this study was 25 months and the clinical end-point was defined as death or clinical deterioration. RESULTS: Coupling parameters (RV GLS/PASP, RV GLS/PVR and RV GLS*PAC) significantly correlated with RV function and standardized uptake value (SUVRV/LV). Patients who experienced a clinical end-point (n = 18) had a significantly worse coupling parameters at the baseline visit. RV GLS/PASP had the highest area under curve in predicting a clinical end-point and patients with a value higher than (-)0.29%/mmHg had significantly worse prognosis. It was also a statistically significant predictor of clinical end-point in multivariate analysis (adjusted R2 = 0.68; p < 0.001). CONCLUSIONS: Coupling parameters are linked with RV hemodynamics and glucose metabolism in PAH. Combining CMR and hemodynamic measurements offers more comprehensive assessment of RV function required for prognostication of PAH patients. TRIAL REGISTRATION: NCT03688698, 09/26/2018, retrospectively registered; Protocol ID: 2017/25/N/NZ5/02689.

Pre-Processing Method for Contouring the Uptake Levels of [18F] FDG for Enhanced Specificity of PET Imaging of Solitary Hypermetabolic Pulmonary Nodules.

BACKGROUND: The paper presents a pre-processing method which, based on positron-emission tomography (PET) images of 18F-fluorodeoxyglucose ([18F] FDG) hypermetabolic pulmonary nodules, makes it possible to obtain additional visual characteristics and use them to enhance the specificity of imaging. MATERIAL AND METHODS: A retrospective analysis of 69 FDG-PET/CT scans of solitary hypermetabolic pulmonary nodules (40 cases of lung cancer and 29 benign tumours), where in each case, the standardised uptake value of the hottest voxel within the defined volume of interest was greater than 2.5 (SUVmax > 2.5). No diagnosis could be made based on these SUVmax values. All of the PET DICOM images were transformed by means of the pre-processing method for contouring the uptake levels of [18F] FDG (PCUL-FDG). Next, a multidimensional comparative analysis was conducted using a synthetic variable obtained by calculating the similarities based on the generalised distance measure for non-metric scaling (GDM2) from the pattern object. The calculations were performed with the use of the R language. RESULTS: The PCUL-FDG method revealed 73.9% hypermetabolic nodules definitively diagnosed as either benign or malignant lesions. As for the other 26.1% of the nodules, there was uncertainty regarding their classification (some had features suggesting malignancy, while the characteristics of others made it impossible to confirm malignancy with a high degree of certainty). CONCLUSIONS: Application of the PCUL-FDG method enhances the specificity of PET in imaging solitary hypermetabolic pulmonary nodules. Images obtained using the PCUL-FDG method can serve as point of departure for automatic analysis of PET data based on convolutional neural networks.

Prognostic role of PET/MRI hybrid imaging in patients with pulmonary arterial hypertension.

OBJECTIVE: Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). Metabolic alterations may precede haemodynamic and clinical deterioration. Increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) was recently associated with progressive RV dysfunction in MRI, but the prognostic value of their combination has not been established. METHODS: Twenty-six clinically stable patients with PAH (49.9±15.2 years) and 12 healthy subjects (control group, 44.7±13.5 years) had simultaneous PET/MRI scans. FDG uptake was quantified as mean standardised uptake value (SUV) for both left ventricle (LV) and RV. Mean follow-up time of this study was 14.2±7.3 months and the clinical end point was defined as death or clinical deterioration. RESULTS: Median SUVRV/SUVLV ratio was 1.02 (IQR 0.42-1.21) in PAH group and 0.16 (0.13-0.25) in controls, p<0.001. In PAH group, SUVRV/SUVLV significantly correlated with RV haemodynamic deterioration. In comparison to the stable ones, 12 patients who experienced clinical end point had significantly higher baseline SUVRV/SUVLV ratio (1.21 (IQR 0.87-1.95) vs 0.53 (0.24-1.08), p=0.01) and lower RV ejection fraction (RVEF) (37.9±5.2 vs 46.8±5.7, p=0.03). Cox regression revealed that SUVRV/SUVLV ratio was significantly associated with the time to clinical end point. Kaplan-Meier analysis showed that combination of RVEF from MRI and SUVRV/SUVLV assessment may help to predict prognosis. CONCLUSIONS: Increased RV glucose uptake in PET and decreased RVEF identify patients with PAH with worse prognosis. Combining parameters from PET and MRI may help to identify patients at higher risk who potentially benefit from therapy escalation, but this hypothesis requires prospective validation.

Prognostic value of late gadolinium enhancement mass index in patients with pulmonary arterial hypertension.

PURPOSE: Dysfunction of the right ventricle (RV) is an important determinant of survival in patients with pulmonary arterial hypertension (PAH). The presence of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) at RV insertion points (RVIPs) has been found in majority of PAH patients and was associated with parameters of RV dysfunction. We hypothesize, that more detailed quantification of LGE may provide additional prognostic information. MATERIAL AND METHODS: Twenty-eight stable PAH patients (mean age 49.9 â€‹± â€‹15.9 years) and 12 healthy subjects (control group, 44.8 â€‹± â€‹13.5 years) were enrolled into the study. Septal LGE mass was quantified at the RVIPs and subsequently indexed by subject's body surface area. Mean follow-up time of this study was 16.6 â€‹± â€‹7.5 months and the clinical end-point (CEP) was defined as death or clinical deterioration. RESULTS: Median LGE mass index (LGEMI) at the RVIPs was 2.75 â€‹g/m2 [1.41-4.85]. We observed statistically significant correlations between LGEMI and hemodynamic parameters obtained from right heart catheterization - mPAP (r â€‹= â€‹0.61, p â€‹= â€‹0.001); PVR (r â€‹= â€‹0.52, p â€‹= â€‹0.007) and from CMR - RVEF (r â€‹= â€‹-0.54, p â€‹= â€‹0.005); RV global longitudinal strain (r â€‹= â€‹0.42, p â€‹= â€‹0.03). Patients who had CEP (n â€‹= â€‹16) had a significantly higher LGEMI (4.49 [2.75-6.17] vs 1.67 [0.74-2.7], p â€‹= â€‹0.01); univariate Cox analysis confirmed prognostic value of LGEMI. Furthermore, PAH patients with LGEMI higher than median had worse prognosis in Kaplan-Meier analysis (log-rank test, p â€‹= â€‹0.0006). CONCLUSIONS: The body surface indexed mass of LGE at RV septal insertion points are suggestive of RV hemodynamic dysfunction and could be a useful non-invasive marker of PAH prognosis.

The Role of the CYP11B2 Promoter Polymorphism in the Diagnosis of Primary Aldosteronism.

BACKGROUND: nowadays, primary aldosteronism (PA) is suggested to be the most frequent cause of secondary hypertension and it reaches 10% of whole hypertensive population. The CYP11B2 promoter polymorphism might cause aldosterone overproduction. The aim of this study was to establish whether the polymorphism CYP11B2 promoter has a significant impact on diagnostic of PA. MATERIAL AND METHODS: study group consisted of 239 hypertensive patients previously diagnosed with adrenal incidentaloma. For diagnose of PA were performed: screening test-aldosterone-renin ratio (ARR) and saline suppression test (SIT) as a confirmatory test. Genotyping was carried out by the real time PCR method. The significance of differences between the groups was evaluated through Student's t-test. RESULTS: our study revealed that genotype TT had plasma aldosterone concentration (PAC), ARR and SIT significantly higher in comparison with CC patients. The mean PAC in CC was 12.71 ng/dL vs. 20.55 ng/dL in TT patients (p = 0.037), which consequently gave a higher ARR in TT patients (119 vs. 44, p = 0.034). Mean aldosterone concentration in SIT was 2.40 ng/dL in CC patients and 9.99 ng/dL in TT patients (p = 0.046). Patients with CC genotype required less hypotensive drugs in comparison with TT genotype (p = 0.044). PA was recognized in 16 patients. Nine patients had TC genotype, six TT, and one with CC genotype. CONCLUSION: our study revealed predisposing TT genotype to PA. Additionally, patients with TT genotype, regardless of the PA presence, had more severe hypertension. The determination of the CYP11B2 promoter polymorphism seems to be useful in the diagnosis of PA, especially in cases where it is difficult to properly prepare patients for hormonal tests or even results of the hormonal test are incoherent.

Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy.

INTRODUCTION: Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-ß, FGF-ß in severe and mild (long-lasting) GO. MATERIAL AND METHODS: Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry. RESULTS: Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-ß, FGF-ß expressions was observed in long-lasting GO. CONCLUSIONS: CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO.

Thyroid carcinoma with atypical metastasis to the pituitary gland and unexpected postmortal diagnosis.

SUMMARY: Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient's case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual. LEARNING POINTS: The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes. Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy. This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.

The interferon-induced helicase C domain-containing protein 1 gene variant (rs1990760) as an autoimmune-based pathology susceptibility factor.

PURPOSE: Autoimmune diseases are a group of complex diseases localized in multiple organ systems, with a wide spectrum of symptoms and still unclear causes. The aim of the present study was to analyse a possible association of three autoimmune disabilities - Multiple sclerosis (MS), LADA diabetes and Graves' disease (GD) with single nucleotide polymorphism (SNP; rs1990760) in the IF IH1 gene (also known as a melanoma differentiation-associated protein 5 - MDA5) within the Polish population. An additional goal was also to look for a correlation between this polymorphism and different clinical patient-related factors. MATERIALS AND METHODS: The study population consisted of four groups of 944 unrelated Polish origin Caucasian patients - 324 with GD, 171 with MS, 49 with LADA diabetes and 400 healthy subjects as a control group. The SNP analysis was performed using the allelic discrimination technique. RESULTS & CONCLUSIONS: There were significant associations of risk T allel of the analyzed polymorphism with all studied autoimmune diseases (GDOR = 1.34, p = 7.02e-03; MSOR = 1.36, p = 2.17e-02; LADA - OR = 3.36, p = 8.73e-07). We also found that the frequency of CT and TT genotypes of the rs1990760 IFIH1 gene only in females (with LADA, GD, MS) was significantly higher than those in the female control group (47%, 41% vs 44%, 34%; p = 1.32e-03, p = 4.39e-04; OR = 2.08, 95%CI: (1.33-3.28), OR = 2.29, 95% CI: (1.44-3.65) respectively). Our research has shown significant differences regarding some clinical features (BMI, TRAb, TSH, HbA1C, anti-GAD antibodies) and age at the beginning of the studied autoimmune disabilities. This study showed an association of rs1990760 polymorphism in the IFIH1 gene in the development of GD, LADA diabetes and MS within the Polish population. To our knowledge, this is the first study to investigate the relationship between IFIH1 polymorphisms and the risk of the development of MS and LADA in Poland.