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.

Efficacy of 99mTc-DTPA SPECT/CT in diagnosing Orbitopathy in graves' disease.

BACKGROUND: The most frequently used methods of assessing Graves' orbithopathy (GO) include: Clinical Activity Score (CAS), ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI). There exists another, slightly forgotten, imaging method: single-photon emission computed tomography (SPECT) with the use of diethylenetriaminepentaacetic acid tagged with 99mTc (99mTc-DTPA). These days it is possible to conduct a SPECT examination fused with a CT scan (SPECT/CT), which increases the diagnostic value of the investigation. The aim of this paper is to evaluate the usefulness of 99mTc-DTPA SPECT/CT in diagnosing Graves orbitopathy, as compared with other methods. METHODS: Twenty-three patients with suspected active (infiltrative-edematous) Graves' orbithopathy were included in the study. Each patient underwent a CAS, an MRI, and a SPECT/CT. The obtained results were analysed statistically, with the assumed statistical significance of p < 0.05. RESULTS: The SPECT/CT and MRI were found to have the highest sensitivity: 0.93 each. The SPECT/CT had the highest specificity: 0.89. MRI and CAS had lower values: 0.78 and 0.56, respectively. The occurrence of an active form of GO had no impact on the exacerbation of exophthalmos or the thickness of the oculomotor muscles. CONCLUSIONS: The 99mTc-DTPA SPECT/CT method provides a very good tool for assessing the active form of GO and can, alongside the MRI scan, be used as a referential diagnostic procedure in GO.

Decreased Frequencies of Peripheral Blood CD4+CD25+CD127-Foxp3+ in Patients with Graves' Disease and Graves' Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells.

Graves' orbitopathy (GO) is characterized by orbital T cell infiltration. We evaluated the regulatory T (Treg) cell fractions induced with IGF-1 in Graves' disease (GD) with and without GO. Peripheral blood mononuclear cells (PBMCs) were obtained from 13 patients with GD without eye manifestations; 10 patients with active GO; and 12 patients with nodular goiter (NG). All the patients from GD, GO, and NG were subclinical hyperthyroid. We analyzed the expression of Treg cell markers (CD4, CD25, CD127-, Foxp3) on T cells and their ability to respond to IGF-1 stimulation. In patients with GD without GO, we found lowered percentages of CD4+ Foxp3+ cells, as compared to nodular goiter 1.77 vs. 5.42% (p=0.0276). Similarly, significantly reduced frequencies of CD4+CD25+CD127-Foxp3+ and CD4+CD25+CD127- cells were observed in GD patients as compared to nodular goiter patients with hyperthyreosis, (0.7 vs. 1.48%) (p=0.0071) and (14.5 vs. 37.2%) (p=0.0051), respectively. In GO with active GO, only the percentage of CD4+CD25+CD127- cells was found to be decreased versus nodular goiter (9.35 vs. 37.2) (p=0.0275). Stimulation of PBMC derived from GO patients with IGF-1 resulted in significant increase of frequency of both CD4+ Foxp3+ and CD4+CD25+CD127- Foxp3 cells. Decreased frequencies of peripheral blood CD4+CD25+CD127-Foxp3+ in patients with GD and GO could be an useful marker of autoimmune process and perhaps a possible target for future therapies. This is the first study demonstrating Treg-enhancing effects of IGF-1. Thus IGF-1 can be accounted for modulating Treg cell-related action in GO.

Disturbances of modulating molecules (FOXP3, CTLA-4/CD28/B7, and CD40/CD40L) mRNA expressions in the orbital tissue from patients with severe graves' ophthalmopathy.

Purpose. To evaluate the relationship between the expression of orbital tissue mRNA for FOXP3, CTLA-4/CD28/CD80/CD86, and CD40/CD40 and the severity of Graves' orbitopathy (GO). Material and Methods. Orbital tissue was obtained from 26 patients with GO, with mild (n = 6) or severe GO (n = 20), and 7 healthy controls. The expression of mRNA of FOXP3, CTLA-4/CD28/CD80/CD86, CD40/CD40L was measured by RT-PCR. TCR and CD3 were evaluated by immunohistochemistry. Results. Higher mRNA for FoxP3 (relative expression: 1.4) and CD40 (1.27) and lower expression of CTLA-4 (0.61) were found in the GO tissues versus controls. In severe GO as compared to mild GO higher mRNA expression for FoxP3 (1.35) and CD40 (1.4) and lower expression for CTLA-4 (0.78), CD28 (0.62), and CD40L (0.56) were found. A positive correlation was found between FOXP3 mRNA and CD3 infiltration (R = 0.796, P = 0.0000001). Conclusions. The enhanced FOXP3 mRNA expression in GO samples may suggest the dysfunction of FOXP3 cells in the severe GO. The diminished mRNA expression of CTLA-4 in severe GO may indicate inadequate T regulatory function. The enhanced mRNA expression of CD40 in severe GO and negative correlation to CRP mRNA may suggest their role in the active and inactive GO.

Markers of inflammation and fibrosis in the orbital fat/connective tissue of patients with Graves' orbitopathy: clinical implications.

PURPOSE: To assess FGF-ß, TGF-ß, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves' orbitopathy. PATIENTS AND METHODS: Orbital tissue was taken from 27 patients with GO: (1) severe GO (n = 18), the mean clinical activity score (CAS) being 8.5 (SD 2.5); and (2) mild GO (n = 9), the mean CAS being 2.2 (SD 0.8), and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-ß, TGF-ß, and COX2 in the orbital tissue was evaluated by immunohistochemical methods. RESULTS: We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-ß expression was seen in all GO. Increased FGF-ß expression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO. CONCLUSIONS: Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-ß and TGF-ß expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO.

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 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.

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.

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 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.

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.

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 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.

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.

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 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.

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.

Problems in diagnostics of primary aldosteronism - analysis of the own data.

INTRODUCTION: During the last few years, increasing evidence suggests that primary aldosteronism is the cause of over 10% of arterial hypertension (AH). There are no "gold standard" methods for PA screening. The aim of study was plasma renin activity (PRA), plasma aldosterone concentration (PAC), and ARR assessment as criteria for diagnosis of PA and their usefulness in clinical practice. MATERIAL AND METHODS: Eighty-one consecutive patients were admitted for diagnosis of primary aldosteronism: 51 women and 30 men, aged 31-69 years. In each patient, PAC and PRA were evaluated by radioimmunoassay. In 65 patients, urine concentration of catecholamine metabolites was assayed, and in 51 patients, diagnostics for hypercortisolaemia was carried out. In patients with adrenal incidentaloma, 16-row computer tomography was performed. RESULTS: The proportion of patients with PAC over 150 pg/ml was 35% (n = 28). The number of patients with PRA under 0.07 ng/ml/h was 19 (n = 15). The ratio of patients whose values of ARR exceeded over 20, 30, 40, 50, and 180 were 55, 47, 37, 28, and 15%, respectively. CONCLUSIONS: The most common indication for primary screening was the presence of incidentally found adrenal mass. The quotient of plasma aldosterone concentration/plasma renin activity at whichever cut-off point is not effective enough for the selection of patients for further diagnostics or its cessation. (Pol J Endocrinol 2010; 61 (1): 2-5).