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.

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.

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.

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.

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.

Enhancing the efficacy of 131I therapy in non-toxic multinodular goitre with appropriate use of methimazole: an analysis of randomized controlled study.

PURPOSE: It is possible to raise the rate of the uptake of 131I in the thyroid gland (RAIU) by increasing the endogenous TSH level through appropriate use of methimazole (MMI) prior to 131I therapy. The purpose of this paper is to assess the impact of pre treatment with MMI on the efficacy of 131I therapy in non-toxic multinodular goitre (NMG). METHODS: Thirty-one patients with NMG received 131I treatment in order to reduce the volume of the thyroid (TVR). Those in group 1 (n = 16) were administered 10 mg of methimazole for 6 weeks. Four days after its discontinuation, they received 131I. Patients in group 2 (n = 15) were given a placebo instead of MMI. The therapeutic activity of 131I was constant (800 MBq) and was repeated every 6 months. Treatment was discontinued when TVR reached <40 ml. RESULTS: In group 1, RAIU increased approximately twofold. Ten patients from group 2 and four patients from group 1 received further doses of 131I. The median of time until TVR decreased below 40 ml was 9 months [6-12 months] and 18 months [14-22 months] in group 2. At 2 years after the 131I therapy, the occurrence of hypothyroidism did not differ significantly (36% in group 1 and 33% in group2, p = 0.074). CONCLUSIONS: Radioiodine treatment of NMG preceded with appropriate application of MMI is efficient thanks to increased RAIU, shorter period of treatment, and lower frequency of 131I administration, without an increase in the incidence of post-treatment hypothyroidism.

The impact of laparoscopic adrenalectomy on renal function. Results of a prospective randomised clinical trial.

INTRODUCTION: Laparoscopic adrenalectomy is the gold standard management of benign adrenal masses and isolated metastases to adrenal glands. Two techniques of endoscopic adrenalectomy: lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) seem to be equally safe and effective. Recent studies suggest advantages of PRA over LTA in terms of lower intensity of postoperative pain, shorter hospital stay, faster recovery, and lower early morbidity. However, PRA involves high insufflation pressure of CO2 within a limited retroperitoneal space. The aim of our study was to prospectively assess the effect of LTA versus PRA laparoscopic adrenalectomies on renal function. MATERIAL AND METHODS: We randomly assigned patients referred for unilateral adrenalectomy to either LTA (n = 33) or PRA (n = 44). The inclusion criteria were: hormonal activity and/or tumour diameter > 4 cm and/or suspicion of metastasis to adrenal gland. The exclusion criteria comprised: tumours > 8 cm, results of imaging studies suggesting primary invasive malignancy, and refusal to undergo randomisation. The patients were prospectively followed for a minimum of six months. Serum creatinine, cystatin C, and urinary neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively and at postoperative days: 1, 7, and 30. RESULTS: We found increased concentrations of urinary NGAL at day 1 following laparoscopic adrenalectomy using PRA, as compared to LTA. Patients undergoing right-sided PRA had increased creatinine concentrations, as compared to left-sided PRA. Patients with aldosterone-producing adenoma had decreased preoperative eGFR as compared to subjects with non-functioning incidentaloma. NGAL increased significantly in this group postoperatively. All the disturbances normalised within one month postoperatively. CONCLUSIONS: Renal function impairment after PRA may result from compression of inferior vena cava by high retroperitoneal pressure during right-sided adrenalectomy. Despite the transient character of the observed abnormalities, we suggest that patients with high risk of acute kidney injury may benefit from an alternative technique of adrenalectomy using LTA.

Value of direct radionuclide cystography in diagnosing vesico-peritoneal fistulae.

A 36-year-old female patient underwent a laparoscopic surgery to remove a uterine fibroid. The procedure failed to relieve the pelvic pain, although its nature changed. After a period of observation, the patient was re-admitted to hospital on suspicion of a vesico-uterine fistula to be differentiated with endometriosis. Diagnostic investigations - cystography, cystoscopy, computed tomography and magnetic resonance - did not reveal a fistula. Laparoscopy was performed, with a possible biopsy in order to eliminate endometriosis. The result was negative, but chronic progressive reactive/inflammatory lesions were noticed, possibly indicating the presence of a vesico-peritoneal fistula. Therefore, a direct radionuclide cystography was performed. The scintigraphic images single-photon emission computed tomography (SPECT/CT) showed a radioactive spot, indicative of a vesico-peritoneal fistula. The fistula was treated for three months by catheterisation of the urinary bladder. The follow-up SPECT-CT did not reveal any urine leakage from the bladder. The clinical symptoms disappeared as well.

Calculation of therapeutic activity of radioiodine in Graves' disease by means of Marinelli's formula, using technetium (99mTc) scintigraphy.

The therapeutic activity of 131I administered to patients with Graves' disease can be calculated by means of Marinelli's formula. The thyroidal iodine uptake (131IUmax) needed for the calculation is usually determined with the use of 131I. The purpose of the paper was to estimate 131IUmax on the basis of technetium uptake in the thyroid at 20 min (99mTcU20min). Eighty patients suffering from Graves' disease were qualified for radioiodine therapy with measurement of fT4, fT3, thyroid-stimulating hormone and its receptor (TRAb). Prior to the treatment, all the patients were euthyroid. 131IUmax for each patient was determined according to the levels of 131I after 24 h (131IU24h), while effective half-life (T eff) according to the measurements of 131IU24h and 131I uptake after 48 h (131IU48h). Additionally, on the day before measuring 131IU24h, 99mTcU20min was calculated for each patient. It was demonstrated that there existed a correlation, with statistical significance at p < 0.05, between the following pairs of values: TRAb and 131IU24h, TRAb and 99mTcU20min, and 99mTcU20min and 131IU24h. The interdependence between 131IU24h and 99mTcU20min at the level of significance p < 0.05 is described by the following algorithms: 131IU24h = 17.72 × ln (99mTcU20min) + 30.485, if TRAb < 10 IU/ml, and 131IU24h = 18.03 × ln (99mTcU20min) + 38.726, if TRAb > 10 IU/ml. It is possible to predict thyroid iodine uptake 131IU24h in Graves' disease on the basis of measuring the uptake of 99mTcU20min. This shortens the time necessary for diagnosis and enables the calculation of 131I activity using Marinelli's formula.

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter.

BACKGROUND: Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. THE AIM OF THE STUDY: was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS: 40 patients (14 male, 26 female, age 57-80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS: The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. CONCLUSIONS: Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation.

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.

Parathyroid gland function after radioiodine ((131)I) therapy for toxic and non-toxic goitre.

INTRODUCTION: The therapeutic effect of radioactive iodine ((131)I) on benign goitre consists of the emission of tissue-destructive beta-radiation. Since the range of beta (131)I radiation in tissue can reach 2.4 mm, it can affect the adjacent parathyroid glands. The purpose of this paper is to assess parathyroid function in patients with toxic and non-toxic goitres, up to five years following (131)I therapy. MATERIAL AND METHODS: The study sample consisted of 325 patients with benign goitres (220 with toxic nodular goitre (TNG), 25 with non-toxic nodular goitre (NTNG), and 80 with Graves' disease (GD) treated with (131)I. The therapeutic activity of (131)I for each patient was calculated using Marinelli's formula. The serum levels of fT3, fT4, TSH, iPTH and Ca(2+), Ca and phosphates were determined one week before (131)I administration, as well as every two months up to a year following the therapy, and then after three and five years post-treatment. RESULTS: After two months following the administration of (131)I, all the treated patients showed a statistically significant above normal increase in iPTH concentrations (amounting to a value almost twice the norm in patients with TNG), which remained stable up to ten months after treatment, to return to normal level in the following months. In all the patients, Ca(2+), Ca, phosphates concentration remained within normal range throughout the course of the study. The concentrations of fT3 and fT4 quickly returned to normal after (131)I administration, and remained within normal range until the completion of the study. CONCLUSION: Radioiodine treatment of benign thyroid disorders results in transient (up to ten months after (131)I administration) hyperparathyroidism. The condition does not influence the level of calcium and phosphates concentration in any significant way.

Pheochromocytoma--analysis of 15 consecutive cases from one centre.

INTRODUCTION: Pheochromocytoma is a rare tumour, but one of great clinical importance as a risk factor of malignancy, cardiovascular diseases and sudden death. MATERIAL AND METHODS: 15 consecutive patients (eight women and seven men) were hospitalised and submitted for adrenalectomy with pheochromocytoma confirmed by histopathologic examination. Adrenalectomies were performed laparoscopically in 14 cases (93.3%): in nine by the retroperitoneal posterior mode and in five by the transperitoneal lateral approach. RESULTS: Molecular-genetic examination of VHL, RET, SDHB, SDHC and SDHD genes revealed inherited predisposition for PHEO in three of 15 patients (20%): RET mutations typical for MEN 2a in two patients and VHL mutation in one patient. Disturbances of the carbohydrate metabolism occurred in nine patients (60%). Ten patients (66%) reported paroxysmal symptoms. In all cases, with the exception of a von Hippel-Lindau patient, density of tumours exceeded 20 HU. In all studied patients, urine concentration of normetanephrines exceeded their normal range and greatly prevailed over metanephrines values, which were increased in six of them (40%). CONCLUSIONS: Urine metoxycatecholamines and increased tissue density are sufficient in pheochromocytoma detection. However, taking into account clinical and supplemental biochemical data may be helpful in the diagnostic process. Laparoscopic adrenalectomy is a fully sufficient and safe method of pheochromocytoma excision.

Interleukin-6 and its considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in postmenopausal women.

BACKGROUND: Thyrotoxicosis is more frequent in postmenopausal women than in the general population, effectively accelerating bone turnover. Interleukin-6 has been shown to be involved in the pathogenesis of bone disorders. Thus, the aim of the present study was to assess the role of IL-6 and its soluble receptor in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women. MATERIAL AND METHODS: The study was carried out in 40 subjects with toxic nodular goitre in three groups: Group 1 - 13 premenopausal females, mean age 36 ± 15 years (PremTx→PremEu); Group 2 - 12 postmenopausal females, mean age 66 ± 14 years (PostTx→PostEu); and Group 3 - 15 males, mean age 45 ± 21 years (MTx→MEu). Overt thyrotoxicosis and euthyreosis after treatment with thyrostatics were confirmed by thyrotropin, free thyroxine and free triiodothyronin concentrations. Serum levels of bone turnover markers: TRACP5b and osteocalcin as well as serum IL-6 and IL-6sR were determined using ELISA kits. RESULTS: TRACP5b/osteocalcin quotient was significantly elevated in the PostTx females compared to the PremTx women (p < 0.02). There was a positive correlation between serum TRACP5b and osteocalcin in the studied patients (R = 0.45, p < 0.001). Levels of serum IL-6 values were significantly elevated in PostTx: 3.0 (2.14-6.40) and MTx: 2.24 (1.60-5.10), compared to PremTx females: 1.39 (0.96-2.14) (p < 0.01 and p < 0.05 respectively). There were significant positive correlations between IL-6 and IL-6sR concentrations (R = 0.22, p < 0.05) and between IL-6sR and TRACP5b serum levels (R = 0.23, p < 0.05). CONCLUSIONS: The results of our study suggest that interleukin-6 plays a considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women.