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The COVID-19 pandemic was a major challenge for all health care employees, but it was also difficult for patients to gain access to health care services. Myxedema coma (MC) is an extremely rare but potentially fatal endocrine emergency. The aim of the study was to report an increased incidence of life-threatening myxedema coma that occurred in relation to the COVID-19 pandemic. In this paper, we report a cohort of 11 patients with MC who were treated at the University Hospital in Krakow, Poland, in the period from 2015 to 2023. Only 1 case of MC was recorded in the period from 2015 to 2019, and, in the same area, 10 cases of MC were recorded after the start of COVID-19 pandemic until present. Hypothyroidism was diagnosed de novo in 2 (18%) patients; the remaining patients were severely hypothyroid due to therapy non-compliance. Nine patients had primary hypothyroidism, and 2 had central hypothyroidism. Besides longstanding hypothyroidism, an additional precipitating factor for MC was identified in 4 (36%) of the patients. Due to the inaccessibility of parenteral levothyroxine, patients were treated with oral, mostly liquid, form of levothyroxine. The mortality rate in this cohort was 27.2%. In conclusion, the increase of the incidence of MC, which is a life-threatening complication of inadequately treated hypothyroidism, during the COVID-19 pandemic, when resources were limited, and in the post-pandemic era, underlines the importance of adequate communication with patients and of long-term availability of primary care for patients with thyroid disease., (© 2024. The Author(s).)

Heme oxygenase-1 (HO-1, HMOX1) degrades heme protecting cells from heme-induced oxidative damage. Beyond its well-established cellular functions, heme has emerged as a stabilizer of G-quadruplexes. These secondary DNA structures interfere with DNA replication. We recently revealed that nuclear HO-1 colocalizes with DNA G-quadruplexes and promotes their removal. Here, we investigate whether HO-1 safeguards cells against replication stress. Experiments were conducted in control and HMOX1-deficient HEK293T cell lines. Immunostaining unveiled that DNA G-quadruplexes accumulated in the absence of HO-1, the effect that was further enhanced in response to δ-aminolevulinic acid (ALA), a substrate in heme synthesis. This was associated with replication stress, as evidenced by an elevated proportion of stalled forks analyzed by fiber assay. We observed the same effects in hematopoietic stem cells isolated from Hmox1 knockout mice and in a lymphoblastoid cell line from an HMOX1-deficient patient. Interestingly, in the absence of HO-1, the speed of fork progression was higher, and the response to DNA conformational hindrance less stringent, indicating dysfunction of the PARP1-p53-p21 axis. PARP1 activity was not decreased in the absence of HO-1. Instead, we observed that HO-1 deficiency impairs the nuclear import and accumulation of p53, an effect dependent on the removal of excess heme. We also demonstrated that administering ALA is a more specific method for increasing intracellular free heme compared to treatment with hemin, which in turn induces strong lipid peroxidation. Our results indicate that protection against replication stress is a universal feature of HO-1, presumably contributing to its widely recognized cytoprotective activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Amiodarone is an iodine-rich molecule and an effective antiarrhythmic drug. It is a first-line treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk. The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition.According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases. ; however, is not always feasible in the clinical setting due to the high anesthetic risk.We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status., Methods: Retrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022., Results: An electronic database search identified 75 patients hospitalized for severe AIT. At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/L (range 0.001-0.35), fT4 63.2 pmol/L (range 9.0 - >100), and fT3 10.2 pmol/L (range 3.8-49.3). All patients received optimal conservative treatment. Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure. In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation). The median dose of 131-I used for the therapy was 784MBq (range 627-860). The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism., Conclusion: The decision regarding the optimal time and type of radical treatment of AIT refractory to pharmacotherapy is critical for patients management and should not be delayed. Urgent therapy with 131-I may be an effective therapeutic option in patients who are unsuitable for thyroidectomy due to the high risk of anesthesia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Jagiellonian Univerity Medical College.)

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Introduction: Up to 5% of all pituitary tumors are hereditary e.g. due to MEN1 or aryl hydrocarbon receptor-interacting protein ( AIP ) genes mutations., Objectives: The study was aimed at the assessment of the frequency and characteristics of AIP -mutation related tumors in patients with apparently sporadic pituitary macroadenomas in the Polish population., Materials and Methods: The study included 131 patients (57 males, 74 females; median age 42 years) diagnosed with pituitary macroadenomas, and with a negative family history of familial isolated pituitary adenoma (FIPA) or multiple endocrine neoplasia type 1 (MEN1) syndromes. Sanger sequencing was used for the assessment of AIP gene variants. The study was approved by the Ethics Board of JUMC., Results: AIP variants were identified in five of the 131 included subjects (3.8%): one diagnosed with Cushing's disease, two with acromegaly, and two with non-secreting adenomas. Patients harboring hereditary AIP gene alterations did not differ from the rest of the study group in median age at diagnosis (41.0 vs. 42.5 years, P=0.8), median largest tumor diameter (25 vs. 24 mm, P=0.6), gender distribution (60.0% vs. 56.3% females, P=0.8), secreting tumor frequency (60.0% vs. 67.5%, P=0.7), or acromegaly diagnosis frequency (40.0% vs.37.3%, P=0.9)., Conclusions: In our series of apparently sporadic pituitary macroadenomas, AIP gene variant carriers did not differ substantially from patients with negative genetic testing. A risk factor-centred approach to AIP genetic screening may result in missing germline variants. Considering the clinical impact of such genetic variants and their relatively low penetrance, it is, however, doubtful if general genetic screening benefits the whole cohort of pituitary macroadenoma patients and their families., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Trofimiuk-Müldner, Domagała, Sokołowski, Skalniak and Hubalewska-Dydejczyk.)

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The N -glycome of immunoglobulin G (IgG), the most abundant glycoprotein in human blood serum, reflects pathological conditions of autoimmunity and is sensitive to medicines applied in disease therapy. Due to the high sensitivity of N -glycosylation, the IgG N -glycan profile may serve as an indicator of an ongoing inflammatory process. The IgG structure and its effector functions are strongly dependent on the composition of N -glycans attached to the Fc fragment, and the binding of antigens is regulated by Fab sugar moieties. Because of the crucial role of N -glycans in IgG function, remodeling of its N -oligosaccharides can induce pathological changes that ultimately contribute to the development of autoimmunity; restoration of their physiological structure is critical to the reduction of disease symptoms. Our recently published data have shown that the pathology of autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), is accompanied by alterations of the composition of IgG N -glycans. The present study is a more in-depth investigation of IgG glycosylation in both AITDs, designed to determine the relationship between the severity of thyroid inflammation and IgG N -glycan structures in HT, and to assess the impact of immunosuppressive therapy on the N -glycan profile in GD patients. The study material consisted of human serum samples collected from donors with elevated anti-thyroglobulin (Tg) and/or anti-thyroperoxidase (TPO) IgGs without symptoms of hypothyroidism (n=68), HT patients characterized by high autoantibody titers and advanced destruction of the thyroid gland (n=113), GD patients with up-regulated IgG against thyroid-stimulating hormone receptor (TSHR) before (n=62) and after (n=47) stabilization of TSH level as a result of methimazole therapy (study groups), and healthy donors (control group, n=90). IgG was isolated from blood serum using protein G affinity chromatography. N -glycans were released from IgG by PNGase F digestion and analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) after 2-aminobenzamide (2-AB) labeling. UPLC-MS chromatograms were integrated into 25 peaks (GP) in the Waters UNIFI Scientific Information System, and N -glycans were assigned based on the glucose unit values and mass-to-charge ratios (m/z) of the detected ions. The Kruskal-Wallis non-parametric test was used to determine the statistical significance of the results (p<0.05). The obtained results suggest that modifications of IgG sialylation, galactosylation and core-fucosylation are associated with the severity of HT symptoms. Methimazole therapy implemented in GD patients affected the IgG N -glycan profile; as a result, the content of the sialylated and galactosylated oligosaccharides with core fucose differed after treatment. Our results suggest that N -glycosylation of IgG undergoes dynamic changes during the intensification of thyroiditis in HT, and that in GD autoimmunity it is affected significantly by immunosuppressive therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trzos, Link-Lenczowski, Sokołowski and Pocheć.)

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G-quadruplexes (G4) are stacked nucleic acid structures that are stabilized by heme. In cells, they affect DNA replication and gene transcription. They are unwound by several helicases but the composition of the repair complex and its heme sensitivity are unclear. We found that the accumulation of G-quadruplexes is affected by heme oxygenase-1 ( Hmox1 ) expression, but in a cell-type-specific manner: hematopoietic stem cells (HSCs) from Hmox1 -/- mice have upregulated expressions of G4-unwinding helicases (e.g., Brip1 , Pif1 ) and show weaker staining for G-quadruplexes, whereas Hmox1 -deficient murine induced pluripotent stem cells (iPSCs), despite the upregulation of helicases, have more G-quadruplexes, especially after exposure to exogenous heme. Using iPSCs expressing only nuclear or only cytoplasmic forms of Hmox1, we found that nuclear localization promotes G4 removal. We demonstrated that the proximity ligation assay (PLA) can detect cellular co-localization of G-quadruplexes with helicases, as well as with HMOX1, suggesting the potential role of HMOX1 in G4 modifications. However, this colocalization does not mean a direct interaction was detectable using the immunoprecipitation assay. Therefore, we concluded that HMOX1 influences G4 accumulation, but rather as one of the proteins regulating the heme availability, not as a rate-limiting factor. It is noteworthy that cellular G4-protein colocalizations can be quantitatively analyzed using PLA, even in rare cells.

Introduction: There is increasing evidence that several autoimmune diseases, as well as their activity, are associated with vitamin D (VD) deficiency. Our study aimed to evaluate the prevalence of VD insufficiency in patients with Addison's disease (AD), as well as to evaluate associations between VD concentrations and various clinical and laboratory parameters of the disease., Materials and Methods: We retrospectively analyzed medical records of 31 adult patients diagnosed with autoimmune Addison's disease, in whom serum VD was measured. We assessed correlations between serum VD and various clinical and laboratory parameters. R e s u l t s: 90.3% of AD patients had inadequate VD concentrations (<30 ng/mL), and 19.3% of them were found to be severely VD deficient (<10 ng/mL). Among assessed laboratory variables, only serum calcium concentrations significantly correlated with VD status (r = 0.53, p = 0.006). The mean serum VD concentration was significantly lower in patients with severe fatigue (15.17 ± 8.41 vs 26.83 ± 12.29 ng/mL, p = 0.011) and limited exercise capacity (12.38 ± 6.9 vs 21.63 ± 10.87 ng/mL, p = 0.016). C o n c l u s i o n s: This study demonstrates a high prevalence of VD deficiency in AD patients, as well as the association between low VD concentrations with symptoms such as severe fatigue or limited exercise capacity. Further studies are needed to clarify if impaired VD status is a risk factor in the pathogenesis of AD and to assess if VD supplementation improves the quality of life of AD patients.

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Objective: The monitoring of the populations' iodine status is an essential part of successful programmes of iodine deficiency elimination. The current study aimed at the evaluation of current iodine nutrition in school children, pregnant and lactating women as a marker of the effectiveness and sustainability of mandatory iodine prophylaxis in Poland., Design: The following iodine nutrition indicators were used: urinary iodine concentration (UIC) (all participants) and serum thyroglobulin (pregnant and lactating women)., Setting: The study was conducted in 2017 within the National Health Programme in five regions of Poland., Participants: The research included 300 pregnant women, 100 lactating women and 1000 school children (aged 6-12 years)., Results: In pregnant women, median UIC was 111·6 µg/l; there was no significant difference in median UIC according to the region of residence. In 8 % of pregnant women, thyroglobulin level was >40 ng/ml (median thyroglobulin 13·3 ng/ml). In lactating women, median UIC was 68·0 µg/l. A significant inter-regional difference was noted (P = 0·0143). In 18 % of breastfeeding women, thyroglobulin level was >40 ng/ml (median thyroglobulin 18·5 ng/ml). According to the WHO criteria, the investigated sample of pregnant and lactating women was iodine-deficient. Median UIC in school children was 119·8 µg/l (with significant inter-regional variation; P = 0·0000), which is consistent with iodine sufficiency. Ninety-four children (9·4 %) had UIC < 50 µg/l., Conclusions: Mandatory iodisation of household salt in Poland has led to a sustainable optimisation of iodine status in the general population. However, it has failed to assure adequate iodine nutrition during pregnancy and lactation.

Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) are involved in destruction of thyroid tissue in Hashimoto's thyroiditis (HT). N -glycosylation of the Fc fragment affects the effector functions of IgG by enhancing or suppressing the cytotoxicity effect. The aim of the present study was to assess the impact of HT-specific IgG glycosylation in ADCC and CDC, using in vitro models. The normal thyroid Nthy-ori 3-1 cell line and thyroid carcinoma FTC-133 cells were used as the target cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors and the HL-60 human promyelotic leukemia cell line served as the effector cells. IgG was isolated from sera of HT and healthy donors and then treated with α2-3,6,8-neuraminidase to cut off sialic acids (SA) from N -glycans. We observed more intensive cytotoxicity in the presence of IgG from HT patients than in the presence of IgG from healthy donors. Removal of SA from IgG N -glycans increased ADCC intensity and reduced CDC. We conclude that the enhanced thyrocyte lysis resulted from the higher anti-TPO content in the whole IgG pool of HT donors and from altered IgG glycosylation in HT autoimmunity., Competing Interests: The authors declare that they have no conflicts of interest.

Introduction: The primary treatment of Conn's syndrome (CS) is laparoscopic adrenalectomy and aims to normalize arterial blood pressure and biochemical parameters., Aim: To analyse short- and long-term results of laparoscopic adrenalectomy for Conn's syndrome (CS)., Material and Methods: The analysis included 44 consecutive patients, who underwent laparoscopic adrenalectomy between 2004 and 2015 for CS. We analysed short- and long-terms results of operations. All patients were followed up 6 and 24 months after surgery to determine changes in the biochemical parameters, and clinical regression of arterial hypertension. We also evaluated the aldosteronoma resolution score (ARS) in predicting the resolution of hypertension., Results: No conversions were needed. Complications occurred in 5 (11.4%) patients. Preoperative hypokalaemia and hypernatraemia were present in 83.4% and 15.8% of patients, respectively. After surgery, both hypokalaemia and hypernatraemia resolved in all patients. At the follow-up 6 months after the surgery, only 11.3% of patients had complete remission (CR) of hypertension. In 43.2% of cases we observed partial remission (PR). After 24 months CR was found in 13.6% of patients, 45.5% patients fulfilled criteria for PR, and 29.5% of patients changed the group of remission comparison to the first follow-up visit. Only 50% of patients with an ARS of 4 or 5 points achieved CR 6 months after surgery., Conclusions: Laparoscopic adrenalectomy is a safe method of treatment for CS. Although it effectively eliminates electrolyte imbalance, it does not allow for the CR of hypertension in the majority of patients, especially in the elderly group. We did not find ARS to be an effective tool in predicting postoperative resolution of hypertension.

Context: Aggressive pituitary tumours causing Cushing's Disease are very rare, difficult to treat, and usually resistant to conventional therapy. There is growing evidence for the use of temozolomide (TZM), an alkylating chemotherapeutic agent, as first line chemotherapy in tumours resistant to repeated neurosurgery, radiotherapy and adrenalectomy., Objective: To present the response to TMZ in a rare case of an aggressive pituitary tumour in the course of Cushing's Disease and to review the literature referring to similar cases., Patient: In this report, we present the case of a 61 year old male patient who was diagnosed with Cushing's Disease in the course of a pituitary invasive macroadenoma in 2011. The patient underwent 4 transphenoidal non-radical neurosurgeries (2012,2013) with rapid tumour progression, repeated non-radical bilateral adrenalectomy (2012, 2013) and stereotactic radiotherapy, and gamma knife surgery (2013, 2015). Histopathological examination revealed macroadenoma with high cell polymorphism and the presence of Crooke's cells, Ki- < 2%. Since 2015 the patient has been treated with 6 cycles of TMZ (320 mg per day for 5 consecutive days, 28-day cycle) with clinical and biochemical improvement and stabilized tumour size and no side effects. TMZ was continued for up to 9 cycles with a stable serum level of cortisol and ACTH being observed. However, clinical symptoms like headaches, visual field impairment, and finally hearing loss started to progress from the eighth cycle. After the ninth cycle of TMZ, there was a sudden increase in the size of the tumour, impairment of the cortisol and ACTH level, marked deterioration of the clinical status with the recurrence of severe headaches, narrowing of the visual field and hearing loss. At the beginning of 2016, a sudden clinical status and sight deterioration, strong headaches, drop of the right eyelid with widening of the pupil were observed. The patient died in February 2016., Lessons: The case of our patient suggests that the response to the TMZ treatment monotherapy in aggressive pituitary tumour causing Cushing's Disease could be partial and restricted to 7-8 cycles followed by rapid progression of the tumor mass. Therefore, further research should be carried out with regard to new methods to extend the responsiveness and duration of TMZ treatment and to investigate predictors of responsiveness. < p > < /p >.

Purpose: The purpose of the study was to evaluate corrosion resistance of Wirobond C® alloy after chemical passivation treatment., Methods: The alloy surface undergone chemical passivation treatment in four different media. Corrosion studies were carried out by means of electrochemical methods in saline solution. Corrosion effects were determined using SEM., Results: The greatest increase in the alloy polarization resistance was observed for passive layer produced in Na2SO4 solution with graphite. The same layer caused the highest increase in corrosion current. Generally speaking, the alloy passivation in Na2SO4 solution with graphite caused a substantial improvement of the corrosion resistance. The sample after passivation in Na2SO4 solution without graphite, contrary to others, lost its protective properties along with successive anodic polarization cycles. The alloy passivation in Na3PO4 solution with graphite was the only one that caused a decrease in the alloy corrosion properties. The SEM studies of all samples after chemical passivation revealed no pit corrosion - in contrast to the sample without any modification., Conclusions: Every successive polarization cycle in anodic direction of pure Wirobond C® alloy enhances corrosion resistance shifting corrosion potential in the positive direction and decreasing corrosion current value. The chemical passivation in solutions with low pH values decreases susceptibility to electrochemical corrosion of Co-Cr dental alloy. The best protection against corrosion was obtained after chemical passivation of Wirobond C® in Na2SO4 solution with graphite. Passivation with Na2SO4 in solution of high pH does not cause an increase in corrosion resistance of WIROBOND C. Passivation process increases alloy resistance to pit corrosion.

Introduction: Prothymosin alpha (PTMA), a nuclear oncoprotein involved in cell cycle regulation, is used as a prognostic marker in many cancers. The histopathology of pituitary carcinomas and locally invasive adenomas is indistinguishable from that of benign tumors. A new marker is needed to differentiate these lesions. We evaluated PTMA in pituitary adenomas to determine its usefulness as a prognostic factor of tumor proliferation., Material/methods: We conducted a retrospective analysis of a group of 27 patients, including 15 females (56%) and 12 males (44%) with a mean age of 58.6±12 years, who underwent pituitary tumor surgery between 2003 and 2012. The Ki-67 and PTMA-nuclear (PTMA-n) and PTMA-cytoplasmic (PTMA-c) indices were determined by immunohistochemical staining. We studied histopathological features, clinical symptoms, and magnetic resonance imaging or computed tomography performed before surgery and one year following surgery to evaluate tumor size and progression., Results: The expression of Ki-67 was revealed in 77.8% of adenomas, PTMA-n in 81.5% and PTMA-c in 92.6%. The mean value of the Ki-67 index was 1.8%, PTMA-n was 1.84%, and PTMA-c was 35.6%. There was a significant positive correlation between Ki-67 and PTMA-n (p=0.009). We did not find any correlation between Ki-67, PTMA-c, and tumor progression. PTMA-n was found to be correlated with tumor size (p=0.045) and was higher in the case of gonadotropinomas (p=0.026)., Conclusions: The positive nuclear expression of Ki-67 and PTMA was observed in the majority of pituitary adenomas. Neither the expression of Ki-67 nor that of PTMA-c was related to tumor recurrence or local invasion.

The present study describes a family with multiple endocrine neoplasia type 1 (MEN1) caused by a previously undescribed in-frame deletion c.1246&#95;1248delGCC (Ala416del) in the MEN1 gene. Evidence for the pathogenic character of this mutation, which triggers an aggressive clinical outcome, is demonstrated. Aggregation analysis in the tested family was strongly suggestive of causality of the detected mutation. This was supported by the analysis of LOH (loss of heterozygosity) in tumor-derived DNA and by computational analysis of the functional and structural implications of the mutation. Different phenotypic characteristics were identified among family members, which is typical for MEN1. Additionally, an unexpected disease inheritance pattern was observed in this kindred, in which either all or none of the siblings of one branch inherited the disease.

Introduction: The unpredictable biology of pituitary adenomas makes it a therapeutic challenge. Moreover ,histopathology of pituitary carcinomas and locally invasive adenomas are indistinguishable from benign tumors and a new marker which would enable to differentiate those lesions is vital. The aim of the study was to evaluate Ki-67 and PTTG (pituitary tumour--transforming gene) expression in pituitary adenomas and their applicationas markers of tumour aggressiveness., Material and Methods: A retrospective analysis of 55 patients: 32 females(58%) and 23 males (42%), mean age 50 ± 16 years who underwent pituitary tumor surgery between 2003-2012. Ki-67 and PTTG indices were determined by immunohistochemical staining. Magnetic resonance imaging or computed tomography was performed beforehand and one year after surgery to figure a potential tumour progression, tumour size and correlation to adjacent tissues., Results: The expression of Ki-67and PTTG was revealed in cell nucleiin 88% and 85% of adenomas, respectively. The median Ki-67 and PTTG indices were 1.4 and 1.0, respectively(p = 0.006). In the group with macroadenoma as compared with the group with microadenoma, median Ki-67 index was higher (1.4% vs. 1.03%; p = 0.02). We did not find correlation between both Ki-67 and PTTG indices and tumour progression. Tumours with positive immunostaining towards FSH revealed lower Ki-67 and PTTG indices than the rest with a negative one (0.6% vs.1.84%, p = 0.0004 and 0.67% vs 1.23%,p = 0.047; respectively). However, PTTG index was higher in the group with acromegaly as compared to the group with clinically non-functioning pituitary adenoma (NFPA) (1.28% vs.0.35%; p = 0.02)., Conclusions: Positive nuclear expression of Ki-67 and PTTG was observed in the majority of pituitary adenomas. Only higher Ki-67 expression was related to the tumour invasiveness found on MRI/CT. Tumour progressionwas not related to both Ki-67 and PTTG expression.

Purpose: Corrosion resistance of titanium used in metal-ceramic restorations in manufacturing is based on the presence of oxide layer on the metal surface. The procedures used during combining metallic material with porcelain may affect the changes in oxide layers structure, and thus anticorrosive properties of metallic material. The aim of the study was an evaluation of potential changes in the structure and selected corrosion properties of titanium after sandblasting and thermal treatment applicable to the processes of ceramics fusion., Methods: Milled titanium elements were subjected to a few variants of the processes typical of ceramics fusion and studied in terms of resistance to electrochemical corrosion. The study included the OCP changes over time, measurements of Icorr, Ecorr and Rp as well as potentiodynamic examinations. Surface microstructure and chemical composition were analyzed using SEM and EDS methods., Results: The results obtained allow us to conclude that the processes corresponding to ceramic oxidation and fusion on titanium in the variants used in the study do not cause deterioration of its anticorrosive properties, and partially enhance the resistance. This depends on the quality of oxide layers structure., Conclusions: Titanium elements treated by porcelain firing processes do not lose their corrosion resistance.

Introduction: Available data on fibrin clot properties and fibrinolysis in hyperthyroidism and hypothyroidism are inconsistent. Our objective was to assess the impact of effective treatment of hyper- and hypothyroidism on fibrin clot characteristics., Material and Methods: In a case-control study, ex vivo plasma fibrin clot permeability (Ks) and efficiency of fibrinolysis were assessed in 35 consecutive hyperthyroid and 35 hypothyroid subjects versus 30 controls. All measurements were performed before and after 3months of thyroid function normalizing therapy., Results: At baseline, hyperthyroid, but not hypothyroid, patients had lower Ks than controls (p<0.0001). Hyperthyroid and hypothyroid groups compared with controls had prolonged clot lysis time (CLT), and lower rate of D-dimer release from clots (D-Drate) (all p<0.05). The regression analysis adjusted for fibrinogen showed that in hyperthyroid patients, pre-treatment thyroid stimulating hormone (TSH) independently predicted Ks, while thrombin activatable fibrinolysis inhibitor (TAFI) antigen predicted CLT. In hypothyroid individuals a similar regression model showed that TSH independently predicts CLT. After 3months of thyroid function normalizing therapy, 32 (91.4%) hyperthyroid and 30 (85.7%) hypothyroid subjects achieved euthyroidism and had improved fibrin clot properties (all p<0.05), with normalization of Ks in hyperthyroid and lysability in hypothyroid patients., Conclusions: Both hyper- and mild-to-moderate hypothyroidism are associated with prothrombotic plasma fibrin clot phenotype and restoration of euthyroidism improves clot phenotype. Abnormal fibrin clot phenotype might contribute to thromboembolic risk in thyroid disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: There is an ongoing search for markers of pituitary tumor proliferation and progression that could facilitate further treatment and patient monitoring., Objectives: We studied topoisomerase IIα (topo IIα) expression in different types of pituitary adenomas to evaluate its prognostic value., Patients and Methods: In a retrospective study of 60 patients (mean age, 46.7 ±17.6 y) who underwent pituitary tumor surgery, expression of topo IIα was assessed by immunohistochemistry and compared with histopathological tumor features, clinical symptoms, magnetic resonance imaging, and postoperative tumor recurrence or progression., Results: Expression of topo IIα was observed in 44 of 60 pituitary adenomas (73%). The highest topo IIα index was observed in adrenocorticotropic hormone (ACTH)-secreting tumors (median, 1.13% [0.37-1.21]), followed by silent-ACTH tumors (0.94% [0.89-1.0]), and hormone immunonegative adenomas (0.8% [0.65-1.55]). There were no differences in topo IIα expression with respect to age or sex. Significant correlations were observed between the topo IIα index and tumor size, its invasiveness, abnormal ocular test results, and postoperative tumor recurrence. In patients with a topo IIα index exceeding 1%, we observed a 3.5-fold higher relative risk of tumor recurrence as compared with patients with a topo IIα index lower than 1% (95% confidence interval: 1.8-6.9; P <0.001). Patients with acromegaly who received somatostatin analogues before the surgery had a lower median topo IIα index compared with untreated patients (0%[0-0.22] vs. 0.71% [0.17-1.0]; P <0.05)., Conclusions: In our study group, a topo IIα index exceeding 1% was a prognostic factor for tumor recurrence or progression, especially in patients with hormonally inactive adenomas, which facilitates patient selection for intensive postoperative treatment. Use of somatostatin analogues in acromegaly inhibits topo IIα expression, providing molecular evidence for the effectiveness of these analogues.

Background: Microvessel density in angiogenesis is regarded as a prognostic factor of tumour invasiveness, independent of cell proliferation. In recent studies of pituitary tumours, correlation between the expression of cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel surface density has been established. We studied the expression of COX-2 in different types of pituitary adenomas to determine the usefulness of COX-2 expression as a prognostic factor of tumour progression or recurrence in patients with hypophyseal tumours., Material/methods: We retrospectively studied a group of 60 patients of mean age 46.7±17.6 (range, 18 to 85) years who underwent pituitary tumour surgery. Expression of COX-2, as determined by immunohistochemistry, was analyzed in relation to histopathology features of tumour, clinical symptoms, MR imaging and post-operative recurrence/progression of disease., Results: COX-2 was expressed in adenomas of 87% of patients, with a median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We found no differences in COX-2 expression with respect to patient age, gender, tumour size, degree of tumour invasiveness, or whether tumours were immunopositive or immunonegative for pituitary hormones, nor have we found any relation between COX-2 expression and recurrence or progression of tumour size., Conclusions: COX-2 does not appear to be a predictive factor for recurrence or progression of tumour size. Nevertheless, due to the observed relatively high expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors are justified in these tumours.

Adrenocortical carcinoma (ACC) is a rare neoplasm with very poor prognosis despite the recent development of aggressive antitumor therapies. The cause of adrenal cancer remains elusive, but some molecular mechanisms could be responsible for its development. Target-specific therapies have been developed for a number of human malignancies and have resulted in therapeutic benefits in some cancer patients. However, these therapies are only effective in cases in which the corresponding targets are expressed in tumor tissues. Molecular analysis has had a significant impact on the understanding of the pathogenetic mechanism of ACC development and the evaluation of prognostic and predictive markers, among which alterations of the IGF system, the Wnt pathway, p53 and molecules involved in cancer cell invasion properties and angiogenesis seem to be very promising. These molecular markers may not just play a role in the biology of these tumors and have prognostic implications, but can also be used as potential targets for treatment. The aim of this review is to summarize the genetic and molecular events implied in the pathogenesis of ACC and to highlight challenges to the development of anticancer agents in recent patents.

Introduction: Sodium-iodine symporter (NIS) belongs to a large family of natrium dependent ion transporters found in normal thyroid cells located on the basilar membrane of tyreocytes. Under physiologic conditions, the NIS is also present in other tissues: salivary glands, gastric mucosa, mammary glands during lactation, and vascular plexus of the fourth ventricle. NIS expression has also been found in many tumors, including breast cancer., Aim: The aim of this study was to evaluate the usefulness of whole body scintigraphy after administration of relatively low activity of 131I (6 MBq)in the diagnostics of breast cancer., Material and Methods: The study included nine women with breast cancer, aged 38-73 years (mean 55.6 +/- 11.7 years) and a control group of 14 women aged 29-84 years (mean 48.8 +/- 16.7 years). The uptake of radioiodine in whole body scintigraphy 24 hours after administration of 131I radioiodine (6 MBq) was compared between the control group and breast cancer patients. No pharmaceuticals reducing thyroid iodine uptake or increasing NIS expression were used., Results: Whole body scans using 6 MBq 131I activity revealed no focal radioiodine uptake outside the thyroid tissue in patients with breast cancer as well as volunteers from the control group., Conclusions: Whole body scintigraphy using 131I, dosed at 6 MBq, with no additional treatment increasing extrathyroidal uptake of radioiodine, appears to be ineffective in the imaging of breast cancer.

Background: We evaluated the predictive value of IGF-1 against hGH in the treatment outcome., Material and Methods: A prospective study was undertaken of 47 patients (mean age 41.1 ± 12.9 years; 44 with macroadenoma and 3 with microadenoma), requiring treatment with octreotide LAR (SSLAR) following incomplete surgery. Concentrations of hGH and IGF-1 were measured three months after surgery and three, six, nine, 12, 18, and 24 months after introducing SSLAR., Results: Following surgery, respective median values of hGH and IGF-1 concentrations were 5.55 ng/mL (IQR = 7.1) and 512.7 ng/mL (IQR = 379.5). After six, 12, and 24 months of SSLAR treatment, median values of hGH decreased significantly: to 2.95 ng/mL (IQR = 5.5, p < 0.05), 2.95 ng/mL (IQR = 4.4, p < 0.05) and 2.00 ng/mL (IQR = 3.6, p < 0.001), respectively. After six, 12, and 24 months of SSLAR treatment, the respective median IGF-1 concentrations significantly decreased to 384.5 ng/mL (IQR = 312.2, p < 0.01), 323.0 ng/mL (IQR = 230.3, p < 0.001) and 334.0 ng/mL (IQR = 328.9, p < 0.01). The differences between median hGH and IGF-1 concentrations at 12 and 24 months were not significant. A statistically significant correlation was found between IGF-1 concentration prior to and after surgery (R = 0.61, p < 0.05) and prior to SSLAR treatment and IGF-1 concentration 24 months later (R = 0.49, p < 0.05). No such correlation was observed for hGH., Conclusions: The level of IGF-1 prior to surgery and prior to SSLAR treatment is a better predictor of the treatment outcome than hGH. Octreotide LAR was most effective over the first 12 months of treatment. No further significant decrease of hGH or IGF-1 levels was observed past this period.

The purpose of this work was to determine trace element levels in urine and evaluate possible associations between urinary iodine concentration (UIC), other trace elements (Cr, Cu, Fe, Mn, Na, Se, Zn), toxic elements (Cd, Pb), anthropometrical measures (body weight and height), glycemic indices (serum insulin and glucose), and several parameters related to thyroid function (thyroid stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, thyroid volume, and thyroid echogenicity) in pregnant women. One hundred sixty-nine participants were recruited. The whole study group, originating from Krakow region, comprised three subgroups belonging to three trimesters: I trimester (n = 28), II trimester (n = 83), and III trimester (n = 58). Trace elements were determined using inductively coupled plasma mass/(atomic emission) spectrometry. Partial least square model was used to reveal correlation structure between parameters investigated, as well as a possible causal relationship between dependent parameters and potentially explanatory parameters. Results obtained for trace and toxic elements in urine were comparable with results of other authors, although the study group was not homogenous. We confirmed (1) low iodine excretion in pregnant women, (2) the existence of statistically significant correlation between UIC and urinary selenium, and (3) lack of correlation between latter parameter and typical indices of thyroid function. Urinary selenium correlated with other urinary trace elements, but physiological significance of this finding remains uncertain. The fact that a large number of pregnant women fail to meet dietary recommendations for iodine is the major reason for concern.

Introduction: A particularly challenging case of concurrent acromegaly and follicular thyroid carcinoma in a patient of the Clinic of Endocrinology, UJCM in Krakow is discussed., Case Description: A 59-year-old male with post total thyroidectomy performed in 2005 and histopathologically confirmed metastases of the follicular thyroid carcinoma to the lungs was admitted to the Clinic in April 2006 for complementary ¹³¹I treatment. Acromegaly was treated in 1996 by trans-sphenoidal surgery. In December 2005 a relapse of pituitary adenoma was shown by MRI, which correlated with increased levels of hGH and IGF-1. Biochemical control of acromegaly was achieved with Sandostatin LAR. Pre-therapeutic whole-body scintigraphy (WBS) revealed numerous conjoined hot spots of ¹³¹I accumulation in both lungs and in thyroid remnants. In May and November 2006 the patient received ¹³¹I treatment. Post-therapeutic WBS in November 2006 revealed complete ablation of the thyroid remnants. Laboratory tests confirmed lowering of thyroglobulin concentration. In the years 2007, 2008, and 2009 the patient was qualified for therapy with ¹³¹I aided by rhTSH, achieving further reduction of Tg levels. Post-therapeutic WBS performed in 2009 revealed weak bilateral tracer uptake in the lung parenchyma. In 2010, chest CT revealed fibrosis in left lung segments, no infiltrative changes, and no lymph node enlargement. Patient follow-up continues at our Department., Conclusions: Disseminated thyroid cancer in a patient with pituitary insufficiency may be successfully treated by rhTSH-supported ¹³¹I treatment.

Introduction: In acromegalic patients, the prevalence of certain benign and malignant neoplasms is higher than that in the healthy population. We retrospectively evaluated the prevalence of tumours in acromegalic patients treated at our department: the regional centre for acromegalic patients for the Małopolskie voivodeship in Poland., Material and Methods: During the years 1983-2008, a hundred and one acromegalic patients (30 males and 71 women), of mean age 51.8 +/- 15.4 years, were diagnosed and treated. Pituitary macroadenoma and microadenoma were stated in 63.4% and 25.7% of these patients, respectively. In 10.9% of these patients no data on tumour diameter were available. The mean observation period was 9.4 +/- 6.5 years. The median levels of hGH and IGF-1 prior to neurosurgery were 20.2 (IQR = 34.9) ng/ml and 764.5 (IQR = 569.6) ng/ml, respectively., Results: In the studied group of patients, we found the following prevalence of various tumours: nodular goitre - 64/101 patients (63.0%), polyps of the colon - 13/101 patients (13.0%); uterine polyps - 4/101 patients (4.0%); and prostate adenoma - 2/101 patients (2.0%). Among malignant tumours, thyroid cancer, endometrium and cervix cancer were the most frequent, each of these occurring in 3 patients (3.0%). Colon cancer prevalence was 2.0% (in 2 patients)., Conclusions: From our retrospective study, we suggest an overall increase of tumour incidence in acromegalic patients. Prospective multicentre studies are required to resolve the significance of this observation. In our study group, the number of malignant neoplasms was significantly higher in patients with long-lasting uncontrolled disease (over 5 years), compared to patients with controlled disease. (Pol J Endocrinol 2010; 61 (1): 29-34).

We present the case of a 68-year-old woman with Graves' disease, orbitopathy and an autonomously functioning thyroid nodule. Initially, the patient was diagnosed with orbitopathy as a sign of euthyroid Graves-Basedow's disease, confirmed by the presence of thyrotropin receptor antibodies. Five years later symptoms of hyperthyroidism occurred. Thyroid scan with iodine-131 (131I) showed a hot nodule in the right lobe. Recurrences of hyperthyroidism and short remissions were observed in the course of the disease - the symptoms typical of hyperthyroidism due to an autonomously functioning thyroid nodule. Fine needle aspiration biopsy of the nodule revealed no atypical follicular cells and the patient was scheduled for 131I treatment. She has been euthyroid for over one year.

Unlabelled: Radioiodine (131I) treatment of patients with Graves-Basedow disease may cause or aggravate the course of orbitopathy (GO) in some 15% of patients; while only 3% of patients treated with methimazole develop GO. The aim of this study was to evaluate the frequency of GO progression in patients with mild GO treated with 131I, compared to a control group., Materials and Methods: The studied group consisted of 21 hyperthyroid patients (mean age 49 +/- 12.8 years) with mild orbitopathy (CAS < 3 pts, NOSPECS < 4 pts). The control group included 18 hyperthyroid patients with Graves-Basedow disease (mean age 50 +/- 9.9 years) with no GO symptoms (CAS = 0 pts, NOSPECS < 1 pts). All patients were treated with 131I. Patients with GO underwent treatment with oral methyloprednisolone (MP) over 30 days in decreasing doses, commencing with a dose of 16 mg/day. TSH, FT4 and hTRAb serum concentrations were measured prior to, and 14, 30, 60 days and 12 months after administration of 131I, always accompanied by an ophthalmic evaluation., Results: In the studied group, mean TSH and FT4 concentrations prior to treatment were 0.05 +/- 0.08 microU/ml and 23.7 +/- 10.7 pmol/l, respectively. Mean 131I activity applied in this group was 605.0 +/- 89.0 MBq. No significant differences were stated between values of respective parameters in the studied and control groups. Prior to treatment, median hTRAb concentrations in the studied and control groups were 6.8 U/l (max 53.8, min 0.1) and 8.9 U/l (max 57.1, min 4.2), respectively, and did not differ significantly. After 14 days post commencing MP treatment the median hTRAb concentration in the studied group decreased (4.5 U/l, max 51.1, min 0.1) with respect to the control group (7.5 U/l, max 50.0, min 2.9). After 60 days and 12 months, median hTRAb concentrations in the studied group were 8.3 U/l (max 16.9, min 0.7) and 8.5 U/l (max 9.8, min 3.0) respectively, being higher than those in the control group and also higher than the initial value in studied group. Cured were 16/21 patients in the studied group and 16/18 patients in the control group. Within 12 months observation, progression of GO symptoms in 2 patients (9%) of the studied group was noted and exophthalmos observed in 3 patients (17%) of the control group., Conclusions: In patients with mild GO treated with methyloprednisolone 131I administration is effective and does not lead to aggravation of GO symptoms, compared with the control group. Long-term elevation of hTRAb concentration in studied and control group of patients with Graves' disease treated with 131I1 was found.

Since acromegaly is associated with high rates of comorbidities and increased mortality risk compared to the general population, over the last few years somatostatin analogues have been used to treat acromegaly patients who, following surgery, have not fulfilled cure criteria (basal hGH < 2.5 ng/ml, IGF-1 below normal ranges for age and sex and hGH < 1.0 ng/ml in the 120th min of the OGTT test). We assessed the efficacy of Octreotide LAR (OCT-LAR) in managing such patients. 72 patients underwent diagnostic tests to qualify them for Octreotide LAR treatment. Treatment efficacy evaluation was based on measuring the concentration of hGH and IGF-1 prior to and 3 and 12 months and performing control MRI 6 and 12 months after the beginning of OCT-LAR treatment. The dose of O ctreotide LAR was 20 mg/month, increased to 30 mg/month if unsatisfactory response was observed. We evaluated the efficacy of Octreotide LAR in 48 acromegaly patients (66.7% of 72 evaluated), in whom criteria of postsurgery cure were not fulfilled. 24 patients (33.3%) did not require further treatment. After 3 months of OCT-LAR treatment, hGH < 2.5 ng/ml was stated in 37.0% of patients, median value--3.4 ng/ml (IQR = 5.3), as compared to median value of 5.5 ng/ml (IQR = 5.6) before treatment (p < 0.05). After 3 months of treatment IGF-1 below normal ranges for age and sex was stated in 55.5% of patients, median value--336.8 ng/ml (IQR = 290.0), as compared to median value of 520.0 ng/ml (IQR = 351.0) prior to OCT-LAR treatment (p < 0.05). After 12 months hGH < 2.5 ng/l ml and IGF-1 below normal ranges for age and sex were found in 63.0% and 54.5% of patients, respectively. In control MRI recurrence, correlated with enhanced concentration of IGF-1, was stated in 7 patients (14.6%). Thus, we conclude that satisfactory acromegaly control, in terms of hGH and IGF-1 levels, was obtained in above 50% of patients treated with Octreotide LAR. Since in the studied group hGH secretion had achieved cure criteria after 3 months in 37.5% as compared to 63.0% after 12-months, assessment of OCT-LAR treatment should be extended over periods exceeding 3 months.

Coexistence of Graves-Basedow disease with orbitopathy and thyroid cancer is believed to be a rare event. A 39-year-old man with clinical features of hyperthyroidism associated with exophthalmos and goitre presented to out patient clinic. Thyroid function tests showed hyperthyroidism with elevated thyroid-stimulating antibodies. Graves-Basedow disease was diagnosed. Ultrasound revealed diffuse thyroid enlargement with hypoechoic pattern and hypoechoic lesions with regular edges of 1.0 cm diameter at the left and right lobe. Fine needle aspiration biopsy was negative. Due to the patient's nodular goitre and mild orbitopathy, after some further 3 months of anti-thyroid medication, near total thyroidectomy was performed. Histologically, papillary microcarcinoma was found. Following surgery, the patient was referred to our Department of Endocrinology, L-thyroxine suppression treatment was commenced. Approximately 8 weeks post surgery, the patient reported with eye discomfort, soft tissue oedema and double vision. On CT thickening of the left superior rectus muscle was found. Methylprednisolone pulse therapy was applied (4 weeks, 2 grams per week). Glucocorticoid therapy resulted in significant improvement of soft tissue inflammation and of diplopia. The patient was qualified for 131I radioiodine complementary therapy (3657 MBq) and orbital irradiation. While some authors suggest that radioiodine therapy may be associated with worsening of pre-existing orbitopathy, so far we have not observed it in our patient, perhaps due to thyroid removal as a source of autoreactive T lymphocytes and the protective effect of applied glucocorticoids.