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Introduction. Epidemiological studies on medullary thyroid cancer (MTC) have shown that neither a change in stage at diagnosis nor improvement in survival has occurred during the past 30 years. In patients with detectable serum calcitonin and no clinically apparent disease, a careful search for local recurrence, and nodal or distant metastases, should be performed. Conventional imaging modalities will not show any disease until basal serum calcitonin is at least 150 pg/mL. The objective of the study was to present the first experience with labelled glucagon-like peptide-1 (GLP-1) analogue [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 in the visualisation ofMTC in humans. Material andMethod. Four patients aged 22-74 years (two with sporadic and two with MEN2 syndrome-related disseminated MTC) were enrolled in the study. In all patients, GLP-1 receptor imaging was performed. Results. High-quality images were obtained in all patients. All previously known MTC lesions have been confirmed in GLP-1 scintigraphy. Moreover, one additional liver lesion was detected in sporadic MTC male patient. Conclusions. GLP-1 receptor imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 is able to detect MTC lesions. GLP-1 scintigraphy can serve as a confirmatory test in MTC patients, in whom other imaging procedures are inconsistent. [ABSTRACT FROM AUTHOR]

Introduction: Normosmic isolated hypogonadotropic hypogonadism (nIHH) is a clinically and genetically heterogeneous disorder. Deleterious variants in over 50 genes have been implicated in the etiology of IHH, which also indicates a possible role of digenicity and oligogenicity. Both classes of genes controlling GnRH neuron migration/development and hypothalamic/pituitary signaling and development are strongly implicated in nIHH pathogenesis. The study aimed to investigate the genetic background of nIHH and further expand the genotype-phenotype correlation., Methods: A total of 67 patients with nIHH were enrolled in the study. NGS technology and a 38-gene panel were applied., Results: Causative defects regarded as at least one pathogenic/likely pathogenic (P/LP) variant were found in 23 patients (34%). For another 30 individuals, variants of unknown significance (VUS) or benign (B) were evidenced (45%). The most frequently mutated genes presenting P/LP alterations were GNRHR ( n = 5) , TACR3 ( n = 3), and CHD7, FGFR1, NSMF, BMP4 , and NROB1 ( n = 2 each). Monogenic variants with solid clinical significance (P/LP) were observed in 15% of subjects, whereas oligogenic defects were detected in 19% of patients. Regarding recurrence, 17 novel pathogenic variants affecting 10 genes were identified for 17 patients. The most recurrent pathogenic change was GNRHR :p.Arg139His, detected in four unrelated subjects. Another interesting observation is that P/LP defects were found more often in genes related to hypothalamic-pituitary pathways than those related to GnRH., Conclusions: The growing importance of the neuroendocrine pathway and related genes is drawing increasing attention to nIHH. However, the underestimated potential of VUS variants in IHH etiology, particularly those presenting recurrence, should be further elucidated., 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 © 2024 Kałużna, Budny, Rabijewski, Dubiel, Trofimiuk-Müldner, Szutkowski, Piotrowski, Wrotkowska, Hubalewska-Dydejczyk, Ruchała and Ziemnicka.)

Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by tumors in multiple organs. Although being a dominantly inherited monogenic disease, disease phenotypes are unpredictable and differ even among members of the same family. There is growing evidence for the role of modifier genes in the alteration of the course of this disease. However, genome-wide screening data are still lacking. In our study, we addressed the different outcomes of the disease, focusing on pituitary and adrenocortical tumors. By means of exome sequencing we identified the affected signaling pathways that segregated with those symptoms. Most significantly, we identified damaging alterations in numerous structural genes responsible for cell adhesion and migration. Additionally, in the case of pituitary tumors, genes related to neuronal function, survival, and morphogenesis were repeatedly identified, while in patients with adrenocortical tumors, TLR10 , which is involved in the regulation of the innate immunity, was commonly modified. Our data show that using exome screening, it is possible to find signatures which correlate with the given clinical MEN1 outcomes, providing evidence that studies addressing modifier effects in MEN1 are reasonable., Competing Interests: The authors declare that they have no conflicts of interest.

There are substantial data confirming the association between autoimmune disorders, including connective tissue diseases (CTDs), and an increased risk of thyroid malignancy. CTDs and thyroid cancer may co-exist as 2 separate diseases because of their relatively high incidence rates in the population. They can arise from each other due to the increased risk of thyroid cancer in patients with idiopathic inflammatory myositis, rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, and systemic lupus erythematosus. Moreover, in some scarce cases, CTDs may act as the paraneoplastic syndromes of thyroid cancer. The presence of CTDs may impact the diagnostic process, especially distorting the results of imaging tests or falsely indicating the increase of thyroglobulin or calcitonin. Finally, TSH suppression is a crucial element of the treatment of differentiated thyroid cancer, which may decrease bone mineral density and increase the risk of osteoporosis by accelerating bone turnover and shortening the bone remodeling cycle. The aim of this review is to emphasise the vital aspects of this interrelationship. The authors discuss this phenomenon aiming at the explanation of possible linking mechanisms. The impact of selected CTDs on thyroid cancer management is presented, as well as the possible effects of cancer therapy on skeletal health.

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Introduction and Objective: A number of studies indicate the presence of a thyroid-gut axis and the important influence of the gut microbiota on thyroid function. As prebiotics, probiotics and synbiotics show therapeutic potential in the treatment of intestinal dysbiosis, the aim of this review is to evaluate the efficacy of their supplementation in primary thyroid diseases., Review Methods: Electronic databases (Ovid MEDLINE, Embase, CENTRAL), registers of clinical trials, and grey literature up to 6 October 2022 were searched for randomised controlled trials (RCTs) meeting pre-specified inclusion criteria. The protocol was registered in PROSPERO (CRD42021235054)., Brief Description of the State of Knowledge: After screening 1,721 references, two RCTs were identified, which included 136 hypothyroid participants in total. Meta-analysis of the results after eight weeks of supplementation with predominantly Lactobacillus and Bifidobacterium strains indicated a clinically and statistically nonsignificant decrease in TSH (MD -0.19 mIU/L; 95% CI -0.43 to 0.06; I 2 = 0%), and no effect on fT 3 levels (MD 0.01 pg/mL; 95% CI-0.16 to 0.18; I 2 = 0%). Data from single studies indicated no significant change in the levels of fT 4, thyroid auto-antibodies, BMI, levothyroxine doses, and severity of symptoms measured with validated scales. Only constipation scores showed significant improvement (MD -8.71 points in the Faecal Incontinence Questionnaire; 95% CI -15.85 to -1.57; I 2 = 0%)., Summary: Low-certainty evidence from two randomised trials, suggests that routine administration of probiotics, prebiotics or synbiotics may result in little to no benefit in patients with primary hypothyroidism.

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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Introduction: Multiple endocrine neoplasia type 1 (MEN1) is a monogenic disease caused by inactivating variants in the MEN1 gene. Although the reason for its development is well-known, disease phenotypes are unpredictable and differ even among carriers of the same pathogenic driver mutation. Genetic, epigenetic, and environmental factors may play a role in driving the individual phenotype. Those factors, however, still mostly remain unidentified. In our work, we focused on the inherited genetic background in pancreatic neuroendocrine neoplasms (pNENs) in MEN1 patients, and the pancreatic tumour subgroup with insulinoma., Material and Methods: Whole exome sequencing was performed in MEN1 patients. The symptoms of interest were pancreatic neuroendocrine tumours in one analysis and insulinoma in the second. The study included families as well as unrelated cases. Genes with variants that are not neutral to the encoded gene product were defined in symptom-positive patients as compared to symptom-negative controls. The interpretation of the results was based on functional annotations and pathways shared between all patients with the given symptom in the course of MEN1., Results: Whole-exome screening of family members and unrelated patients with and without pNENs revealed a number of pathways that are common for all the analysed cases with pNENs. Those included pathways crucial for morphogenesis and development, proper insulin signalling, and structural cellular organization. An additional analysis of insulinoma pNEN patients revealed additional pathways engaged in glucose and lipid homeostasis, and several non-canonical insulin-regulating mechanisms., Conclusions: Our results show the existence of pathways that are identified in a non-literature-predefined manner, which might have a modifying function in MEN1, differentiating the specific clinical outcomes. Those results, although preliminary, provide evidence of the reasonableness of performing large-scale studies addressing the genetic background of MEN1 patients in determining their individual outcomes.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs., Design: Register-based cross-sectional study., Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated., Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs., Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

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Thyroid hormones influence female fertility, directly stimulating oocyte maturation and regulating prolactin and sex hormone binding globulin (SHBG) concentrations. Hyperthyroidism affects 1-2%, overt hypothyroidism 0.3%, and subclinical hypothyroidism up to 15% of women of childbearing age. Approximately 10% of euthyroid women have elevated concentrations of anti-thyroid peroxidase antibodies (aTPO) and/or anti-thyroglobulin (aTg) antibodies. Hypothyroidism can cause menstrual and ovulation disorders, and impact fertility. Studies carried out to date have not conclusively demonstrated that subclinical hypothyroidism or elevated aTPO/aTg concentrations make it harder to conceive, but they do increase the risk of pregnancy loss. Subclinical hypothyroidism and elevated aTPO/aTg concentrations without thyroid disorders are more common in polycystic ovary syndrome, premature ovarian insufficiency, and idiopathic infertility. Fertility problems are therefore an indication for screening for thyroid diseases (in females as well as in some males). A thyroid disorder diagnosed in subfertile couples should be treated appropriately, especially before attempting assisted reproductive techniques. These recommendations are intended as a guide for the management of thyroid diseases associated with infertility.

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

Background: Although the disease-causing effect of pathogenic variants in the gene RET has been unambiguously identified, there is a lack of consensus regarding the possible impact of common variants in this gene. Our study aimed to test whether variants in exons 10, 11, and 13-16 that are commonly detected during routine diagnostic testing might have any modifying effect on MTC. Methods: In sporadic MTC patients with no pathogenic variants but with or without common variants in RET , the following variants were evaluated: rs1799939 (p.G691S), rs1800861 (p.L769=), rs1800862 (p.S836=), rs2472737 in intron 14, and rs1800863 (p.S904=). Results: After Bonferroni correction, none of the variants were statistically significantly associated with disease outcome when analysed independently. The MTC group was divided into three genetically different clusters by unsupervised k-means clustering. Those clusters differed significantly in the age at diagnosis. A trend towards the association of given clusters with metabolic disorders and with remission state was identified. Conclusions: Although common variants in RET are not responsible for the risk of MTC, their analysis might turn out useful in the prediction of a patient's clinical outcome. Importantly, this analysis would come with no additional cost in laboratories with a diagnostic procedure based on exon sequencing.

Kallmann syndrome (KS) is a combination of isolated hypogonadotropic hypogonadism (IHH) with olfactory dysfunction, representing a heterogeneous disorder with a broad phenotypic spectrum. The genetic background of KS has not yet been fully established. This study was conducted on 46 Polish KS subjects (41 males, 5 females; average age: 29 years old). The studied KS patients were screened for defects in a 38-gene panel with next-generation sequencing (NGS) technology. The analysis revealed 27 pathogenic and likely pathogenic (P/LP) variants, and 21 variants of uncertain significance (VUS). The P/LP variants were detected in 20 patients (43.5%). The prevalence of oligogenic P/LP defects in selected genes among KS patients was 26% (12/46), whereas the co-occurrence of other variants was detected in 43% (20 probands). The examined KS patients showed substantial genotypic and phenotypic variability. A marked difference in non-reproductive phenotypes, involving defects in genes responsible for GnRH neuron development/migration and genes contributing to pituitary development and signaling, was observed. A comprehensive gene panel for IHH testing enabled the detection of clinically relevant variants in the majority of KS patients, which makes targeted NGS an effective molecular tool. The significance of oligogenicity and the high incidence of alterations in selected genes should be further elucidated.

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.

Appropriate care of pregnant women with coexisting thyroid dysfunction is still a subject of much controversy. In recent years, there has been a dynamic increase in the number of scientific reports on the diagnosis and treatment of thyroid diseases in women planning pregnancy, pregnant women, and women in the postpartum period. These mainly concern the management of hypothyroidism, autoimmune thyroid diseases, and fertility disorders. Therefore, the Polish Society of Endocrinology deemed it necessary to update the guidelines on principles of diagnostic and therapeutic management in this group of patients, previously published in 2011. The recommendations were prepared by Polish experts according to evidence based medicine principles, if such data were available.

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.

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels., (© 2020 Martin et al.)

Purpose: To evaluate the optimal tracer uptake time, the minimal amount of radioactivity and the inter-observer agreement for 11 C-choline positron emission tomography/computed tomography (PET/CT) in patients with primary hyperparathyroidism (pHPT)., Methods: Twenty-one patients with biochemically proven pHPT were retrospectively studied after injection of 6.3 ± 1.2 MBq/kg 11 C-choline. PET data of the first nine patients, scanned for up to 60 min, were reconstructed in 10-min frames from 10- to 60-min postinjection (p.i.), mimicking varying 11 C-choline uptake times. Parathyroid adenoma to background contrast ratios were calculated and compared, using standardized uptake values (SUVs). Data was reconstructed with varying scan durations (1, 2.5, 5, and 10 min) at 20-30-min p.i. (established optimal uptake time), mimicking less administered radioactivity. To establish the minimal required radioactivity, the SUVs in the shorter scan durations (1, 2.5, and 5 min) were compared to the 10-min scan duration to determine whether increased variability and/or statistical differences were observed. Four observers analyzed the 11 C-choline PET/CT in four randomized rounds for all patients., Results: SUVpeak of the adenoma decreased from 30 to 40 p.i. onwards. All adenoma/background contrast ratios did not differ from 20- to 30-min p.i. onwards. The SUVs of adenoma in the scan duration of 1, 2.5, and 5 min all differed significantly from the same SUV in the 10-min scan duration (all p = 0.012). However, the difference in absolute SUV adenoma values was well below 10% and therefore not considered clinically significant. The inter-observer analysis showed that the Fleiss' kappa of the 1-min scan were classified as "moderate," while these values were classified as "good" in the 2.5-, 5-, and 10-min scan duration. Observers scored lower certainty scores in the 1- and 2.5-min scans compared to the 5- and 10-min scan durations., Conclusion: The optimal time to start PET/CT scanning in patients with pHPT is 20 min after mean injection of 6.3 MBq/kg 11 C-choline, with a recommended scan duration of at least 5 min. Alternatively, the radioactivity dose can be lowered by 50% while keeping a 10-min scan duration without losing the accuracy of 11 C-choline PET/CT interpretation.

Objectives: The diagnosis and treatment of thyroid diseases in pregnant women remains a challenge. Various medical associations recommend establishing the reference intervals for thyroid hormones by a local laboratory. Considering differences within geophysical, socioeconomic conditions, and iodine prophylaxis in various populations, it is advisable to assess reference intervals for thyroid hormones specific to a region of residence. The objective was to assess trimester-specific reference intervals for TSH, fT 3 , and fT 4 for pregnant women in the Polish population., Methods and Results: We conducted a prospective study in 4 centers representing different regions of Poland (Krakow, Warsaw, Poznan, and Bialystok). Our study included consecutive, healthy pregnant women (172 patients), with an age range of 27-47 years. All women had a negative history for thyroid diseases, normal thyroid peroxidase antibody levels, and proper iodine prophylaxis. All newborns had TSH levels in the appropriate reference range. Serum TSH, fT 3 , fT 4 , and thyroid-peroxidase antibodies were measured in each trimester. The reference intervals were calculated using the percentile method, as recommended by the International Federation of Clinical Chemistry. The reference values calculated were 0.009-3.177, 0.05-3.442, and 0.11-3.53 mIU/L for TSH; 3.63-6.55, 3.29-5.45, and 3.1-5.37 pmol/L for fT 3 ; and 11.99-21.89, 10.46-16.67, and 8.96-17.23 pmol/L for fT 4 in consecutive trimesters of pregnancy. Reference intervals for pregnant women when compared to the general population showed a lower concentration of TSH in every trimester of pregnancy and lower fT 4 in the 2nd and 3rd trimesters., Conclusions: Using appropriate trimester-specific reference intervals may improve care of pregnant women by preventing misdiagnosis and inadequate treatment.

A number of detected neuroendocrine neoplasms (NENs) has been on the increase due to our awareness of the NENs risk and the development of different imaging techniques. Therapy of NENs involves surgery, chemotherapy, "cold" somatostatin analogs (SSA), peptide receptor radionuclide therapy (PRRT) and kinase inhibitors in pancreatic NENs. The aim of this study is to assess the efficacy of SSA in combination with "hot" somatostatin analogs, and the survival rate of our patients with advanced NENs. Seventy nine patients with metastatic NEN and positive somatostatin receptor scintigraphy (SRS) were enrolled in the study. Every patient was supposed to receive a dose of 7.4 GBq/m 2 PRRT in 4-5 cycles every 4-9 weeks. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST). SSA were administered one month after the last cycle of PRRT and have been continued during the whole follow up period. Median observation time was 33 months (IQR 13.6-55.6), median time to progression was 28 months (IQR 12.1-39.2) and median time to event was 28 months (IQR 12.1-39.2). Overall survival for this group of patients was 60 months. PFS was 39 months and EFS was equal to 33 months. In our group of patients not many serious adverse events were observed. PRRT using radiolabelled somatostatin analogs followed by therapy with "cold" somatostatin analogs is a promising treatment option for patients with metastatic or inoperable somatostatin receptor-positive NENs with the possibility of survival prolongation.

Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) are rare and heterogeneous tumours with variable biology. The aim of this study was to evaluate the epidemiology of GEPNEN in the population of Krakow and Krakow district in 2007-2011., Material and Methods: The Database of the Chair and Department of Endocrinology, Jagiellonian University Medical College, comprising the data on NEN cases collected from the Endocrinology Department, University Hospital in Krakow and from independent sources: surgery, pathology, and endocrinology departments located in the Krakow area, was searched for cases of GEPNEN patients living in Krakow and Krakow district, diagnosed between 2007 and 2011. Eighty-eight such patients (39 males, 49 females, median age at diagnosis 59 ± 17 years) were identified and characterised., Results: The mean follow-up time was 2.67 ± 1.6 years. The most frequent primary location of GEPNEN was small intestine (20%), followed by the appendix (18%), stomach (16%), pancreas (16%), rectum (15%), and colon (15%). NENG1 predominated (64%) in the analysed group. Most well-differentiated GEPNEN (63%) were diagnosed at stage I; however, 18% of them were diagnosed at stage IV. Metastases at diagnosis were found in 31% of patients. The GEPNEN incidence rate in 2007-2011 was 2.1/100000 inhabitants/year, without significant increase during the studied period., Conclusions: GEPNEN incidence and epidemiology in the population of Krakow and Krakow district is similar to the incidence observed in most European countries. Registers are important tools to evaluate GEPNEN epidemiology. (Endokrynol Pol 2017; 68 (1): 42-46).

Introduction: The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma., Materials and Methods: Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions., Results: Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient)., Conclusions: 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective surgical treatment. This imaging technique may eliminate the need to perform invasive procedures in case of occult insulinoma.

Background: Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin's lymphoma. Standard first-line treatment for this aggressive subtype comprises the anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone. If patients receiving such treatment have an early relapse, or their disease is initially refractory to such treatment, standard salvage regimens may not be effective. There is therefore a high unmet clinical need for new targeted agents that might improve the outcome for such patients. CD19 is a B-lymphocyte lineage-specific cell surface antigen that is expressed by most B-cell non-Hodgkin's lymphomas. MOR208 is an fragment-crystallizable engineered humanized monoclonal antibody with enhanced antitumor activity that targets CD19 and that may consequently have clinical utility in this setting., Case Presentation: We describe the case of a 33-year-old Caucasian man who presented with a 3-month history of general symptoms and who was admitted to our pulmonology ward with dyspnea due to pneumonia and severe anemia. A histopathological examination of an enlarged right suprasternal lymph node confirmed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma, an uncommon morphological variant of diffuse large B-cell lymphoma. Our patient had a complete response to first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone, but had an early relapse 5 months after the end of treatment. After intensive salvage therapy consolidated with an autologous stem-cell transplant, our patient again had an early relapse and was subsequently enrolled in a phase IIa trial of single-agent MOR208. Following a scheduled 3 months of weekly treatment, a partial response was confirmed and MOR208 was continued as maintenance therapy, with administration every second week. Positron emission tomography-computed tomography confirmed a complete response 9 months later. This response is ongoing, with a duration of 24 months. MOR208 was well-tolerated by our patient and his quality of life and performance status remain high. No hospitalizations were required and our patient engaged in full-time work and physical activities., Conclusion: Third-line single-agent therapy with the CD19 antibody MOR208 was highly effective in this patient, despite a history of early relapse after standard first-line and second-line treatment regimens. These data provide support for future randomized studies of MOR208.

Introduction. Epidemiological studies on medullary thyroid cancer (MTC) have shown that neither a change in stage at diagnosis nor improvement in survival has occurred during the past 30 years. In patients with detectable serum calcitonin and no clinically apparent disease, a careful search for local recurrence, and nodal or distant metastases, should be performed. Conventional imaging modalities will not show any disease until basal serum calcitonin is at least 150 pg/mL. The objective of the study was to present the first experience with labelled glucagon-like peptide-1 (GLP-1) analogue [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 in the visualisation of MTC in humans. Material and Method. Four patients aged 22-74 years (two with sporadic and two with MEN2 syndrome-related disseminated MTC) were enrolled in the study. In all patients, GLP-1 receptor imaging was performed. Results. High-quality images were obtained in all patients. All previously known MTC lesions have been confirmed in GLP-1 scintigraphy. Moreover, one additional liver lesion was detected in sporadic MTC male patient. Conclusions. GLP-1 receptor imaging with [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 is able to detect MTC lesions. GLP-1 scintigraphy can serve as a confirmatory test in MTC patients, in whom other imaging procedures are inconsistent.

Aim of the Study: To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland., Material and Methods: A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013., Results: 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%)., Conclusions: These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.