Liquid levothyroxine in the treatment of myxoedema coma.

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Prevalence of Selected Single-Nucleotide Variants in Patients with Neuroendocrine Tumors-Potential Clinical Relevance.

INTRODUCTION: The genetic basis of neuroendocrine tumors (NETs), whose incidence is continuously increasing, is still not fully defined. The majority of NETs are sporadic, and only a small percentage occur as part of hereditary genetic syndromes. However, the associations of multiple genetic variants have been found as clinically relevant in several neoplasms. The aim of this study was to evaluate whether selected, literature-based genetic variants may have a potential role in NET susceptibility and clinical outcome in Polish patients. MATERIALS/METHODS: A total of 185 patients recruited from one clinical center were enrolled. In the first part of the study, the molecular analysis including four single-nucleotide variants (rs8005354 (DAD1, NM_001344 intronic T/C substitution), rs2069762 (T/G substitution in the promoter region of the IL2 NM_000586), rs3731198 (CDKN2A, NM_000077 intronic A/G substitution), and rs1800872 (C/A substitution in the promoter region of the IL10 NM_000572)) was performed in 107 participants (49 patients with NETs with different primary site NETs and a control group of 58 healthy adult volunteers). In the second stage, the same single-nucleotide polymorphisms (SNPs) were assessed in 127 patients with NET and analyzed in terms of clinical data (primary site, serum CgA concentration, and metastatic disease). RESULTS: The analysis of homozygotes revealed a statistically significant higher prevalence of TT homozygotes of variant rs3731198 in the control group (p = 0.0209). In NET patients, there was a statistically significant higher prevalence of GG homozygotes of variant rs1800872 (p = 0.003). There was a statistically significant correlation between the rs3731198 variant and lymph node metastases (p = 0.0038 with Bonferroni correction). CONCLUSIONS: Our study indicates that GG homozygotes of variant rs1800872 are more often observed in NET patients, while TT homozygotes of variant rs3731198 are less frequent in this group. The rs3731198 variant may be related to an increased risk of lymph node metastasis. Further, larger multicenter studies are warranted to evaluate the potential genetic factors of sporadic NETs.

Clinical challenges and dilemmas in the management of advanced pancreatic neuroendocrine tumour - the first manifestation of von Hippel-Lindau disease in a young patient.

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Efficacy of multimodal anticancer therapy in the course of pancreatic neuroendocrine carcinoma.

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Epidemiology of gastroenteropancreatic neuroendocrine neoplasms in Krakow and Krakow district in 2007-2011.

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).

Does combination of "cold" and "hot" somatostatin analogs prolong survival of patients with neuroendocrine neoplasms?

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/m2 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.

NEN - the role of somatostatin receptor scintigraphy in clinical setting.

Detection of neuroendocrine neoplasms (NENs) and monitoring of their response to therapy is still challenging due to huge heterogeneity of that group of tumors. Actually, NENs visualization is mainly based on molecular imaging while in the past it was relied on less effective structural imaging including CT and MRI. Molecular imaging techniques in combination with structural imaging (hybrid imaging), especially in patients with well-differentiated NENs, in addition to morphological provide the functional information about tumor which benefits in a more accurate patient management, including more sensitive visualization of primary tumors, more precise staging and better therapy follow-up. Overexpression of somatostatin receptors (SSTR) on NENs' cell membrane was a basis for development of somatostatin receptor scintigraphy (SRS) using single photon emission tomography SPECT, which is today a well-established standard in molecular imaging of NENs, and further imaging improvement in the field of positron emission tomography (PET). Use of hybrid imaging (SPECT/CT, PET/CT) increased sensitivity of examination, mainly resulting in better detection of small lesions. Generally, somatostatin receptor imaging with PET/CT is an emerging technique, although still with limited access, but due to several advantages over SSTR SPECT/CT, should be used if available. It is worth mentioning, that both SSTR PET/CT and SSTR SPECT/CT have some limitations, such as relatively low detection rate of benign insulinomas, poorly differentiated GEP-NETs and liver metastases. For that reason further improvement of NETs imaging is necessary. The most promising new tracers' families are based on SSTR antagonists, 64Cu-radiolabeled ligands and glucagon-like peptide-1 receptor (GLP-1R) imaging. Finally, in case of poor-differentiated neuroendocrine cancers 18F-FDG PET/CT may be beneficial in comparison with molecular imaging based on somatostatin receptor modalities.

99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma.

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.

Gastroenteropancreatic neuroendocrine neoplasms: a 10-year experience of a single center.

INTRODUCTION: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a rare and heterogeneous group of tumors with varied biology. OBJECTIVES: The aim of this study was to establish the clinical characteristics of patients with GEP-NEN and identify factors influencing their 5-year survival. PATIENTS AND METHODS: The study included 122 patients living in Kraków or its administrative region, who were diagnosed with GEP-NEN between 2002 and 2011. RESULTS: The mean follow-up period was 4.9 ±2.8 years. The most frequent primary site of the tumor was the small intestine (n = 25; 20%), followed by pancreas (n = 23; 19%), rectum (n = 23; 19%), stomach (n = 21; 17%), appendix (n = 19; 16%), and colon (n = 11; 9%). There were 84 tumors classified as NEN G1; 31, as NEN G2; 5, as neuroendocrine carcinoma; and 1, as mixed adenoneuroendocrine carcinoma. Most well-differentiated GEP-NENs (n = 57; 57%) were diagnosed at stage I according to the American Joint Committee on Cancer / Union for International Cancer Control (AJCC/UICC) classification; 77% of NEN G1 (n = 64) were diagnosed at stage I, but the majority of NEN G2­at stage IV (n = 18; 58%). Metastases at diagnosis were found in 38 patients (34%). In 90% of the cases (n = 101), tumors were hormonally nonfunctional. The overall 5-year survival was 85%. In the univariate analysis, NEN G2 (P = 0.003), higher stage according to the AJCC/UICC classification (P <0.001), and metastases at diagnosis (P <0.001) were associated with poorer prognosis. In standardized multivariate models, higher stage (P = 0.02) and metastases at diagnosis (P = 0.02) were independent risk factors for death. CONCLUSIONS: The most important factors affecting survival of patients with GEP-NENs are tumor stage and the presence of metastases at diagnosis. The analysis of single-center data improves identification of patients with poorer prognosis requiring a more aggressive approach.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients - results from the prospective 12-month phase of Lanro-Study.

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.

Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC- 99mTc/EDDA)NH2]-exendin-4 for the detection of insulinoma.

PURPOSE: The objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4. METHODS: Studies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed. RESULTS: Both sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis. CONCLUSION: [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.

Case report of a patient with initially inoperable well-differentiated midgut neuroendocrine tumor (WDNT)--PRRT and long-acting somatostatin analogs as the neoadjuvant therapy.

A 43-year-old man was admitted to Surgery Department because of abdominal pain, vomiting, weight loss and flushes. Computed tomography (CT) examination revealed upper and middle abdomen tumor of about 110 × 110 mm. Histopathological analysis of the tissues obtained during the exploratory laparotomy confirmed WDNT (well-differentiated neuroendocrine tumor according to the WHO classification 2000). The patient received 5 doses of chemotherapy without any response. A positive result of 99mTc-[EDDA/Hynic] Octreotate scintigraphy (SRS) gave the possibility of PRRT (peptide receptor radionuclide therapy). The patient was treated with the total dose of 400 mCi of 90Y-DOTA-TATE. CT performed after the PRRT revealed regression of the tumor size to 72 × 94 mm. A decrease of CgA level and release of symptoms were also observed. Aiming at the removal of the considerable diminished tumor the patient was qualified for the second laparotomy. "Cytoreduction" surgery with partial excision of the tumor was performed. Additionally tumor-affected appendix was removed. The second focus of WDNT (according to the WHO classification 2000) with Ki67 < 1% was found in the appendix. Pathologists confirmed the above-mentioned lesions as independent (an extremely rare clinical situation). The following treatment with long-acting somatostatin analogs and 300 mCi of 90Y-DOTA-TATE resulted in further regression of the tumor size to 25 × 35 mm. Consecutive laparotomy is considered. If complete tumor removal might be achieved is an open question. The above case report shows the efficacy of combined therapy with the use of "hot" and "cold" somatostatin analogs not only in controlling the symptoms of the disease but also in obtaining tumor size regression making surgical intervention possible. Such a neoadjuvant therapy seems to be a promising tool in the management of patients with initially inoperable neuroendocrine tumors.

Are RECIST criteria sufficient to assess response to therapy in neuroendocrine tumors?

MATERIAL AND METHODS: Within the group of 47 patients treated with peptide receptor radionuclide therapy (PRRT), four patients were chosen: three with inoperable tumors without liver metastases and one with two lesions in the pancreas and metastases. RESULTS: In all patients, after PRRT, the changes in the sum of the longest diameters of tumors were between -1% and -21%, resulting in stable disease reported [strict Response Evaluation Criteria in Solid Tumors (RECIST)]. But the measurements of tumor volume and attenuation in computed tomography and the tumor to nontumor ratio in somatostatin receptor scintigraphy resulted in different response assessments. CONCLUSIONS: The RECIST standard may be not sufficient to properly assess the therapy response in patients with neuroendocrine tumors.

Repeated cycles of peptide receptor radionuclide therapy (PRRT)--results and side-effects of the radioisotope 90Y-DOTA TATE, 177Lu-DOTA TATE or 90Y/177Lu-DOTA TATE therapy in patients with disseminated NET.

PURPOSE: PRRT is a known tool in the management of patients with disseminated and inoperable NETs. The aim of study was to assess the effectiveness of the repeated cycles of PRRT in patients with disseminated and inoperable NETs. MATERIAL AND METHODS: Eighty nine patients were included in the PRRT. Among them 16 patients (18%) were qualified for a repeated PRRT cycle due to progression of the disease. In one of the patients qualified for the repeated cycle, PRRT was used as neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT were analyzed. RESULTS: Disease stabilization was observed in 10 patients 6 months after the repeated PRRT cycle and in 5 patients after 12 and 18 months. Ten of the patients who had received repeated PRRT cycles died. In the case of neoadjuvant therapy, further reduction of the tumor size was observed, enabling qualification for surgery. Clinically significant reduction in the mean values of morphological parameters was not observed. Only after 12 and 18 months the mean values of creatinine levels were higher than the normal range (only in 2 patients). CONCLUSIONS: The repeated cycles of PRRT did not cause a clinically significant increase of the toxicity of PRRT. The changes in kidney and blood morphology parameters were transient. The repeated cycles of PRRT enabled stabilization of the disease.

Efficacy and safety of 90Y-DOTATATE therapy in neuroendocrine tumours.

BACKGROUND: The aim of this study was to assess the efficacy and toxicity of peptide receptor radionuclide therapy (PRRT) with the use of the high affinity somatostatin receptor subtype 2 analogue, (90)Y labelled Tyr3-octreotate, ((90)Y-DOTATATE) in neuroendocrine tumours (NETs). MATERIAL AND METHODS: 46 patients with disseminated or non-operable NET were enrolled in this study. The (90)Y-DOTATATE therapeutic activity was calculated per total body surface area up to a total of 7.4 GBq/m(2) administered in three to five cycles, repeated every four to nine weeks. Before and after the therapy, blood tests for haematology, kidney and liver function, and chromogranin A were performed. RESULTS: Out of 46 (90)Y-DOTATATE treated patients, one died before completing the therapy and 16 died after completing the therapy, among them one due to myocardial infarction. After 12 month follow-up, stabilisation of disease was observed in 47%, partial remission in 31%, and progression in 9% of the 45 patients who completed the therapy. Five patients died before completion of 12 months of follow-up. One of the patients died due to myocardial infarction. In one case, the information after 12 months is incomplete. The progression free survival was 37.4 months. During 12 months follow-up, transient decrease of PLT, WBC and haemoglobin values was observed. A transient increase of creatinine level (within normal ranges) and decrease of GFR values were found. CONCLUSIONS: NETs (90)Y-DOTATATE therapy results in symptomatic relief and tumour mass reduction. The mild critical organ toxicity does not limit the PRRT of NETs.

Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs).

PURPOSE: Neuroendocrine tumours (NET) are a heterogeneous group of neoplasms of diffuse neuroendocrine cells. Surgery is the main aim in the treatment of NETs, which becomes impossible in the case of large tumours or infiltration into other tissues and/or important blood vessels. Neoadjuvant therapy might be helpful in decreasing NET size also, leading us to the point where a tumour, previously considered inoperable, becomes operable. The aim of the study was to assess the usage of peptide receptor radionuclide therapy (PRRT) as a neoadjuvant treatment, enabling surgical intervention in primary inoperable NET. METHODS: Among 47 patients treated with PRRT, 6 patients were chosen with large, inoperable tumours, for whom enabling of complete surgical excision of the lesions might offer the prospect for a cure. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST). RESULTS: The mean tumour size decreased from 6.9 (min. 3.1 cm, max. 9.6 cm) before therapy to 5.4 cm (min. 3.1 cm, max. 9.5 cm) after the treatment. According to RECIST, stabilization of the disease was observed in four and partial responses in two patients. In two patients, reduction of the tumour size enabled surgical intervention. CONCLUSION: (1) PRRT might be considered a neoadjuvant therapy in primary inoperable NETs. (2) According to RECIST, stabilization of the disease was observed in the majority of patients. (3) We suggest that not only tumour diameter changes, but also tumour volume and contrast enhancement changes in computed tomography should be taken into consideration in assessment of the response to the therapy. (4) Somatostatin receptor scintigraphy is an important tool for qualification of the radioisotope therapy and also for the assessment of the response to PRRT.

Can treatment using radiolabelled somatostatin analogue increase the survival rate in patients with non-functioning neuroendocrine pancreatic tumours?

BACKGROUND: The aim of the study was to assess the effectiveness of peptide receptor radionuclide therapy (PRRT) in patients with non-functioning neuroendocrine pancreatic tumours (NFPNTs) and to compare survival rates in patients with NFPNTs and in patients with other neuroendocrine tumours (NETs) treated using radiolabelled somatostatin analogue in our Department. We would like to analyze factors potentially determining the effectiveness of the therapy and also to assess the myelo- and nephrotoxicity. MATERIAL AND METHODS: Fourteen patients with disseminated disease and/or inoperable NFPNT were qualified to PRRT based on positive SRS (somatostatin receptor scintigraphy). There were 5 men and 9 women, with Karnofsky's index>70%. RESULTS: In the whole group of patients, partial response was observed in 21.4%, stabilization of the disease in 42.9%, and progression of the disease in 35.7% of patients. Mean observation time was 19±13 months, mean time to progression was 12±9 months, and mean time to death was 16±9 months. Six patients died--four of them due to progression of the disease, two due to myocardial infarction. After PRRT we did not observe clinically significant haemotoxicity and/or nephrotoxicity. CONCLUSIONS: 1. Peptide receptor radionuclide therapy may be a safe and effective treatment option in patients with NFPNTs, leading to stabilization or regression of the disease in the majority of patients. 2. There is no statistically significant difference in survival rate between patients with NFPNTs and NETs of other localization treated with PRRT.

[Evaluation of radioiodine 131I treatment in Graves' disease patients with mild orbitopathy]. / Ocena wyników leczenia radiojodem 131I pacjentów z choroba Gravesa-Basedowa i lagodna orbitopatia.

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.

New forms of radionuclide therapy with (90)Y in oncology.

BACKGROUND: Currently, there is growing interest in the use of the beta emitter (90)Y in systemic therapy in oncology. For successful therapy, an appropriate ligand is chosen to carry the isotope to the place of its action. As well as performing this function, the type of the ligand influences both the course and the side effects of the treatment. For RIT of lymphomas, bone marrow becomes the critical organ; in NET patients treated with labelled somatostatin analogues, increased kidney irradiation can occur. The aim of this study was to evaluate the side effects of therapy using 90Y associated with different ligands, depending on the charge to critical organs after treatment in two groups of patients: those with neuroendocrine tumours and those with non-Hodgkin's lymphomas. MATERIAL AND METHODS: 32 patients with histopathologically confirmed NET treated with (90)Y-DOTATATE (7.4 GBq/m(2) cumulative dose) and 30 NHL patients treated with (90)Y-ibritumomab tiuxetan (1200 MBq max dose) were enrolled in the study. The kidney function and changes of blood indices were assessed during the course of the therapy. RESULTS: 59% of NET patients treated with (90)Y-DOTATATE displayed transient reduction of blood indices, the largest after cycles III and IV of therapy. After 5 months an increase in creatinine level was noticed, but no statistically important changes in creatinine level and GFR were observed. In the group of patients with NHL, the change of haematological indices after RIT concerned mainly PLT, ANC and WBC. The reduction of the average PLT and WBC values started in the first weeks after the treatment application, reaching nadir in the 6(th) week and 8(th) week, respectively. No life threatening infections were observed in either group of patients. CONCLUSIONS: After treatment with the use of the (90)Y radionuclide, no significant treatment toxicity, including disorders involving the critical organs for both types of therapies, was found in the groups of neuroendocrine tumour and non-Hodgkin's lymphoma patients.

[A case of GH and TSH secreting pituitary macroadenoma]. / Przypadek makrogruczolaka przysadki wydzielacego hormon wzrostu i tyreotropin.

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).