Prothymosin-alpha and Ki-67 expression in pituitary adenomas.

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.

PTTG and Ki-67 expression in pituitary adenomas.

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.

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.

Expression of cyclooxygenase-2 (COX-2) in pituitary tumours.

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.

Functional and Morphological Changes in the Visual Pathway in Patients with Graves' Orbitopathy.

BACKGROUND: The aim of the study was to perform a functional and structural evaluation of the anterior visual pathway in patients with Graves' Orbitopathy (GO) using electrophysiological tests and OCT, as well as to identify potential parameters that could be useful in detecting early optic nerve damage. METHODS: 47 GO patients were enrolled in the study and divided into three groups, depending on their disease severity: Group 1 with mild GO, Group 2 with moderate-to-severe GO, and Group 3 with dysthyroid optic neuropathy (DON). Pattern visual evoked potential (PVEP), flash visual evoked potential (fVEP), pattern electroretinogram (pERG), and optical coherence tomography (OCT) findings were compared between the groups. RESULTS: In the DON Group (Group 3), N75, P100, and P2 latencies were significantly extended, whereas P100, P50, and N95 amplitudes were significantly reduced as compared to the non-DON group (Groups 1 and 2). Group 3 also had significantly thinner peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC). In Group 2, as compared to Group 1, P100 amplitudes were significantly reduced for all check sizes, while P100 latency was elongated for the check size of 0.9°. Group 2 also had a significantly thinner average GCC and GCC in the superior quadrant. CONCLUSIONS: Electrophysiological examinations may be of use in diagnosis of DON. OCT findings and electrophysiological responses vary in patients with different GO severity. Including regular electrophysiological evaluation and OCT in the examination of patients with GO could be of benefit. However, more research is needed to establish the true significance of pVEP, fVEP, pERG, and OCT in monitoring patients with GO.

Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych doroslych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022].

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.

Efficacy and complications of neurosurgical treatment of acromegaly.

The aim of the study was to evaluate the frequency of occurrence of pituitary failure following neurosurgery and the efficacy of transsphenoidal tumour resection in acromegalic patients. We retrospectively evaluated 85 patients (60 female and 25 male), of mean age 43.9 ± 13.2 years, treated by transsphenoidal neurosurgery. Macroadenoma and microadenoma of pituitary were found in 66 (77.6%) and 19 (22.4%) of these patients, respectively. Criteria of cure following neurosurgery were: basal GH<2.5 µg/l, GH at 120 min in OGTT<1.0 µg/l and serum concentration of IGF-1 within normal ranges for age and sex. After surgery 32 patients (37.6%) were cured and 53 patients (62.4%) required somatostatin analogue treatment. In patients cured by surgery, lower levels of basal GH (P<0.05), IGF-1 (P<0.001), GH at 120 min in OGTT and smaller size of pituitary tumour (P<0.05) were found at diagnosis, as compared to patients in whom surgery was unsuccessful. Significant correlation between basal serum level of GH at diagnosis and size of pituitary tumour was found (P<0.001). Invasive tumours were found in 45 of 53 (84.9%) patients not cured and in only 8 of 32 (25.0%) patients cured (P<0.001). Impaired function of pituitary anterior lobe after surgery was observed in 30% and 4% of patients with macro- and microadenoma, respectively (P<0.05). The efficacy of neurosurgery is affected by concentration of basal serum GH and IGF-1, GH at 120 min in OGTT, tumour size and invasiveness. Hypopituitarism after surgery is more frequent in patients with macroadenoma. Pituitary insufficiency, as a consequence of surgery, was found in 21% of patients with normal pituitary function prior to operation.

[The risk assessment of lungs' apices injury in patients after radioactive iodine therapy due to hyperthyroidism]. / Ocena ryzyka uszkodzenia szczytów pluc u pacjentów po leczeniu radiojodem z powodu nadczynnosci tarczycy.

In the light of recent research data hypothesis on radioactive iodine therapy leading to inflammatory reaction in lungs' apices has lately gained wider acceptance among pulmonologists. The study published of late showed that in one female patient previously treated with radioiodine due to toxic multinodular goiter 99mTc-Tectreotide uptake was found in the lung apex. The aim of study was evaluation of the risk assessment of inflammatory reaction in lungs' apices among patients treated with radioactive iodine due to hyperthyroidism. The study was carried out in 15 female patients (mean age 75 years +/-10 years) with large toxic multinodular goiter and fine needle aspiration biopsy negative for malignancy and who did not qualify for thyreoidectomy. Mean radioactive iodine therapeutic dose used in the study was 940 MBq. Chest SPECT scan (99mTc-Tectreotide) was performed one year after radioiodine therapy. Trace uptake in lung apex has been noted only in one patient. In 14 out of 15 patients in the study tectreotide uptake has not been found in any lungs' apices. All of 15 patients became euthyroid six months after radioactive iodine therapy and had their thyroid gland shrinked. No significant correlation between inflammatory reaction in lung apices and radioiodine therapy in patients with hyperthyroidism and large multinodular goiter was found in conducted study.

[Gastrointestinal tract polyps in acromegaly patients]. / Polipy przewodu pokarmowego u chorych z akromegalia.

Acromegaly is a rare, chronic disease due to hypersecretion of growth hormone (GH) by pituitary adenoma arising from somatotrophs. The course of the disease is related to long-term organ and systemic complications and malignancies. Colon polyps seem to constitute the most frequent tumours in acromegaly apart from thyroid nodules. The aim of this study was to evaluate the prevalence of colon polyps in patients with acromegaly. Thirty one acromegaly patients, 22 females and 9 males (mean age 46.3 +/- 11.9 yrs), were enrolled to the study. Colonoscopy with histopathological assessment of specimens taken during examination was carried out in all patients. Colon polyps were found in 13 patients (41.9%) i.e. 8 females and 5 males. In two patients multiple polyps were discovered (2 and 3 respectively). Polyps were histopatologically verified as tubular adenoma with low-grade dysplasia (10 patients, 76.9%) and hyperplastic polyps (3 patients, 23.1%). The prevalence of colon polyps was significantly related to the duration of uncontrolled acromegaly (p < 0.01). Median duration of uncontrolled acromegaly in patients with and without colon polyps were 10.0 (IQR = 2.0) yrs and 6.5 (IQR = 5.0) yrs, respectively. IGF-1, GH basic and in 120 min of OGTT serum concentrations on diagnosis were not significantly related to the prevalence of colon polyps. Our study indicates that duration of uncontrolled acromegaly, contrary to IGF-1, GH basic and in OGTT serum concentrations at diagnosis are essential for the colon polyps development. Colonoscopy is considered to be routine in patients with acromegaly.

Radioiodine ablation of thyroid remnants in patients with differentiated thyroid carcinoma (DTC) following administration of rhTSH - a comparison with L-thyroxine withdrawal.

INTRODUCTION: A group of differentiated thyroid carcinoma (DTC) patients receiving post thyroidectomy rhTSH-aided radioiodine treatment (group I) was compared with patients treated with ¹³¹I following endogenous stimulation of TSH (group II) after L-thyroxine withdrawal. MATERIAL AND METHODS: Group I consisted of 66 patients of mean age 51.7 ± 16.2 years (58 females and 8 males). Group II included 76 patients of mean age 54.8 ± 14.7 years (67 females and 9 males). All patients underwent total thyroidectomy and central lymph node dissection and additionally lateral lymph node excision, if required. Prior to radioiodine treatment thyroid volume (VT) and 24-hour ¹³¹I uptake were evaluated. TSH and Tg concentrations were measured prior to and after endogenous and exogenous stimulation of TSH. Whole-body post-therapeutic scintigraphy was evaluated. Basic statistics, W Shapiro-Wilk, Wilcoxon, and U Mann-Whitney tests were applied. RESULTS: Median values of VT and of 24-hr ¹³¹I uptake in groups I and II were not significantly different. The differences between median values of serum TSH concentration after stimulation in groups I and II were statistically significant (p < 0.05), respective medians being 100.0 µU/mL (IQR = 107.3) and 78.8 µU/mL (IQR = 47.7). Median values of serum Tg concentrations in groups I and II following TSH stimulation prior to radioiodine treatment were 2.6 ng/ml (IQR = 8.4) and 4.9 ng/mL (IQR = 12.6), respectively, the difference not being statistically significant. Following rhTSH treatment no adverse effects were observed compared to LT4 withdrawal. CONCLUSIONS: rhTSH may be safely used for ¹³¹I thyroid remnant ablation in low-risk DTC patients.

A case of acromegaly and disseminated follicular thyroid carcinoma.

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.

The prevalence of benign and malignant neoplasms in acromegalic patients.

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 Malopolskie 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).

Therapeutic effect of presurgical treatment with longacting octreotide (Sandostatin® LAR®) in patients with acromegaly.

INTRODUCTION: The aim of this study was to assess the therapeutic effect and the safety of pre-surgical treatment with long-acting octreotide in patients with acromegaly. MATERIAL AND METHODS: This project was conducted in 25 centres across Poland as a non-interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18-86 years (51.3 ± 13.4). RESULTS: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. CONCLUSION: We have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with long-acting somatostatin analogues in acromegaly patients.

[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.

[Evaluation of the efficacy of Octreotide LAR in the treatment of acromegaly--a yearly observation]. / Ocena skutecznosci leczenia Oktreotydem LAR u chorych z akromegalia--obserwacja roczna.

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.

[A case of Graves-Basedow disease with orbitopathy and papillary thyroid cancer]. / Przypadek pacjenta z choroba Gravesa-Basedowa, orbitopatia i rakiem brodawkowatym tarczycy.

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.

Markers of proliferation and invasiveness in somatotropinomas.

Introduction In the search for markers of invasiveness of pituitary adenomas, we studied the expression of Ki-67 antigen, TOPO 2A (topoisomerase 2 alpha), AIP (Aryl Hydrocarbon Receptor-Interacting Protein) and VEGF (Vascular Endothelial Growth Factor) in somatotropinomas. Material and Methods We retrospectively studied a group of 31 patients who underwent pituitary tumour surgery. Expression of Ki-67, TOPO 2A, AIP and VEGF in surgical specimens was determined by immunohistochemistry. Relations between quantitatively determined markers and clinical symptoms, tumour features, and MR imaging, were analysed. Acromegaly was confirmed by hormonal tests in all patients studied. Local invasiveness (cavernous sinus penetration, optic chiasm compression or suprasellar extension) was observed in 18/31 patients (58,1%). Results Ki-67 was expressed in 77.4%, TOPO 2A in 87.1%, AIP in 83.8%, and VEGF in 87.1% of 31 cases of somatropinoma. Median values of Ki-67, TOPO 2A, AIP and cytoplasmic VEGF indices were 1.2% [IQR=2.2], 1.5% [IQR=1.6], 21.26% [IQR=20.1] and 20.4% [IQR=15.4], respectively. Ki-67, TOPO 2A, AIP and VEGF expression was not correlated with age nor with patient gender (p > 0.05). Only Ki-67 and TOPO 2A correlated with tumour size (for Ki-67: r=0.42, p=0.025; for TOPO 2A: r=0.53, p=0.003). Ki-67 and TOPO 2A levels were significantly higher in invasive compared to noninvasive somatropinomas (Ki67 mean values: 1.85±1.33% vs. 0.95±1.07%, p=0.024; TOPO 2A mean values: 2.19±1.63% vs. 1.45±1.23%, , p=0.011). Conclusions Ki-67, TOPO 2A, AIP and VEGF were expressed in over 70% of all somatotropinomas. Only Ki-67 and TOPO 2A expression correlated with tumour size and tumour invasiveness.

Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma. 2018 Update.

Significant advances have been made in thyroid can-cer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines "Diagnostics and Treatment of Thyroid Carcinoma" have been formulated at the "Thyroid Cancer and Other Malignancies of Endocrine Glands" conference held in Wisla in November 2015 [1].

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Zelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.

Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.