Predictive factors determining incomplete response to radioiodine therapy in patients with differentiated thyroid cancer.

BACKGROUND: Although differentiated thyroid cancer (DTC) has relatively favorable course, factors predicting the course of the disease are intensively searched. The aim of the study was to identify the clinical factors determining incomplete response to radioiodine therapy in patients with DTC. METHODS: We retrospectively analyzed 385 consecutive patients with DTC treated and followed-up at a single tertiary reference center. We investigated clinical factors detectable during first hospitalization 3-6 months following total thyroidectomy due to DTC, which may serve as prognostic factors determining response to DTC therapy in a long-term follow-up. RESULTS: Stimulated thyroglobulin (sTg) was the only parameter significantly correlated with the cumulative radioiodine activity (r=0.247, P<0.001). The need for repeated radioiodine administration (≥3 doses) was best predictable on the basis of sTg concentration assessed at the moment of qualification to radioiodine therapy (P=0.003). Predictive value of the sTg for incomplete response to radioiodine has been confirmed with the ROC curve analysis and the best proposed cut-off value was 8.17 ng/mL (sensitivity 55%, specificity 77%, positive predictive value 42.1%, negative predictive value 84.7%); sTg over 8.17 ng/mL increases the risk of incomplete response to therapy 2.5-folds (P=0.002). CONCLUSIONS: sTg, assessed at the moment of qualification to radioiodine therapy, as the most important factor determining incomplete response to radioiodine therapy in patients with DTC, should be particularly taken into consideration in predicting the future course of the disease as well as treatment and follow-up planning. Radical thyroidectomy may help to increase the effectiveness of treatment.

Fractionated dosage of radioiodine for the ablation of low-risk differentiated thyroid cancer has no impact on survival.

INTRODUCTION: Due to a limited number of hospital beds dedicated to radioiodine therapy (RIT) in some countries, a fractionated dose of radioiodine may be considered as the ablation therapy of differentiated thyroid cancer (DTC). The aim of the study was to compare the late effects of ablation therapy with single and fractionated dose of radioiodine in patients with DTC. PATIENTS AND METHODS: Patients with low-risk DTC referred to our institution 5-16 weeks after thyroidectomy, treated with 2.2 GBq of 131I, either in a single dose (2.2 GBq, group 1) or in two fractions (1.1 GBq+1.1 GBq administered with a 24 h interval, group 2) were retrospectively included. Clinical outcome of the treatment and overall survival (OS) was evaluated. RESULTS: 83 patients treated with single dose and 186 patients treated with fractionated dose of radioiodine were included. Mean duration of follow-up was 8.0 vs.7.8 years, respectively (p=ns). There were no significant differences between the groups in male to female ratio, age at the time of the first RIT, proportion of papillary thyroid cancers, volume of the thyroid tissue, thyroid-stimulating hormone and thyroglobulin levels before first RIT. RIT was repeated in 55.4% and 54.8% of patients from group 1 and 2 respectively (p=ns). There were no significant differences including the course and outcomes of the treatment between the groups, measured by: cumulative dose of 131I, mean number of 131I administrations and mean thyreoglobulin concentration at the follow-up. Also the overall survival did not differ significantly between the groups. Probability of 5-year OS was 98.6% for patients treated with single and 99.5% with fractionated dose of 131-I, 10 year OS - 98.6 and 97.1% respectively, 15 year OS - 95.5 and 92.9% respectively (p=ns). CONCLUSIONS: In the long-term follow-up, radioiodine ablation therapy with fractionated doses in low-risk DTC patients is equally effective as with single dose. < p > < /p >.

Incidence of pituitary autoantibodies in idiopathic diabetes insipidus.

Diabetes insipidus is a disorder resulting from insufficient action of vasopressin (ADH) characterized by excretion of highly diluted urine in large amounts. Idiopathic diabetes insipidus is associated with the presence of both autoantibodies against ADH-secreting neurons and pituitary autoantibodies. The aim of the present study was to evaluate the occurrence of autoantibodies against the pituitary microsomal fraction. The study included 33 sera of diabetes insipidus patients and 10 control sera obtained from 10 healthy persons. In all patients the secretion of pituitary hormones and thyroid autoantibodies was assessed. Human pituitaries were obtained during autopsy and homogenized in 0.01 mol/l pH 7.4 phosphate buffer. In addition, for the autoantibody evaluation, the electrophoretic method of separation in polyacrylamide gel and western blot were employed. Among the 33 subjects, in 23 patients the presence of autoantibodies against the pituitary was shown. Sera of 15 patients reacted with the pituitary microsomal fraction protein of 55 kDa. In other cases, 10 sera reacted with the pituitary antigen of 67 kDa. In addition, 5 sera reacted with the 60 kDa antigen, 5 sera with 52 kDa protein, 3 sera with 105 kDa protein, 3 sera with the 97 kDa antigen and 2 sera with pituitary antigen of 92 kDa weight. In our study, based on the immunoblotting method, we observed that pituitary autoantibodies against 55, 60 and 67 kDa antigens occurred frequently.

Hindgut neuroendocrine neoplasms - characteristics and prognosis.

INTRODUCTION: The aim of the study was to analyze the clinicopathologic characteristics and prognostic factors of hindgut-rectal neuroendocrine neoplasms. MATERIAL AND METHODS: The study included 38 patients with rectal neuroendocrine tumors who were treated at the Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland from February 2010 to December 2015. The clinicopathological data were retrospectively reviewed, extracted, analyzed, and patients were followed up to determine their survival status. Follow-up data were available for all 38 patients. Uni- and multivariate Cox regression analyses were performed to determine the prognostic factors significantly associated with overall survival. RESULTS: The tumors occurred mostly in the middle and lower rectum, and the most typical symptoms experienced by patients were hematochezia and diarrhea. The median distance between the tumors and the anal edges was 4.7 ±1.3 cm, and the median diameter of the tumors was 0.9 ±1.2 cm. The major pathological types were neuroendocrine neoplasm G1 in 31 patients, and neuroendocrine neoplasm G2 in 7 patients. Tumor-node-metastasis (TNM) stages I, II, III and IV tumors accounted for 76.3% (29/38), 5.3% (2/38), 7.9% (3/38) and 10.5% (4/38) of patients, respectively. The main treatment method was transanal extended excision or endoscopic resection. The 1-, 3- and 5-year survival rates of the whole group of patients were 100%, 83.7%, and 75.3%, respectively. CONCLUSIONS: Univariate analysis showed that age (p = 0.022), tumor diameter (p < 0.001), histological type (p < 0.001), and TNM stage (p < 0.001) were all prognostic factors.

Management of the hormonal syndrome of neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Somatostatin have a broad range of biological actions that include inhibition of exocrine and endocrine secretions, gut motility, cell proliferation, cell survival and angiogenesis. Five somatostatin receptors (SSTR1-SSTR5) have been cloned and characterized. Somatostatin analogues include octreotide and lanreotide are effective medical tools in the treatment and present selectivity for SSTR2 and SSTR5. During treatment is seen disapperance of flushing, normalization of bowel movements and reduction of serotonin and 5-hydroxyindole acetic acid (5-HIAA) secretion. Telotristat represents a novel approach by specifically inhibiting serotonin synthesis and as such, is a promising potential new treatment for patients with carcinoid syndrome. To pancreatic functionig neuroendocrine tumors belongs insulinoma, gastrinoma, glucagonoma and VIP-oma. Medical management in patients with insulinoma include diazoxide which suppresses insulin release. Also mTOR inhibitors may inhibit insulin secretion. Treatment of gastrinoma include both proton pump inhibitors (PPIs) and histamine H2 - receptor antagonists. In patients with glucagonomas hyperglycaemia can be controlled using insulin and oral blood glucose lowering drugs. In malignant glucagonomas smatostatin analogues are effective in controlling necrolytic migratory erythemia. Severe cases of the VIP-oma syndrome require supplementation of fluid losses. Octreotide reduce tumoral VIP secretion and control secretory diarrhoea.

Chromogranin A - unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls.

Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration.

Familial syndromes associated with neuroendocrine tumours.

Neuroendocrine tumours may be associated with familial syndromes. At least eight inherited syndromes predisposing to endocrine neoplasia have been identified. Two of these are considered to be major factors predisposing to benign and malignant endocrine tumours, designated multiple endocrine neoplasia type 1 and type 2 (MEN1 and MEN2). Five other autosomal dominant diseases show more heterogeneous clinical patterns, such as the Carney complex, hyperparathyroidism-jaw tumour syndrome, Von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1) and tuberous sclerosis. The molecular and cellular interactions underlying the development of most endocrine cells and related organs represent one of the more complex pathways not yet to be deciphered. Almost all endocrine cells are derived from the endoderm and neuroectoderm. It is suggested that within the first few weeks of human development there are complex interactions between, firstly, the major genes involved in the initiation of progenitor-cell differentiation, secondly, factors secreted by the surrounding mesenchyme, and thirdly, a series of genes controlling cell differentiation, proliferation and migration. Together these represent a formula for the harmonious development of endocrine glands and tissue.

Clinical features of gastroenteropancreatic tumours.

Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively.

Peptide receptor radionuclide therapy of differentiated thyroid cancer: efficacy and toxicity.

In rare cases of differentiated thyroid carcinoma (DTC), radioiodine treatment is no longer effective due to cell dedifferentiation. Targeting somatostatin receptors in DTC cells by radiolabelled somatostatin analogues could provide an alternative therapy option. The aim of this study was to evaluate safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced, non-iodine avid DTC. Eleven patients aged 47-81 years (median: 65 years) with a history of several courses of radioiodine therapy, increasing thyroglobulin (Tg) and negative whole body scan, were qualified to the study. After confirming receptor expression by somatostatin receptor scintigraphy, PRRT with yttrium-90 labelled analogue was initiated. Fractionated treatment protocol was used with four doses of (90)Y-DOTA-TOC in 12-week intervals. Activity of each dose was 3.7 GBq (100 mCi). Of 11 patients, 5 died before receiving the fourth course of PRRT. In the remaining six patients, morphological response, evaluated 3 months after the last course using RECIST criteria showed partial remission (PR) in one patient, stable disease (SD) in two patients and progressive disease (PD) in three patients. Biochemical response based on Tg measurements before and after PRRT showed PR in one patient, SD in four patients and PD in one patient. Median survival was 21 months from the first course of PRRT. Only minor and transient hematological toxicity was observed in some patients. We conclude that PRRT is generally well-tolerated and may be a valuable option for some patients with radioiodine-refractory DTC.

The usefulness of standardized uptake value in differentiation between benign and malignant thyroid lesions detected incidentally in 18F-FDG PET/CT examination.

INTRODUCTION: In the last decade, (18)F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET and PET/CT) has become one of the major diagnostic tools used in oncology. A significant number of patients who undergo this procedure, due to non-thyroidal reasons, present incidental uptake of (18F-FDG) in the thyroid. The aim of the study was to compare the SUVmax (standardized uptake value) of thyroid focal lesions, which were incidentally found on PET/CT, in relation to the results of thyroid fine-needle aspiration biopsy (FNAB) and/or histopathological evaluation. MATERIALS AND METHODS: Patients referred for PET/CT examination, due to non-thyroidal illness, presented focal 18F-FDG uptake in the thyroid and were advised to undergo ultrasonography (US), hormonal evaluation, FNAB and/or total thyroidectomy at our institution. RESULTS: 6614 PET/CT examinations performed in 5520 patients were analyzed. Of the 122 patients with focal thyroid 18F-FDG activity, 82 patients (67.2%) underwent further thyroid evaluation using FNAB. Benign lesions were diagnosed in 46 patients, malignant - in 19 patients (confirmed by post-surgical histopathology), while 17 patients had inconclusive results of cytological assessment. Mean SUVmax of benign lesions was 3.2±2.8 (median = 2.4), while the mean SUVmax value for malignant lesions was 7.1±8.2 (median = 3.5). The risk of malignancy was 16.7% for lesions with a SUVmax under 3, 43.8% for lesions with a SUVmax between 3 and 6, and 54.6% for lesions with a SUVmax over 6. In the group of malignant lesions, a positive correlation between the lesion's diameter and SUVmax was observed (p = 0.03, r = 0.57). CONCLUSIONS: Subjects with incidental focal uptake of 18F-FDG in thyroid are at a high risk of thyroid malignancy. A high value of SUVmax further increases the risk of malignancy, indicating the necessity for further cytological or histological evaluation. However, as SUVmax correlated with the diameter of malignant lesions, small lesions with focal uptake of 18F-FDG should be interpreted cautiously.

The role of serum C-reactive protein measured by high-sensitive method in thyroid disease.

The aim of this study was the evaluation of serum C-reactive protein (CRP) concentration as a marker of the inflammatory state in many different thyroid diseases and its dependence on the stage and duration of disease. We conducted a retrospective analysis of 444 randomly selected patients with different kinds of thyroid disease (106 men and 338 women, ranging 18-72 years of age; mean 56.2 ± 5.0 years; median 52 years). Group 1 (G1) comprised 250 patients with hyperthyroidism. Group 2 (G2) consisted of 72 euthyroid patients. Group 3 (G3) consisted of 122 patients with hypothyroidism. Free T4, free T3, and thyrotropin (TSH) levels were measured using the electrochemiluminescent method. Human serum thyroglobulin autoantibodies (Tg-Abs), thyroperoxidase autoantibodies (TPO-Abs), and autoantibodies against the thyrotropin receptor (TSHR-Abs) levels were measured by radioimmunoassay. The high-sensitive CRP (Hs-CRP) level (reference range <3 mg/L) was determined with a highly sensitive latex-based immunoassay. The mean value of Hs-CRP in G1 was 3.6 ± 2.8 mg/L, in G2 2.5 ± 1.5 mg/L and in G3 5.9 ± 5.8 mg/L. Hs-CRP (in mg/L) medians, interquartile and the total ranges in G1 were 3.0 (2.0 [0.1-21.0] 4.0); in G2: 2.3 [1.8 (0.2-9.2) 3.2]; and in G3: 4.3 [2.2 (0.3-31.5) 7.8]. We found statistically significant differences (Kruskal-Wallis test) in serum Hs-CRP values between G1 and G2 (P = 0.007), G1 and G3 (P = 0.001), G2 and G3 (P < 0.001). In G1, statistically significant correlation was confirmed between Hs-CRP and Tg-Abs (r = -0.22, P = 0.0016), CRP and TPO-Abs (r = -0.26, P < 0.001), and also between Hs-CRP and TSHR-Abs (r = -0.18, P = 0.02). In the remaining cases, differences between Hs-CRP and TSH levels (r = -0.09, P = 0.16) were not statistically significant. In G2, no statistically significant correlation was observed: Hs-CRP and Tg-Abs (r = -0.18, P = 0.13), Hs-CRP and TPO-Abs (r = -0.17, P = 0.15), Hs-CRP and TSH (r = 0.01, P = 0.91), Hs-CRP and TSHR-Abs (r = -0.19, P = 0.17). In G3, a statistically significant correlation was confirmed between Hs-CRP and Tg-Abs (r = 0.22, P = 0.012), Hs-CRP and TSH (r = -0.28, P = 0.001). No statistically significant correlation was observed between Hs-CRP and TPO-Abs (r = 0.20, P = 0.06) and between Hs-CRP and TSHR-Abs (r = -0.23, P = 0.11). Hs-CRP is increased in various types of hypothyroidism. This is particularly relevant in postpartum thyroiditis and in patients after radioiodine treatment. The impact of this situation on human health requires further research, however, one might assume that some types of thyroid disease may lead to systemic inflammatory reactions that are reflected in elevated CRP levels.

Purification of pituitary autoantigen by column liquid chromatography and chromatofocusing.

INTRODUCTION: Pituitary autoantibodies can be determined both in patients with pituitary disease as well as patients with autoimmune endocrine diseases. The purpose of the study was to isolate and purify pituitary autoantigen using sera of patients and the microsomal fraction of the pituitary. MATERIAL AND METHODS: To isolate a pituitary autoantigen, patient sera were used, which showed a strong immune response to pituitary antigens. Pituitary microsomal fractions were prepared from pituitary tissue homogenates. In the study, sera of patients with pituitary disease, Addison and Graves' disease were used. The initial stages were carried out by affinity chromatography on CN -Br sepharose column whereas purification was continued by column liquid chromatography on AcA54 Ultrogel. Chromatofocusing was performed by Polybuffer exchanger PBE 94. RESULTS: (125)I-labeled pituitary antigens after isolation appeared in column chromatography in three peaks. The first peak contained 50-70 kDa proteins, the second peak - 17 to 22 kDa proteins and the third peak contains (125)-iodides. Three fractions obtained from filtration on Ultrogel were separated in a polyacrylamide gel. In the first peak two bands 67 and 55 kDa appeared. The second peak contained low molecular weight substances, and the third peak contained (125)I. The first peak from Ultrogel was isolated by chromatofocusing - the first peak with pH 5.9 and the second one with pH 4.9. CONCLUSIONS: Isolation and purification of pituitary autoantigen with the use of column liquid chromatography and chromatofocusing resulted in obtainment of two antigenic proteins of specific gravity of 67 and 55 kDa.

Radioisotope therapy of bone metastases.

Radionuclide therapy has been an integral part of systemic treatment of patients with advanced and disseminated cancer for 50 years. Specific radioisotopes (b- or a-emitters) with selective concentration at sites of bone cancer damage are used in the treatment. Radioisotopes are an important addition to the armamentarium of clinicians who take care of patients with advanced cancer and painful cancer bone metastases (especially osteoblastic and mixed type). They offer a high degree of efficacy with minimal toxicity and simple administration, fulfilling the fundamental criteria for palliative treatment that should combine minimal patient discomfort and toxicity with maximal clinical effect.

[Isolation of pituitary autoantigen by affinity chromatography]. / Izolacja autoantygenu przysadkowego metoda chromatografii powinowactwa.

INTRODUCTION: In sera of pituitary disease patients and other autoimmune endocrine disease are detectable pituitary autoantibodies. Until now characterization of pituitary antigen is still unknown. The aim of our study was isolation and characterization of pituitary autoantigen by affinity chromatography. For isolation we have used microsomal fraction of human pituitary. MATERIAL AND METHODS: For immunoglobulins isolation have been used sera of pituitary disease, Addison disease and Graves-Basedow disease patients with detectable pituitary autoantibodies. For pituitary antigen isolation have been used microsomal fraction of human pituitary obtained by ultracentrifugation and solubilisation. Immunoglobulins isolation was performed on Sepharose 4B-Protein A. Immunosorbent was performed on CNBr-activated Cl-4B Sepharose. Desorbtion was conducting by 0.2 mol/L glicine and 1 mol/L, 3 mol/L guanidine. The estimation of isolated proteins was performed by immunoblotting. RESULTS: Isolation of immunoglobulins from patients sera was done 12 times receiving from 8.5 up to 13.5 mg of IgG from 1-1.5 ml of sera. In desorbtion we have received from 0.026 up to 0.150 mg of antigen proteins. For molecular weight estimation isolated proteins have been labeled by (125)I and run on SDS/PAGE with autoradiography. Autoradiography shown us two lines with 67 kDa and 55 kDa and low weight protein line. CONCLUSIONS: Isolation of pituitary autoantigen by affinity chromatography shown two different antigen proteins with 67 kDa and 55 kDa.

Benefit of whole pelvic radiotherapy combined with neoadjuvant androgen deprivation for the high-risk prostate cancer.

AIM: To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only. MATERIAL AND METHODS: Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts. RESULTS: The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively. CONCLUSIONS: The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed.

[The incidence of the thyroid microsomal autoantibodies in Alzheimer disease]. / Wystepowanie autoprzeiwcial przeciw frakcji mikrosomalnej tarczycy w chorobie Alzheimare.

BACKGROUND: Alzheimer disease is associated with degeneration of brain by deposition of beta-A4 amyloid protein. Above protein is a product of amyloid protein precursor proteolysis. This protein is coded by chromosom 21 together with histocompatibility antigens on surface of thyroid follicle. Until now the study suggest coexistence of autoimmune thyroid disease and Alzheimer disease. The aim of the study was evaluation of thyroid autoantibodies in Alzheimer disease. MATERIAL AND METHODS: Study were performed in 34 Alzheimer disease patients. Sera of control subjects were obtained from 20 patients with vascular dementia. Incidence of thyroid autoantibodies was assessed by polyacrylamide electrophoresis gel and western-blotting. Thyroid microsomes were obtained from human thyroid tissues by ultracentrifugation and solubilization in 1% desoxycholic acid. RESULTS: In 21 sera from 34 we detected autoantibodies against thyroid microsomal antigens reacting with 91 kDa antigen. 16 sera were reacting with 97 kDa, 13 sera with 55 kDa, and 7 sera with 67 kDa proteins. CONCLUSIONS: In sera of Alzheimer disease patients autoantibodies against thyroid microsomal antigens can be frequently detected. The most frequent are antibodies against 91 kDa. It is important to note that Alzheimer disease patients should be screen for thyroid hormones.

Therapy of large multinodular goitre using repeated doses of radioiodine.

OBJECTIVE: To evaluate the efficacy of radioiodine therapy using I in a group of patients with large multinodular goitre (LMG). METHODS: The study was carried out in patients with goitre volume greater than 100 cm and in patients with LMG who were disqualified from surgery. The study included 34 female participants (age range: 62-84 years) with LMG: 26 patients were hyperthyroid and eight patients had a nontoxic goitre. The patients were treated with 800 MBq of radioiodine administered four times at 3-month intervals (total activity of 3.2 GBq). Before each therapy course, serum thyrotropin, free thyroxin, free triiodothyronine and antithyroid antibodies were measured, ultrasonography and thyroid scan were performed. Patients were followed up for a minimum of 24 months. Fine-needle biopsy was done before qualification to the study. RESULTS: Before therapy, median thyroid volume was 145 cm. It decreased during therapy to 65-76 cm after 12 months and to 50-62 cm after 24 months. After 24 months, 60% of patients were euthyroid and 40% of patients were hypothyroid. During therapy, significant increases in TSHRAb, TPOAb and TgAb levels were observed. No correlation between the levels of antithyroid antibodies, radioiodine uptake, reduction of goitre volume and hormonal status was found. CONCLUSION: In most cases of LMG, repeated administration of radioiodine is safe and effective. The highest response of the thyroid volume is observed after the first course of treatment. On account of a high incidence of hypothyroidism, the patients should be monitored during and after therapy.

[Salivary gland damage after 131I therapy in patients with differentiated thyroid cancer. Preliminary report]. / Uszkodzenie slinianek po terapii 131I u pacjentów ze zróznicowanym rakiem tarczycy. Doniesienie wstepne.

INTRODUCTION: The purpose of the study was to evaluate salivary gland dysfunction after a high-dose radioiodine therapy administered to patients with differentiated thyroid carcinoma. MATERIAL AND METHODS: The study group consisted of 60 patients (age range 20-78 years). Detailed history about complaints from the oral cavity were taken, followed by the ultrasonography and dynamic scintigraphy. The procedure was performed on 40 patients before and one year after radioiodine administration, and a single-time on 20 patients treated with multiple doses in the past. RESULTS: Data analysis shows no statistically significant increase of subjective sufferings after first radioiodine dose (60-150 mCi), small decrease of uptake ratio UR (< 10%) and diminished parotid glands transverse diameter (approximately 10%). The patients after multiple therapies (i.e. average dose of 250 mCi) informed more often about problems connected with decreased salivation (approximately 20% patients), in scintigraphy there was a reduction of parotid UR 21-23% and parotid maximal secretion MS 7-13%. Ultrasonography did not show changes in salivary glands echogenicity after 12 months from the first dose of 131I. There was no close relationship between scintigraphically revealed dysfunctions and the occurrence of complaints; no correlation between appearance of acute sialadenitis symptoms after radioiodine therapy and subsequent dysfunctions. CONCLUSIONS: The main conclusion is that a single dose of 131I has no significant influence on salivary gland function; a repeated high-doses therapy is connected with an essential risk of side-effect occurrence. Scintigraphy can evaluate salivary gland function with high sensitivity. Parotid glands are more radiosensitive than submandibular.

[The incidence of the pituitary autoantibodies in Addison disease]. / Wystepowanie autoprzeciwcial przysadkowych w chorobie Addisona.

INTRODUCTION: Addison disease (primary insufficience of adrenal cortex) characterized by clinical signs and symptoms associated with deficiency of adrenal hormones. The most frequent etiopathogenesis of Addison disease is related with autoimmunization. In sera of Addison patients are detectable autoantibodies against another endocrine glands. The aim of the study was evaluation of pituitary autoantibodies in Addison disease patients using immunoblotting methods. MATERIAL AND METHODS: Studies were performed in 19 Addison disease patients, 16 women (age range: 28-63 yrs, median: 43.5 +/- 8.9) and 3 men (age range: 18-45 yrs, median: 30.6 +/- 9.8). All patients presented signs and symptoms typical of primary insufficiency of adrenal cortex. Sera of control subjects were obtained from 10 healthy blood donors, 7 women, 3 men (age range 21-45 yrs, median: 30.6 +/- 7.1). Incidence of pituitary autoantibodies was assessed by polyacrylamide electrophoresis gel and western-blotting. Pituitary microsomes were obtained from human pituitary tissues by ultracentrifugation and solubilisation in 1% desoxycholic acid. RESULTS: In 14 sera from 19 we detected autoantibodies against pituitary microsomal antigen 67 kDa, 12 sera were recting with 60 kDa and 10 sera with 55 kDa. It is important to note that 10 sera were reacting with 67 and 55 kDa, and 9 sera with 55, 60 and 67 kDa. CONCLUSIONS: In sera of Addison disease patients autoantibodies against pituitary microsomal antigens can be frequently detected. The most frequent are antibodies against 55, 60 and 67 kDa antigens.

[The incidence of the pituitary autoantibodies in Graves' disease]. / Wystepowanie autoprzeciwcial przysadkowych w chorobie Gravesa-Basedowa.

INTRODUCTION: It is known that in the sera of patients with Graves, Addison and other autoimmune endocrine diseases we can detect autoantibodies against pituitary antigens. The aim of the study was evaluation of pituitary autoantibodies in Graves' disease patients using immunoblotting methods. MATERIAL AND METHODS: Studies were performed in 32 Graves' disease patients, 25 women (age range: 31-67 yrs, median: 49.9 +/- 9.4) and 7 men (age range: 41-58 yrs, median: 51.0 +/- 7.1). All patients presented signs and symptoms typical of thyrotoxicosis. The diagnosis was confirmed by laboratory tests (TSH, fT(3), fT(4), TSH-R antibodies). Sera of control subjects were obtained from 10 healthy blood donors, 7 women, 3 men (age range 21-45 yrs, median: 30.6 +/- 7.1). Incidence of pituitary autoantibodies was assessed by polyacrylamide electrophoresis gel and western-blotting. Pituitary microsomes were obtained from human pituitary tissues by ultracentrifugation and solubilisation in 1% desoxycholic acid. RESULTS: In 23 sera from 32 we detected autoantibodies against pituitary microsomal antigens. 16 sera were reacting with 55 kDa antigen, 10 sera with 67 kDa, 6 sera with 60 kDa, 5 sera with 52 kDa and 4 sera with 105 kDa. It is important to note that 6 sera were reacting with 57 and 55 kDa, and 5 sera with 55, 60 and 67 kDa. CONCLUSIONS: In sera of Graves' disease patients autoantibodies against pituitary microsomal antigens can be frequently detected. The most frequent are antibodies against 55, 60 and 67 kDa antigens.