Anti­livin antibodies in Hashimoto thyroiditis.

INTRODUCTION: Livin belongs to the family of apoptosis inhibitors. High livin expression is observed in malignancies of the gastrointestinal tract, lungs, breast, and kidneys, but it is not present in differentiated adult tissues. In some malignant processes, anti­livin antibodies are present. OBJECTIVES: The aim of the study was to evaluate the prevalence of anti­livin antibodies in Hashimoto thyroiditis, a disease characterized by rapid and widespread thyrocyte apoptosis. PATIENTS AND METHODS: The study comprised 65 women with Hashimoto thyroiditis and the control group of 40 healthy women. In the majority of the patients, clinical manifestations of hypothyroidism were observed; all patients had high levels of serum antithyroid peroxidase antibodies. A solid­phase radioimmunoassay in livin­coated polyethylene tubes using 125I-labeled protein A was used to determine anti-livin antibodies. RESULTS: Significant amounts of anti-livin antibodies were reported in 18 patients (26.8%); 3 patients (4.6%) had borderline antibody levels; while in controls only 1 patient was positive (2.5%, P <0.0001). CONCLUSIONS: In Hashimoto thyroiditis, an autoimmune process is more general and involves numerous autoantibodies including an antibody against apoptosis inhibitor - livin. Anti­livin antibodies cannot serve only as a marker of malignancy because they are also present in autoimmune processes.

The analysis of exogenous ghrelin plasma activity and tissue distribution.

OBJECTIVES: Ghrelin presents a multiplicity of biological functions, what is consistent with widespread expression of this peptide and its receptors. Ghrelin may act locally, but it may also influence distant cells. The aim of the study was to assess plasma activity of exogenous ghrelin and its distribution in rats. DESIGN: Plasma radioactivity of (125)I-ghrelin (cpm) was analyzed in blood specimens collected after (125)I-ghrelin administration. Tissue uptake of (125)I-ghrelin (cpm/mg) was evaluated in 27 tissues obtained during an autopsy performed 1, 2 and four hours after (125)I-ghrelin administration. The radioactivity of the tissue specimen (cpm) was divided by the weight of the specimen (mg). RESULTS: Plasma (125)I-ghrelin radioactivity decreased rapidly after peptide administration. The half-life time of (125)I-ghrelin was 15-18 minutes. The analysis of (125)I-ghrelin distribution revealed three profiles of its tissue uptake. The first profile was characterized by decreasing radioactivity (e.g. brain, kidney, liver). Increasing tissue radioactivity followed by a gradual decrease (second profile) was observed for example in stomach, intestine and thyroid. The third profile was described as a relatively stable radioactivity (e.g. lung, myocardium). Despite of Lugol's solution administration, thyroid uptake of (125)I-ghrelin was notably higher than in other tissues (second and third profile). CONCLUSIONS: Exogenous ghrelin uptake in tissues that produce this peptide suggests, that ghrelin influences the biology and function of these cells also in endocrine way. Similarly, the accumulation of peptide observed in the third profile (e.g. thyroid) may reflect a potential role of ghrelin in these organs.

Ghrelin and obestatin in thyroid dysfunction.

INTRODUCTION: Ghrelin and obestatin derive from the same precursor. Ghrelin is an energy balance regulator and obestatin's role in metabolic processes cannot be excluded. The aim of this study was to assess plasma ghrelin and obestatin changes in thyroid disorders. MATERIAL AND METHODS: We evaluated plasma ghrelin and obestatin levels in severe hypothyroidism, hypothyroidism after thyreoidectomy and 4-weeks L-thyroxine withdrawal, and in hyperthyroidism. We also re-evaluated plasma ghrelin and obestatin levels in patients with severe hypothyroidism and hyperthyroidism after treatment. RESULTS: Severe hypothyroidism was associated with a reasonably high ghrelin level (p = 0.055) and hyperthyroidism with a significantly lower ghrelin level (p = 0.01) compared to healthy subjects. Ghrelin in hypothyroid patients after L-thyroxine withdrawal did not differ from the control group (p = 0.3). Compared to healthy subjects, obestatin level in hyperthyroidism was decreased (p = 0.03) and did not differ in severe hypothyroidism due to thyroiditis (p = 1) or after L-thyroxine withdrawal (p = 0.6). Ghrelin and obestatin levels correlated positively. Both peptides levels correlated positively with TSH and negatively with free thyroid hormones. In patients with severe hypothyroidism, ghrelin level significantly decreased after treatment (p 〈 0.01) and in hyperthyroid patients significantly increased after treatment (p = 0.04). There were no significant changes in obestatin levels in hypo- or hyperthyroid patients after treatment. CONCLUSIONS: Plasma ghrelin changes and its correlation with TSH and thyroid hormones may indicate a compensatory role of ghrelin in metabolic disturbances associated with thyroid dysfunction. The positive correlation between ghrelin and obestatin levels may suggest a modulatory role of obestatin in these processes.

Technological difficulties in ghrelin and obestatin assays.

In recent years we have performed more than 1,000 radioimmunoassays of ghrelin and obestatin. In these assays, we have encountered several technological obstacles. Another difficulty was the enormous discrepancy of plasma ghrelin results published by different authors. The aim of this article is to comment on these problems. Not all peptides of the hypothalamus and intestines are present in blood circulation. Several neuropeptides do not cross the blood-brain barrier, and several gastrointestinal peptides are present in extremely low concentrations in the blood. That requires time-consuming and laborious extraction. In these procedures, considerable amounts of peptides may be lost. In addition, these peptides are very unstable and prone to enzymatic degradation. This makes it mandatory to add enzymatic inhibitors to plasma samples. The peptides are also unstable in elevated temperatures, hence the assays should be performed in air-conditioned laboratories and the kits should be transported in proper low temperature conditions. Peptides may appear in several isoforms of different biological activity, but antibodies routinely used in these assays are polyclonal and do not differentiate between these forms. This complicates clinical evaluation of the results. To date, there are no international standards of ghrelin, obestatin or other active peptides, probably because of their extreme instability. Because of technological difficulties, the results of peptide assays performed in different scientific research institutions vary greatly and cannot be compared to each other. This disadvantage may be partially diminished by including samples of healthy subjects in each assay run to check whether the peptide concentrations of the patients differ significantly from that of control subjects.

Anti-livin antibodies: novel markers of malignant gastrointestinal cancers.

INTRODUCTION: Livin represents apoptosis inhibitors and may be important in cancer. OBJECTIVES: The aim of the study was to develop an anti-livin auto antibody assay and investigate its usefulness in the clinical practice in relation to gastrointestinal cancers (GIC). PATIENTS AND METHODS: We studied sera obtained from 36 patients with GIC and 59 healthy controls. A solid-phase radioimmunoassay to detect anti-livin antibodies in serum was developed. Polipropylene tubes were coated with recombinant human livin, and 100-fold dilutions of sera were incubated in these tubes. On the next day, the tubes were decanted, washed and labeled 125-I protein A was added. After 2-hour incubation, the tubes were washed and radioactivity was measured using the gamma counter. RESULTS: We observed a statistically significant difference between the presence and levels of anti-livin antibodies in sera of patients with GIC and in control subjects. Anti-livin auto antibodies were detected in 9 patients with GIC. Of note, the level of anti-livin antibodies was significantly elevated in 25% of GIC patients. The presence of anti-livin antibodies was confirmed with sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. CONCLUSIONS: A high prevalence of anti-livin antibodies in patients with GIC indicates that they may be useful in the diagnosis of these malignancies.

[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.

[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.

[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.

Two peptide receptor ligands (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide and (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin for scintigraphy of medullary thyroid carcinoma.

UNLABELLED: Somatostatin and gastrin receptors are overexpressed in medullary thyroid carcinoma (MTC) cells; hence, both of them are potential targets for peptide receptor scintigraphy and radiotherapy. Therefore, the aim of our study was to assess the clinical value of two technetium-99m-labeled peptides, a new gastrin analog, the EDDA/HYNIC-(D)Glu-octagastrin and a somatostatin analog, EDDA/HYNIC-Tyr(3)-octreotide (EDDA/HYNIC-TOC) for scintigraphy in patients with MTC to detect recurrences and metastases and select patients for peptide receptor radiotherapy. MATERIAL AND METHODS: Thirty (30) patients, 20 females and 10 males, 22-83 years of age (mean, 52.7) with the diagnosis of MTC in different stages of the disease (preoperative, postsurgery, remission, recurrence, or metastatic disease) were included in this study. Before surgery, in all patients serum calcitonin concentrations were elevated. The diagnosis of MTC was confirmed in all cases by histopathology of the removed tumor and immunohistochemical staining giving positive reactions for calcitonin and chromogranin A. Imaging studies using (99m)Tc-EDDA/HYNIC-TOC and a new minigastrin analog, (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin, were performed in each patient and the results compared with each other and with other imaging methods. Scans of the whole body, head, neck, and chest were performed 2 and 4 hours after injections of the tracer, 500-600 MBq in each case, using a double-head Varicam (Elscint, Israel) gamma camera. RESULTS: (99m)Tc-EDDA/HYNIC-TOC detected somatostatin receptor-positive lesions in 20 patients with MTC, whereas (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin displayed gastrin receptors in 11 patients. In 9 cases, the scans were positive in both methods, although in 2 cases different pathologic foci were visualized. In 12 cases, only (99m)Tc-EDDA/HYNIC-TOC scintigraphy was positive, whereas in 3 other cases only (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin revealed pathologic lesions. CONCLUSIONS: Scintigraphy using (99m)Tc-HYNIC-TOC permits the visualization of somatostatin receptor-positive MTC in the majority of cases. The new gastrin analog, (99m)Tc-HYNIC-(D)Glu-octagastrin, is well tolerated, shows no renal retention, and in some cases of MTC, provides additional information on the expression of gastrin receptors. However, inferior quality of octagastrin scans indicates the need for further improvement of this radiopeptide.

[Arterial stiffness in hypopituitary patients with life-long growth hormone deficiency]. / Sztywnosc tetnicza u chorych na niedoczynnosc przysadki z dlugoletnim niedoborem hormonu wzrostu.

INTRODUCTION: Patients with hypopituitarism have a shorter survival period from and premature mortality due to cardiovascular complications. OBJECTIVES: The aim of our study was to evaluate the arterial stiffness and hemodynamic parameters based on pulse wave analysis in 22 adult patients with long-life growth hormone (GH) and insulin-like factor I (IGF-I) deficiencies, lasting from 22 to 57 years. PATIENTS AND METHODS: In all patients, a combined pituitary hormone deficiency was diagnosed. All patients were on substitution therapy, receiving levothyroxine, sex hormones and hydrocortisone (when required), but none of the patients had ever received recombinant GH therapy. A control group consisted of 36 healthy subjects strictly matched to patients by age and body mass index. In the patients and control subjects pulse wave analysis was performed with the use of Sphigmocor MX reconstructing the aortic pulse wave in a real time. RESULTS: The peripheral and central augmentation indexes were significantly increased in the hypopituitary patients compared with the control subjects. The central pulse pressure was also elevated in the patients. These hemodynamic parameters pointed to an increased arterial stiffness. CONCLUSIONS: In patients with hypopituitarism, the life-long GH and IGF-I deficiencies lead to an increase in the arterial stiffness.

[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.

The prevalence of autoantibodies to: myosin, troponin, tropomyosin and myoglobin in patients with circulating triiodothyronine and thyroxine autoantibodies (THAA).

OBJECTIVE: Anti-thyroglobulin, anti-thyroid-peroxidase and anti-TSH receptor antibodies have been observed with high frequency in autoimmune thyroid diseases. Thyroid hormone auto-antibodies (THAA): anti-thyroxine (T4) and anti-triiodothyronine (T3), conversely, have been reported rarely. In both hyperthyroidism and hypothyroidism, patients suffer from muscle weakness and function disorders. The aim of our study was the evaluation of the occurrence rate of autoantibodies targeting muscle proteins in a group of 24 patients with circulating anti-T3 and/or anti-T4 autoantibodies. The control group consisted of 41 healthy blood donors. METHODS: In polyethylene tubes coated with muscle antigens: actin, myosin, myoglobin, troponin and tropomyosin solid-phase radioimmunoassay was performed to detect autoantibodies. A reaction with 125I-labelled staphylococcus protein A was used for the detection of antibodies bound to the antigens on the tubes. RESULTS: We found a high occurrence of antibodies to muscle proteins in patients with THAA. Anti-myoglobin autoantibodies were most frequent (54.2% of subjects), the binding index values was very high and exceeded normal values two to four fold. Anti-myosin autoantibodies were detected in 50% of subjects; anti-troponin autoantibodies in 33.3%, and anti-tropomyosin autoantibody in 3 patients (12.5%). Differences between the patients and the controls were statistically significant. The antibody binding index to actin was low and statistically insignificant. CONCLUSIONS: Our study indicates that muscle protein antibodies, especially to myoglobin, myosin and troponin, are very frequently present in patients with autoimmune thyroid disease and circulating anti-T3 and anti-T4 autoantibodies, as well as in most cases of chronic thyroiditis with clinical symptoms of hypothyroidisms.

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PURPOSE: Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. METHODS: Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. RESULTS: In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. CONCLUSION: (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Abnormalities in bone mineral density distribution and bone scintigraphy in patients with childhood onset hypopituitarism.

The aim of our study was to evaluate the effects of long-life severe growth hormone deficiency on bone mineral density (BMD) and bone scintigraphy in adult patients with childhood onset (CO) hypopituitarism never treated with growth hormone. Our studies included 22 adult patients with CO hypopituitarism never treated with growth hormone (13 males and 9 females, aged 25-66 yr). The patients received replacement therapy with thyroxine, sex steroid hormones, and patients with secondary adrenocortical deficiency, hydrocortisone, but none of the patients had ever received GH treatment. In 22 patients, the total body with regional distribution of BMD, the lumbar spine L2-L4, and radial (33% site) BMD were determined by dual energy X-ray absorptiometry (DXA). In addition, 12 patients had the femoral neck BMD examined. In 10 cases, bone scintigraphy using 99-technetium labeled methylene diphosphonate was performed. Our studies revealed abnormalities, not yet described, in the regional distribution of BMD and bone scintigraphy in adults with CO hypopituitarism never treated with GH. In all patients, the results obtained from the total body showed definite disproportion in the regional distribution of BMD with a significantly advanced bone mineral deficit in the legs and a moderate deficit in the arms and total body. Local BMD measured at the radial (33% site) and lumbar spine L2-L4 revealed also a more pronounced bone mineral deficit in the cortical bone (33% distal radius) than in the trabecular bone (spine L2-L4). Bone scintigraphy showed a decrease in tracer accumulation in the shafts of the long bones but normal uptake in the spine, ribs, sternum, skull, and periarticular areas, indicating suppressed skeletal metabolism of cortical bone. Our studies indicate that long-life growth hormone deficiency leads to deficient and abnormal distribution of bone mineralization, a more pronounced deficit of BMD at the cortical bone, mainly expressed in the shafts of the long bones of the legs and arms, and moderately reduced BMD at the trabecular bone. Bone scans displaying low diphosphonates uptake in the shafts of the long bones point to greatly suppressed skeletal metabolism of the cortical bone in the patients with CO hypopituitarism never treated with GH.

[The role of scintigraphy with the use of 99mTc-HYNIC-TOC in the diagnosis of medullary thyroid carcinoma]. / Znaczenie scyntygrafii uzyciem 99mTc-HYNIC-TOC w diagnostyce raka rdzeniastego tarczycy.

INTRODUCTION: Recently a new somatostatin analogue labelled with (99m)Tc ((99m)Tc-HYNIC-TOC) has been synthetized. Aim of this study was to evaluate the utility of (99m)Tc-HYNIC-TOC in the radionuclide imaging in patients with medullary thyroid carcinoma (MTC). MATERIAL AND METHODS: 30 patients with MTC aged 22-83 years in different stages of the disease were investigated. In 6 patients (group 1) scintigraphy was performed before surgery directly after diagnosis of MTC. Four patients (group 2) were qualified to the study in the phase of remission after surgical treatment that had been confirmed by low concentrations of calcitonin. Twenty patients (group 3) were investigated due to stagnation or recurrence confirmed by persistent hypercalcitoninemia. The scintigraphy using (99m)Tc-HYNIC-TOC (Tektrotyd, POLATOM) was performed 2 and 4 hours post injection of 20 mCi (740 MBq) of the tracer. Other imaging techniques were also employed and analysed in individual cases (US, CT, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-octreotide and FDG-PET). RESULTS: Images obtained 2 and 4 hours p.i. were similar. In group 1, uptake of the tracer was found in the primary tumour of MTC in all patients. In group 2, a false positive result was found in 1 of 6 patients. In the remaining 5 of 6 cases no pathological foci were visualised. In group 3, uptake in the thyroid bed was found in 3 of 20 cases and in the lymph nodes in 14 of 20 patients. In 3 of 20 cases uptake in the bone metastases was found. Globally, sensitivity of the scintigraphy using (99m)Tc-HYNIC-TOC was 86.4%, specificity - 75.0%, and accuracy - 84.6%. CONCLUSION: The scintigraphy using (99m)Tc-HYNIC-TOC showed high utility in the diagnosis of MTC. Confirmation of the presence of somatostatin receptors with this method may be used for treatment planning: surgery or radionuclide therapy.

[The use of a new analogue DGlu-Octagastrin in scintigraphy of medullary thyroid carcinoma]. / Zastosowanie nowego analogu DGlu-Oktagastryny w scyntygrafii raka rdzeniatego tarczycy.

INTRODUCTION: Medullary thyroid carcinomas (MTC) reveal overexpression of several peptide receptors particularly of gastrin and cholecystokinin 2 (CCK2). Experimental studies of various CCK-2/gastrin analogues found that a C-terminal, 8-aminoacid peptide, (D)Glu-octagastrin, has optimal properties. Thus, the aim of our studies was to prepare (99m)Tc-labelled HYNIC-octagastrin, to evaluate its biologic tolerance in animals and introduce for scintigraphy in patients with MTC. MATERIAL AND METHODS: HYNIC-(D)Glu-octagastrin was from piCHEM (Graz, Austria), (99m)Tc generator from Amersham (Health), other reagents were purchased from Sigma. Labelling of the peptide was performed in phosphate buffer of pH 6.0 for 10 minutes at 100(o)C using EDDA and tricine as coligands. RESULTS: The labeling yields were high (above 95%); the specific activity amounted to 1200 to 1430 microCi/microg. Radiochemical purity on SepPak cartridge and ITLC ranged from 94 to 98%. No adverse effects were observed in mice after administration of 10 to 50 times greater doses that those used in patients. Clinical studies comprised 20 patients with MTC and high serum calcitonin. (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin, 500 to 700 MBq, was administered iv and whole body scintigraphy was performed using a double head gamma-camera (Varicam, Elscint) 2 and 4 hours later. Increased accumulation of the tracer in foci of MTC and its metastases was found in 8 patients. CONCLUSIONS: Scintigraphy with a new gastrin analogue ((D)Glu-octagastrin) makes it possible to detect MTC with overexpression of CCK-2/gastrin receptors and to select patients for receptor-mediated radiopeptide therapy using DOTA-gastrin analogues labelled with (177)Lu and (90)Y.

Premature fusion and excessive calcification of coronal sutures in patients with Klinefelter syndrome.

OBJECTIVE: The purpose of this paper is to report on radiographic features of the cranial vault abnormalities frequently seen but not yet described in detail in patients with Klinefelter syndrome. SUBJECTS: Our studies comprised 72 patients with Klinefelter syndrome and 47,XXY karyotype. The majority of the patients were young between the ages of 16 to 28 years. METHODS: Plain skull radiographs were taken in the frontal and lateral projections. RESULTS: Several abnormalities were observed on skull radiographs of the Klinefelter patients. The most frequent was a premature fusion of the coronal sutures that occurred in 54 of 62 younger patients. In 42 cases extensive calcifications of these sutures were observed. The calcified sutures were dense and widened. In 24 patients the inner table in the anterior part or the parietal bone displayed a marked disruption with thinning of the calvaria at this place. In the posterior part of the parietal bone in 21 patients the inner table was thickened and excessively dense. On frontal radiographs, in 30 patients, there was a flattening of the squamous part of the temporal bones. CONCLUSIONS: Skull radiographs in Klinefelter patients frequently display abnormalities: premature fusion and excessive calcifications of the coronal sutures, irregularities of the inner table of the parietal bone, and flattening of the temporal bones. These radiographic features, when present, may draw attention to the XXY syndrome as the underlying cause of the abnormalities.

[New somatostatin analogue 99mTc-HYNIC-TOC in the scintigraphic diagnosis of medullary thyroid carcinoma]. / Nowy analog somatostatyny 99mTc-HYNIC-TOC w diagnostyce scyntygraficznej raka rdzeniastego tarczycy.

Medullary thyroid carcinoma (MTC) origins from parafollicular cells and secretes calcitonin. It accounts for 5-10% of malignant thyroid tumors. In MTC, radionuclide imaging is employed as complementary method in addition to the routine radiological procedures. Especially, scintigraphy using labelled peptides that specifically bind to the somatostatin receptors is used. Recently a somatostatin analogue labelled with 99mTc (99mTc-HYNIC-TOC) was synthetized. As shown in previous studies, it has favourable pharmacokinetic and clinical characteristics. Aim of this study was to evaluate the utility of 99mTc-HYNIC-TOC in the radionuclide imaging in patients in different stages of MTC. 32 patients in following stages of the disease were studied: evaluation before thyroidectomy (6 patients), remission after surgical treatment (5 patients), stagnation or recurrence after surgical therapy (21 patients). The classification was based on the calcitonin concentrations. The study group included 19 women and 13 men aged 14 to 83 years. Whole body scintigraphy was performed twice: 2 and 4 hours after injection of 20 mCi 99mTc-HYNIC-TOC using dual-head Varicam gamma camera (Elscint). The obtained results were compared to the clinical data and other employed imaging modalities. The scintigraphy using 99mTc-HYNIC-TOC showed 20 true positive, 4 true negative, 1 false positive and 7 false negative results. The sensitivity of this method was 74,1% and specificity - 80,0%. These results are better than those obtained by other authors using other imaging methods. The current study showed high utility of the new peptide tracer in the diagnosis of MTC. Its diagnostic accuracy allows us to recommend it for diagnosis and treatment planning (including radionuclide therapy) in patients with MTC on the routine basis.

Reduced brain perfusion and neurocranial shape abnormalities of the temporal regions in patients with Klinefelter syndrome.

OBJECTIVES: In patients with Klinefelter syndrome dissocial behaviour, learning difficulties and low intelligence are common. Thus, the aim of our study was to perform brain perfusion studies and cranial cephalometry in 27 cases of Klinefelter syndrome and compare the results with those in a group of 26 healthy subjects. METHODS: Single photon emission tomography (SPECT) was performed after injection of 20 mCi 99mTc-HMPAO and the data from transaxial slices were analyzed for 46 regions of interest in the cerebellar, thalamic, ventricular and parietal planes. Right/ left ratios were calculated and differences above 10 per cent were considered abnormal. Skull radiographs in frontal and lateral view were taken and measurements of the cerebral part were made. RESULTS: SPECT imaging in 27 Klinefelter patients revealed 82 hypoperfusion foci, most frequently in temporal regions, less frequently in temporoparietal and frontal regions, whereas only 11 hypoperfusion foci in 6 of the 26 control subjects were found. Skull radiography revealed the following abnormalities : flattening of the temporal regions, reduced width of the vault, shortening of the anterior cranial fossa and definitely reduced angle of the cranial base; all these anomalies differed significantly from those in the skulls of the control subjects. CONCLUSIONS: The high coincidence of the location on the temporal regions of brain perfusion defects and the neurocranial shape anomalies indicate that an extra X chromosome in Klinefelter patients has detrimental effects on the temporal lobe development and function.

Pneumadin in the ventral prostate of rats during postnatal development: a radioimmunological and immunocytochemical study.

We have recently demonstrated that the ventral prostate of adult rats contains high levels of pneumadin (PNM), a decapeptide originally isolated from mammalian lung, and that testosterone is needed for the maintenance of a normal level of the peptide in the prostate. Hence, we have investigated, by radioimmunoassay (RIA) and light ultrastructural immunocytochemistry (ICC), PNM concentration and localization in the rat ventral prostate during postnatal development. RIA showed that PNM content increased steadily from day 20 to day 90 of postnatal life, parallel to the increase in the prostate weight. In contrast, PNM concentration remained rather stable, although it showed a marked rise at day 40 when rat testes are known to reach their full maturation. ICC demonstrated that PNM immunoreactivity was mainly located in the apical pole of epithelial cells of rat ventral prostate, especially in the subcellular organelles involved in protein secretion, i.e. rough endoplasmic reticulum cisternae, vacuoles and granules. Taken together our study suggests the involvement of PNM in the functional control of rat prostate during postnatal maturation, although its exact role remains to be elucidated.