Relacorilant or surgery improved hemostatic markers in Cushing syndrome.

PURPOSE: Glucocorticoid-mediated hypercoagulability can persist in patients with endogenous Cushing syndrome (CS) after curative surgery and may transiently worsen early postoperatively. These studies aimed to characterize coagulation markers at baseline in patients with CS and the impact of relacorilant or remission post-surgery in an open-label, phase 2 study (NCT02804750) and a retrospective, longitudinal, surgical cohort study. METHODS: In the relacorilant study, 34 patients received relacorilant (100-200 mg/day for up to 12 weeks or 250-400 mg/day for up to 16 weeks) and had postbaseline data. Coagulation markers were assessed before and during treatment. In the surgical study, conducted at "Federico II" University of Naples, Italy, coagulation markers were assessed in 30 patients before surgery and after biochemical remission. RESULTS: In the relacorilant study, significant mean changes from baseline to last observed visit were reported in factor VIII (- 18.9%, P = 0.022), activated partial thromboplastin time (aPTT) (+ 1.5 s, P = 0.046), and platelet count (- 68.8*109/L, P < 0.0001), whereas von Willebrand factor was unchanged. In the surgical study, the mean time to hemostasis assessment was 6.2 months. Significant mean changes from baseline to hemostasis assessment were reported in factor VIII (- 24.2%, P = 0.044), von Willebrand factor (- 20.6%, P = 0.018), and aPTT (+ 2.0 s, P = 0.031), whereas platelet count was unchanged. CONCLUSIONS: Several coagulation markers improved in patients with CS after 3-4 months of relacorilant treatment and within an average of 6 months after surgery. Relacorilant's positive effects on coagulation markers support further investigation of its use preoperatively in patients with CS or in patients who are not eligible for surgery. CLINICAL TRIAL REGISTRATION NUMBER: NCT0280475 (registration date: 15 June 2016).

Prevalence of other autoimmune diseases in polyglandular autoimmune syndromes type II and III.

PURPOSE: Polyglandular autoimmune syndromes (PAS) are complex, heterogeneous disorders in which various autoimmune diseases can occur, affecting both endocrine and non-endocrine organs. In this meta-analysis, the prevalence of associated autoimmune disorders was investigated in PAS II and III. METHODS: A comprehensive search in MEDLINE and Embase databases identified 479 studies with the keywords of PAS II and PAS III. 18 records containing a total of 1312 patients fulfilled our inclusion criteria (original studies reporting at least 10 cases and containing the combination of other autoimmune disorders) and were selected for further analysis. A meta-analysis of prevalence was performed using the random-effects model with the calculation of 95% confidence intervals (CI). Results of each meta-analysis were displayed graphically using forest plots. RESULTS: Distinction between PAS II and PAS III was made in 842 cases, of which 177 and 665 were PAS II and III (21.1 vs 78.9%), respectively. The prevalence of Hashimoto's thyroiditis was significantly higher than that of Graves's disease (39% [95% CI 17-65%] vs. 4% [95% CI 0-10%], respectively; p = 0.001). In PAS II, Addison's disease (AD) coexisted with AITDs, T1DM or the combination of these conditions in 65, 18 and 10% of cases, respectively. In addition, one other endocrine and five non-endocrine organ-specific autoimmune disorders were reported. In PAS III, two other autoimmune endocrinopathies, six non-endocrine organ-specific, and four systemic autoimmune disorders were found in combination with AITDs. CONCLUSIONS: AITDs, T1DM and AD are the most common combinations in PAS, thus screening for these conditions seems to be reasonable.

Can early clinical parameters predict post-traumatic pituitary dysfunction in severe traumatic brain injury?

BACKGROUND: Post-traumatic hypopituitarism is a major complication after severe head trauma. The aim of our study was to evaluate the possible role of early clinical parameters in the development of endocrine deficits. METHODS: Data on endocrine function, on-admission clinical-, laboratory-, and ICU-monitored parameters were available in 63 patients of the surviving 86 severe head injury patients (post-resuscitation GCS under 8) treated at one neurosurgical center during a 10-year period. RESULTS: Hypopituitarism was diagnosed in 68.3 % of the patients. The most frequently affected pituitary axis was the growth hormone (GH): GH deficiency or insufficiency was present in 50.8 %. Central hypogonadism affected 23.8 % of male patients; hypothyroidism and secondary adrenal failure were found in 22.2 and 9.5 % of the investigated population, respectively. Early onset (within 1 year of brain injury) hypopituitarism was found in 24 patients. No connection was found between the development of hypopituitarism and any of the clinical parameters assessed on-admission or at ICU. Significant correlations were found between early endocrine dysfunctions and surgical intervention (OR: 4.64) and the diagnosis of subdural hematoma (OR: 12). In our population, after road traffic accidents, the development of late-onset hypopituitarism was less prevalent (OR: 0.22). CONCLUSIONS: Since our results do not indicate any reliable predictive parameter for the development of endocrine dysfunction in a cohort of patients with severe traumatic brain injury, regular endocrine screening of this specific patient population seems obligatory.

Addition of chlorine during water purification reduces iodine content of drinking water and contributes to iodine deficiency.

Drinking water is the major natural source of iodine in many European countries. In the present study, we examined possible sites of iodine loss during the usual water purification process.Water samples from 6 sites during the technological process were taken and analyzed for iodine content. Under laboratory circumstances, prepared iodine in water solution has been used as a model to test the effect of the presence of chlorine. Samples from the purification sites revealed that in the presence of chlorine there is a progressive loss of iodine from the water. In the chlorine concentrations employed in the purification process, 24-h chlorine exposure eliminated more than 50% of iodine when the initial iodine concentration was 250 µg/l or less. Iodine was completely eliminated if the starting concentration was 16 µg/l.We conclude that chlorine used during water purification may be a major contributor to iodine deficiency in European communities.

Relationship of serum resistin level to traits of metabolic syndrome and serum paraoxonase 1 activity in a population with a broad range of body mass index.

UNLABELLED: The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, P<0.05), waist circumference (r=-0.28, P<0.05), serum levels of leptin (r=-0.28, P<0.05), non-esterified fatty acids (NEFA) (r=-0.23, P<0.05), and HbA (1C) (r=-0.26, P<0.05), systolic BP (r=-0.28, P<0.05), and lipid peroxidation (measured by TBARS) (r=-0.40, P<0.01), and correlated positively with PON1 (r=0.24, P<0.05). No association was detected between the serum concentrations of resistin and the following investigated parameters: diastolic BP, levels of uric acid, glucose, insulin, or insulin resistance (measured by homeostasis model assessment, HOMA-IR), triglyceride, total cholesterol, LDL-C, and HDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not. CONCLUSIONS: Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.

Inflammatory cytokine regulation of TRAIL-mediated apoptosis in thyroid epithelial cells.

Death receptor-mediated apoptosis has been implicated in target organ destruction in chronic autoimmune thyroiditis. Depending on the circumstances, inflammatory cytokines such as IL-1, TNF and IFNgamma have been shown to contribute to either the induction, progression or inhibition of this disease. Here we demonstrate that the death ligand TRAIL can induce apoptosis in primary, normal, thyroid epithelial cells under physiologically relevant conditions, specifically, treatment with the combination of inflammatory cytokines IL-1beta and TNFalpha. In contrast, IFNgamma is capable of blocking TRAIL-induced apoptosis in these cells. This regulation of TRAIL-mediated apoptosis by inflammatory cytokines appears to be due to alterations of cell surface expression of TRAIL receptor DR5 and not DR4. We also show the in vivo presence of TRAIL and TRAIL receptors DR5 and DcR1 in both normal and inflamed thyroids. Our data suggests TRAIL-mediated apoptosis may contribute to target organ destruction in chronic autoimmune thyroiditis.

Nongenomic effect of thyroid hormone on free-radical production in human polymorphonuclear leukocytes.

Over the past few years increasing evidence has suggested the nongenomic effects of thyroid hormone, such as the activation of the signal transduction pathways and the activation of nuclear factor-kappaB by the induction of oxidative stress. The present study was undertaken to investigate the effect of thyroid hormone on human polymorphonuclear leukocytes (PMNLs) which are known as important sources of reactive oxygen species in the circulation. The production of superoxide anion (O2-) and the activity of myeloperoxidase were determined in the presence and absence of several inhibitors of the signalling pathway. L-thyroxine (T4) l-3,5,3'-tri-iodothyronine (T3) and L-3,5-di-iodothyronine (T2) stimulated O2- production in PMNLs in a dose-dependent manner within a few minutes of addition to cells. Thyroid hormone-stimulated O2- production was partially inhibited by pertussis toxin, an inhibitor of GTP-binding G protein, and was completely abolished by the protein kinase C inhibitors calphostin C and Ro-32-0432, and by a calcium chelator (BAPTA; bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid). Thyroid hormone stimulated myeloperoxidase activity and induced 125I- incorporation into PMNLs. Furthermore, thyroid hormone pre-incubation enhanced O2- production for n-formyl-methionyl-leucyl- phenylalanine (FMLP) stimulation. In conclusion, novel nongenomic actions of thyroid hormone, the induction of superoxide anion production and the stimulation of myeloperoxidase activity in PMNLs were demonstrated. The induction of O2- production requires calcium and is mediated by a pertussis toxin-sensitive G protein via stimulation of protein kinase C(s). These results suggest the existence of a membrane-bound binding site for thyroid hormone in PMNLs and a physiological role for thyroid hormone in the cellular defence mechanisms by stimulating free-radical production.

Establishment of the hu-PBL-SCID mouse model for the investigation of thyroid cancer.

New experimental models of human neoplastic diseases attempt to mimic the human environment that fostered the development of disease in cancer patients. The aim of the present study was to establish a human lymphocyte-engrafted, severe combined immunodeficient (hu-PBL-SCID) mouse model to investigate thyroid cancer and to evaluate the potential use of this model for cancer immunotherapy. Thyroid neoplastic tissues were obtained from ten patients (one follicular adenoma, five papillary, one follicular, one anaplastic and two medullary cancers). One 8 x 4 x 3 millimeter sample from each tumor was cut into two pieces of identical size and transplanted into two SCID mice. In each case, one of the two mice was injected intraperitoneally with lymphocytes from the same tumor patient for the reconstitution of the human immune system (Group A), while the other animal received no lymphocytes (Group B). The engraftment of the tumors was successful in all cases. The growth rate was highly dependent on the histological type. When histologies were compared before implantation and after the removal of the implants, the characters of the tumors proved to be unchanged, except one case where an anaplastic cancer arose from a papillary tumor. Macrophages were present in all but one papillary cancer. All differentiated thyroid cancers were infiltrated by T and B lymphocytes. Lymphocytes and macrophages disappeared from 19/20 grafts by week 16. However, in one case from group A lymphocytes were detected four months after the transplantation. In another case from group A, one papillary cancer spontaneously decreased in size and disappeared. Before implantation, HLA-DR expression was detected in every papillary cancer. HLA-DR expression in the grafts was not seen in 3/5 cases by week 16. In conclusion, an animal model has been established for the investigation of human thyroid cancer, by which the analysis of anti-tumor immunity, as a postulate of immune therapy, may be possible.

Heterogeneous signal pathways through TSH receptors in porcine thyroid cells following stimulation with Graves' immunoglobulin G.

OBJECTIVE: We compared different signal transduction pathways through thyroid stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating immunoglobulin samples (TSI) obtained from patients with Graves' disease. DESIGN: Following stimulation with TSI, the level of inositol trisphosphate (IP3) and [Ca2+]i, as well as the membrane bound protein kinase C (PKC) activity and the intensity of the arachidonic acid (AA) cascade, were determined in PTC. RESULTS: Seven out of eleven TSI samples activated PTC through IP3 generation, elevated [Ca2+]i from the intracellular pools, exhibited verapamil-insensitive membrane-bound PKC activation, and enhanced release of [14C]AA derivates (however, one of the samples was also able to take up Ca2+ from the extracellular space). Four out of eleven TSI samples did not activate the phospholipase C (PLC) system in which case the Ca2+ signal occurred only in the presence of extracellular Ca2+, the membrane bound PKC activation was verapamil sensitive, and in two of these four TSI samples, the AA release was extremely high. CONCLUSIONS: The simultaneous examination of the majority of the known signal pathways using TSI samples showed that TSI samples from different patients activate thyroid cells through different pathways. Their effects differ from that of TSH and, to a certain extent, from each other. The results give a certain new insight into the intracellular mechanisms exerted by TSI.

Graves' ophthalmopathy: eye muscle involvement in patients with diplopia.

BACKGROUND: Diplopia identifies patients with eye muscle involvement in Graves' ophthalmopathy (GO). OBJECTIVE: To identify clinical parameters that could eliminate the need for magnetic resonance imaging (MRI) to assess the activity of inflammation in the eye muscles of GO patients with diplopia. METHODS: In 43 patients with GO with recently developed diplopia, orbital ultrasound and MRI were performed. Muscle diameters and MRI T2 relaxation times were measured, and the amount of orbital connective tissue was calculated from MRI scans and compared with ultrasound readings, diplopia grades, degree of protrusion, ocular pressure, tear production, antibody levels and hormonal parameters of thyroid function. RESULTS: No correlation was found between diameters of 233 extraocular muscles measured by MRI and by ultrasound. For each of the four muscles, there was a diameter above which ultrasound was always unreliable. MRI data were used in further analysis. Of the muscles examined, the inferior rectuses were the most frequently enlarged - at least one, in 93% of cases. Medial, lateral and superior rectuses were enlarged in 59%, 37% and 34% of the orbits respectively. The pattern of muscle involvement of the two orbits tended to be symmetric (r=0.49, P=0.003), particularly for the medial rectuses (r=0.90, P=0.000). Proptosis correlated with the sum of the muscle diameters for a given eye (right eye: r=0.54, P=0.003; left eye: r=0.57, P=0.001), but it failed to correlate with the amount of orbital connective tissue. In 53% of the patients, normal T2 relaxation times were found in all eight muscles. There was only a weak correlation between muscle thickness and T2 relaxation time (r=0.49, P=0.003), indicating that muscle enlargement alone is not a sign of disease activity. The severity of diplopia was independent of T2 relaxation time. The amount of orbital connective tissue showed a negative correlation with the greatest T2 relaxation time for a given eye (r= -0.52, P=0.004); this suggests that disease types exist that have predominant muscle involvement and predominant connective tissue expansion. No correlation between connective tissue expansion and proptosis, diplopia grade, muscle thickness or disease duration was found - that is, connective tissue expansion is not a major factor in diplopia. Both muscle and connective tissue findings were independent of thyroid function. CONCLUSION: Ultrasound and MRI eye muscle diameter readings do not correlate, because of the inherent inaccuracy of orbital ultrasound. Muscle enlargement alone does not mean oedematous swelling and active disease. Neither ultrasound, nor any combination of 11 clinical and laboratory parameters provided the degree of information on muscles and connective tissue that was obtainable by MRI. In unclear cases of recently developed diplopia, before orbital decompression surgery, in the case of treatment failure or if, for any other reason, imaging is needed in GO, MRI is the method of choice.

Prevalence of iodine deficiency and goitre during pregnancy in east Hungary.

OBJECTIVE: To assess the iodine nutritional status and the prevalence of goitre during pregnancy in a region of Hungary that appeared to be iodine sufficient in previous studies. DESIGN: A cross-sectional voluntary screening study was organized in which 313 pregnant women participated. METHODS: Urine iodine concentration and the volume of the thyroid gland were measured in every woman. In the presence of low urinary iodine concentrations, goitre, or both, thyroid function tests were performed. RESULTS: Iodine deficiency was found in 57.1% of the pregnant women, and was severe in 15.6%. The volume of the thyroid gland was enlarged in 19.2% of individuals. Nodular goitre was found in 17 women (5.4%). The frequency of goitre and the mean thyroid volume were increased in the group of iodine-deficient women. In the 89 cases of iodine deficiency or goitre, thyrotrophin concentrations were in the normal range; however, the free triiodothyronine:free throxine ratio was increased in 97% of them, indicating that the thyroid gland was in a stimulated state in these individuals. CONCLUSIONS: Iodine deficiency with high prevalence of goitre was recognized among pregnant women in an area that previously appeared to be iodine sufficient. An unexpected mild iodine deficiency was also noted in the non-pregnant control group. Reassessment and continuous monitoring of iodine nutritional status is warranted even in populations that are apparently considered to be 'at no risk' of iodine deficiency, especially in pregnant women. Regular administration of iodine, starting at preconception or in early pregnancy and continuing during the period of nursing, is recommended in these regions.

Calculation of the radioiodine dose for the treatment of Graves' hyperthyroidism: is more than seven-thousand rad target dose necessary?

Some authors recently suggested a significant increase in the target dose of radioiodine treatment in Graves' disease. The aim of the present study was to investigate the impact of thyroid gland mass on the success rate of radioiodine treatment. For this purpose, the thyroid function of 105 consecutive Graves' patients was assessed 6 and 12 months after a 131I treatment and correlated to the gland mass. The patients were categorized according to the gland mass into small (< or = 30 g; 19 patients), medium size (31-50 g; 40 patients), and large size (> 50 g; 46 patients) groups (S, M, L groups, respectively). None of the patients received more than a 10,000-rad (100-Gy) target dose. During the calculation of administered 131I activity, late uptake measurement has also been routinely used, in addition to the usual maximal uptake parameter. The established effective half-life of 131I was highly variable (5 +/- 1.2 days; range: 2-7.6 days) and could not be predicted based on other clinical data without measuring an extended radioiodine uptake curve of the given patient. However, the correlation between the administered activity calculated from the complete set of uptake values and that of only a single late one was excellent (r = 0.99). Six months after the 131I treatment, hyperthyroidism was cured in 81% of patients with small and medium size thyroid glands, with 62% euthyroid and 19% hypothyroid ratios respectively. In the early phase of study for large goiters, the same linear mass activity function was used during calculation as in smaller glands. In these 17 patients the nonhyperthyroid result was comparable to the results of treatment of the small and medium size gland groups only after 1 year (77%), but the 6-month success rate was significantly lower (53%; p < 0.05). After obtaining these results, the usual 7000-rad target dose was increased to 8000-10,000 rad (depending on the gland mass) in another group of 29 patients with large thyroid glands that result in an acceptable 6-month success rate of 72%. In conclusion, instead of the "mCi 131I/g gland mass/maximal uptake" dose calculation, we suggest a method in which (1) the late 131I uptake measurement is taken into account and (2) for large goiters there is an additional dose adjustment, ie, increase is needed over the usual linear, size driven calculation. No overall increase of target dose over 10,000 rad is necessary if no antithyroid medication is given shortly before 131I treatment.

Differentiated thyroid cancer and outcome in iodine deficiency.

AIMS: Factors influencing prognosis and long-term outcome of thyroid cancer have been described by several groups. We wished to asses the previously described prognostic factors in a moderately iodine deficient region in Hungary. METHODS: Four hundred and fifty-four out of 492 patients who had surgery for papillary thyroid cancer (PTC, 386 cases) and follicular thyroid cancer (FTC, 106 cases) between 1971 and 1998 were analyzed. Survival curves were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: The 10 and 20-year survival rates were 87.9 and 84% for PTC, and 78.2 and 78.2% for FTC. In PTC, extrathyroidal invasion (p<0.0001), lymph node metastasis (p<0.0001), distant metastasis (p<0.0001), and age over 40 years (p=0.002) were significant adverse predictors. In FTC, extrathyroidal invasion (p=0.003) distant metastases (p<0.0001), and age over 40 years (p=0.011) were significant adverse predictors. CONCLUSION: Iodine intake did not appear to influence survival. The incidence of follicular cancer, which has less favourable prognosis, was higher in iodine deficient regions. This supports the importance of iodine supplementation in these areas.

Parameters of respiratory burst and arachidonic acid metabolism in polymorphonuclear granulocytes from patients with various thyroid diseases.

The oxidative processes (oxygen consumption, superoxoid anion generation, arachidonic acid cascade) of human polymorphonuclear granulocytes (PMNs) obtained from patients suffering from thyroid disorders of autoimmune origin (Graves' disease and Hashimoto's thyroiditis), and non autoimmune origin (toxic adenoma) were investigated. All Graves' and toxic adenoma patients were hyperthyroid. Hashimoto's thyroiditis patients were euthyroid. Healthy age and sex matched volunteers served as controls. The results are as follows: 1) In PMNs from both hyperthyroid groups (Graves' disease and toxic adenoma), independently from the autoimmune origin of the disease, a significantly increased Antimycin A sensitive mitochondrial oxygen consumption and a slightly increased superoxide anion generation were detected. 2) In both autoimmune thyroid disease groups (Graves' disease and Hashimoto's thyroiditis)--depending on the functional state of the thyroid gland--a significantly altered intracellular killing activity was measured. 3) An increased arachidonic acid cascade--triggered by opsonized zymozan (OZ)--was detected in both autoimmune thyroid diseases. The increased arachidonic acid cascade was sensitive to phospholipase A2 inhibiting Mepacrin treatment. 4) The PMNs from both autoimmune thyroid diseases produced large amount of leukotriens (LTs)--LTC4 and LTB4--after stimulation through their Fc receptors but the synthesis of prostagalandins (PGs) has not changed. There are no data indicating local, specific effects of circulating leukotriens in the thyroid gland itself, but based on authors' data, their general, regulating role on both the endocrine-- as well as on the immune system--seems to be plausible.

[Molecular biology of thyroid diseases]. / A pajzsmirigy betegségeinek molekuláris biológiája.

Recent developments in molecular biology and the accessibility of techniques for clinical research have led to a better understanding of the background of common thyroid diseases. The cloning and sequencing of the thyroid stimulating hormone receptor, thyroid peroxidase and thyroglobulin, and the characterization of the protein-DNA interaction during thyroid hormone action, as well as the discovery of intracellular signal transduction pathways were the most important steps which resulted in new diagnostic and therapeutic approaches. New explanations of thyroid autoimmune processes are being investigated.

[Lipoprotein (a) studies in thyroid diseases]. / Lipoprotein (a) vizsgálatok pajzsmirigybetegségekben.

High lipoprotein (a) levels have been established as a risk factor for atherosclerosis. The physiological and pathological function of lipoprotein (a) and the effect of other factors of lipoprotein (a) plasma concentrations are not well known. The role of thyroid hormones concerning Lp(a) plasma concentrations are not fully cleared. The Lp(a) levels are genetically determined, relatively stable, while the thyroid hormones react differently. 30 hyperthyroid and 29 hypothyroid patients were studied. The thyroid status and lipid parameters were investigated. A significant correlation was observed between the cholesterol, triglyceride, LDL-cholesterol, Apolipoprotein B and the thyroid hormone levels. The HDL-cholesterol and Apolipoprotein A correlated inversely with the thyroid hormone levels. Data obtained on the Lp(a) and thyroid hormone was in contrast with those of other studies. Hyperthyroid patients were increased Lp(a) concentrations as compared those of euthyroid subjects. In severe thyreotoxicosis (especially with high levels of antithyroid antibodies) elevated Lp(a) plasma concentrations were found. In hypothyroid patients the high levels of Lp(a) were measured as described in previous studies. Authors concluded that further studies are needed to investigate this phenomenon.

[Differentiated thyroid carcinoma: prognostic factors]. / Differenciált pajzsmirigy carcinoma: prognosztikai faktorok vizsgálata.

Factors influencing prognosis and long term outcome of thyroid cancer have been described by several groups. It is, however, not clear how the moderate iodine deficiency in Hungary can influence the previously described prognostic factors by other means than shifting differentiated cancer incidence toward the follicular type. Data of 423 out of 472 patients who had been operated on for papillary (372) and follicular (100) thyroid cancer between 1971 and 1997 at our institution have been analyzed retrospectively. Histological specimens were re-evaluated and, if needed, revised. Survival curves were compared using the Kaplan-Meier method. The overall 5 and 10 year survival rates were 93% and 89% for papillary, and 92% and 80% for follicular carcinoma. As an independent factor extrathyroidal invasion (papillary p = 0.000, follicular p = 0.000), lymph node involvement (papillary p = 0.000, follicular 0.011), distant metastases (papillary p = 0.000, follicular p = 0.000), and age over 40 years (papillary p = 0.000, follicular p = 0.000) had negative influence on survival. Multifocality, gender, type of surgery (total or near-total thyroidectomy vs. less than near-total thyroidectomy), and lymphocytic infiltration did not influence survival. Iodine intake did not influence survival, however, the incidence of follicular cancer was higher in iodine deficient regions. When analyzing the papillary and follicular groups separately by Cox regression, extrathyroidal invasion (p = 0.008), lymph node metastasis (p = 0.004), distant metastasis (p = 0.000), and age over 40 years (p = 0.000) were significant predictors in the papillary group, while only tumor extrathyroidal invasion (p = 0.019), and distant metastases (p = 0.000) were significant negative factors in the follicular group.

Antiplatelet effect of acetylsalicylic acid, metamizole and their combination - in vitro and in vivo comparisons.

BACKGROUND: Acetylsalicylic acid (ASA) plays an important role in the treatment and prevention of cardiovascular diseases. Metamizole (MET) is an analgesic and antipyretic medicine, it is not used as an antiplatelet drug. OBJECTIVES: We aimed to examine the antiplatelet effect of MET and the possible interactions between the drugs. METHODS: In our in vitro investigations different concentrations of ASA and MET solutions were added to blood. To examine the interactions MET and ASA were added together. In our in vivo crossover study intravenous MET, oral ASA or both drugs together were administered. Epinephrine and adenosine-diphosphate induced platelet aggregation was determined by optical aggregometry. RESULTS: Epinephrine-induced aggregation was completely inhibited in all ASA and MET concentrations in vitro. Lower, ineffective concentration of MET prevented the antiplatelet effect of ASA. The inhibition was completely restored when higher concentration of ASA was used or when ASA was added first. Our in vivo study showed that in the MET group rapid onset of inhibition was developed and there was no inhibition after one day. In the ASA group platelet aggregation decreased slowly but still had significant inhibitory effect after 72 hours. Combined therapy showed similar changes to the MET group. CONCLUSION: Antiplatelet effect of MET and ASA did not differ significantly in vitro. The observations may indicate a competitive interaction between the two drugs. The in vivo experiments showed that intravenously administered MET is an effective antiplatelet drug and can be considered as a therapeutic alternative, when ASA cannot be used in oral form.

Technetium-99m-sestamibi/pertechnetate subtraction scintigraphy vs ultrasonography for preoperative localization in primary hyperparathyroidism.

A prospective study was performed to evaluate the efficacy of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scanning and US for imaging parathyroid glands in primary hyperparathyroidism. Sixty-three patients were surgically treated for primary hyperparathyroidism (HPT). Preoperative scintigraphy and US were performed in all cases. Bilateral neck exploration was carried out on each patient. Results of radionuclide studies and US were compared with surgical and histological findings. In 57 patients with primary HPT the radionuclide scanning gave true-positive results. Four false-negative and two false-positive scintigrams were obtained. The sensitivity and the positive predictive value (PPV) of scintigraphy were 93 and 97%, respectively. Forty-one cases were correctly localized by the US. Seventeen US results were false negative and five were false positive. The sensitivity and the PPV for US were 71 and 89%, respectively. There was a statistically significant difference between the sensitivity of the scintigraphy compared with the US ( p=0.001). Sensitivities of radionuclide scans and US were higher for adenomas (100 and 83%) than for hyperplastic glands (75 and 40%). The sensitivity of technetium-99m-sestamibi and technetium-99m-pertechnetate subtraction scintigraphy was significantly higher compared with US. This sensitive method could help surgeons in performing a rapid and directed parathyroidectomy.

Surgically treated Hashimoto's thyroiditis.

The primary way to treat Hashimoto's thyroiditis is conservative. However, it has a relatively high occurrence in operated patients, up to 13% in the literature. Indications for surgery are suspicion of malignancy, and/or trachea/esophagus compression. 2818 thyroid operations were performed at our department between 1986 and 1995. 279 patients suffered from thyroid cancer and 2539 had benign disease. Histology revealed Hashimoto's thyroiditis in 118 cases. Coexisting malignant thyroid tumor was found in 14 cases (11.8%): 9 papillary, 2 follicular, 1 anaplastic cancer, and 2 non-Hodgkin lymphoma. Postoperative recurrent laryngeal nerve paralysis occurred in 8 cases, of which 6 remained permanent. This relatively high incidence supports the importance to identify the laryngeal nerve during every operation for Hashimoto's thyroiditis. Four patients had temporary and one had permanent hypoparathyroidism. Coexistence of Hashimoto's thyroiditis and thyroid carcinoma, the increased risk for the development of non-Hodgkin's lymphoma in chronic lymphocytic thyroiditis and the need for thyroxin supplementation in many cases justify a careful, long-term follow-up of patients with Hashimoto's disease.