Risk of malignancy in follicular thyroid neoplasm: predictive value of thyrotropin.

UNLABELLED: The cytological diagnosis of follicular neoplasm is a common finding in fine needle aspiration cytology (FNAC) of thyroid nodules and includes benign disease as well as differentiated thyroid cancer. The aim of the study is to determine if thyrotropin is a predictive factor for a malignant nature of follicular neoplasm. PATIENTS, METHODS: The records of 119 patients with follicular neoplasm on FNAC, who underwent surgery for final diagnosis, were reviewed retrospectively. The predictive value of serum parameters including thyrotropin, thyroglobulin, and anti-thyroid antibodies, ultrasonographic criteria and clinical variables was evaluated by univariate analysis and logistic regression analysis. RESULTS, DISCUSSION: Patients with malignant nodules showed a higher thyrotropin concentration compared to patients with benign nodules (median 1.6 mU/l, interquartile range 1.4-3.0 mU/l vs. median 1.2 mU/l, interquartile range 0.8-1.6 mU/l, p < 0.01). ROC-analysis of thyrotropin revealed an optimal cut off value to differentiate benign and malignant nodules of 1.34 mU/l. The incidence of malignancy was 30.3% for a thyrotropin concentration higher than 1.34 mU/l compared to 6.4% for a thyrotropin concentration lower than or equal to 1.34 mU/l. On univariate analysis thyroglobulin higher than 300 ng/ml, positive anti-thyroid antibodies, hypoechogenicity, and ill-defined margins, respectively, were also significantly associated with malignancy. On logistic regression analysis higher thyrotropin concentrations, ill-defined margins, and thyroglobulin higher than 300 ng/ml, respectively, were independent predictive factors for malignancy (OR 20.0, 10.7, and 22.7, respectively). CONCLUSION: Higher thyrotropin concentrations are predictive for a malignant nature of follicular neoplasm.

[Spectrometric assessment of thyroid depth within the radioiodine test]. / Spektrometrisches Verfahren zur Tiefenbestimmung der Schilddrüse im Rahmen des Radioiodtests.

UNLABELLED: Aim of this study is the validation of a simple method for evaluating the depth of the target volume within the radioiodine test by analyzing the emitted iodine-131 energy spectrum. PATIENTS, METHODS: In a total of 250 patients (102 with a solitary autonomous nodule, 66 with multifocal autonomy, 29 with disseminated autonomy, 46 with Graves' disease, 6 for reducing goiter volume and 1 with only partly resectable papillary thyroid carcinoma), simultaneous uptake measurements in the Compton scatter (210 +/- 110 keV) and photopeak (364-45/+55 keV) windows were performed over one minute 24 hours after application of the 3 MBq test dose, with subsequent calculation of the respective count ratios. Measurements with a water-filled plastic neck phantom were carried out to perceive the relationship between these quotients and the average source depth and to get a calibration curve for calculating the depth of the target volume in the 250 patients for comparison with the sonographic reference data. Another calibration curve was obtained by evaluating the results of 125 randomly selected patient measurements to calculate the source depth in the other half of the group. RESULTS: The phantom measurements revealed a highly significant correlation (r = 0,99) between the count ratios and the source depth. Using these calibration data, a good relationship (r = 0,81, average deviation 6 mm corresponding to 22%) between the spectrometric and the sonographic depths was obtained. When using the calibration curve resulting from the 125 patient measurements, the overage deviation in the other half of the group was only 3 mm (12%). There was no difference between the disease groups. CONCLUSION: The described method allows on easy to use depth correction of the uptake measurements providing good results.

[Concept and validation of a simple model of the intrathyroidal iodine kinetics]. / Prinzip und Validierung eines einfachen Modells der intrathyroidalen Iodkinetik.

UNLABELLED: AIM of this study is the introduction and validation of a simple model of the intrathyroidal iodine kinetics, designed for optimizing radioiodine therapy planning and dose measurement in a routine clinical setting. METHODS: The new model defines the intrathyroidal iodine kinetics as balance of the thyroidal iodine intake and -excretion, characterized by the two exponential equations A(t) = A(0) * (1-exp(-lambda(1) t)) and A(t) = A(0) * (exp(-lambda(2) t) -1), respectively. A(0) describes the theoretically maximum iodine uptake when the thyroidal iodine excretion is ignored, lambda(1) and lambda(2) represent the constants characterizing the iodine intake and excretion, respectively. The thyroidal iodine content at the time t equals the sum of both functions, which is A(t) = A(0) * (exp(-lambda(2) t)-exp(-lambda(1) t)). In 25 patients with autonomous goiter / nodules (n = 18), Graves' disease (n = 5), or endemic euthyroid goiter (n = 2), the iodine uptake in the thyroid during the radioiodine therapy as fraction of the applied activity was determined daily, with the remaining body covered by a lead shield. On average, 7.2 measurements were performed per patient (minimum 4, maximum 13). With these uptake values, individual regression curves were fitted using the above equation, and the difference between the actual measurements and the corresponding values of the regression curves was determined. RESULTS: The average deviation of the 179 uptake values from the calculated points of the respective regression curves was only 1.4%. There was no significant difference between the three disease groups. The distribution of the relative deviations during the individual courses was constant, systematic errors were not detected. CONCLUSION: Our results suggest that the intrathyroidal iodine kinetics can be precisely described with the model A(t) = A(0) * (exp(-lambda(2) t)-exp(-lambda(1) t)). With only three measurements, the trend of the curve can be calculated, which allows to determine the total radioiodine storage in the thyroid.

Results of a standardized protocol for sentinel node imaging in breast cancer with Tc-99m labeled nanocolloidal albumin.

AIM: Of this study was to evaluate the results of a standardized protocol for sentinel node (SN) detection in breast cancer using Tc-99m labeled nanocolloidal albumin and a combined intra- and subdermal injection technique. METHODS: One hundred and fifty-five women with proven breast cancer (disease stages Tis-T2) were included. Four injections of 10 to 15 MBq of Tc-99m nanocolloid in 0.1 ml physiologic saline were administered intra- and subdermally at the 3, 6, 9 and 12 o'clock positions in the skin overlying the tumor. Planar scintigraphic images in lateral and anterior projections were obtained once between 2.5 and 18 hours after tracer administration. Guided by a gamma probe, all radioactive lymph nodes in the axilla were resected, then complete dissection followed. RESULTS: In 151 of the 155 women (97.4%), nodal tracer uptake (range 1-7 foci, average 2.2) was scintigraphically revealed. In one of these cases, drainage was only to the internal mammary lymphatic chain. Three of the 4 women with detection failure presented with histologically proven tumor infiltration of the lymphatics and axillary involvement. In 49 of the patients with visualized axillary lymph nodes (32.7%), at least one SN was metastatic. In 21 cases, this SN was the only positive node. The remaining 101 patients with negative SN included 4 cases with axillary involvement. The sensitivity of the SN with respect to the histological status of the entire axilla was thus 92.5%, the negative predictive value was 96.0%. The overall accuracy of the method was 97.3%. There was a significant difference between the number of totally detected radioactive nodes in the groups with and without nodal metastases (3.49 vs. 2.57, p < 0.01). CONCLUSION: The described protocol represents an easy reproducible and reliable method for SN detection in breast cancer that additionally allows flexible timing of surgery. Further, we found evidence that the number of scintigraphically visualized nodes also reflects the histological status of the axilla.

Development of the parafollicular cells in recurrent goiter.

OBJECTIVE: To provide more data for the discussion on whether thyroid hormones, iodide and other factors controlling the thyroid also influence the parafollicular (PF) cells, as the answer is of great importance for optimization of the medical treatment of medullary thyroid carcinoma (MTC) after surgery. DESIGN: We compared the density of the PF cells in patients who underwent surgery for the second time due to recurrent goiter with that in normal-sized thyroid glands after the first operation. METHODS: In 20 patients with only one operation, all specimens were taken from morphologically and functionally normal lobular thyroid parenchyma. The second group consisted of 30 patients who had already undergone a nearly total resection of at least one thyroid lobe several years before. Then another surgery of the same side was performed due to recurrent goiter. Immunohistochemical staining of the PF cells was performed using primary antibodies to calcitonin and chromogranin. RESULTS: An average of 78 PF cells (median 12.5) was found in the sections with the highest density of the first group. The average number of PF cells in the second group was just 5 (median 0). The Wilcoxon test revealed a highly significant difference in the total PF cell content between the groups (P < 0.001). CONCLUSIONS: Our study suggests that the stimulating factors that lead to growth of the thyroid parenchyma do not influence the PF cells. Hence a non-suppressive thyroid hormone replacement seems to be sufficient after resection of an MTC.

Lymphoscintigraphic sentinel node imaging and gamma probe detection in breast cancer with Tc-99m nanocolloidal albumin: results of an optimized protocol.

PURPOSE: The purpose of this study was to aid in the standardization of lymphoscintigraphy for detecting the sentinel node (SN) in breast cancer using Tc-99m-labeled nanocolloidal albumin. MATERIALS AND METHODS: One hundred twenty-three women with proved breast cancer were enrolled. Four injections of 10 to 15 MBq (0.27 to 0.41 mCi) Tc-99m nanocolloid in 0.1 ml physiologic saline were administered intra- and subdermally at the margin of the skin overlying the tumor. Planar scintigraphic images in the lateral and anterior projections were obtained 2.5 to 18 hours after tracer administration. With a gamma probe used as a guide, all radioactive lymph nodes in the axilla were resected. Complete dissection then followed. RESULTS: In 116 of the 123 (94%) women, axillary nodal tracer uptake was revealed. Six of the 7 women in whom detection failure occurred had histologically proved tumor infiltration of the lymphatics and axillary involvement. In 36 (31%) of the patients with visualized lymph nodes, the SN was metastatic. The remaining 80 patients with negative SN included three cases with axillary involvement. The sensitivity of the SN with respect to the histologic status of the entire axilla thus was 92.3%, and the negative predictive value was 96.3%. The overall accuracy of the method was 97.4%. The number of hot nodes in women with and without axillary involvement was significantly different. CONCLUSIONS: The described protocol represents an easily reproduced and reliable method for SN detection in breast cancer. Furthermore, the number of visualized axillary nodes reflects the histologic status of the axilla.

[Impact of serum thyroglobulin concentration in the diagnosis of benign and malignant thyroid diseases]. / Stellenwert des Serum-Thyreoglobulinspiegels bei der Diagnostik benigner und maligner Schilddrüsenerkrankungen.

UNLABELLED: AIM of this study is to evaluate new and controversially discussed indications for determining the thyroglobulin (Tg) level in different thyroid diseases to support routine diagnostics. METHODS: The following groups were included: 250 healthy subjects without goiter, 50 persons with diffuse goiter, 161 patients with multinodular goiter devoid of functional disorder (108 of them underwent surgery, in 17 cases carcinomas were detected), 60 hyperthyroid patients with autonomously functioning nodular goiter, 150 patients with Hashimoto's thyroiditis and 30 hyperthyroid patients with Graves' disease. RESULTS: The upper limit of the normal range of the Tg level was calculated as 30 ng Tg/ml. The evaluation of the collective with diffuse goiter showed that the figure of the Tg level can be expected in a similar magnitude as the thyroid volume in milliliters. Nodular tissue led to far higher Tg values then presumed when considering the respective thyroid volume, with a rather high variance. A formula for a rough prediction of the Tg levels in nodular goiters is described. In ten out of 17 cases with thyroid carcinoma, the Tg was lower than estimated with thyroid and nodular volumes, but two patients showed a Tg exceeding 1000 ng/ml. The collective with functional autonomy had a significantly higher average Tg level than a matched euthyroid group being under suppressive levothyroxine substitution. However, due to the high variance of the Tg values, the autonomy could not consistently be predicted with the Tg level in individual cases. The patients with Hashimoto's thyroiditis showed slightly decreased Tg levels. In Graves' disease, a significantly higher average Tg level was observed compared with a matched group with diffuse goiter, but 47% of all Tg values were still in the normal range (< 30 ng/ml). CONCLUSION: Elevated Tg levels indicate a high probability of thyroid diseases, such as malignancy, autonomy or Graves' disease. However, as low Tg concentrations cannot exclude the respective disorder, a routine Tg determination seems not to be justified in benign thyroid diseases.

[Effect of iodine and thyroid hormones in the induction and therapy of Hashimoto's thyroiditis]. / Effekte von Iodid und Schilddrüsenhormonen bei der Induktion und Therapie einer Thyreoiditis Hashimoto.

AIM: The effect of an iodine prophylaxis on the induction of Hashimoto's thyroiditis as well as the influence of various therapeutic approaches on the course of antithyroglobulin (TgAb) and antiperoxidase (TPOAb) antibodies in manifest diseases are evaluated. METHOD: A collective of 375 euthyroid subjects without relevant goiter received daily doses of 200 micrograms iodide, weekly doses of 1.53 milligrams iodide, or no medication. A second group of 377 patients suffering from Hashimoto's thyroiditis was treated with a non-suppressive hormone medication, a suppressive hormone administration, a combination of a non-suppressive hormone therapy with low dose iodide (50-150 micrograms/day), mere iodide in doses of 200 micrograms/day, or received no therapy. The mean observation period in these two groups was 860 and 848 days, respectively. RESULTS: There was no significant increase of the antibody levels in the subgroup with 200 micrograms iodide/day and in the non-treated subjects of the first collective. However, the group that received 1.53 milligrams iodide/week presented a distinct increase of the TgAb as well as the TPOAb, and the incidence of Hashimoto's thyroiditis was 4-fold higher than in the two other subgroups. The patients of the second collective revealed a significant decrease of the TgAb in the subgroups treated with up to 200 micrograms iodide/day, while the reduction of the TPOAb depended on the thyrotropin level and was most significant in the suppressed group (p < 0.0001). CONCLUSION: To lower the incidence of autoimmune thyroid diseases in predisposed subjects, a daily iodine supplementation seems to be superior to high-dose weekly administrations. A hormone therapy combined with a daily, low-dose iodine medication is able to reduce the TgAb and the TPOAb levels even in patients with Hashimoto's thyroiditis.

[Hyperthyroidism in a premature infant due to transplacental passage of maternal thyrotropin receptor antibodies]. / Frühgeborenenhyperthyreose durch diaplazentar übertragene TSH-Rezeptor-Antikörper der Mutter.

The duration of the stimulating effect of transplacental transferred thyrotropin-receptor-antibodies (TRAb) is discussed by the example of a 23 years old woman suffering from Graves' disease with a severe hyperthyroidism. She became pregnant six weeks after the diagnosis was obtained and then discontinued her antithyroid medication on her own responsibility. On a check-up in the 20th week of pregnancy, a hyperthyroidism was once more found, leading to a therapy with propylthiouracil, which however, was again interrupted by the patient a few weeks later. In the 32nd week, she gave birth to a male child that already presented with distinct signs of thyrotoxicosis and developed a continuous deterioration of the condition, including a tachycardia with up to 190 beats per minute, fever, tremor and a respiratory disorder. Assay of the newborn serum revealed a severe hyperthyroidism. The TRAb level was 180 U/l (normal range < 15). A therapy with propranolol and prednisolone was initiated, leading to a significant improvement of the general condition. Nevertheless, after 12 days, there was still no notable decrease of the hormone levels. Therefore an antithyroid medication was started, which caused normal thyroid hormone levels within 9 days. However, after the therapy was stopped, a hyperthyroidism was again observed within one week, requiring another, low-dose antithyroid medication, which was administered for 26 days. After this period, the TRAb level was down to 25 U/l and no more hyperthyroidism was found. The biological half-life of the TRAb was 20 days in our case.

[Individual calculation of the minimal effective levothyroxine dose in prolonged suppression tests]. / Individuelle Bestimmung der minimal erforderlichen Levothyroxindosis bei Langzeit-Suppressionstests.

AIM: A formula for calculating the minimum suppressive levothyroxine dose in prolonged suppression tests using body weight and TSH level is derived from a large number of cases. METHOD: In 1239 euthyroid patients (TSH > 0.30 mU/l) a suppression test with levothyroxine substitution for at least 6 weeks was performed. The hormone dose was primarily based on the initial TSH level using the empirical value TSH x 100, with a range between 50 and 150 micrograms per day. RESULTS: In 900 patients (73%), the TSH level was suppressed during the medication (TSH < 0.30 mU/l). Among them, we found 211 cases with an intermediate TSH suppression (TSH between 0.10 and 0.20 mU/l). Following the formula f = levothyroxine dose [microgram]/(body weight [kg] x initial TSH level [mU/l]) an average factor of 1.57 was calculated to obtain the suppressive dose in this group. As usually a complete TSH suppression (< 0.10 mU/l) is required, we recommend factor 2 for practical use. A consideration of the body weight revealed that 313 patients actually received a hormone dose equivalent to 2 x weight x TSH. In this group, a TSH suppression was found in 262 patients (84%), a factitial hyperthyreosis was not observed. When contemplating the three subgroups of this collective, who received daily doses of 50, 75 and 100 micrograms levothyroxine, respectively, we neither found a significant difference in the average body weight, nor in the value of the suppressed TSH. However, the correlation between the average initial TSH levels in these groups and the respective suppressive hormone doses clearly demonstrates their dependence on the thyroid regulation. CONCLUSION: The minimum suppressive levothyroxine dose does not only depend on the body weight, but also on the initial TSH level. It can be estimated using the formula 2 x body weight x initial TSH (range between 50 and 150 micrograms per day).

[Individual outcome monitoring of TSH receptor antibody level for predicting the prognosis of Graves' disease]. / Individuelle Verlaufskontrolle der TSH-Rezeptor-Antikörper-Titer zur Einschätzung der Prognose eines M. Basedow.

AIM: This retrospective study is intended to provide further information on the controversially discussed ability of a Thyrotropin Receptor Antibody (TRAb) monitoring for predicting the outcome of Graves' disease. METHOD: The study is based on 1480 blood samples of 346 patients (292 female, 54 male; age among 9 and 91 years) suffering from Graves' disease. A comparison between the TRAb levels and the serum free thyroid hormones as well as the basal thyrotropin was performed in the entire collective, in the group of non-treated patients and in 182 individual courses. RESULTS: Even in comparable states of function, the individual TRAb levels were quite divergent. In the group with persistent dysfunction, they initially varied between 6 and 482 U/l (normal range < 15 U/l). A global evaluation of the particular groups hence did not show any correlation between the functional disorder and the respective TRAb levels. However, when considering the individual courses, a distinct dependence upon the development of the TRAb could be observed. As the limit for separating the group suffering from persistent malfunction or recurrence and the collective in remission, a decline of the individual TRAb level below 50% of the initial value has proven to be most suitable. This was observed in 94% of all remissions. In 90% of all relapsed patients, we either found persistent high TRAb levels (i.e. a maximum decrease down to 50% of the initial value) or another increase of the TRAb levels. The positive and negative predictive values of the method are 97% and 58%, respectively. CONCLUSION: The outcome of Graves' disease depends on the individual changes of the TRAb levels rather than on their absolute values. In case of persistent TRAb, you have to expect a continuing dysfunction or a recurrence.

[Simultaneous measumrement of the renal excretion of 131I-hippuran and 99mTc-MAG3]. / Simultane Messung der renalen Ausscheidung von 131J-Hippuran und 99mTc-MAG3.

This study describes methods of measuring simultaneously the renal excretion of two radiopharmaceuticals and of evaluating their different kinetics. For quantification of the dynamic contributions of scattered radiation in a double-radionuclide study a high-resolution pure germanium detector was used. The geometry of the arrangement was a semi-shielded whole-body counter according to E. Oberhausen. An intra-individual comparison of the renal elimination of 99mTc-MAG3 and 131I-Hippuran shows a systemic difference between both tracers depending on the time after injection, its average being around 11% between the 10th and 20th min. The inter-individual comparison shows deviations from the mean between -29 and +20%.

[Estimate of the dosage for radioiodine ablation of the thyroid gland in male Wistar rats]. / Abschätzung der Dosis zur Radiojodresektion der Schilddrüse bei männlichen Wistar-Ratten.

The aim of this investigation was to determine the radioiodine dose necessary for the ablation of the thyroid gland in male Wistar rats. By a mathematical extrapolation of the kinetics of iodine-131, the radioisotope dose in the thyroid was calculated to be 467971 or 401540 rad after an intraperitoneal administration of 1 x 0.8 mCi (29.6 MBq) or 1 x 1.0 mCi (37.0 MBq) iodine-131, respectively. Because lower radioiodine activities did not result in a complete destruction of the thyroid (controlled by scintigraphic methods), it can be concluded that about 400,000 rad are necessary for the complete ablation of the thyroid gland by radioiodine.

[Determination of cerebral blood flow using an 81Rb/81mKr generator system]. / Bestimmung des zerebralen Blutflusses mittels des 81Rb/81mKr-Generatorsystems.

A method is being developed which not only measures cerebral blood flow as a static quantity but also its changes with time. For that purpose a semiconductor device ascertains the proportion of intracerebral 81 Rb and 81mKr activities. By opening the hemato-encephalic barrier in animal experiments a sufficient concentration of intracerebral 81 Rb could be attained and the modified blood circulation after step-wise ligature of all brain arteries brought into relation to the corresponding Rb/Kr quotient. Over the range from undisturbed to completely interrupted cerebral blood flow this quotient varied up to 25% of its initial value.

[The effect of metamizole on gastric emptying and small intestine transit in the rat]. / Einfluss von Metamizol auf Magenentleerung und Dünndarmtransit bei der Ratte.

The effect of the pyrazolone derivative metamizole on the motility of the upper gastrointestinal tract of the rat was investigated. An animal model for simultaneous quantification of gastric emptying and small intestinal transport was used. A test meal with different radioactive labels was administered by means of previously implanted tubes both to the stomach (1.0 ml; 51Cr) and to the duodenum (0.25 ml; 99mTc), and the spatial distribution of both isotopes in a gastrointestinal preparation was determined after a transport time of 30 min. It has been shown that intravenously administered metamizole reduces significantly the percentage of the test meal discharged by the stomach (control: 70.9 +/- 2.8; 50 mg/kg metamizole: 26.3 +/- 6.9, p less than 0.001; 250 mg/kg metamizole: 3.8 +/- 1.5, p less than 0.001); 1250 mg/kg metamizole: 1.1 +/- 0.3; p less than 0.001). The 50- and 250-mg/kg doses had no negative effect on the propulsion of the small intestine. A dose of 1250 mg/kg induced a significant reduction in small intestinal transport (p less than 0.001).

Investigations on the effect of metamizol on ureteral motility.

The aim of this comparative study was to obtain quantitative information on the effect that metamizol has on ureteral motility. Renal Tc-99m-MDP excretion and ureteral urine transport against gravity were examined in five patients, once without (control) and, several days later, with metamizol treatment. In each of these ten scanning sessions, renograms of both kidneys were recorded. They were corrected for background activity and compared with respect to the following parameters: the curve amplitude at 30 min p.i. normalized to the respective maximum amplitude; the 6-30 min and 40 s-6 min integrals of a corrected curve. Under metamizol medication, the flow of radioactivity to the bladder was thus found to be significantly reduced (p less than 0.001). The comparison of the Tc-99m-MDP retention curves obtained with and without metamizol treatment did not reveal a statistically significant drug effect on renal Tc-99m-MDP excretion.

[Results of scintigraphy with labeled leukocytes for the diagnosis of infectious hip prosthesis loosening]. / Ergebnisse der Szintigraphie mit markierten Leukozyten zur Diagnostik der entzündlichen Hüftgelenksendo-prothesenlockerung.

The present paper reports on the results of a specific scintigraphic examination method for diagnosing infections in cases of loosening of hip prostheses by means of labeled granulocytes. In 103 patients the result of the examination was compared with the result of the bacteriological and/or histological investigation following removal or replacement of the implant. Where there was an infectious loosening of the prosthesis the findings were in agreement with the results of the scintigraphic examination in 83.1% of the cases. It was possible to rule out infectious loosening of the prosthesis in 93% of the cases thus investigated.