The role of FDG-PET in localization of recurrent lesions of differentiated thyroid cancer (DTC) in patients with asymptomatic hyperthyroglobulinemia in a real clinical practice.

INTRODUCTION: Available methods, including serum thyroglobulin (Tg) measurement and whole-body scan (WBS) performed after radioiodine administration, allow for a precise diagnostics in differentiated thyroid cancer (DTC). However, some asymptomatic patients demonstrate negative WBS despite a high Tg serum concentration. In these subjects, fluorodeoxyglucose-positron emission tomography (FDG-PET) should be considered. The primary aim of our study was to evaluate a diagnostic value of FDG-PET in asymptomatic hyperthyroglobulinemia. The secondary one was to determine a prognostic value of a negative FDG-PET result in DTC patients with elevated Tg level. MATERIAL: One hundred and ten FDG-PET/CT scans were retrospectively analyzed, 85 scans were done under TSH stimulation and 25 on LT4 suppressive therapy. Follow-up ranged between 4 and 9 years. RESULTS: The first FDG-PET/CT detected cancer foci in 49 subjects with a global sensitivity of 45%. When the sensitivity was evaluated with reference to TSH stimulation and suppression, its values were 50 and 28% respectively. In 42 patients, FDG-PET failed to diagnose the reason for elevated Tg level. During further follow-up, in 17 of them, DTC recurrence was detected by other methods (CT, MRI, US). Fourteen subjects with asymptomatic hyperthyroglobulinemia were free of DTC progression for at least 4 years. CONCLUSIONS: FDG-PET in DTC patients with asymptomatic hyperthyroglobulinemia constitutes a valuable diagnostic tool. Negative FDG-PET demonstrated a limited prognostic significance, as only every third patient did not show DTC progression. Moreover, negative FDG-PET does not justify less strict DTC monitoring, because it is related to 40% risk of relapse during the 5-year follow-up.

Risk of malignant tumors in first-degree relatives of patients with differentiated thyroid cancer -- a hospital based study.

In presented study the risk of incidence of familial differentiated thyroid cancer as well as the risk of other malignant tumors in families of DTC patients was evaluated. 999 patients with differentiated thyroid cancer and 825 persons without any history of malignant disease were evaluated on the occurrence of malignant neoplasm within their families. Information about 6614 first degree relatives of DTC index patients and 4939 first degree relatives of control persons were recorded. The incidence of cancers at various sites was compared between first-degree relatives of index patients and control persons and odds ratio with 95% confidence intervals (CI) were calculated for thyroid cancer and other cancer sites. Within 999 families of thyroid cancer index patients 23 families with more than one case of DTC were found. The risk of the development of thyroid cancer in the first degree was 6 (95% CI 1.8-19) times greater in the index group than in the control group. No increased risk for development of other malignancies was observed. Results of our study confirm previous reports of increased risk of thyroid cancer in first-degree relatives of differentiated thyroid cancer patients. However, the relatively small number of first-degree relatives affected with thyroid cancer (24/6614) does not justify at present any screening in the first-degree relatives of patients affected with differentiated thyroid cancer. Simultaneously, no increased risk of other malignant neoplasm was observed in the differentiated cancer families.

Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic patients.

PURPOSE: The study was undertaken to evaluate the frequency of inherited medullary thyroid carcinoma (MTC) among patients with apparent sporadic disease. A stepwise algorithm was used depending on clinical indices and the age of patient at MTC diagnosis. PATIENTS AND METHODS: One hundred sixteen patients with MTC verified by postoperative pathologic examination were subjected to genetic analysis of RET exons 10, 11, 13, 14, and 16 by means of polymerase chain reaction, restriction endonuclease digestion, and DNA sequencing. RESULTS: Among 116 apparent sporadic MTC patients, we identified eleven (9.5%) RET germline mutation carriers. Seven of these (6.0%) were found by routine analysis (exons 10 and 11). The frequency of inherited disease among patients younger than 45 years at diagnosis was 10.2% by analysis of typical mutations in exons 10 and 11. Extended genetic analysis (sequencing of exons 11, 13, 14, and 16) yielded 6.1% additional diagnoses, giving a risk of 16.3% in this age group. One previously unreported mutation in exon 11 affected codon 649 (TCG>TTG, Ser>Leu). In the true sporadic MTC patients younger than 30 years at diagnosis, frequencies of 36% and 4.5% in polymorphic variants L769L and S836S, respectively, were observed. The frequency for L769L was higher than in older patients (P <.05). CONCLUSION: The frequency of inherited disease among apparent sporadic medullary thyroid carcinoma patients is close to 10% in the Polish population of MTC patients. The extended analysis of all known RET proto-oncogene mutation sites is obligatory in patients younger than 45 years at diagnosis, but we also see the need to analyze the impact of rarer mutations in older patients.

[Prospective analysis of criteria for interpreting measurements of thyroglobulin serum concentration during conditions of endogenous TSH stimulation in serum of patients with differentiated thyroid carcinoma]. / Prospektywna analiza kryteriów interpretacyjnych oznaczania stezenia tyreoglobuliny w warunkach stymulacji endogennym TSH w surowicy chorych na zróznicowane raki tarczycy.

The aim of this study was the assessment of diagnostic value of thyroglobulin serum measurement in patients with DTC during endogenous TSH stimulation. Thyroglobulin was measured by immunofluorometric method (Delfia-Wallac) in patients after combined surgery and I131 ablation. Predictive values for two threshold levels 10 and 30 ng/ml were compared. At 5 years follow up it has been demonstrated, that Tg values higher than 10 ng/ml were the true signals of DTC relapse only in 46% patients. Tg values higher than 30 ng/ml were associated with disease progression in 65% of patients. Thus, we accept Tg concentration of 30 ng/ml measured during endogenous TSH stimulation as a good cut-off limit for the detection of DTC progression. Reduction of this threshold up to 10 ng/ml is associated with the increased risk of false positive results.

[Comparison of efficacy of various methods of thyroglobulin measurements in differentiated thyroid cancer]. / Porównanie skutecznosci róznych metod oznaczania tyreoglobuliny jako markera zróznicowanego raka tarczycy.

Monitoring patients with differentiated thyroid carcinoma (DTC) by thyroglobulin (Tg) measurements requires selecting optimal methods used for detection of this marker. An increase the thyroglobulin concentration in serum is a predictor of tumor recurrence. All serum thyroglobulin assays can be falsified by presence of Tg autoantibodies, which are present in approximately 20% of DTC patients. The aim of this study was a comparison of the clinical utility of two different methods for determining serum Tg concentration in monitoring patients with DTC during thyroxine treatment. Tg concentration was measured in serum samples of 1530 patients with DTC during replacement thyroid hormone using two methods: fluoroimmunometric assay (IFMA) Wallac Delfia Thyroglobulin and immunoradiometric assay (IRMA) Brahms DYNOtest Tg-S. 1847 values of Tg concentration and recovery test detected between 1992 and 1995 years using IFMA methods and 1187 values of Tg and thyroglobulin autoantibodies concentration measured in 2000 year using IRMA methods were also included. The correlation between Tg values in all patients group wasn't good (r = 0.83; p < 0.05), but when we excluded patients with incorrect recovery test determined by IRMA, the correlation factor was higher (r = 0.94; p < 0.05). The estimation of Tg recovery test obtained in IRMA assay eliminated from monitoring only 3% patients with DTC, when IFMA assay excluded nearly 1/5 patients, whereas the estimation Tg autoantibodies 7% from all patients. The IRMA method is the most resistant to interference and allows to monitor a reliably greater group of patients with DTC during thyroxine treatment.

[Evaluation of bone density in women after thyroid cancer surgery and treatment with suppressive doses of L-thyroxine]. / Ocena gestosci kosci u kobiet po operacji raka tarczycy, leczonych supresyjnie L-tyroksyna.

The aim of this work was to evaluate the degree of bone resorption and incidence of osteoporosis in female postmenopausal patients with differentiated thyroid cancer treated with suppressive doses of thyroxine. During the regular follow-up of women with differentiated thyroid cancer, densitometry of lumbar spine (L2-L4) and femoral head were performed. urine concentration of deoxypyridinoline and calcium-phosphate metabolism were also evaluated. Osteoporosis was diagnosed in 11% of patients, all without hormone replacement therapy (HRT). Mean bone density was significantly higher in patients treated with HRT. A decrease in bone mass was related to the duration of thyroxine therapy. The best results of bone mass density were obtained in patients on HRT and with short duration of thyroxine therapy. Deoxypiridinoline estimation did not exhibit significant differences between groups, however it was useful in the individual evaluation of bone resorption.

Multivariate analysis of prognostic factors for differentiated thyroid carcinoma in children.

At most centres, the standard treatment for differentiated thyroid cancer (DTC) comprises total thyroidectomy, radioiodine treatment and thyroid-stimulating hormone (TSH) suppressive therapy. There is, however, considerable disagreement over the appropriate treatment for DTC in children. Some dispute the use of total thyroidectomy and/or question the routine application of iodine-131 therapy in children. The aim of this study was to perform a retrospective analysis of treatment results and prognostic factors for DTC in children treated at our centre. The study included 109 children with DTC (aged 6-17 years). The primary treatment comprised total thyroidectomy in 81 cases, radioiodine therapy in 85 cases and TSH suppressive therapy with L-thyroxine in all patients. Uni- and multivariate analysis of prognostic factors for disease-free survival was performed using the Cox regression method. The actuarial survival rate was 100%, and the 5- and 10-year actuarial disease-free survival rates were 80% and 61% respectively. Univariate analysis revealed that older age, total thyroidectomy and radioiodine treatment had a positive impact on disease-free survival whereas there were no statistical differences with regard to the child's sex, histological type of cancer or lymph node status. On multivariate analysis, radical surgery was estimated to be the most significant factor (P=0.007) for disease-free survival, while less than total thyroidectomy increased the relative risk of relapse by a factor of 10. Radioiodine treatment decreased the relative risk of relapse by a factor of 5, but with borderline significance (P=0.07). Permanent postoperative complications were observed in 17% of children: in 11 laryngeal palsy occurred, in six there was hypoparathyroidism, and one suffered from both. It is concluded that total thyroidectomy and radioiodine treatment significantly improve recurrence-free survival in children and should be routinely applied even in young children as the primary treatment of DTC.

Early diagnosis of brain damage in prematures with birthweight below 1250 g in the light of follow up examinations.

A follow up study of 67 prematures born with a low birthweight (1250 g or less) was made since July 1962 at the Premature Department and Aftercare Clinic of the Medical School in Warsaw. The study consisted of physical, psychological and anthropometrical examinations. Results revealed a high percentage of children with developmental disturbances such as brain damage, behavioural and visuo-motor disturbances. No evident, statistically significant interrelation between these disturbances and the course of the neonatal period could be found. The interrelation was more evident between these disturbances and the course of pregnancy. Haemorrhage in the first half of pregnancy seemed to be a most serious complication. It is difficult to predict the chances of a normal psychophysical development of the smallest prematures. Such prognosis depends on many different and complicated factors.