Urokinase plasminogen activator and its inhibitor type-1 as prognostic factors in differentiated thyroid carcinoma patients.

OBJECTIVE: To investigate the prognostic value of urokinase-type plasminogen activator (uPA) and its inhibitor, type-1 plasminogen activator inhibitor (PAI-1), in differentiated thyroid cancer. STUDY DESIGN: Prospective cohort study. SETTING: University hospital. SUBJECTS AND METHODS: Cytosolic concentrations of uPA and PAI-1 were determined in 105 patients with differentiated thyroid carcinoma and normal matched tissues using an enzyme-linked immunoassay (ELISA). RESULTS: Both uPA and PAI-1 concentrations were significantly higher in differentiated thyroid tumors (uPA = 0.509 ± 0.767 and PAI-1 = 6.337 ± 6.415 ng/mg) compared to normal tissues (uPA = 0.237 ± 0.051, P < .001; PAI-1 = 2.368 ± 0.418 ng/mg, P < .001). uPA and PAI-1 were significantly higher if extrathyroidal invasion (uPA, P = .015; PAI-1, P < .001) or distant metastasis (PAI-1 P < .001) was present, as well as in tumors whose size exceeded 1 cm in diameter (uPA, P = .002; PAI-1, P = .001). Survival analysis revealed the significant impact of both uPA and PAI-1 on progression-free survival (PFS) (82.22 vs 49.478 months for patients with low and high uPA, respectively, P < .001; 87.068 vs 44.964 months for patients with low and high PAI-1, respectively, P < .001). Univariate analysis showed that gender, tumor size, tumor grade, extrathyroid invasion, local lymph node involvement, distant metastasis, uPA, and PAI-1 were significant predictors of PFS. However, multivariate analysis identified only distant metastasis and tumor tissue uPA and PAI-1 as independent prognostic factors. CONCLUSION: These findings indicate that high uPA and PAI-1 levels represent independent unfavorable prognostic factors in patients with differentiated thyroid carcinoma.

Thyroid metastasis from breast carcinoma resembling medullary thyroid carcinoma.

We are reporting a case of a 42-yr-old female with a history of right breast carcinoma. She was surgically treated (breast quadrantectomy with axillary dissection) and receiving a third cycle of adjuvant chemotherapy when a feeling of a constant pressure in the front of the neck and lack of air occurred. Subsequent work-up revealed a node in the right thyroid lobe with enlarged paratracheal bilateral and right mid and lower jugular lymph nodes. Fine-needle aspiration cytology, repeated within a 20 days window and analyzed by two different cytologists, showed a medullary thyroid carcinoma with a cervical lymph nodes metastasis so the patient underwent total thyroidectomy with selective and paratracheal neck dissection. Histology and immunohistochemistry revealed the specimen to be metastasis of breast carcinoma. During regular follow-up of our patient, eighteen months after initial diagnosis, no new metastases were found. To our best knowledge, this is the first described case of a thyroid metastasis of breast carcinoma that was cytologically misdiagnosed as a medullary thyroid carcinoma.

[Surgical treatment of thyroid gland diseases in childhood--our results]. / Kirursko lijecenje bolesti stitne zlijezde u djecjoj dobi--prikaz nasih bolesnika.

Thyroid gland diseases are the most common endocrinopathies in children. Vast majority of these conditions are treated with medical therapy but in individualised cases surgery is indicated. Decision about surgical treatment is made in cooperation of pediatric endocrinologist and surgeon, treatment options depend on the nature of the disease while the extent of surgical procedure is determined by the pathological changes present in the gland. In this paper we represent the results of surgical treatment of 41 children at our department from 1991 to 2009 and current trends in surgical treatement of thyroid gland diseases.

[Croatian Thyroid Society guidelines for rational detection of thyroid dysfunction]. / Smjernice hrvatskog drustva za stitnjacu za racionalnu dijagnostiku poremecaja funkcije stitnjace.

Thyroid dysfunction is common in the population, especially in women, and thyroid diagnostic tests are among the most often used diagnostic procedures nowadays. Many thyroid societies developed guidelines for the detection of thyroid dysfunction. An interdisciplinary team of experts from the Croatian Thyroid Society studied guidelines of other thyroid societies and international publications, and according to our tradition and clinical practice developed guidelines for rational detection of thyroid dysfunction; hypothyroidism and hyperthyroidism. The aim of these guidelines is to recommend evidence-based and rational approach to the detection of thyroid dysfunction.

Psychosis and EEG abnormalities as manifestations of Hashimoto encephalopathy.

Hashimoto encephalopathy (HE) is a distinct form of encephalopathy, which can manifest itself with purely psychiatric symptoms. A 38-year-old female with history of rheumatoid arthritis was treated with psychotropic drugs for a couple of years in psychiatric structures because of the onset of depressive symptoms, psychoticlike manifestations, and impairment of cognitive functions. The electroencephalography (EEG) was characterized by general slowing with high voltage (2 to 3 Hz) delta biphasic and triphasic waves. Once a firm diagnosis of HE was made, corticosteroid treatment resulted in resolution of her psychiatric symptoms, marked EEG improvement, and partial improvement in her cognitive functions. HE should be suspected in young females with history of autoimmune disorders and EEG abnormalities.

Urokinase-type plasminogen activator and its inhibitor in thyroid neoplasms: a cytosol study.

PURPOSE: Higher levels of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) are linked to the poor prognosis in a variety of malignances. uPA and PAI-1 were expressed in most thyroid carcinomas, as had been measured immunohistochemically. However, no relationship between their expression and clinicopathological parameters were found. Aim of the present study was to investigate the expression and clinical relevance of uPA and PAI-1 in thyroid cancer. PATIENTS AND METHODS: uPA and PAI-1 in paired cytosol samples of thyroid tumor and normal tissue were determined in 23 patients using enzyme-linked immunosorbent assay and correlated to the known prognostic features. RESULTS: Both uPA and PAI-1 concentrations were significantly higher in malignant thyroid tumors (uPA=1.342 +/- 2.944 and PAI-1=17.615 +/- 31.933 ng/mg protein) than in normal tissue (uPA=0.002 +/- 0.009, P=0.011 and PAI-1=2.333 +/- 0.338 ng/mg protein, P=0.001) with positive correlation of the two proteins in the tumors. There were no differences in proteins' levels between benign tumors and normal tissue. Both proteins' concentrations were significantly different among various histological grades (uPA P=0.024 and PAI-1 P=0.017), showing higher values in higher tumor grades (grade I uPA=0.116 +/- 0.247 and PAI-1=4.802 +/- 4.151 ng/mg protein; grade III uPA=8.45 +/- 2.192 and PAI-1=94.65 +/- 59.468 ng/mg protein). The uPA and PAI-1 levels showed significant differences among different histological types of thyroid cancer (uPA P=0.049 and PAI-1=0.017). The lowest values were in adenomas (uPA=0.013 +/- 0.025 and PAI-1=2.785 +/- 1.069 ng/mg protein) and the highest in anaplastic carcinomas (uPA=8.45 +/- 2.192 and PAI-1=94.65 +/- 59.468 ng/mg protein). uPA and PAI-1 were significantly higher in anaplastic vs. well-differentiated cancers (uPA P=0.014 and PAI-1 P=0.026), if extrathyroidal invasion (uPA P=0.019 and PAI-1 P=0.009) or distant metastases (uPA P=0.006 and PAI-1 P=0.003) had been present, and in tumors whose size exceeded 1 cm in diameter (uPA P=0.009 and PAI-1 P=0.035). Only PAI-1, but not uPA was significantly higher in multicentric vs. solitary tumors (P=0.012) and lymph node positive compared to lymph node negative patients (P=0.042). The differences of uPA and PAI-1 did not reach the significant level when patients with well-differentiated tumors below and above 40 years of age had been compared. Survival analysis revealed the significant impact of both uPA and PAI-1 on the Progression-Free Survival (PFS) (38.84 vs. 3.67 months for patients with low and high uPA, respectively, P<0.001; 38.2 vs. 12 months for patients with low and high PAI-1, respectively, P=0.016). CONCLUSIONS: The correlation of high uPA and PAI-1 with the known prognostic factors of poorer outcome and with lower PFS rate in patients with thyroid cancers proved that these proteins could be an additional prognostic parameter.