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T Rago, P Vitti, L Chiovato, S Mazzeo, A De Liperi, P Miccoli, P Viacava, F Bogazzi, E Martino, and A Pinchera

The aim of the present study was to establish the usefulness of conventional thyroid ultrasonography (US) and color flow-doppler (CFD) sonography in the assessment of 'cold' thyroid nodules. One hundred and four consecutive patients with thyroid nodules who were to undergo surgery were examined by US and CFD before thyroidectomy. Conventional US evaluated the presence of a halo sign, hypoechogenicity and microcalcifications. The vascular pattern on CFD was classified as follows: Type I, absence of blood flow; Type II, perinodular blood flow; Type III, marked intranodular blood flow. On histology, 30 nodules were diagnosed as malignant (carcinoma, CA) and 74 as benign nodules (BN). On US, the echographic pattern most predictive for malignancy was absent halo sign, which was found in 20/30 CA and in 17/72 BN (P = 0.0001; specificity 77.0%; sensitivity 66.6%). The most specific combination on US, absent halo sign/microcalcifications, was found in 8/30 CA and in 5/74 BN (P < 0.005; specificity 93.2%, sensitivity 26.6%). The Type III pattern on CFD was found in 20/30 CA and 38/74 BN (not statistically significant). The combination of absent halo sign on US with Type III pattern on CFD was found in 15/30 CA and in 8/74 BN (P < 0.0001; specificity 89.0%, sensitivity 50.0%). The combination of absent halo sign/microcalcifications on US with Type III pattern on CFD was the most specific combination of the two techniques, being found in 5/30 CA and in only 2/74 BN (P < 0.01; specificity 97.2%, sensitivity 16.6%). In conclusion, findings on US and CFD become highly predictive for malignancy only when multiple signs are simultaneously present in a thyroid nodule. Thus the predictive value of these techniques increases at the expense of their sensitivity. Only in a small proportion of patients with thyroid carcinoma is US and CFD information highly predictive of malignancy.

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C Marcocci, S Mazzeo, G Bruno-Bossio, A Picone, E Vignali, M Ciampi, P Viacava, AG Naccarato, P Miccoli, P Iacconi, and A Pinchera

OBJECTIVE: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperparathyroidism. METHODS: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. RESULTS: Based on the results of neck US and parathyroid scintigraphy, patients were divided into two groups. Group 1: 16 patients (seven with nodular goiter) with concordant positive US and scintigraphic results. In all but one patient, PTHa was detectable and often markedly elevated (> 1000 pg in 12 patients, between 292 pg and 803 pg in three patients and 53 pg in one patient). The patient with undetectable PTHa had a small lower left parathyroid adenoma (8x8x10 mm). Group 2: 17 patients (12 with nodular goiter) with discordant US and scintigraphic results. PTHa established the parathyroid nature of the mass in 13 cases (> 1000 pg in 8 patients, between 501 pg and 953 pg in three patients and 90 and 79 pg in two patients): 11 of these had a suspected lesion by US examination but the scintigraphy results were negative; two had a mass that gave positive scintigraphy results but was of uncertain origin according to US: in both cases an intrathyroidal parathyroid adenoma was found. PTHa was undetectable in four cases (three with nodular goiter): all of these had equivocal US results, and three had positive scans and one a negative scan. CONCLUSIONS: Assay of PTHa is a simple method and should be useful for confirming the parathyroid nature of a cervical mass in patients with discordant or non-diagnostic US and scintigraphic results.

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F Bogazzi, F Ultimieri, F Raggi, D Russo, R Vanacore, C Guida, P Viacava, D Cecchetti, G Acerbi, S Brogioni, C Cosci, M Gasperi, L Bartalena, and E Martino

OBJECTIVE: The objective of the study was to evaluate the expression and functional activity of Peroxisome proliferator-activated receptor (PPAR) gamma in pituitary adenomas from 14 consecutive acromegalic patients and to establish its role in apoptosis. SUBJECTS AND METHODS: Fourteen consecutive acromegalic patients were enrolled in the study. Wistar-Furth rats were used for in vivo studies. Expression of PPARgamma was evaluated by RT-PCR and Western blot. Apoptosis and cell cycle were assessed by FACS analysis. The effects of PPARgamma ligands on transcriptional regulation of GH gene were evaluated by RT-PCR and electromobility shift assay. RESULTS: PPARgamma was expressed in all human GH-secreting adenoma (GH-oma), in normal pituitary tissue samples (39+/-24% and 78+/-5% of immunostained nuclei respectively; P<0.0002; ANOVA), and in rat GH-secreting (GH3) cells. A PPRE-containing reporter plasmid transfected into GH3 cells was activated by ciglitazone or rosiglitazone (TZDs), indicating that PPARgamma was functionally active. Treatment of GH3 cells with TZDs increased apoptosis in a dose-dependent manner (P=0.0003) and arrested cell proliferation, reducing the number of cells in the S-phase (P<0.0001 vs untreated cells). TZDs increased the expression of TRAIL, leaving unaffected that of p53 and Bax. TZDs reduced GH concentrations in the culture media from 43.7+/-5.4 ng/ml to 2.1+/-0.3 ng/ml (P<0.0001) and in cell extracts (P<0.004). PPARgamma-RXRalpha heterodimers bound to GH promoter, inhibiting its activity and reducing GH mRNA levels (1.8 x 10(6) vs 5.7 x 10(6) transcripts respectively vs untreated cells; P<0.002). Subcutaneous GH-oma developed in rats injected with GH3 cells; tumor growth increased in placebo-treated rats and to a lesser extent in TZDs-treated animals (24.1+/-2.0 g, and 14.8+/-4.2 g respectively, P<0.03). Serum GH concentrations were lower in TZDs-treated rats than in controls (871+/-67 ng/ml vs 1.309+/-238 ng/ml; P<0.05). CONCLUSIONS: The results of this study indicate that PPARgamma controls GH transcription and secretion as well as apoptosis and growth of GH-oma; thus, TZDs have the potential of a useful tool in the complex therapeutic management of acromegalic patients.