CHD risk in acromegalic patients, predicted by FS as in nonacromegalic subjects, is low; AS might have adjunctive role only in a subset of patients. However, most patients have systemic complications of acromegaly, which participate in the assessment of global CHD risk.

Amiodarone-induced thyrotoxicosis (AMT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities and is believed to be due to increased thyroid hormone synthesis and release; Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone-induced destructive process of the thyroid. Management differs in the two forms of AIT, since Type 1 usually responds to combined thionamides and potassium perchlorate therapy, while Type 2 is generally responsive to glucocorticoids. Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and destructive phenomena, may require a combination of the two therapeutic regimens. In this cross-sectional prospective study, 55 consecutive untreated patients, whose AIT was subtyped according to clinical and biochemical criteria, were evaluated to assess the specificity of color flow doppler sonography (CFDS) and thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen patients (6 men, 10 women, age 66+/-13 yr), who had diffuse or nodular goiter with or without circulating thyroid autoantibodies, were classified as Type 1 AIT; 39 patients (27 men, 12 women, age 65+/-13 yr) with apparently normal thyroids were classified as Type 2 AIT. All Type 1 patients had normal or increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal or elevated thyroidal 3-h and 24-h RAIU values (range 6-37% and 10-58%, respectively), in spite of elevated values of urinary iodine excretion; the remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had low 3-h and 24-h RAIU values (range 1.1-3.0% and 0.9-4.0%, respectively). The latter patients, who were unresponsive to the combination of methimazole and potassium perchlorate, became euthyroid after the addition of glucocorticoids. Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4-3.7% and 0.2-3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU values (6% and 13%, respectively). In conclusion, CFDS can accurately distinguish between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus, assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and help in selecting the appropriate therapy. Finally, in long standing iodine sufficient areas, such as the United States, where the thyroid RAIU is consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and available method to differentiate between Type 1 and Type 2 AIT.

CMR is considered to be the gold standard for evaluating cardiac hypertrophy, fibrosis and systolic function. Using CMR, 72% patients with untreated active acromegaly had LV hypertrophy, which was only detected in 36% patients by echocardiography. However, cardiac fibrosis was absent in all patients irrespective of the estimated duration of disease. Although a very small increase in collagen content (as suggested by increased cardiac reflectivity at IBS), not detectable by CMR, could not be ruled out, it is unlikely that it would significantly affect cardiac function.

Objective: The objective of the study was to evaluate the expression and functional activity of Peroxisome proliferator-activated receptor (PPAR) g 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 PPARg was evaluated by RT-PCR and Western blot. Apoptosis and cell cycle were assessed by FACS analysis. The effects of PPARg ligands on transcriptional regulation of GH gene were evaluated by RT-PCR and electromobility shift assay. Results: PPARg 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 PPARg was functionally active. Treatment of GH3 cells with TZDs increased apoptosis in a dose-dependent manner (P ¼ 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). PPARg-RXRa heterodimers bound to GH promoter, inhibiting its activity and reducing GH mRNA levels (1.8 £ 10 6 vs 5.7 £ 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 PPARg 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.