Serum from patients with erectile dysfunction inhibits circulating angiogenic cells from healthy men: relationship with cardiovascular risk, endothelial damage and circulating angiogenic modulators.

Erectile dysfunction (ED) is an early manifestation of arteriosclerosis associated with endothelial damage/dysfunction and to a blunted ability of cultured mononuclear circulating cells (MNCs) to differentiate circulating angiogenic cells (CACs), putatively involved in endothelial damage repair. Here we explored effects of human serum (HS) from patients with ED and cardiovascular risk factors (VRFs) but no clinical atherosclerosis, on cultured MNCs of healthy men to differentiate CACs and to form colonies. Effect of HS on number of CACS and of colony forming units (CFUs) was correlated with circulating markers of endothelial damage and with angiogenic modulators. MNCs from healthy men were cultured in standard conditions or with 20% HS from 35 patients with ED and from 10 healthy men. CACs were identified after 7 days of culture by uptake of acetylated low-density lipoprotein with concomitant binding of Ulex europaeus agglutinin I. CFUs were counted after 5 days of culture. Enzyme-linked immunosorbent assays assessed plasmatic soluble (s) form of E-selectin, Endothelin (ET)-1, tissue type plasminogen activator (tPA), vascular endothelial growth factor (VEGF)(165) and sVEGF receptor (R)-1. The number of CACs and of CFUs from healthy men was reduced after culturing MNCs with HS compared to standard medium. The inhibitory effect was significantly higher with HS from ED patients with higher or lower VRF exposure compared to healthy men. Inhibition was positively correlated with VRFs exposure, with ED severity, with common carotid artery intima media thickness measured using B-mode ultrasound, and to a lesser extent with plasmatic sE-Selectin, sET-1 and sVEGFR-1. Dysfunction of cells involved in vascular homoeostasis is induced by soluble factors still unknown and already present in a very initial systemic vascular disease in men with ED and VRFs.

Ultrasoundelastography: Can it provide valid information for differentiation of benign and malignant thyroid nodules?

Ultrasoundelastography (USE) is a new imaging technique that is performed with a normal ultrasound transducer. It provides improved characterization of a tissue or nodule based on the latter's elasticity and stiffness. The aim of the present, prospective study was to assess the validity of USE in characterizing thyroid nodules. USE patterns were analyzed in light of nodule cytology (British Thyroid Association classification) to determine whether these patterns can be used to decide whether or not fine-needle aspiration cytology (FNAC) is indicated. We examined a consecutive series of 617 thyroid nodules in patients referred for the first time to the Endocrinology Unit of Atri Hospital (Atri, [TE]). Patients underwent ultrasonographic and USE examinations of their thyroid nodules, which were then subjected to FNAC. All nodules with Thy 1 cytology were excluded, leaving 567 nodules for analysis. USE findings were classified on the basis of the degree and distribution of elasticity within the lesion: four patterns were identified (1, 2, 3a, 3b, or 4).None of the nodules with Thy 4 cytology (malignant) had USE pattern 1 or 2; patterns 3 and 4 were associated with higher cytologic grades. In conclusion, USE provides additional information on thyroid nodules, which can be used with ultrasound features of the nodules, to decide whether FNAC is indicated. In fact, patterns 1 and 2 do not seem to be associated with Thy 4 cytology.

Unusual clinical manifestation of pheochromocytoma in a MEN2A patient.

A case of unusual clinical manifestation of pheochromocytoma in a type 2A multiple endocrine neoplasia (MEN2A) patient is presented. A 27-year-old man affected by MEN2A syndrome, complaining of anxiety and depression, was admitted in our Division. Past medical history included a total thyroidectomy for medullary carcinoma in 1985, and left adrenalectomy for pheochromocytoma in 1994. Blood pressure was 130/ 85 mmHg without orthostatic hypotension and pulse rate was 72 beats/min. Laboratory data revealed thyroid hormones and carcinoembryonic antigen (CEA) in the normal range and high basal serum calcitonin levels (158 pg/ml). Plasma catecholamines and vanillylmandelic acid resulted in normal levels but epinephrine/norepinephrine ratio was elevated (0.65). The glucagon stimulation test showed positive clinical and biochemical response. Magnetic resonance imaging (MRI) and meta-iodobenzylguanidine (MIBG) scintiscan confirmed the presence of bilateral adrenal masses. Bilateral adrenalectomy by laparoscopic anterior approach was performed. Histology was consistent with adrenal pheochromocytomas. After surgical approach, psychiatric findings disappeared and did not recur at follow-up in spite of no medication for two years. In conclusion, bilateral pheochromocytoma is more frequent in MEN2A syndrome and probably understimated if the follow-up is not prolonged. In these cases clinical features are often aspecific and basal hormonal data may be normal in a great number of patients. Therefore long-term observation is justified in these patients. Pheochromocytoma was described as the "great mimic" for the numerous subjective manifestations. Differential diagnosis among typical features of neuropsychiatric disorders and pheochromocytoma must be considered.

Prevalence of dementia and apolipoprotein e genotype distribution in the elderly of buttapietra, verona province, Italy.

We investigated the prevalence of dementia and the apolipoprotein E (APOE) genotype distribution in the elderly of Buttapietra, a village near Verona, Italy. All residents over the age of 74 (n = 238), including those who were institutionalized, were studied using a direct-contact, single-phase design. The overall prevalence of dementia, clinically defined by DSM-III-R criteria, was 15.8 cases per 100 population, with age-specific figures increasing steeply with advancing age in both sexes. Alzheimer's disease (AD) was the most frequent dementing disorder (43%). APOE genotyping was determined after DNA amplification by restriction isotyping. We found that the epsilon4 allele and the epsilon3/epsilon4 genotype were associated with all types of dementia, although only the association of epsilon3/epsilon4 with AD reached statistical significance (odds ratio 4.5, 95% confidence interval 1.3-16.1). However, as reported in other Mediterranean countries, the frequency of the epsilon4 allele in our population was low (8.9%), suggesting that the population-attributable risk for AD, at least for elderly individuals (> or =75 years), could be small.

Effect of finasteride in idiopathic hirsutism.

Increased 5 alpha-reductase activity has been found in hair follicles of hirsute women, suggesting a pathogenetic role. The aim of the present study was to evaluate the effect of finasteride in the treatment of idiopathic hirsutism. Twenty-seven women with idiopathic hirsutism, aged 16-35 years, were treated for 6 months with finasteride, 5 mg once daily. Fourteen patients were on finasteride alone (group A), while the remaining received in addition an oral contraceptive (group B). Clinical, hormonal and biochemical evaluation were performed before, and after 3 and 6 months of treatment. Clinical evaluation was repeated 6 months after drug discontinuation in seven patients. Treatment was well tolerated by all patients; no side effects or adverse reactions were reported. A significant improvement of hirsutism was obtained by finasteride; clinical score observed at the 6th month of therapy was reduced from 11.71 +/- 2.23 to 7.92 +/- 1.81 (p < 0.05) and from 14.92 +/- 6.13 to 9.3 +/- 2.75 (p < 0.05) in group A and B, respectively. Clinical score in seven patients was still 8.61 +/- 2.28 (p < 0.05) 6 months after the end of therapy. Finasteride treatment alone (group A) induced a slight increase, though not significant, in serum androgens; DHT and SHBG did not change. In group B (finasteride plus oral contraceptive) total testosterone and free testosterone showed no significant decrease; after 6 months of therapy DHT was reduced significantly, while SHBG levels were increased. These data demonstrate that 5 alpha-reductase inhibition may be an effective treatment in women suffering from idiopathic hirsutism. This approach may be attractive due to the absence of adverse reactions, although the necessity of an adequate contraception should be kept in mind.

Laparoscopic adrenalectomy: a report on 50 operations.

OBJECTIVE: To investigate the feasibility, safety and results of laparoscopic transperitoneal adrenalectomies performed with the patient supine, in patients affected by secreting and silent adrenal lesions. METHODS: Exclusion criteria were suspected adrenal primary malignancies. Fifty patients (33 women and 17 men; mean age 49.6 years, range 19-75 years) underwent 51 laparoscopic adrenalectomies (one bilateral). After complete endocrinological evaluation, computed tomography or magnetic resonance imaging, or a combination thereof, 14 non-secreting adenomas, 13 aldosterone-producing adenomas, 13 cortisol-producing adenomas, eight phaeochromocytomas (one bilateral), one androgen-secreting adenoma, and two metastases were considered eligible for adrenalectomy. In five patients, associated procedures were performed during surgery. RESULTS: The lesions ranged in size from 1.5 to 10 cm. There were no intraoperative complications and no blood transfusions were required. The postoperative course was uneventful and painless in all patients. Mean postoperative hospital stay was 2.5 days. In all hypertensive patients, significant improvement or cure of hypertension was observed at follow-up (mean 18 months). In patients with secreting adenomas, normalization of hormone concentrations was obtained after removal of the tumour. In six patients with incidentaloma, the exaggerated 17-hydroxyprogesterone response to ACTH disappeared after surgery. CONCLUSIONS: Secreting and non-secreting adrenal lesions were treated safely by laparoscopy. Relatively small incidentalomas and subclinical hormonally active tumours can be removed by laparoscopy. Early diagnosis enhances prevention and treatment.

[Comparison between the diagnostic accuracy in diagnosis of thyroid nodules with fine needle biopsy an intraoperative histological evaluation of frozen tissue]. / Raffronto dell'accuratezza diagnostica nella diagnosi dei noduli tiroidei fra biopsia con ago sottile e valutazione istologica intraoperatoria su tessuto congelato.

BACKGROUND: The aim of this study was to compare the diagnostic accuracy of fine needle biopsy (FNB) and intraoperative frozen-section biopsy (FS) regarding the surgical management of thyroid nodules. METHODS: A total of 812 patients with solitary nodule or dominant nodule in a multinodular goiter were evaluated. The patients underwent preoperative FNB and intraoperative FS diagnosis. RESULTS: The definitive histological diagnosis (HD) was: i) 222 malignant lesions (118 papillary, 67 follicular, 16 anaplastic and 8 medullary cancers); ii) 590 benign lesions. FNB accuracy was 90.6%, sensitivity 96.8% and specificity 87.1%. FS accuracy was 97.4%, sensitivity 91.3% and specificity 100%. False negative (FN) were 10 for FNB and 21 for FS. False positive (FP) were 74 for FNB and 0 for FS. FS was less sensitive for the diagnosis of papillary cancer (more FN) and more specific for the diagnosis of follicular thyroid cancers (no FP). CONCLUSIONS: In conclusion, FS is useful in patients undergoing surgery for a thyroid nodule having a "suspicious" cytology. It adds no information in patients with an FNB diagnosis of malignancy and is of limited use in those in whom an FNB benign lesion is diagnosed.

[Evaluation of the role of repeat needle biopsy in the diagnosis and follow-up of thyroid nodules]. / Valutazione del ruolo della ripetizione dell'agoaspirato nella diagnosi e follow-up del nodulo tiroideo.

The goal of the present study was to determine in what percentage of cases was an initial benign cytological diagnosis modified to malignant or suspicion of malignancy by a second aspiration biopsy. The study group consisted of 708 patients, 98 males and 610 females, mean age 46.3 +/- 13.7; FNB was always repeated on the same nodule. The first FNB (cytology I), classified the nodule as: non-diagnostic (group I, 205 cases) or diagnostic (group II, 503 cases); these latter were classified as benign (471) or suspect (32). In 82 cases of group I the second examination after six months (cytology II) was still unable to arrive at a diagnosis; in the remaining 123 cases, it was able to classify 120 as benign and 3 as suspect (the latter being followed up by diagnostic surgery). In group II, cytology II modified the initial diagnosis from benign to suspect (8 cases) or non-diagnostic (7 cases). On the other hand, 29 cases had a change of their initial diagnosis from suspect to benign. The remaining cases of group II repeated a thyroid FNB after one year (cytology III) with a result of benign (486) or non-diagnostic (6). In the 14 cases followed up by diagnostic surgery, due to a second biopsy diagnosis of suspicion, histology showed the presence of Follicular Adenoma in 12 cases and Hashimoto's Thyroiditis in the remaining 2. Based on follow-up surgery, the suspicious lesions seen on the second biopsy turned out to be all non-malignant. However, it is important to underline the greater number of cases where the second examination gave a benign diagnosis when the first examination was judged suspicious. One can conclude that it may be useful to repeat FNB: 1) when the first exam resulted in an inadequate sample, as a second biopsy allows one to classify the nodule 60% of the time; 2) in all cases where there is an initial benign diagnosis, when non-surgical follow-up (clinical and/or echographic) is suspicious.

[Cytological diagnosis of thyroid nodules. Comparison of results obtained with guided echography with those from of a "blind" biopsy]. / Diagnosi citologica dei noduli tiroidei. Comparazione dei risultati ottenuti con guida ecografica rispetto a quelli ottenuti a "cielo coperto"

The goal of the study was to verify if echographic fine needle biopsy (US-FNB) improved the diagnostic accuracy of thyroid nodules with respect to a "blind" technique (B-FNB). The study group involved 6,693 patients who underwent aspiration biopsies (989 males and 5,704 females; mean age 46.3 +/- 13.7; range 5-88 years). Total biopsies were 7,952 as some patients underwent two or more biopsies in different nodules. 7,324 nodules with B-FNB and 628 nodules with US-FNB were studied; in this latter cases 136 nodules were not palpable. The diagnosis of malignancy was higher in US- FNB than B-FNB. However, non-diagnostic samples were more prevalent in US-FNB with respect to B-FNB. A histological diagnosis was available in 27 patients with US-FNB and 379 with B-FNB. In US-FNB, accuracy was 81.8%, sensitivity 86.6% and specificity 77.7%. In B-FNB, accuracy was 80.6%, sensitivity 85.1% and specificity 78.1%. These data show that US-FNB diagnostic accuracy was not better than B-FNB. The higher incidence of malignancy found in US-FNB was not dependent on better accuracy, sensitivity or specificity of the US-FNB technique with respect to the B-FNB examination. It is possible that the higher number of malignancies in patients studied with US-FNB was due to the fact that the US-FNB technique aspirated smaller nodules and particular areas of echographic suspicion, thus increasing the possibility of finding a malignancy. Based on our data, we feel that US-FNB results in a greater number of diagnostically inadequate samples. This may depend in part on the smaller size of the biopsied nodules (which are relatively more vascular than larger nodules) and in part on the greater difficulty in carrying-out this technique which directed towards particular echographic areas of suspicion resulting in greater biopsy blood contamination. The authors feel that US-FNB should be carried-out in all cases of non-palpable nodes found incidentally so as to rule out malignancy.

[Anti-microsomal, anti-thyroglobulin antibodies and thyroid stimulants in hyperthyroid subjects. Analysis of 315 patients followed-up for 3 years at a single medical center]. / Anticorpi anti micrsomi, anti tireoglobulina e tiroido stimolanti in soggetti ipertiroidei. Analisi di 315 pazienti seguiti per tre anni presso un unico centro medico.

The objective of the study was to evaluate the significance of the determination of antithyroid antibodies in hyperthyroid patients. Two-hundred-fifteen untreated Graves' hyperthyroid patients (active toxic diffuse goiter-TDG), 54 Plummer's hyperthyroid patients (focal hyperthyroidism) and 46 subjects with other forms of hyperthyroidism were studied. Serum levels of T4, T3, TSH, TSH receptor antibody (TRAb), microsomal antibody (TMAb), and thyroglobulin antibody (TGAb) were evaluated before starting treatment, at regular intervals during therapy, and during the follow-up period after therapy was withdrawn. The antibodies were positive in all patients with active and non-active TGD but positive in only two patients (3.7%) with focal hyperthyroidism. During the treatment interval, TRAb, TMAb and TGAb serum levels fell with a nadir in the 7th month of therapy. In particular, TRAb fell to normal levels in all patients who had basal levels less than 500 U/l (97.7% of the cases) while TMAb and TGAb remained positive. Relapses, following the completion of therapy, occurred in 20.4% after one year and in 33% after two years. Relapses were always linked to a new increase in TRAb. In conclusion, TRAb can be useful in the determination of early disease and in diagnosing remission. It did not appear useful as a prognostic indicator for relapse in individual patients.

Treatment with a gonadotropin-releasing hormone agonist in acne or idiopathic hirsutism.

Six women with acne and six women with hirsutism were treated with the GnRH analog [D-Ser(Bu(t))6] LHRH-(1-9)ethylamide (Buserelin) for 6 months (nasal spray, 1,200 micrograms/day) to suppress ovarian steroidogenesis. All women were eumenorrheic and did not demonstrate any adrenal or ovarian dysfunction. During treatment, ovarian steroids, LH and FSH decreased, while DHEA-S showed minor modifications; the clinical score for both acne and hirsutism showed a significant reduction. Moreover, acne and hirsutism were still well controlled 6 months after therapy. Gonadal function resumed in all patients after discontinuation of therapy. Three patients suffered from hot flashes from the 4th month. These data demonstrate that suppression of ovarian steroid secretion might be an efficient treatment in women suffering from acne or idiopathic hirsutism, indicating that ovarian steroids may have a key-role in the pathogenesis of these conditions.