Role of IL33 in chronic inflammation and microvascular damage as a reflection of organ damage on a cohort of patients with acromegaly.

AIM: Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-1) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC). METHODS: IL33 have been assessed in 40 AP and 40 HC. IL 33 was determined and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations. RESULTS: IL33 was significantly higher in AP compared to HC [45.72 pg/ml (IQR 28.74-60.86) vs 14 pg/ml (IQR 6.5535); p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [53.39 pU (IQR 40.94-65.44) vs 87 pU (IQR 80-98) p < 0.001]. The median values of ROI1, ROI2 and ROI3 were significantly lower in AP compared to HC [97.32 pU (IQR 50.89-121.69) vs 131 pU (IQR 108-135); p < 0.001], [58.68 pU (IQR 37.72-84.92) vs 83 pU (IQR 70-89), p < 0.05] and HC [52.16 (34.47-73.78) vs 85 (78-98), p < 0.001], respectively. The proximal-distal gradient (PDG) was observed in 18 of 40 (45%) AP. CONCLUSION: Serum IL33 is higher in AP compared to HC; conversely a reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction, strictly dependent on acromegaly and are not influenced by the choice of treatment.

Erectile function and androgen and estrogen beta receptor gene polymorphisms in acromegalic men.

PURPOSE: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms. METHODS: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERß gene polymorphisms analyses and filled out the IIEF-15 questionnaire. RESULTS: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERß receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present. CONCLUSIONS: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.

Evaluation of trans-sphenoidal surgery in pituitary GH-secreting micro- and macroadenomas: a comparison between microsurgical and endoscopic approach.

AIM: Acromegaly is caused by a GH-secreting pituitary adenoma, associated with many comorbidities and increased risk of mortality. Surgery is the first-line therapy. Success of therapy is measured by symptomatic improvement, preservation of pituitary function and biochemical control. Trans-sphenoidal surgery (TSS), endoscopic or microscopic, is the preferred treatment. To evaluate surgery effectiveness and individuate the technique associated with a higher remission rate, patients undergoing TSS were retrospectively selected. METHODS: Thirty-seven consecutive patients underwent surgery between 1996 and 2006. Tumors were classified into macroadenomas or microadenomas and into intrasellar, extrasellar and extrasellar with cavernous sinus invasion. Surgery was performed in 22 patients with endoscopic technique, in 15 patients with microsurgical approach. The hormonal assays were performed 6 months and yearly after surgery for an average of 5 years. RESULTS: Ten patients were affected by microadenoma, 27 by macroadenoma. In microadenomas remission rate was independent of the used technique. Within macroadenomas, remission percentage in endoscopic approach (68.75%) was significantly higher than in microscopic approach (18.18%) (P=0.018). Postsurgical biochemical remission was calculated combining the surgical technique and tumor extension: the endoscopic approach was associated with a significantly higher remission rate in extrasellar than both in intrasellar and extrasellar with cavernous sinus invasion. In the latter group, any technique had not reached biochemical remission. CONCLUSION: TSS is able to induce a long-term remission of acromegaly, with low risk of recurrence and complications. Endoscopic approach is more suitable than microscopic technique in macroadenomas and adenomas with suprasellar extension.

Minimally invasive thyroidectomy and the differentiated lesions: the way to follow.

BACKGROUND AND OBJECTIVES: Nowadays, the conventional thyroidectomy may appear an overly aggressive treatment in patients undergoing intervention for small suspicious lesions harboring in low volume glands. In these cases a minimally invasive approach may be a safe and appropriate option. This work aims to evaluate the effectiveness of minimally invasive thyroidectomy in patients indicated to surgery for small lesions with preoperative suspicion of malignancy. PATIENTS AND METHODS: 71 patients, undergoing minimally invasive total thyroidectomy as a single procedure between May 2005 and April 2009, were enrolled in this study. They were indicated to surgery for small suspicious or malignant lesions (up to 20 mm lenght by US; cT1 according to UICC 2002) and satisfied the inclusion criteria of minimally invasive thyroidectomy, with gland volume up to 25 ml, no evidence of locally advanced disease and no previous neck surgery. The outcomes were considered in terms of complication rate, postoperative pain, hospitalisation stay, cosmetic results and completeness of surgical resection in malignancies. RESULTS: A low complication rate was registered. The surgical completeness, with mean serum thyroglobulin of 4.41 +/- 4.03 ng/ml and radioiodine uptake of 2.91 +/- 2.46%, was considered acceptable if compared with other experiences reported in literature. Excellent results with respect to patient comfort, postoperative pain and cosmetic outcome were obtained. CONCLUSION: This study confirms, where a correct selection of patients is made, the safety and the effectiveness of minimally invasive approach in the treatment of small suspicious and malignant nodules, which seem to represent its best indication.

A case of GH deficiency and beta-thalassemia.

A 23-year-old male patient, who suffers from beta-thalassemia major, came to us for an endocrine-metabolic evaluation. Medical history showed a diagnosis of heart disease with heart failure since the age of 16, type 1 diabetes mellitus diagnosed at the age of 18, treated with an intensive insulin therapy with a poor glycometabolic control. Patient performed regular blood transfusions and iron chelation with deferasirox. An echocardiogram revealed an enlarged left ventricle. Patient had undergone a comprehensive study of buoyancy both basal and hormone-stimulated and it was therefore carried out a diagnosis of GH deficiency and hypogonadotropic hypogonadism. A recombinant GH replacement therapy was then prescribed. After six months of therapy, the patient reported a net improvement of asthenic symptoms. Physical examination showed a reduction in abdominal adiposity in waist and an increase of 5 cm in stature. Laboratory tests showed an amelioration of glycometabolic control, such as to justify a reduction in daily insulin dose. The stature observed was thought appropriate to begin the administration of testosterone. Moreover, the cardiological framework showed a reduction of left ventricular dilatation, good ventricular motility, global minimum persistent tricuspid but not mitral regurgitation and no alteration on ECG.

Diagnostic accuracy of mammography readers and their memory performance have no correlation with each other.

INTRODUCTION: The study aims to determine if any association exists between visual memory performance and diagnostic accuracy performance in a group of radiologist mammogram readers. MATERIALS AND METHODS: One hundred proven mammograms (23 with cancers) were grouped into 5 sets of 20 cases, with sets being of equal difficulty. Pairs of sets were presented in 5 reads (40 cases per read, order random) to a panel of 8 radiologist readers (either present or past screening readers, with experience range from <1 year to >20 years). The readers were asked to either 'clear' or 'call back' cases depending on need for further workup, and at post-baseline reads to indicate whether each case was 'new' or 'old' (i.e. remembered from prior read). Two sets were presented only at baseline (40 cases per reader), and were used to calculate the reader's false recollection rate. Three sets were repeated post-baseline once or twice (100 cases per reader). Reading conditions were standardised. RESULTS: Memory performance differed markedly between readers. The number of correctly remembered cases (of 100 'old' cases) had a median of 10.5 and range of 0-58. The observed number of false recollections (of 40 'totally new' cases) had a median of 2 and range of 0-17. Diagnostic performance measures were mean (range): sensitivity 0.68 (0.54-0.81); specificity 0.82 (0.74-0.91); positive predictive value (PPV) 0.55 (0.50-0.65); negative predictive value (NPV) 0.89 (0.86-0.93) and accuracy 0.78 (0.76-0.83). Confidence intervals (CIs; 95%) for each reader overlapped for all the diagnostic parameters, indicating a lack of statistically significant difference between the readers at the 5% level. The most sensitive and the most specific reader showed a trend away from each other on sensitivity, specificity, NPV and PPV; their accuracies were 0.76 and 0.82, respectively, and their accuracy 95% CIs overlapped considerably. Correlation analysis by reader showed no association between observed memory performance and any of the diagnostic accuracy measures in our group of readers. In particular, there was no correlation between diagnostic accuracy and memory performance. CONCLUSION: There was no association between visual memory performance and diagnostic accuracy as a screening mammographer in our group of eight representative readers. Whether a radiologist has a good or a bad visual memory for cases, and in particular mammograms, should not impact on his or her performance as a radiologist and mammogram reader.

[Efficacy of external conventional radiotherapy in short and long term control of acromegaly; a comparison with stereotactic irradiation]. / Efficacia della Radioterapia Convenzionale nel controllo abreve e a lungo termine della malattia acromegalica: confrontocon la metodica stereotassica.

AIMS: The aim of this study was to follow up two groups of patients with active acromegaly, who underwent to external irradiation and radio-surgery and to value the efficacy of irradiation in the control of the growth of the adenoma, hypersecretion and incidence of adverse events. MATERIALS AND METHODS: In 2 groups of patients, (A) of 47 subjects treated with conventional irradiation at a dose of 45 Gy, (B) of 6 subjects irradiated with stereo taxis radiotherapy at a dose of 15-20 Gy, were evaluated GH, IGF1 levels and pituitary function at 2, 5, 10 and 15 years after treatment. A cerebral MRI scan with detailed study of the sellar region was performed every year. RESULTS: Group (A): decrease of GH levels in 9% of patients after 2 years from therapy, 29% after 5 years, 52% after 10 years, 77% after 15 years; normalization of IGF1 levels in 8% of cases after 2 years, 23%, 42% and 61% respectively after 5, 10 and 15 years; hypopituitarism in 57, 78, 85% of patients, respectively after 5, 10 and 15 years. Group (B):normalization of IGF1 levels in 4 of 6 patients after 5 years and in all subjects after 10 and 15 years; progressive decrease of GH levels in all patients and GH normalization in 2 of 6 cases after 10 years; hypopituitarism in 1 patient after 2 years. CONCLUSIONS: We confirm the long term efficacy of external Radiotherapy in active acromegaly. Stereo taxis annuls the risks of neurological and neurovascular complications of conventional RT. Although comparison between the two techniques is not statistical significant in our cases we can affirm a faster normalization of IGF1 levels after stereotactic treatment.

Prevalence of celiac disease in patients with autoimmune thyroiditis.

AIM: Many autoimmune disorders are associated to celiac disease (CD) but the association with autoimmune thyroiditis has been more frequently documented; this is in part explained by a shared immunogenetic make-up, and in part caused to time gluten-exposition, as suggested by the significant correlation observed in celiac patients between the increase occurrence of autoimmune diseases and the length of exposure to gluten. The aim of this study was to establish the prevalence of celiac disease in a group of subjects with autoimmune thyroiditis newly diagnosed on the basis of antibodies anti-peroxidase (TPO). METHODS: A total of 113 untreated patients with TPO >70 IU/mL were enrolled. CD was screened by measuring anti-endomysial antibodies (EMA) both IgA and IgG; an high prevalence of positive serology was resulting in this group, justified, in part, from EMA IgG investigation. RESULTS: In fact 31/113 patients showed IgA and/or IgG positivity and were diagnosed as celiacs with jejunal biopsy. CONCLUSION: On the basis of this paper, such as in according to current research-setting studies, the greater frequency of CD in association to autoimmune thyroid disease suggests that all subjects with TPO should be routinely screened for CD, through EMA IgA and IgG. However, the performance of this screening has never been evaluated until now, even if it could, in fact, be valid in order to increment diagnosis of CD, today still undiagnosed.

Temporomandibular joint air in fractures of the skull base.

Basilar skull fractures involving the temporal bone extend through the tympanic part of the temporal bone in two-thirds of cases. The anatomical relationship of this part of the temporal bone and the temporomandibular joint enables air to pass from the auditory canal into the joint. Air in the temporomandibular joint is demonstrated on CT scans as an indirect sign of temporal bone fracture.

Reduced HDL2 levels in myocardial infarction patients without risk factors for atherosclerosis.

Out of a total of 170 patients with a first myocardial infarction, aged below 65 years, consecutively admitted to the Coronary Care Unit of a large urban hospital, only 14 did not present with any risk factor(s) for atherosclerosis (smoking, hypertension, diabetes and obesity). None of these 14 patients showed significant hyperlipidemia. Compared to a control series of normal individuals of the same age (50.0 +/- 5.8 years for males and 61.6 +/- 3.0 years for females), they showed a significant reduction of high-density lipoprotein (HDL)-cholesterol and of apolipoprotein A-I (respectively -18.2 and -9.5%). However, the most striking abnormality was a 30% decrease of the HDL2 mass and of HDL2 cholesterol; both HDL2 and HDL3 had a reduced cholesteryl ester content in the patients. Reduced HDL2 mass and cholesterol levels in plasma, accompanied by significant alterations in HDL subfraction composition, are consistent with a defective cholesterol esterification in HDL. HDL2 deficiency may be a primary alteration in myocardial infarction patients without other significant risk factors.