Cardiovascular accidents represent the most important cause of death in patients with Cushing’s syndrome. This prospective study aims at evaluating carotid arteries by echo-Doppler ultrasonography and clinical and metabolic markers of atherosclerosis in 25 patients with Cushing’s disease (CD) before and after 1 yr of remission. Thirty-two sex- and age-matched subjects (control-1) and 32 body mass index-matched subjects (control-2) served as controls. At diagnosis, CD patients had higher body mass index, waist to hip ratio (WHR), total, low-density lipoprotein-cholesterol and total/high-density lipoprotein (HDL) ratio, glucose and insulin, as well as lower HDL-cholesterol than control-1; they had higher WHR and total/HDL ratio and lower HDL-cholesterol than control-2. They also had higher intima-media thickness (IMT), and lower systolic lumen diameter and distensibility coefficient (DC) than either control group. Atherosclerotic plaques were detected in 31.2% of patients, 0 control-1, and 6.2% of control-2 subjects. One year after remission, WHR, LDL-cholesterol, and IMT significantly decreased, whereas systolic lumen diameter and DC significantly increased. However, all of the above parameters were still abnormal compared with control-1, but not control-2. A significant correlation was found between WHR, glucose and insulin levels, and right and left carotid IMT. WHR was the best predictor of left IMT and left DC in active, but not in cured, patients. The duration of hypercortisolism was the best predictor of right DC in active but not in cured patients. In conclusion, patients with CD have severe atherosclerotic damage. The persistence of a metabolic syndrome, vascular damage, and atherosclerotic plaques after cortisol level normalization makes these subjects still at high cardiovascular risk despite disease remission.

Typing somatostatin receptor expression in neuroendocrine tumors is of relevance to target somatostatin analogue-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect somatostatin receptors is to date not paralleled by an accurate methodological setting and standardized interpretation of the results. A multicentric study was designed to compare somatostatin receptor immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of neuroendocrine tumors. After methodological setting by testing different somatostatin receptor antibodies, 107 cases of neuroendocrine tumors with available somatostatin receptor scintigraphy data and pathological material were retrospectively analyzed for somatostatin receptor types 2A, 3 and 5 immunohistochemical expression, and compared with scintigraphic images and, whenever available, with the clinical response to somatostatin analogue treatment. Restricting ‘positive cases’ to the presence of a membrane pattern of staining, an overall somatostatin receptor type 2A immunohistochemistry/somatostatin receptor scintigraphy agreement of 77% (χ² test P<0.0001) was reached. Lower concordance ratios were detected in preoperative and metastatic tumor samples, possibly as a consequence of somatostatin receptor expression heterogeneity. Pure somatostatin receptor type 2A cytoplasmic staining showed poor correlation with somatostatin receptor scintigraphy (54% concordance rate). The immunohistochemical detection of somatostatin receptor types 3 and 5, which showed almost exclusively a cytoplasmic pattern, did not improve the concordance with scintigraphic data. In a pilot series, somatostatin receptor type 2A immunohistochemistry correlated with clinical response in 75% of cases. In conclusion, we propose a scoring system for somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors correlated with in vivo data, based on the evidence that only membrane (rather that cytoplasmic) staining should be considered for a reliable, standardized and clinically relevant report.

Based on the current medical literature, the worldwide incidence of neuroendocrine tumours (NETs) seems to have increased; however, a systematic literature overview is lacking. This study aimed to collect all available data on the incidence of gastroenteropancreatic (GEP)-NETs and characteristics of population to establish their epidemiology. A sensitive MEDLINE search was carried out. The papers were selected via a cascade process that restricted the initial pool of 7991 articles to 33, using predefined inclusion and exclusion criteria. Original articles evaluating the incidence of sporadic GEP-NETs in regional, institutional and national registries were considered. The majority of data originated from the US National Cancer Institute Surveillance, Epidemiology and End Results database and from national cancer registries in Western Europe. Generally, because of the retrospective nature of existing databases the outcomes of studies might be biased, which hinders the drawing of firm conclusions. The age-adjusted incidence of GEP-NETs has increased steadily over the past four decades (1973–2007), increasing 3.65-fold in the USA and 3.8- to 4.8-fold in the UK. Incidence has changed variably from one anatomical site to another. The greatest increase in incidence occurred for gastric and rectal NETs, while the smallest increase occurred for small intestine NETs. There were gender and racial differences, which differed site by site and, in some cases, changed over time. The incidence rates (IRs) of GEP-NETs have increased significantly in the last 40 years. Data are only available from North America, Western Europe and Japan. A site-by-site analysis revealed that the IRs of some NETs increased more than those of others.

Background: The role of dopamine agonists in the treatment of Cushing’s disease (CD) has been previously debated. Aim: The aim of this study was to evaluate the effectiveness of short-term (3 months) and long-term (12–24 months) treatment with cabergoline in patients with CD. Patients and Methods: 20 patients with CD unsuccessfully treated by surgery entered the study. Cabergoline was administered at an initial dose of 1 mg/wk, with a monthly increase of 1 mg, until urinary cortisol levels normalized or the maximal dose of 7 mg/wk was achieved. The responsiveness to treatment was evaluated according to changes in urinary cortisol excretion. A decrease greater than 25% was considered as a partial response, whereas complete normalization was considered as a full response at short-term evaluation; persistence of normal cortisol excretion was the only criterion to evaluate the response at long-term evaluation. Results: After short-term treatment, 15 (75%) patients were responsive to cabergoline treatment. Among these, normalization of cortisol excretion was maintained in 10, whereas treatment escape was observed in five patients after 6–18 months. Among the 10 long-term responsive patients, eight were followed for 24 months, whereas the remaining two were followed for 12–18 months, due to cabergoline withdrawal for intolerance. A sustained control of cortisol secretion for 24 month cabergoline treatment at the maximal dose ranging from 1-7 mg/wk (median: 3.5) without significant side effects, was obtained in eight of 20 (40%) patients. Conclusions: The results of this study demonstrated that cabergoline treatment is effective in controlling cortisol secretion for at least 1–2 yr in more than one third of a limited population of patients with CD. If this evidence is confirmed by additional studies, this agent may be considered as a useful treatment option in patients with CD who are unsuccessfully treated by neurosurgery.

Percutaneous radiofrequency thermal ablation (RTA) is a promising new therapeutic approach to manage thyroid nodules (TNs). The aim of this study was to investigate the long-term effectiveness of RTA in inducing shrinkage of TNs as well as in controlling compressive symptoms and thyroid hyperfunction in a large series of elderly subjects with solid or mainly solid benign TNs. Ninety-four elderly patients with cytologically benign compressive TNs were prospectively enrolled in the study; 66 of them had nontoxic goiter and 28 had toxic or pretoxic goiter. RTA was performed by using a RITA StarBurst Talon hook-umbrella needle inserted in every single TN under ultrasonographic real-time guidance. TN volume, TN-related compressive symptoms and thyroid function were evaluated at baseline and 12 to 24 months after RTA. All TNs significantly decreased in size after RTA. The mean decrease in TN volume 12 months after RTA was from 24.5 +/- 2.1 to 7.5 +/- 1.2 mL (p < 0.001), with a mean percent decrease of 78.6 +/- 2.0%. Two years after RTA, a 79.4 +/- 2.5% decrease of TNs size was observed. Compressive symptoms improved in all patients and completely disappeared in 83 of 94 (88%) patients. Hyperthyroidism resolved in most patients allowing methimazole therapy to be completely withdrawn in 79% of patients with pretoxic and toxic TNs (100% with pretoxic TNs and 53% with toxic TNs). The treatment was well tolerated by all patients. No patient needed hospitalization after RTA and no major complications were observed. RTA is an effective and simple procedure for obtaining lasting shrinkage of TNs, controlling compressive symptoms, and treating thyroid hyperfunction. When performed in experienced medical centers, RTA may be a valid alternative to conventional treatments for nontoxic and pretoxic TNs. It is particularly attractive for elderly people for whom surgery and radioiodine therapy are often contraindicated or ineffective.

BACKGROUND: Gender differences in tumor size are supposed to exist in hyperprolactinemia since microadenomas are more commonly found in women and macroadenomas in men. Whether this reflects only a delay in diagnosis in men or a true gender difference in tumor pathogenesis is still unclear. OBJECTIVE: To prospectively analyze gender differences in the presentation and response to cabergoline treatment in 219 consecutive newly diagnosed patients with hyperprolactinemia. DESIGN: An open prospective design. SUBJECTS: Of the 219 patients of which 145 were women; 107 patients had macroprolactinoma, 97 had microprolactinoma, and 15 had non-tumoral hyperprolactinemia. METHODS: Presenting clinical symptoms, prolactin levels and tumor size at magnetic resonance imaging were measured before and 3-6 Months after cabergoline therapy. RESULTS: Prevalence of microprolactinomas (56% vs 22%, P=<0.0001) and non-tumoral hyperprolactinemia (10% vs 0%, P=0.01) was higher in women than in men. Men and women were of similar age (median 32 vs 29 Years; P=0.2) and a similar number had gonadal/sexual dysfunction (85 vs 83%, P=0.6); weight gain (70 vs 46%; P=<0.0001) and galactorrhea (52 vs 19%; P=<0.0001) were more common in women. Prolactin levels were higher in men than in women, whether exhibiting macro- (2848+/-2954 vs 1132+/-2351 microg/l, P=<0.0001) or microadenomas (187.8+/-51.8 vs 135.4+/-60.5 microg/l, P=0.009) and the size of the adenoma was larger in men than in women irrespective of macro- (25.8+/-12.4 vs 17.2+/-7.2 mm, P=<0.0001) or microadenoma diagnosis (8.0+/-1.4 vs 7.1+/-1.6 mm, P=0.04). After treatment, prolactin levels decreased by 89.2-96.4% in all groups, and normalized more frequently in micro- than in macroadenoma patients (86 vs 64%, P<0.0001), regardless of gender (70% vs 69%, P=0.9). Menses resumed in 82% of women, libido disturbances improved in 57% of men. Tumor size was reduced by 45+/-25% and 52+/-24% in macroprolactinoma patients and by 44+/-31 and 38+/-29% in microprolactinoma patients in women and men respectively. Visual field defects disappeared in 61% of women and in 71% of men (P=0.6). CONCLUSIONS: Prevalence of macroprolactinomas was similar in men and women; microprolactinomas and non-tumoral hyperprolactinemia were more frequent in women. Clinical symptoms at presentation differed according to gender, with galactorrhea and weight gain more frequent in women. The successful response to cabergoline treatment for 6 Months was higher in micro- than in macroprolactinoma patients and was similar in women and men.