Is Melanoma Progression Affected by Thyroid Diseases?

Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic-pituitary-thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients.

Prevalence of breast cancer in thyroid diseases: results of a cross-sectional study of 3,921 patients.

Results from national cancer registries reveal an association of thyroid cancers with extra-thyroidal malignancies. In this study, we evaluated the prevalence of breast cancer (BC) in women affected by both benign and malignant thyroid diseases (TD) in comparison to the general population. To this end, 3,921 female patients from central and southern regions of Italy were evaluated. Age-matched analysis of the prevalence of BC was carried out after dividing the patients into three diagnostic categories: (1) 1,149 patients with non-nodular TD; (2) 2350 patients with nodular TD; (3) 422 patients affected by differentiated thyroid cancers. Furthermore, the patients were grouped according to the absence (2,344 patients) or presence (1,453 patients) of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) or anti-TSH receptor auto-antibodies (124 patients). BC prevalence in TD patients as a whole was significantly higher compared to the general population, with an odds ratio (OR) of 3.33. Age-matched analysis showed that the risk of a BC in TD patients was higher in younger patients (age 0-44 years), with an OR of 15.24, which decreased with increasing age. Patients without thyroid auto-antibodies showed a higher OR for BC (p = 0.0005) than TD patients with TgAb and/or TPOAb. The results demonstrate that women affected by either benign or malignant thyroid disease have a significantly greater risk of BC, which is higher at a younger age. Furthermore, thyroid auto-antibodies appear to be protective against BC. These findings may contribute to the identification of common genetic and environmental factors underlying this disease association.

IRE1α deficiency promotes tumor cell death and eIF2α degradation through PERK dipendent autophagy.

Sensors of endoplasmic reticulum (ER) stress function in a co-ordinated manner. In the present study we investigated the relationship between IRE1α and PERK pathways and survival of ER stressed U937 cells and BC3 cells. To this end, we investigated the effects of a subcytotoxic concentration of Tunicamycin in IRE1α-proficient and in IRE1α-deficient cells, by pharmacological inhibition with 4µ8 C or down-regulation by specific siRNA. We show that either type of IRE1α deficiency affects eIF2α expression and causes cell death increase. GSK2606414, a PERK inhibitor, and PERK specific siRNA prevent eIF2α down-regulation and restore cell survival. Degradation of this protein is due to autophagy, as it is prevented by bafilomycin and not by proteasome inhibition. Furthermore, activation of the autophagy flux is PERK dependent. Also the Cathepsin B inhibitor CA074 prevents eIF2α from degradation and reduces cell death. Altogether, these results show that IRE1α deficiency in ER stressed cells leads to an unexpected decrease of eIF2α, an important molecule for protein translation, through PERK dependent autophagy. Thus, IRE1/XBP1 inhibitors may represent a feasible strategy for tumor therapy, while PERK inhibitors may vanish the goal.

Correction to: IRE1α deficiency promotes tumor cell death and eIF2α degradation through PERK-dependent autophagy.

[This corrects the article DOI: 10.1038/s41420-017-0002-9.].

Cardiovascular risk in chronic autoimmune thyroiditis and subclinical hypothyroidism patients. A cluster analysis.

BACKGROUND: Subclinical hypothyroidism (SCH) and chronic autoimmune thyroiditis (CAT) are linked to an increased risk of atherosclerosis and coronary heart disease (CHD). The aim of this study was to look for positive markers of CHD and correlations with thyroid blood tests in patients with SCH or CAT, but no symptoms of CHD, so as to identify CHD risk conditions that otherwise would likely be missed. METHODS: We measured a series of thyroid, clinical-metabolic and cardiovascular parameters in 30 consecutive endocrinology patients enrolled in our ambulatory endocrinological referral center of "Sapienza" University of Rome. (19 with CAT, 11 with SCH) from January 2015 to March 2015. 13 asymptomatic subjects were enrolled as controls. In each patient, we measured a series of 34 thyroid, clinical-metabolic and cardiovascular parameters. RESULTS: in the statistical analysis of collected data, the oblique principal components clustering procedure (OPC) revealed the presence of an interesting mixed cluster, composed of a thyroid parameter (TPO-Ab), a metabolic parameter (homocysteine level) and a cardiovascular parameter (MAPSE), in which we assessed the relationships between the single components. Our preliminary results indicate that in both groups of patients elevated TPO-Ab, when accompanied by reduced MAPSE and increased IMT and homocysteine values, may be taken to indicate the presence of clinically unrecognized CHD. CONCLUSIONS: Confirmation of these results in larger series of patients could justify hormone therapy for prevention of CHD in these thyroid patients versus placebo treatment.

The Role of Sleeve Gastrectomy in Reducing Cardiovascular Risk.

BACKGROUND: Obesity is an independent cardiovascular risk factor and a catalyst of other cardiovascular risk factors, such as hypertension, dyslipidemia, type 2 diabetes mellitus (DM2) and metabolic syndrome. METHODS: We analyzed cardiovascular risk in obese patients before and after sleeve gastrectomy (SG). To this end, we studied changes in body mass index (BMI), blood chemistry parameters that characterize the risk of atherosclerosis and instrumental parameters (objective markers of this risk), namely intima-media thickness (IMT) and flow-mediated dilation (FMD), the latter reflecting endothelial function. We also considered purely cardiac parameters-mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE)-which describe cardiac risk more specifically than the ejection fraction. Alteration of one or more of these parameters determines an increase in cardiovascular morbidity and mortality. RESULTS: The results showed that weight loss, in patients undergoing SG, is accompanied by a reduced BMI and a marked improvement in blood chemistry, confirming what has already been shown in many other studies, but the most interesting finding was the effect of SG on the instrumental markers of atherosclerosis. In particular, carotid IMT was significantly reduced (p < 0.001) and FMD significantly improved. MAPSE and TAPSE also improved significantly at both follow-up assessments (p < 0.001). CONCLUSIONS: This study suggests that SG should be considered from a broader perspective, i.e. as a weight loss treatment that also improves obesity-related morbidity and mortality, benefitting both the patient and, in an economic sense, the society as a whole.

Is Carotid Stenosis in Women a Gender-Related Condition?

BACKGROUND: We set out to study, through ultrasound examinations, the carotid bifurcation in men and women with/without carotid stenosis to look for anatomical and electrophysiologic differences. We evaluated other variables to look for differences that might explain the dissimilar behavior of this disease in the two sexes and the presence and impact of risk factors. METHODS: We examined 974 subjects aged 25 to 88 years (478 men and 496 women) in whom we considered heart rate, smoking status, and the presence of hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia. Ultrasound examination of the neck vessels included measurement of intimal medial thickness (IMT), vessel diameter, and outflow area/inflow area ratio. We established plaque location, echogenicity and echostructure, and the percentage of stenosis owing to plaque and measured systolic velocity, flow direction, and the depth of detection of these parameters. We used the apnea and hyperpnea test to assess cerebrovascular reactivity. RESULTS: Hypertension and hypercholesterolemia were the most frequent risk factors. Women had a higher heart rate, whereas men had significantly greater IMT. The presence of atheromatous plaque was significantly correlated with age in both sexes, with men having a higher prevalence of carotid plaques. The sexes differed significantly with regard to plaque location, echogenicity, echostructure, and intracranial circulation. Women had a slightly higher blood flow velocity in the intracranial arteries. Risk factors affected plaque formation and extent more in men than in women. CONCLUSIONS: These findings suggest that carotid stenosis is a gender-related trait.

[Ontogenesis of congenital abnormalities of the left gonadal vein and their clinical relevance]. / Ontogenesi delle anomalie congenite della vena gonadica sinistra e loro rilevanza clinica.

The anatomy of the gonadal vein has been the subject of several studies relating particularly to the aetiology and therapy of varicocele and left ovarian vein syndrome. Venography shows the presence of valves, the collateral branches, the anastomoses between the left gonadal vein and the retroperitoneal venous networks and the effective pathways of venous reflux. The authors observed a particular congenital anomaly of the left gonadal vein in the dissection of a female cadaver, and studied the venographic pattern of a male patient with left idiopathic varicocele. The aim of this study was to investigate, with the aid of a review of the literature, the embryo-pathogenetic basis of congenital abnormalities of the left gonadic vein, stressing those factors most conducive to errors in the diagnosis and therapy of varicocele and left ovarian vein syndrome, particularly in the scleroembolisation therapy of idiopathic varicocele.

A multicentre, randomized study of telmisartan versus carvedilol for prevention of atrial fibrillation recurrence in hypertensive patients.

INTRODUCTION: Atrial remodelling, leading to atrial fibrillation (AF), is mediated by the renin-angiotensin-aldosterone system. METHODS: Mild hypertensive outpatients (systolic/diastolic blood pressure 140-159/90-99 mmHg) in sinus rhythm who had experienced ≥ 1 electrocardiogram (ECG)-documented AF episode in the previous six months received randomly telmisartan 80 mg/day or carvedilol 25 mg/day. Blood pressure and 24-hour ECG were monitored monthly for one year; patients were asked to report symptomatic AF episodes and to undergo an ECG as early as possible. RESULTS: One hundred and thirty-two patients completed the study (telmisartan, n=70; carvedilol, n=62). Significantly fewer AF episodes were reported with telmisartan versus carvedilol (14.3% vs. 37.1%; p<0.003). Left atrial diameter, assessed by echocardiography, was similar with telmisartan and carvedilol (3.4±2.3 cm vs. 3.6±2.4 cm). At study end, both regimes significantly reduced mean left ventricular mass index, but the reduction obtained with telmisartan was significantly greater than with carvedilol (117.8±10.7 vs. 124.7±14.5; p<0.0001). Mean blood pressure values were not significantly different between the groups (telmisartan 154/97 to 123/75 mmHg; p<0.001; carvedilol 153/94 to 125/78 mmHg; p<0.001). CONCLUSIONS: Telmisartan was significantly more effective than carvedilol in preventing recurrent AF episodes in hypertensive AF patients, despite a similar lowering of blood pressure.