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Background In recent years, scientific research has increasingly focused on Endocrine Disrupting Chemicals (EDCs) and demonstrated their relevant role in the functional impairment of endocrine glands. This induced regulatory authorities to ban some of these compounds and to carefully investigate others in order to prevent EDCs-related conditions. As a result, we witnessed a growing awareness and interest on this topic. Aims This paper aims to summarize current evidence regarding the detrimental effects of EDCs on pivotal endocrine glands like pituitary, thyroid and adrenal ones. Particularly, we directed our attention on the known and the hypothesized mechanisms of endocrine dysfunction brought by EDCs. We also gave a glimpse on recent findings from pioneering studies that could in the future shed a light on the pathophysiology of well-known, but poorly understood, endocrine diseases like hormone-producing adenomas. Conclusions Although intriguing, studies on endocrine dysfunctions brought by EDCs are challenging, in particular when investigating long-term effects of EDCs on humans. However, undoubtedly, it represents a new intriguing field of science research.

Purpose That thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI. Methods This retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation. Results Serum fT3 levels were positively associated with an increased risk of late post-traumatic seizures (LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22–2.61, p Conclusions Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

Several ultrasound (US) risk stratification systems (US-RSSs) have been proposed to stratify the risk of malignancy (ROM) of thyroid nodules. This risk might be overestimated due to selection bias and comparison with the cytological report alone. Our study aimed to compare ROM and diagnostic performance of three guidelines (ATA, AACE/ACE/AME, EUTIRADS) and evaluate the changes in unnecessary biopsy according to the nodule size cutoff for biopsy, using histology as gold standard. This retrospective observational study included 146 consecutive patients who underwent surgery after US and cytological characterization. We analyzed the effectiveness and accuracy of three US-RSSs. 46.6% of nodules were diagnosed as malignant. Applying US-RSS, the percentage of nodules that should have been analyzed by biopsy was 84.25% with ATA, 69.86% with EUTIRADS and 64.38% with AACE/ACE/AME systems. The ROM was 94.9%, 86.0%, 87.0% for high-risk category, 36.4%, 32.0%, 35.4% for intermediate-risk category and 22.9%, 0.0%, 22.9% for low-risk category by ATA, AACE/ACE/AME and EUTIRADS systems, respectively. EUTIRADS and AACE/ACE/AME systems were more accurate in differentiating malignant from benign cases. ATA score was the more sensitive US-RSS to identify malignant tumors within the high-risk category. About the unnecessary biopsies, in the intermediate-risk category, the application of the size criterion helps to increase specificity in all systems. The US categorization of low and high-risk thyroid nodules using current US-RSSs helps alone to determine the optimal treatment option. Nodule size remains relevant to recommend biopsy for the intermediate-risk category.

Papillary thyroid microcarcinoma (mPTC) is defined as a papillary thyroid cancer sized 10 mm or less. Despite their generally indolent clinical course and good prognosis, a subset of mPTCs shows potentially aggressive behaviour. To search for predictors of clinical outcome of mPTCs, we retrospectively evaluated the genetic tumour profile of 100 patients (23 M/77 F, mean age ± SD 53.8 ± 13.4 years) with histologically confirmed mPTCs through analysis of BRAF, NRAS and TERT promoter mutations as well as RET/PTC translocations. Mean follow-up period was 8.4 ± 3.6 years. In 55 cases, mPTC were detected incidentally after surgery. Capsular invasion, bilateralism and multifocality were found in 11/100, 17/100 and 24/100 cases, respectively, while lymph-nodes metastases were present at diagnosis in 9/100 cases. After 3.5 ± 2.0 years, tumour relapse occurred in 6/100 cases and was locoregional in five (two in the thyroid bed, three in laterocervical lymph-nodes), while lung metastasis occurred in one case. Biochemical persistence of disease was seen in 1/100 case. Mutations occurred in 55/100 cases; BRAFV600E was the most frequently detected (49/100) and was associated with higher tumour size, bilateralism and follicular variant but not with capsular invasion. RET/PTC rearrangements were found in 2/100 cases, NRASQ61R in 4/100, while no mutations of TERT promoter gene were detected. Despite the observed association between BRAFV600E mutation and unfavourable histopathological features, we found no direct association with tumour recurrence, distant metastases and mortality. In our study, the search for the most frequent genetic alterations as prognostic markers in mPTCs would not have changed the therapeutic strategy.

Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aim of this study was to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory (ITCO) database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p=0.65), tumor size >2 cm (OR 1.45, p=0.34), aggressive PTC histology (OR 0.55, p=0.15), and age at diagnosis (OR 0.90, p=0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27, 95% CI, p=0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and non-treated patients (p=0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease.

The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.

Background: One of the most widely used risk stratification systems for estimating individual patients' risk of persistent or recurrent differentiated thyroid cancer (DTC) is the American Thyroid Association (ATA) guidelines. The 2015 ATA version, which has increased the number of patients considered at low or intermediate risk, has been validated in several retrospective, single-center studies. The aims of this study were to evaluate the real-world performance of the 2015 ATA risk stratification system in predicting the response to treatment 12 months after the initial treatment and to determine the extent to which this performance is affected by the treatment center in which it is used. Methods: A prospective cohort of DTC patients collected by the Italian Thyroid Cancer Observatory web-based database was analyzed. We reviewed all records present in the database and selected consecutive cases that satisfied inclusion criteria: (i) histological diagnosis of DTC, with the exclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features; (ii) complete data of the initial treatment and pathological features; and (iii) results of 1-year follow-up visit (6-18 months after the initial treatment), including all data needed to classify the estimated response to treatment. Results: The final cohort was composed of 2071 patients from 40 centers. The ATA risk of persistent/recurrent disease was classified as low in 1109 patients (53.6%), intermediate in 796 (38.4%), and high in 166 (8.0%). Structural incomplete responses were documented in only 86 (4.2%) patients: 1.5% in the low-risk, 5.7% in the intermediate-risk, and 14.5% in the high-risk group. The baseline ATA risk class proved to be a significant predictor of structural persistent disease, both for intermediate-risk (odds ratio [OR] 4.67; 95% confidence interval [CI] 2.59-8.43) and high-risk groups (OR 16.48; CI 7.87-34.5). Individual center did not significantly influence the prediction of the 1-year disease status. Conclusions: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability.

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited tumor syndrome, associated with parathyroid, pituitary, and gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs). MEN1 is usually consequent to different germline and somatic mutations of the MEN1 tumor suppressor gene, although phenocopies have also been reported. This review analyzed main biomedical databases searching for reports on MEN1 gene mutations and focused on aggressive and aberrant clinical manifestations to investigate the potential genotype-phenotype correlation. Despite efforts made by several groups, this link remains elusive to date and evidence that aggressive or aberrant clinical phenotypes may be related to specific mutations has been provided by case reports and small groups of MEN1 patients or families. In such context, a higher risk of aggressive tumor phenotypes has been described in relation to frameshift and non-sense mutations, and predominantly associated with aggressive GEP NETs, particularly pancreatic NETs. In our experience a novel heterozygous missense mutation at c.836C>A in exon 6 was noticed in a MEN1 patient operated for macro-prolactinoma, who progressively developed recurrent parathyroid adenomas, expanding gastrinomas and, long after the first MEN1 manifestation, a neuroendocrine uterine carcinoma. In conclusion, proof of genotype-phenotype correlation is limited but current evidence hints at the need for long-term interdisciplinary surveillance in patients with aggressive phenotypes and genetically confirmed MEN1.

Aim of our study was to search for variables associated with worse outcomes in patients treated with radioactive iodine (RAI) for hyperthyroidism by a dosimetric-based approach. Four hundred twenty-four patients with hyperthyroidism related to Toxic Multinodular Goiter (TMG; n = 213), Grave’s disease (GD; n = 150) and toxic adenoma (TA; n = 61) treated with RAI between 2000 and 2018 and with at least 12 months follow-up were retrospectively evaluated. Association between outcomes (response vs. no response) at 6 and 12 months and baseline TSH values, anti-thyroid drugs (ATD) duration and posology, RAI absorbed dose and dimensional reduction of target mass at ultrasound was evaluated by Mann–Whitney test. Risk factors for response vs. no-response were analysed by binary logistic regression model. Overall response rate was 78.7 and 83% at 6 and 12 months, respectively. Both at 6 and 12 months higher TSH baseline values (p

The role of insulin resistance and adipocytokines in determining the phenotype and recurrence of differentiated thyroid cancer (DTC) is still unknown. In a previous study, we observed an association between metabolic setting, circulating adipocytokines and thyroid cancer phenotype. The aim of this study was to evaluate the clinical follow-up of patients with DTC and the predictive role of metabolic setting on the risk of tumour relapse. Between September 2016 and January 2017, 57 patients were admitted to our institution to undergo total thyroidectomy because of suspected DTC. Thirty patients with post-surgical histological diagnosis of DTC were included in the study. Each subject underwent pre-surgical analysis of anthropometric parameters, thyroid function and autoimmunity, glucose metabolism, insulin resistance (HOMA-IR) and levels of unacylated and acylated ghrelin, obestatin, leptin and adiponectin. Tumour recurrence at 1 and 3 years from diagnosis was assessed. Most patients were females (21F, 9M) with a median age at diagnosis of 50.0 (41.0–58.8). At baseline, overweight was found in 7 patients and obesity in 6 cases. Insulin resistance was detected in 14 patients. Overall, 17 patients (56.7%) underwent radioiodine treatment after surgery. During the follow-up, we observed a persistent biochemical disease in one patient whereas tumour relapse was found in six patients at 1 year from diagnosis (lymph node metastases) and in one patient at 3 years from diagnosis (lung metastases). Independently from age, sex, stage of disease and the presence of lymph node metastasis at diagnosis, higher BMI, leptin and insulin levels as well as HOMA-IR were associated with a higher risk of tumour relapse (p

The major aim of ultrasound (US)-based risk stratification systems is to reduce unnecessary thyroid biopsies without losing the ability to recognize nodules with clinically significant malignancy. Each of the classic suspicious features of a thyroid nodule detected on US scan (hypoechoic pattern, microcalcifications, irregular margin, taller than wide shape, irregular vascularization) is significantly independently associated with the probability of malignancy, but none of them has good diagnostic accuracy. Thus, we evaluated the predictive value of a binary score simply based on the combination of these US features, regardless of the specific predictive value of each US feature, against the outcome of suspected malignancy at cytological diagnosis (TIR3 to TIR5 categories by SIAPEC-IAP [TIR+]). 1009 thyroid nodules from 1081 patients were considered. The US features of suspicion of all nodules were categorized in 5 binary scores (U1 to U5), each including from 1 to 5 of those features. U2 (at least 2 US suspicious features) was the most balanced predictor of TIR+ (PPV 0.48, NPV 0.93, LR+ 3.05 and LR- 0.24). Weighting the predictivity of the single features did not improve the estimate. Using U2 as the criterion to send nodules to FNAC would have reduced the number of biopsies by 60 % (604 patients) and the false negatives would have only accounted for 41 cases out of 237 TIR+ (17 %) with 39 cases of TIR3 and 2 cases of TIR4, including only 6 malignant nodules on histological examination. U2 performed much better than the ATA recommendations for detecting those nodules, resulting in TIR+ at cytology. This simple and reproducible sonographic score based on 2 US features of suspicion of malignancy has quite a good performance with respect to identifying thyroid lesions categorized by cytology as medium-high risk of malignancy and could allow us to reduce cytology costs for low-risk nodules.ZIEL: Das Hauptziel von Systemen zur Risikostratifizierung mittels Ultraschalls (US) ist die Reduktion unnötiger Schilddrüsenbiopsien ohne jedoch den Verlust der Fähigkeit, Knoten mit klinisch bedeutsamer Malignität zu erkennen. Jedes der klassischen verdächtigen sonografischen Kriterien eines Schilddrüsenknotens (hypoechogene Struktur, Mikrokalzifizierungen, irregulärer Randsaum, Tiefer-als-breit Form, unregelmäßige Vaskularisierung) ist signifikant unabhängig mit der Wahrscheinlichkeit einer Malignität assoziiert, aber keines davon hat eine gute diagnostische Genauigkeit. Deshalb haben wir den Vorhersagewert eines binären Scores, der auf der Kombination dieser US-Kriterien basiert, unabhängig vom spezifischen Vorhersagewert jedes einzelnen US-Kriteriums bewertet in Bezug auf die Ergebnisse der vermuteten Malignität in der Zytologie (Kategorien TIR3 bis TIR5 der SIAPEC-IAP (TIR+)). 1009 Schilddrüsenknoten von 1081 Patienten wurden eingeschlossen. Die US-Kriterien für den Verdacht aller Knoten wurden in 5 binäre Scores (U1 bis U5) unterteilt, die jeweils 1 bis 5 dieser Kriterien beinhalten. U2 (mindestens 2 verdächtige US-Kriterien) war der ausgewogenste Prädiktor für TIR+ (PVW 0,48, NVW 0,93, LR+ 3,05 und LR– 0,24). Die Gewichtung des Vorhersagewerts der einzelnen Kriterien hat die Abschätzung nicht verbessert. Mit U2 als Kriterium für die Weiterleitung der Knoten an die FNAC würde die Anzahl der Biopsien um 60 % reduziert (604 Patienten) werden und die falsch negativen hätten nur 41 von 237 TIR+-Fällen (17 %) ausgemacht, davon 39 Fälle mit TIR3 und 2 Fälle mit TIR4, einschließlich von lediglich 6 malignen Knoten in der Histologie. Für den Nachweis dieser Knoten erwies sich U2 besser als die ATA-Empfehlungen und ergab TIR+ in der Zytologie. Dieser einfache und reproduzierbare sonografische Score, der auf 2 US-Kriterien für den Verdacht auf Malignität basiert, hat eine recht gute diagnostische Leistung bei der Identifizierung von Schilddrüsenläsionen, die in der Zytologie als mittelhohes Malignitätsrisiko eingestuft werden, gezeigt und könnte eine Kostensenkung in der Zytologie für risikoarme Knoten erlauben.

Context General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity. Objective We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism. Setting Tertiary care center. Design Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body composition, and indirect calorimetry. LT4 users were classified into low TSH (4.2 mU/L). Results LT4 users constituted 13.9% of the incident population. TSH was low in 7.5%, high in 17.2%, and normal in 75.2% of LT4 users. Overtreatment decreased with aging and more LT4 users ≥65 years of age had normal TSH than those Conclusions Obesity is associated with milder rates of inadequate LT4 treatment compared with nonobese populations. LT4 adequacy increases with aging. Age, body composition, and sex are main determinants of LT4 requirements in obesity.

Vitamin D is a secosteroid with a pleiotropic role in multiple physiological processes. Besides the well-known activity on bone homeostasis, recent studies suggested a peculiar role of vitamin D in different non-skeletal pathways, including a key role in the modulation of immune responses. Recent evidences demonstrated that vitamin D acts on innate and adaptative immunity and seems to exert an immunomodulating action on autoimmune diseases and cancers. Several studies demonstrated a relationship between vitamin D deficiency, autoimmune thyroid disorders, and thyroid cancer. This review aims to summarize the evidences on the immunomodulatory effect of vitamin D on thyroid diseases.

Thyroid cancer represents the most frequent endocrine neoplasm and is epidemiologically linked to a growing incidence worldwide, which is only in part explained by the increased detection of small cancers in a preclinical stage. Understanding the molecular pathogenesis of well-differentiated thyroid cancers and poorly-differentiated thyroid cancers has prompted interest into the identification of crucial signaling pathways and molecular derangements related to genetic and epigenetic alterations. Increasing attention has been recently focused on inflammation and immunity as major culprit mechanisms involved in thyroid tumourigenesis, through the detection of activated immune cells, pro-inflammatory cytokines, as well as signal integrations between inflammatory and proliferative pathways within the thyroid tumour micro-environment. In addition to playing important roles in tumour surveillance and rejection, the presence of tumour-associated macrophages and the activation of NF-κB signaling pathway are now reckoned as hallmarks and crucial mediator of inflammation-induced growth and progression of thyroid cancer. Thorough understanding of this immunological link and identification of novel molecular targets could provide unprecedented opportunities for research and development of diagnostic, prognostic and treatment strategies for thyroid cancer.

Unlike GLP-1, liraglutide is not cleared by the glomerulus and its pharmacokinetic is not altered in patients with mild renal impairment. The aim of our study was to analyze the effects of liraglutide on renal function in patients with type 2 diabetes. A twelve-month longitudinal prospective post-marketing study was performed. According to eGFR (estimated glomerular filtration rate) calculated with CKD-EPI equation, 84 consecutive patients were divided in Group A (eGFR90 ml/min) and Group B (eGFR90 ml/min). BMI, glucose, HbA1c, serum creatinine, microalbuminuria, and eGFR were evaluated at baseline and after 12 months of treatment. A reduction in fasting plasma glucose (p0.01), HbA1c (p0.003), BMI (p0.01), and systolic (p0.01) and diastolic blood pressure (p0.006) was recorded irrespective of eGFR category. Concerning renal function, creatinine levels had a trend to decrease in both groups. eGFR did not change in Group A, while it increased in Group B (p0.05) independently from the concomitant changes of other parameters. Moreover, seven out of 41 patients of Group B had increased eGFR levels which reached the normal values (90 ml/min). At baseline, five patients had pathological microalbuminuria, but at 12 months three of them returned to normal albuminuria (p0.006). Total microalbuminuria levels improved in both groups (p0.02). According to preliminary data in animals, our study shows that liraglutide is effective in preserving eGFR in diabetic patients, increasing it in those with reduced renal function. This was associated with a decrease of frequency of patients positive to microalbuminuria. Further studies are needed to confirm these data.

We evaluated the risk of altered glucose levels and new-onset diabetes (NOD) associated with statins according to glucose levels at baseline in a population treated for dyslipidemia on primary prevention for >5 years. DESIGN. The retrospective study included 308 subjects (265 on statins and 43 controls on diet) with a follow-up of 5–15 years. The cohort was classified according to glucose tolerance at both baseline and follow-up. The cumulative incidence of NOD was 13.6% (9.3% in controls and 13.5% in treated patients). NOD was diagnosed after 3.4±1.8 years. In the group with normal glucose levels at baseline, a family history of diabetes (OR: 3.4, 95% CI 1.3–8.9), BMI >30 kg/m2 (OR: 8.5, 95% CI 2.0–35.8), treatment with thiazide (OR: 21.9, 95% CI 1.2–384.2) and no alcohol consumption (OR: 0.3, 95% CI 0.1–0.8) reduced the risk of developing altered glucose levels or NOD. No effects of statins were seen. In the group with altered glucose levels at baseline, hypertension (OR: 5.0, 95% CI 1.0–25.3) and hypertriglyceridemia (OR: 3.5, 95% CI 1.0–11.8) increased the risk of remaining with altered glucose levels or developing NOD. Treatment with statins (OR: 7.5, 95% CI 1.5–37.4), in particular atorvastatin, was associated with an increased risk. In the whole population, statin therapy (OR: 4.0, 95% CI 1.1–14.1, p

The aim was to retrospectively analyse the clinical–histopathological characteristics of patients with newly diagnosis of differentiated thyroid cancer (DTC) referred to two Italian centres, one in Northern and the other in Southern Italy, between 2000 and 2013. 1081 patients were included and subdivided into two groups: group A (474 patients from Novara) and group B (607 patients from Naples). The group A came from the industrial area of Novara, while the Group B came from the areas around Vesuvius and Campi Flegrei. The two groups were comparable for iodine levels, body mass index, diagnostic timing and clinical procedures. For all patients, demographic and clinical data were collected. No difference was found in gender, whereas the age at diagnosis was later in the group A (group A 53.1 ± 15.16 years, group B 41.9 ± 14.25 years, p < 0.001). In both groups, the most frequent histotype was papillary thyroid cancer (PTC) with prevalence of follicular variant in group A (p < 0.0001) and classical variant in group B (p < 0.0001). Aggressive histological features were mainly seen in group A (bilaterality p < 0.0001, multifocality p < 0.0001 and thyroid capsular invasion p < 0.0001). Microcarcinomas were more frequent in group A (p < 0.0001) but mostly characterized by bilaterality (p < 0.001) and multifocality (p < 0.04). In both groups, tumour-associated thyroiditis showed a significant increase over the years (group A p < 0.05, group B p < 0.04). Environmental factors could justify the differences found in our study. These preliminary data should stimulate the need for an Italian Cancer Registry of DTC in order to allow an epidemiological characterization, allowing the identification of specific etiological factors and an improvement in the management of the disease

Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, the treatment of radio-resistant papillary-type, of undifferentiated anaplastic, and of medullary-type thyroid cancers remains unsatisfactory. Autophagy is a vesicular process for the lysosomal degradation of protein aggregates and of damaged or redundant organelles. Autophagy plays an important role in cell homeostasis, and there is evidence that this process is dysregulated in cancer cells. Recentin vitropreclinical studies have indicated that autophagy is involved in the cytotoxic response to chemotherapeutics in thyroid cancer cells. Indeed, several oncogenes and oncosuppressor genes implicated in thyroid carcinogenesis also play a role in the regulation of autophagy. In addition, some epigenetic modulators involved in thyroid carcinogenesis also influence autophagy. In this review, we highlight the genetic and epigenetic factors that mechanistically link thyroid carcinogenesis and autophagy, thus substantiating the rationale for an autophagy-targeted therapy of aggressive and radio-chemo-resistant thyroid cancers.

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients.Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated.The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p0.01) and altered glucose metabolism (p0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p0.05) and HOMA-IR (p0.02) were higher in hypopituitaric TBI patients.We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle.

Differentiated thyroid cancer (DTC) is an important clinical entity in our population (Novara, Piedmont, Italy) which is characterized by important environmental influences, as iodine deficiency (ID) and subsequent supplementation, thyroiditis and occupational exposure. To evaluate the features of DTC in our population 20 years after the iodine-prophylaxis pondering the effects of the introduction of the new guidelines for diagnosis and management of DTC after 2005. 322 patients [244 females, age: mean (±SD) 53.8 ± 15.8 years] treated for DTC in a tertiary care center between 1997 and 2010 were retrospectively evaluated. Medical history, demographics, and pathological features were considered. Patients were subdivided into two groups: A (n = 139, diagnosis 1997–2005) and B (n = 183, diagnosis 2006–2010). The population of group A showed a mild ID, while normal iodine status was recorded in group B. A significant increase in histological tumor-associated thyroiditis was found from group A to B (p = 0.021). Recurrent or persistent diseases were found to be correlated with lymph nodes metastases and/or a distant disease at diagnosis, stimulated thyroglobulin levels at the first follow-up and an additional radioiodine therapy. Twenty percent of our patients were females employed in textile industries. The tumor-related inflammation and the occupational exposure should be considered as important factors in the pathogenesis of DTC. Further studies are required in order to confirm our findings.

Background Regulating thermogenesis is a major task of thyroid hormones (THs), and involves TH-responsive energetic processes at the central and peripheral level. In severe obesity, little is known on the relationship between THs and resting energy expenditure (REE) before and after weight loss. Methods We enrolled 100 euthyroid subjects with severe obesity who were equally distributed between genders. Each was examined before and after completion of a 4-wk inpatient multidisciplinary dieting program and subjected to measurement of thyroid function, REE, fat-free mass (FFM, kg) and percent fat mass (FM). Results Baseline REE was lower than predicted in 70 obese patients, and overall associated with BMI, FFM and FM but not thyroid-related parameters. By the study end, both BMI and REE decreased (5.5% and 4.1%, p

Metastatic carcinomas to the pituitary gland are uncommon, occurring in only 1% of the pituitary masses. They often originate from breast or lung carcinomas and may resemble a nonfunctioning pituitary adenoma both clinically and radiologically. Here we describe a patient with pituitary metastasis from follicular thyroid carcinoma and discuss the unique features of these lesions.A 45-year-old woman was admitted to the emergency rescue room of our hospital with a 2-month history of progressive headache and blurred vision. Evaluation revealed right eye amaurosis, with a mild abducens and oculomotor palsy. Pituitary magnetic resonance imaging showed a mass that was hypo-intense in T1-weighted and hyper-intense in T2-weighted-images, located from the sphenoid sinus up to chiasmatic cisterns, raising and deflecting the optic chiasm, down to hypopharynx region, and distorting the cavernous sinuses. No evidence of anterior or posterior hypopituitarism was recorded. The immediate trans-sphenoidal surgery was uncomplicated with partial improvement of the visual fields and headache. Histopathology revealed a metastasis with well-differentiated follicular thyroid architecture. Total thyroidectomy and lymph node dissection was performed with a final histopathological diagnosis of follicular thyroid carcinoma. Subsequently, her headache became more severe. 131-I ablation treatments were performed 15 days and 12 months after thyroidectomy with decrease in headache and a decline in serum thyroglobulin levels.Pituitary metastases from thyroid carcinoma are very uncommon. As this patient illustrates, they tend to produce symptoms relating to space-occupying expansion in the parasellar region rather than to those due to destruction of the pituitary gland. Although rare, pituitary metastases caused by thyroid malignancy should be considered in patients with expanding parasellar lesions if they have thyroid cancer or uncharacterized thyroid diseases. They are unlikely to be amenable to complete resection and should be considered for 131-I treatment, perhaps avoiding the need for extensive neurological surgery.

ContextAlthough coronary flow reserve (CFR) is reduced in patients with subclinical hypothyroidism (SHypo), the endothelial response of coronary vasomotion has never been explored in this clinical setting.ObjectiveTo investigate the endothelial response of coronary flow in young and middle-aged patients with SHypo, without associated cardiovascular risk factors compared with healthy control subjects.Patients and methodsThe study population consisted of 20 women (mean age 38.4+12.1 years) with newly diagnosed, untreated and persistent SHypo due to Hashimoto's thyroiditis. A total of 15 volunteers served as controls. Age, gender, body surface area, glucose, insulin levels, heart rate, systolic, diastolic, and mean blood pressure were similar in patients and controls. Body mass index was significantly higher in SHypo patients. Total cholesterol and low-density lipoprotein cholesterol, despite not significant, tended to be higher, and high-density lipoprotein cholesterol to be lower in SHypo. Coronary blood flow velocities were recorded in patients at rest and after the cold pressor test (CPT), a stimulus that can be considered totally endothelium-dependent. CFR was calculated as the ratio of hyperemic-to-resting diastolic peak velocities.ResultsCoronary diastolic peak velocities at rest did not differ between the two groups but were significantly lower after CPT in patients with SHypo, thereby resulting in a lower CFR. The difference remained significant after adjusting resting and CPT velocities for the respective mean blood pressures. TSH was inversely correlated with CFR in the pooled population.ConclusionPatients with SHypo without associated cardiovascular risk factors have a coronary endothelial dysfunction that appears in response to a physiological stimulus (the CPT).

The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

Tall cell variant (TCV) cancer is considered more aggressive than the classic variant of papillary thyroid cancer (PTC). Distant metastases are more common among this variant and affect survival. Little is known about the molecular pattern of this histotype.This is a report of 2 cases of unusual metastases from TCV, BRAF V600E-positive.A 38-year-old woman developed subcutaneous metastases during short-term follow-up; at medium-term follow-up, the patient showed detectable stimulated serum thyroglobulin without disease evidence at imaging. A 33-year-old man presented incidental thymic metastases at time of surgical treatment; this is the first case of not ectopic thymic metastases from PTC.TCV may present with unusual metastases already during early follow-up. The more aggressive behavior could be linked to the higher prevalence of BRAF point mutations, but only a long-term follow-up might clarify if this association could worsen the prognosis. Moreover, skin metastases have been predictive factors of worse outcome in our patients, but not thymic metastases.

Aim of this review is to highlight how and when Traumatic Brain Injury (TBI) as well as Subarachnoid Haemorrhage (SAH) and primary Brain Tumours (pBT) of the Central Nervous System (CNS) can induce hypopituitarism, an under-diagnosed clinical problem. Moreover, this review aims to clarify, on the basis of the recent evidences, how these patients have to be tested for pituitary-function. Both retrospective and prospective studies recommended that patients with more severe form of Brain Injuries (BI) and in particular, those with fractures of the base of the skull or early diabetes insipidus, have to be closely monitored for signs and symptoms of endocrine dysfunction. Further studies will be crucial to raise awareness and remind physicians on the prevalence of hypopituitarism in patients with BI and to elucidate any incremental benefits these patients may receive from hormone replacement.

Herein we report on a young girl with recurrent, functioning paraganglioma of the organ of Zuckerkandl and severe and sustained arterial hypertension (systolic pressure > 200, diastolic pressure > 120 mmHg); with evidence of cardiac damage induced by chronic cathecolamine excess. She promptly and steadily improved after the institution of doxazosin (6 mg/day) plus atenolol (50 mg bid) treatment. This case demonstrates that a correct therapeutic strategy in the long-term management of patients with inoperable catecholamine-producing neuroendocrine tumors (pheochromocytomas and paragangliomas) can maintain arterial pressure in the normal range and reverse the cardiac damage induced by chronic cathecolamine excess.

Eleven patients who had undergone total thyroidectomy for differentiated thyroid cancer and who were on chronic TSH-suppressive therapy with levothyroxine (l-T4), underwent 24-h Holter electrocardiogram and Doppler-echocardiography before and after acute recombinant human TSH (rhTSH) administration for disease staging. The treatment, which was generally well tolerated, did not affect circulating thyroid hormones levels, nor did it have measurable effects on heart rate, rhythm, left ventricular morphology, or systo-diastolic function. Notably, arterial blood pressure tended to be slightly reduced after rhTSH administration, although in no instance did the patients become frankly symptomatic. Our data demonstrate that rhTSH does not alter cardiovascular function acutely. Consequently, it can safely be used in the routine staging of patients affected by differentiated thyroid cancer.

The identification of patients with von Hippel-Lindau (VHL) disease dictates accurate genetic counseling of family members, whereas screening for early detection of visceral and neurological involvement is usually performed by a combination of radiological and nuclear medicine techniques such as ultrasonography or contrast-enhanced computed tomography of the upper abdomen, magnetic resonance imaging of the central nervous system and (131)I-metaiodobenzylguanidine-scintigraphy. The role of (111)-indium-diethylenetriaminepentaacetic acid [(111)In-DTPA(0)] octreotide scintigraphy in this clinical context has never been investigated. Here, we report imaging findings in a VHL patient and in 3 consecutive family members undergoing clinical and radiological screening that included [(111)In-DTPA(0)] octreotide scintigraphy in addition to the above-mentioned procedures. Somatostatin receptor expression was investigated in vitro by immunohistochemistry in pancreatic tumor sections. On the basis of in vivo and in vitro findings, octreotide long-acting release treatment followed by (90)Y-1,4,7,10-Tetraazacyclododecane-N, N',N '',N '''tetralacetic acid (DOTA(0))-Tyr(3)-octreotide led to a lack of progression in this patient although this result is a possibility which needs to be proved by further investigation and longer follow-up. The results of this study suggest that [(111)In-DTPA(0)] octreotide scintigraphy may be helpful in the routine work-up of VHL patients for diagnostic and therapeutic purposes.