Glycemic control and cancer outcomes in oncologic patients with diabetes: an Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical view.

BACKGROUND:  Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies. Of note, diabetes has been associated with a ∼10% increase in mortality for all cancers in comparison with subjects who did not have diabetes. Diabetes is associated with a worse prognosis in patients with cancer, and more recent findings suggest a key role for poor glycemic control in this regard. Nevertheless, the association between glycemic control and cancer outcomes in oncologic patients with diabetes remains unsettled and poorly debated. PURPOSE:  The current review seeks to summarize the available evidence on the effect of glycemic control on cancer outcomes, as well as on the possibility that timely treatment of hyperglycemia and improved glycemic control in patients with cancer and diabetes may favorably affect cancer outcomes.

Effectiveness of oral semaglutide on glucose control and body weight up to 18 months: a multicenter retrospective real-world study.

AIM: Oral semaglutide, an innovative orally administered GLP-1 receptor agonist for type 2 diabetes (T2D) management was herein evaluated for its effectiveness in a multi-center retrospective real-world study. METHODS: We included new-users of oral semaglutide from 18 specialist care centres and collected retrospective data on baseline clinical characteristics. Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. RESULTS: The study included 166 individuals with T2D, predominantly men (64.5%), with a mean age of 64.4 years and a mean diabetes duration of 10.1 years. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. At baseline, mean BMI was 28.9 kg/m2 and HbA1c was 7.5%. During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of - 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. Additionally, there was a substantial reduction in body weight, with an estimated change of - 3.4 kg at 18 months, and 30.3% of patients experienced a 5% or greater reduction in baseline body weight. Only 24.2% of patients reached the 14 mg dose. Subgroup analysis revealed that baseline HbA1c > 7%, persistence on drug, not being on a prior therapy with DPP-4 inhibitors, and loosing 5% or more the initial body weight were associated with greater HbA1c reductions. CONCLUSION: This study supports oral semaglutide as an effective option for T2D treatment, offering improved glucose control and weight management in a real-world setting.

A novel likely pathogenetic variant p.(Cys235Arg) of the MEN1 gene in multiple endocrine neoplasia type 1 with multifocal glucagonomas.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects. METHODS: While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses. RESULTS: NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient's clinical phenotype, pointed toward a possible causative role. CONCLUSION: Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.

Ketogenic nutritional therapy (KeNuT)-a multi-step dietary model with meal replacements for the management of obesity and its related metabolic disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-diet therapies in endocrinology and metabolism.

PURPOSE: The ketogenic nutritional therapy (KeNuT) is an effective dietary treatment for patients with obesity and obesity-related comorbidities, including type 2 diabetes, dyslipidaemia, hypertension, coronary artery disease, and some type of cancers. However, to date an official document on the correct prescription of the ketogenic diet, validated by authoritative societies in nutrition or endocrine sciences, is missing. It is important to emphasize that the ketogenic nutritional therapy requires proper medical supervision for patient selection, due to the complex biochemical implications of ketosis and the need for a strict therapeutic compliance, and an experienced nutritionist for proper personalization of the whole nutritional protocol. METHODS: This practical guide provides an update of main clinical indications and contraindications of ketogenic nutritional therapy with meal replacements and its mechanisms of action. In addition, the various phases of the protocol involving meal replacements, its monitoring, clinical management and potential side effects, are also discussed. CONCLUSION: This practical guide will help the healthcare provider to acquire the necessary skills to provide a comprehensive care of patients with overweight, obesity and obesity-related diseases, using a multistep ketogenic dietary treatment, recognized by the Club of the Italian Society of Endocrinology (SIE)-Diet Therapies in Endocrinology and Metabolism.

Tumor enlargement in adrenal incidentaloma is related to glaucoma: a new prognostic feature?

PURPOSE: The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). METHODS: We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007-2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). RESULTS: Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6-240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight (p < 0.03), dehydroepiandrosterone sulfate (DHEAS) (p < 0.05) and direct renin concentration (DRC) (p < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia (p < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. CONCLUSIONS: Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Transition in endocrinology: predictors of drop-out of a heterogeneous population on a long-term follow-up.

PURPOSE: To evaluate: (1) clinical and epidemiological characteristics of outpatients transitioned from Pediatrics Endocrine (PED) to Adult Endocrine Department (AED) in a tertiary center; (2) transition process features, and predictors of drop-out. METHODS: Demographic, clinical, and transition features of 170 consecutive patients with pediatric onset of chronic endocrine or metabolic disease (excluded type 1 diabetes) who transitioned from PED to AED (2007-2020) were retrospective evaluated. RESULTS: The age at transition was 18.4 ± 4 years (F:M = 1.2: 1), and mean follow-up 2.8 years. The population was heterogeneous; the most (69.4%) was affected by one, 24.1% by two or more endocrine diseases, 6.5% were followed as part of a cancer survivor's surveillance protocol. The comorbidity burden was high (37, 20.6, and 11.2% of patients had 2, 3, 4, or more diseases). The number of visits was associated with the number of endocrine diseases and the type of them. Adherent subjects had a higher number of comorbidities. Thyroid disorders and more than one comorbidity predicted the adherence to follow-up. Having performed one visit only was predictive of drop-out, regardless of the pathology at diagnosis. CONCLUSION: This is the first study that analyzed a specific transition plan for chronic endocrine diseases on long-term follow-up. The proposed "one-size-fits-all model" is inadequate in responding to the needs of patients. A structured transition plan is an emerging cornerstone.

Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

PURPOSE: Registered trials and real-world evidence (RWE) studies provided evidence on the efficacy of once-weekly (OW) semaglutide on hyperglycaemia and cardiovascular risk factors as add-on or de-novo treatment in type 2 diabetes (T2D). METHODS: In a retrospective analysis of electronic data files from 258 T2D patients, this RWE study aimed to explore the impact of OW semaglutide on biochemical and anthropometric outcomes after 6 and 12 months in patients receiving at least one prescription of OW semaglutide between September 2019 and May 2021. RESULTS: During the study period, 154 and 56 consecutive patients completed the 6 and 12 months of OW semaglutide treatment. HbA1c levels decreased by -1.02±0.1% after 6 months and -1.1±0.1% after 12 months of OW semaglutide (p<0.0001 for both). At these time-points, HbA1c values were <7% in 61% and 57% of cases. HbA1c reduction was greater in patients with higher baseline HbA1c levels and it occurred irrespective of gender, age, insulin therapy and complications. The residual number of cases with HbA1c ≥9% by the study end was low (5.3% vs 18.9% at baseline). Weight loss occurred in 73.5% and 78.1% of cases and, compared to baseline, it was ≥5% in 21.2- 25.4% and ≥10% in 6.8-18.2% after 6 and 12 months, respectively. Significant predictors of HbA1c reduction after 6 months of OW semaglutide treatment were baseline HbA1c (p<0.0001), bodyweight reduction (p<0.0001) and disease duration (p<0.001), while baseline HbA1c was the only predictor of HbA1c response after 12 months (p<0.0001). Reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients.

Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome.

PURPOSE: Angiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predicts non-alcoholic fatty liver disease (NAFLD) and altered metabolic homeostasis in the general population as well as in persons with common and genetic obesity, including the Prader-Willi syndrome (PWS). However, its metabolic correlate in paediatric patients with respect to PWS is unknown. METHODS: This cross-sectional study investigated circulating ANGPTL8 and adipocytokines levels in 28 PWS and 28 age-, sex- and BMI-matched children and adolescents (age, 7.0-17.8y) in relation to NAFLD and metabolic homeostasis assessed by OGTT, paediatric metabolic index (PMI) and fatty liver index (FLI), liver ultrasonography (US), as well as dual-energy X-ray absorptiometry (DEXA) for analysis of fat (FM) and fat-free mass (FFM). RESULTS: At the set level of significance, PWS children showed lower values of FFM (p < 0.01) but healthier insulin profiles (p < 0.01) and PMI values (p < 0.05) than matched controls. By US, the prevalence of NAFLD was similar between groups but less severe in PWS than controls. Analysis of ANGPTL8 levels showed no difference between groups, yet only in PWS ANGPTL8 levels were associated with ALT levels, FLI values and NAFLD. In stepwise multivariable regression analysis on merged data, ANGPTL8 levels were independently predicted by BMI SDS, leptin levels and NAFLD. CONCLUSION: ANGPTL8 levels are similar in PWS and controls and, overall, they are directly associated with the presence and severity of NAFLD in patients with PWS.

Clinical picture and the treatment of TBI-induced hypopituitarism.

Traumatic brain injury (TBI) is an important public health problem with an increasing incidence in the last years. Relatively few cases are fatal; most individuals will survive and, in the long-term, the sequalae of TBI will include neuroendocrine dysfunctions with a much higher frequency than previously suspected. Patients who develop hypopituitarism after TBI present manifestations due to the number of deficient hormones, severity of hormonal deficiency, and the duration of hypopituitarism without diagnosis and treatment. The clinical spectrum of hypopituitarism is very large and many signs and symptoms of TBI survivors such as fatigue, concentration difficulties, depressive symptoms are nonspecific and overlap with symptoms of post-traumatic stress disorder and variably severe hypopituitarism related to brain damage remaining undiagnosed. This can explain why the diagnosis of hypopituitarism is often missed or delayed after this condition with potentially serious and hazardous consequences for the affected patients. Moreover, clinical experience cumulatively suggests that TBI-associated hypopituitarism is associated with poor recovery and worse outcome, since post-traumatic hypopituitarism is independently associated with cognitive impairment, poor quality of life, abnormal body composition, and adverse metabolic profile. In the present review, the current data related to clinical consequences of pituitary dysfunction after TBI in adult patients and therapeutic approaches are reported.

Analysis of characteristics and outcomes by growth hormone treatment duration in adult patients in the Italian cohort of the Hypopituitary Control and Complications Study (HypoCCS).

PURPOSE: To examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients. METHODS: In the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables. RESULTS: At baseline, treatment duration groups did not differ significantly for age, gender, body mass index, GHD onset, IGF-I SDS, lipid profile, and quality of life. Mean initial GH dose did not differ significantly according to treatment duration group in any subgroup, except female patients, with highest mean dose seen in the longest duration group. In the longest duration group for patients overall, adult-onset patients and male patients, there were significant decreases in GH dose from baseline to last visit, and in total and low-density lipoprotein (LDL)-cholesterol concentrations. IGF-I SDS increased, to a greater extent, in the longest duration group for patients overall and female patients. CONCLUSIONS: The results show that long-term GH treatment is associated with decreasing GH dose, increased IGF-I, decreased LDL-cholesterol and the presence of surrogate markers that help to give confidence in a diagnosis of GHD.

Non-surgical ablative therapies for inoperable benign insulinoma.

PURPOSE: Benign insulinoma is the most common functioning neuroendocrine tumor of the pancreas. The gold-standard therapeutic approach for insulinoma is surgery, which allows for tumor removal, histology and immunochemical analyses. If surgery is not feasible, minimally invasive ablative procedures performed by interventional radiology can lead to partial or complete remission of hormone hypersecretion and tumor control in insulinoma patients. METHODS: We performed a review of existing literature on non-chemotherapeutic/radioactive ablative techniques employed for the treatment of benign, otherwise inoperable, pancreatic insulinoma. For this purpose, feasibility, effectiveness and safety of ablative treatments for pancreatic insulinoma were reviewed from literature data published from 1982 to date. RESULTS: A total of 44 insulinoma cases treated with non-surgical ablative techniques were desumed, and divided as follows: 7 cases of tumor embolization, 26 ethanol ablations, 7 radiofrequency ablations, 2 high intensity focused ultrasound ablation, 1 irreversible electroporation and 1 percutaneous microwave ablation. Most cases involved single insulinoma, predominantly located in the pancreas head and body. In the majority of patients, ablation was chosen instead of surgery due to severe comorbidities. After an average follow-up of 16 months, the overall success rate of non-surgical ablative treatments of insulinoma was 84%, the recurrence/persistence rate was 16%, and transient adverse events were noted in 23% of cases. Adverse events were usually self-limiting and medically manageable. CONCLUSIONS: Non-surgical ablation is a feasible, safe and repeatable procedure in patients with pancreatic insulinoma, who are not candidate to surgery or refuse it. Partial or complete control of symptoms and tumor growth is experienced by the majority of patients.

Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality among diabetic patients, and the neutrophil-to-lymphocyte ratio (NLR) has recently emerged from among inflammatory parameters as a potential indicator of vascular complications and poorer outcome in patients with diabetes. This study aimed to evaluate: 1) the impact of diabetes on NLR; and 2) the role of NLR on the extent of CAD among diabetic patients undergoing coronary angiography. METHODS: Consecutive patients undergoing coronary angiography were included. Diabetic status and main chemistry parameters were assessed at the time of admission. Significant CAD was defined as at least one vessel with stenosis>50%, while severe CAD was left main and/or three-vessel disease, as evaluated by quantitative coronary angiography (QCA). RESULTS: Diabetes was observed in 1377 of 3756 patients (36.7%); they were older, and displayed higher-risk cardiovascular profile and more complex CAD. Diabetic status was also associated with a significant increase in NLR (P=0.004). Among diabetics, higher NLR tertile values were related to ageing (P<0.001), dyslipidaemia (P<0.001), renal failure (P<0.001), body mass index (P<0.001), previous percutaneous coronary revascularization (P=0.004) and cerebrovascular events (P=0.003), acute presentation (P<0.001), treatment at admission with beta-blockers/statins/ASA (all P<0.001), diuretics (P=0.01) or clopidogrel (P=0.04), platelet count (P=0.03), white blood cell count, creatinine, glycaemia and C-reactive protein (P<0.001), and inversely related to haemoglobin, triglyceride levels (P<0.001) and smoking (P=0.03). NLR was associated with multivessel disease (P<0.001), degree of stenosis (P=0.01), type C lesions (P=0.02), coronary calcifications and intracoronary thrombus (P<0.001), but inversely with in-stent restenosis (P=0.003) and TIMI flow grade (P=0.02). Also, NLR was directly related to CAD prevalence (P<0.001; adjusted OR [95% CI]: 1.62 [1.27-2.07], P<0.001) and CAD severity (P<0.001; adjusted OR [95% CI]: 1.19 [1.00-1.43], P=0.05). CONCLUSION: NLR is increased among diabetic patients and, in such patients, is independently associated with the prevalence and severity of CAD. Further studies are now needed to confirm present results and to evaluate the underlying pathophysiological mechanisms behind our findings.

Growth hormone treatment of adolescents with growth hormone deficiency (GHD) during the transition period: results of a survey among adult and paediatric endocrinologists from Italy. Endorsed by SIEDP/ISPED, AME, SIE, SIMA.

Treatment of adolescents with growth hormone deficiency (GHD) during the transition period is a controversial issue. This paper is a contribution from the Italian community of paediatric and adult endocrinologists surveyed in a Delphi panel. The Delphi method is a structured communication technique, originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answer questionnaires in two or more rounds. There was substantial agreement on the definition of the problems associated with the diagnosis and treatment of adolescents with GHD in the transition period, as well as on the identification of the controversial issues which need further studies. There is general consensus on the need of re-testing all isolated idiopathic GHD after at least 30-day withdrawn from treatment, while in patients with multiple pituitary deficiency and low IGF-I levels there is generally no need to re-test. In patients with permanent or confirmed GHD, a starting low rhGH dose (0.01-0.03 mg per day) to be adjusted according to IGF-I concentrations is also widely accepted. For those continuing treatment, the optimal therapeutic schedule to obtain full somatic maturation, normalization of body composition and bone density, cardiovascular function and Quality of Life, need to be evaluated.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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 (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients. CONCLUSIONS: 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.

Quality of life, mood disturbances and psychological parameters in adult patients with GH deficiency.

An increased prevalence of depression, emotional lability, decreased energy levels, and poor quality of life have been reported in adults with GH deficiency (GHD). The impairment of psychological parameters depends on the aetiology of GHD and the presence of other pituitary hormone deficiencies because of hormonal effects on neural cell metabolism. Cognitive dysfunctions appear to be specifically related to GHD itself, whereas the lower emotional well-being and reduced motor performance are attributed to other pituitary hormone deficiencies. Traumatic Brain Injury causes very often hypopituitarism and GHD as well as other many psychological symptoms: cognitive impairment, sleeping disorders, and depression. Many neurobehavioral symptoms of postconcussion syndrome (PCS) are the same suffered by adult GHD and hypopituitaric patients but there are no data about the occurrence of hypopituitarism in PCS. In some studies treatment with rhGH is reported to have a beneficial effect and GHD could contribute itself to the global impairment of psychological dysfunctions. The link between psychosocial impairments and GHD is not fully understood. The effects of long-term rhGH therapy on cognitive functions are largely unknown. Thus, long-term placebo-controlled double-blind studies are required to investigate whether psychological dysfunctions are reversible on GH substitution.

Loss of expression of the oncosuppressor PTEN in thyroid incidentalomas associates with GLUT1 plasmamembrane expression.

AIM: Molecular imaging diagnosis with FDG-PET ((18)F-fluorodeoxyglucose positron emission tomography with computed tomography) can reveal the presence of un-suspected thyroid cancer that are referred to as "incidentaloma" because of the incidental finding. The glucose analogue (18)FDG is internalized in the cells by glucose transporters belonging to the GLUTs family. The surface expression of GLUT is under the control of the PI3k/Akt pathway. PTEN is an oncosuppressor frequently mutated or deleted in thyroid cancers. The lipid phosphatase activity of wild type PTEN switches off the Akt pathway. Here we tested the hypothesis that PTEN expression might affect the surface expression of GLUT1 and therefore influence the possibility of "incidental" detection of thyroid cancer based on FDG-PET. METHODS: The biopsy of 8 patients, who were incidentally diagnosed with PTC by (18)F-fluorodeoxyglucose positron emission tomography with computed tomography, was assayed by immunofluorescence for the co-expression of the PTEN oncosuppressor and of GLUT1. RESULTS: Loss of PTEN expression was detected in the majority of investigated cases (N.=6/8). Strikingly, while the two PTEN positive cases were negative for GLUT1 expression, the PTEN negative cases showed intense expression of GLUT1 at the cell surface. CONCLUSION: The present observations, though made in a limited number of cases, suggest that PTEN negative thyroid cancers have high chances to be revealed as incidentalomas at FDG-PET.

Clinical-pathological changes in differentiated thyroid cancer (DTC) over time (1997-2010): data from the University Hospital "Maggiore della Carità" in Novara.

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 1997­2005) and B (n = 183, diagnosis 2006­2010). 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.

Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism.

Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.

Thyroid incidentaloma identified by ¹8F-fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT): clinical and pathological relevance.

OBJECTIVE: The percentage of patients with thyroid cancer incidentally diagnosed during a (18) F-fluorodeoxyglucose Positron Emission Tomography with computed tomography (CT) (FDG-PET/CT) for nonthyroid diseases ranges between 26% and 50%. DESIGN: Retrospective assessment of the clinical and pathological features of thyroid incidentalomas at FDG-PET/CT, aiming to identify potential predictors of malignancy. PATIENTS: Fifty-two patients with incidental thyroid uptake at FDG-PET/CT were retrospectively included [38 W, age 64·1 ± 12·5 years (mean ± SD)]. An arbitrary cut-off level of 5·0 for the 'maximum standardized uptake value' (SUV max) was chosen to differentiate benign from malignant tumours. Complete thyroid function, neck ultrasonography (US) features, and cyto-histological results were reported for all cases. RESULTS: In our institution, the prevalence of incidental thyroid (18) F-fluorodeoxyglucose ((18) F-FDG) uptake was nearly 1·76%. The prevalence of focal uptake correlated with greater risk of malignancy (P < 0·01). In particular, the euthyroidism (P < 0·003) and a SUV max >5·0 (P < 0·0001) were associated with the diagnosis of thyroid cancer. Diffusely increased FDG-PET/CT uptake in the thyroid was related to benign conditions. CONCLUSIONS: The presence of focal uptake with high SUV max and euthyroidism correlate with high likelihood of malignancy. Performing a neck US would have to be recommended in all patients with euthyroidism and an incidental FDG-PET/CT focal thyroid uptake. We do not suggest to use FDG-PET/CT as a screening tool for thyroid cancer in the general population, because of both its high cost and low incidence of thyroid incidentaloma at FDG-PET/CT.