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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., (© 2024. The Author(s).)

Purpose: Chronic kidney disease (CKD) is a serious health concern with an estimated prevalence of about 13.4% worldwide. It is cause and consequence of various comorbidities, including cardiovascular diseases. In parallel, common pathological conditions closely related to ageing and unhealthy dietary habits increase the risk of CKD development and progression, including type 2 diabetes and obesity. Among these, obesity is either independent risk factor for new onset kidney disease or accelerates the rate of decline of kidney function by multiple mechanisms. Therefore, the role of diets aimed at attaining weight loss in patients with obesity is clearly essential to prevent CKD as to slow disease progression. Various dietary approaches have been licensed for the medical dietary therapy in CKD, including low-protein diet and Mediterranean diet. Interestingly, emerging evidence also support the use of low-carbohydrate/ketogenic diet (LCD/KD) in these patients. More specifically, LCD/KDs may efficiently promote weight loss, improve metabolic parameters, and reduce inflammation and oxidative stress, resulting in a dietary strategy that act globally in managing collateral conditions that are directly and indirectly related to the kidney function., Conclusion: This consensus statement from the Italian Society of Endocrinology (SIE), working group of the Club Nutrition - Hormones and Metabolism; the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals "KetoNut-SINut"; and the Italian Society of Nephrology (SIN) is intended to be a guide for Endocrinologist, Nutritionists and Nephrologist who deal with the management of patients with obesity with non-dialysis CKD providing a practical guidance on assessing nutritional status and prescribing the optimal diet in order to best manage obesity to prevent CKD and its progression to dialysis., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Immunotherapy with immune checkpoint inhibitors (ICI) is increasingly employed in oncology. National and international endocrine and oncologic scientific societies have provided guidelines for the management of endocrine immune-related adverse events. However, guidelines recommendations differ according to the specific filed, particularly pertaining to recommendations for the timing of endocrine testing. In this position paper, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) offers a critical multidisciplinary consensus for a clear, simple, useful, and easily applicable endocrine-metabolic assessment checklist for cancer patients on immunotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: V.R. has received a travel grant from Androlabs. M.G. has received honoraria for speaker fees and/or travel grants for scientific meetings from AAA, AstraZeneca, Boehringer-Ingelheim, Bruno Farm., Eli-Lilly, IBSA, Lifescan, Mundipharma, Novo Nordisk and Sanofi, and served on scientific advisory panels for Boehringer-Ingelheim, Merck Sharp & Dohme and Novo Nordisk. S.F. serves on the scientific advisory board of, has a consulting relationship with and reports receiving support for travel expenses from Novartis, Teva, Roche, BMS, Lilly and Ipsen. R.D. serves on the scientific advisory board and has a consulting relationship with Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Gilead, EUSA Pharma; and reports support for travel, accommodation and expenses from Ipsen and Sanofi Genzyme. F.G. has served as an advisor for AstraZeneca, Eli Lilly and Novo Nordisk; has served as a research investigator for Eli Lilly and Roche Diabetes Care; has served as a speaker for AstraZeneca and Eli Lilly; has served as a consultant for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Roche Diabetes Care and Sanofi; and has received grants from Eli Lilly, Lifescan and Roche Diabetes Care. N.S. received fees for consulting from Roche, Lilly, Servier. All other authors declare no conflict of interest. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. The Author(s).)

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 < 0.01). Measured at admission, fT3 values higher than 2.76 pg/mL discriminated patients with late post-traumatic seizures from those without, with a sensitivity of 74.2% and a specificity of 60.9%. Independently from the presence of post-traumatic epilepsy and TBI severity, increasing TSH levels and decreasing fT3 levels were associated with worse neurological and functional outcome, as well as with higher risk of mortality within 6 months from the TBI event., 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., (© 2021. The Author(s).)

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study., (© 2021. The Author(s).)

Aims: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA 1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed., Methods: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA 1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration., Results: HbA 1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00-pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05)., Conclusions: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM., Clinical Trial Registration: EudraCT 2015-001167-39.

Introduction: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions., Materials and Methods: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded., Results: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006), and platelet count ( χ 2 5.39; p = 0.02), along with age ( χ 2 87.6; p < 0.001) and gender ( χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/ μ L was, conversely, protective (OR: 0.45 (0.32-0.63))., Conclusion: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2021 Mattia Bellan et al.)

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO 2 /FiO 2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Aims: People with uncontrolled type 2 diabetes (T2DM) often delay initiating and titrating basal insulin. Patient-managed titration may reduce such deferral. The Italian Titration Approach Study (ITAS) compared the efficacy and safety of insulin glargine 300 U/mL (Gla-300) initiation and titration using patient- (nurse-supported) or physician-management in insulin-naïve patients with uncontrolled T2DM., Materials and Methods: ITAS was a multicentre, phase IV, 24-week, open-label, randomized (1:1), parallel-group study. Insulin-naïve adults with T2DM for ≥1 year with poor metabolic control initiated Gla-300 after discontinuation of SU/glinides, and were randomized to self-titrate insulin dose (nurse-assisted) or have it done by the physician. The primary endpoint was change in HbA 1c . Secondary outcomes included hypoglycaemia incidence and rate, change in fasting self-monitored plasma glucose, patient-reported outcomes (PROs), and adverse events., Results: Three hundred and fifty five participants were included in the intention-to-treat population. At Week 24, HbA 1c reduction from baseline was non-inferior in patient- vs physician-managed arms [least squares mean (LSM) change (SE): -1.60% (0.06) vs -1.49% (0.06), respectively; LSM difference: -0.11% (95% CI: -0.26 to 0.04)]. The incidence and rates of hypoglycaemia were similarly low in both arms: relative risk of confirmed and/or severe nocturnal (00:00-05:59 hours) hypoglycaemia was 0.77 (95% CI: 0.27 to 2.18). No differences were observed for improvement in PROs. No safety concerns were reported., Conclusions: In the T2DM insulin-naïve, SU/glinides discontinued population, patient-managed (nurse-assisted) titration of Gla-300 may be a suitable option as it provides improved glycaemic control with low risk of hypoglycaemia, similar to physician-managed titration., (© 2020 SANOFI. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Purpose: Unrecognized and untreated hyperthyroidism leads to serious clinical complications with adverse outcomes for patients and increasing costs for the health care system. Hence, adequate knowledge of the epidemiological features of such condition is desirable to plan effective interventions. The aim of our study was to estimate incidence and prevalence of hyperthyroidism in the mildly iodine-deficient Italian Region of Piedmont., Methods: A retrospective cohort study was conducted using Administrative Health Databases of the Piedmont Region, Italy (2012-2018). Hyperthyroidism cases were defined as the subjects who had at least one of the following claims: (i) hospital discharge records with hyperthyroidism diagnosis code; (ii) exemption from co-payment for hyperthyroidism; (iii) prescription of one of the following medications: methimazole, propylthiouracil, or potassium perchlorate., Results: The overall prevalence was 756 per 100,000 inhabitants [95% CI 748-764], and the overall incidence was 81 per 100,000-person year [95% CI 80-82]. The prevalence and incidence increased with age and were two-fold higher among women than men. Women also showed two distinct peaks in incidence at the age of 30 and 50; after the age of 60, the trend became similar between sexes. With regard to the geographic distribution, an increasing gradient of incidence was observed from the northern to the south-western areas of the Region., Conclusion: This is the first Italian study based on health databases to estimate the incidence and prevalence of hyperthyroidism in the general population. This approach can represent an inexpensive and simple method to monitor patterns of hyperthyroidism in iodine-deficient areas.

The available data on the natural history of pheochromocytomas and paragangliomas after radical surgery are heterogeneous and discordant. The aim of our retrospective multicenter study was to find predictors of recurrence in patients with pheochromocytomas and sympathetic paragangliomas submitted to radical surgery in Piedmont (a region in northwest Italy). We collected data from 242 patients diagnosed between 1990 and 2016. Forty-two patients (17.4%) had disease recurrence. Multivariate analysis showed that genetic mutation (HR = 3.62; 95% CI 1.44-9.13; p = 0.006), younger age (HR = 0.97; 95% CI 0.95-0.99; p = 0.031) and larger tumor size (HR = 1.01; 95% CI 1.00-1.02; p = 0.015) were independently associated with a higher recurrence risk of pheochromocytoma and paraganglioma; in pheochromocytomas, genetic mutation (HR = 3.4; 95% CI 1.00-11.48; p = 0.049), younger age (HR = 0.97; 95% CI 0.94-0.99; p = 0.02), higher tumor size (HR = 1.01; 95% CI 1.00-1.03; p = 0.043) and PASS value (HR = 1.16; 95% CI 1.03-1.3; p = 0.011) were associated with recurrence. Moreover, tumor size was the only predictor of metastatic pheochromocytoma and paraganglioma (HR = 4.6; 95% CI 1.4-15.0; p = 0.012); tumor size (HR = 3.93; 95% CI 1.2-16.4; p = 0.026) and PASS value (HR = 1.27; 95% CI 1.06-1.53; p = 0.007) were predictors of metastatic pheochromocytoma. In conclusion, our findings suggest that the recurrence of pheochromocytoma and sympathetic paraganglioma develops more frequently in younger subjects, patients with a family history of chromaffin tissue neoplasms, mutations in susceptibility genes, larger tumors and higher values of PASS. We recommend genetic testing in all patients with PPGL and strict follow-up at least on an annual basis.

Background and Aims: Fostering patient's self-managing of basal insulin therapy could improve glucose control, by removing patient's and physician's barriers to basal insulin initiation, titration and glucose monitoring. The Italian Titration Approaches Study (ITAS) aims at demonstrating non-inferiority (<0.3% margin) in efficacy of glucose control (change in glycated hemoglobin [HbA1c] after 24 weeks) by the same titration algorithm of insulin glargine 300 U/mL (Gla-300), managed by the (nurse assisted) patient versus the physician, in insulin naïve patients with Type 2 Diabetes Mellitus (T2DM), uncontrolled with previous treatments., Methods and Results: ITAS is a phase IV, 24-week, national, multicenter, open label, randomized (1:1) parallel group study. 458 patients were enrolled, 359 randomized, and 339 completed the study, in 46 Italian centers. Baseline characteristics and previous medications of the ITT population (N = 355) are reported. Mean ± SD age, T2DM duration, HbA1c, FPG and BMI were 64.0 ± 9.8 years, 11.6 ± 7.6 years, 8.79 ± 0.65%, 170.9 ± 42.3 mg/dL, and 30.3 ± 5.6 kg/m 2 , respectively. Vascular and metabolic disorders were most frequent (73.8% and 58.3%, respectively). More than 90% of patients were on metformin., Conclusion: ITAS is the first study to compare two different managers (nurse-assisted patient vs physician) of the same titration algorithm of Gla-300 in insulin naïve patients with T2DM in unsatisfactory glucose control. This study might provide novel evidence on the efficacy/effectiveness of patient-managed titration algorithm of Gla-300 in a pragmatic setting and may reduce barriers to basal insulin initiation and its titration., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: Recent studies from national registries have described changing patterns in epidemiology of acromegaly. Our retrospective study used administrative databases to estimate prevalence and incidence of acromegaly in the Piedmont Region, Italy., Methods: This study was conducted in Piedmont between 2012 and 2016 on administrative health databases for inpatients and outpatients of any age. Enrollees were included if claims suggestive of acromegaly were identified in at least two of the following databases: Drug Claims Registry, Hospital Information System, Co-payment Exemption Registry and Outpatient Specialist Service Information System., Results: 369 individuals (M = 146, F = 223) met our criteria. Overall incidence was 5.3 per million person years (95% CI 4.2-6.7), and prevalence was 83 cases per million inhabitants (95% CI 75-92). Mean age was 50.9 years. Both incidence and prevalence were slightly higher among women (rate ratio 1.08, prevalence ratio 1.43). Age-specific incidence was similar between sexes up to 39 years and diverged thereafter, with an increasing trend recorded among men. Prevalence was higher in women aged 40-79 years, and increased continuously up to 79 years in both sexes., Conclusions: This is the first population-based study conducted in Italy to estimate incidence and prevalence of acromegaly and results show a higher prevalence than previously reported. Although our algorithm requires proper validation, it constitutes a promising tool to describe the epidemiology of acromegaly.

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.

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.

In 2007 the Italian COM.E.T.A. (COMorbidities Evaluation and Treatment in Acromegaly) study group started to assess the application in a clinical setting of the Versailles criteria for management of acromegaly complications by a first questionnaire focusing on cardiovascular co-morbidities. A further questionnaire on sleep apnea syndrome (SAS) was delivered by the COM.E.T.A. study group to 107 endocrine centers in Italy. The results of our survey suggest that SAS is a well-known comorbidity even if its estimated prevalence is lower than in the literature. Polysomnography is the preferred tool for diagnosis. Control of SAS is considered relevant both for quality of life and co-morbidities. Continuous positive airway pressure is the cornerstone of therapy, but patients' acceptance may be critical. Control of GH/IGF-I secretion is important to improve SAS. Management of SAS requires cooperation between specialists.

Serum IGF-I levels were measured in 547 non-hypopituitaric, non-acromegalic healthy subjects of both sexes in Italy to develop reference values in relation to age and sex. Participant subjects were stratified in three age classes (25- 39, 40-59 and >or=60 yr) and IGF-I assay was carried out by double-antibody radio immunoassay. Pearson's correlation coefficient between age and IGF-I values was calculated by sex and predefined age ranges. IGF-I levels significantly decreased with age (p<0.001, Kruskal-Wallis test) while sex was not a significant factor. The median IGF-I levels were 206 ng/ml in the 25-39 yr range, 147 ng/ml in the 40-59 yr range and 103 ng/ml in the >or=60 yr range. Pearson's correlation coefficient confirmed the negative correlation between age and IGF-I levels in the total sample of subjects (r=-0.529). The r coefficient between age and IGF-I levels did not differ between sexes (r=-0.570 in males and r=-0.529 in females), thus reflecting no sex-effect on IGF-I levels decline over years. No correlations were found in the 25-39 yr range (r=-0.036) or in the 40-59 yr range (r=-0.080) either, while in subjects aged >60 yr, IGF-I levels tended to further decrease with increased age (r=0.389). Ranges of normal values set at the 2.5th-97.5th percentile in the three age ranges were 95.6-366.7 ng/ml between 25 and 39 yr, 60.8-297.7 ng/ml between 40 and 59 yr and 34.5-219.8 ng/ml in subjects aged >or=60 yr. This study may contribute to the development of age-specific reference ranges for IGF-I determination in serum of normal subjects of both sexes in Italy.

Objective: The aim of this study is to estimate the annual incidence and prevalence rate of the GH treatment exposure in patients under the age of 18 treated for hypopituitarism or isolated GH deficiency (GHD) in Piedmont, during the period January 1, 2002 to December 31, 2004., Methods: The selection criteria for recombinant human GH (rhGH) treatment in childhood were approved by the Ministry of Health in Italy in the yr 1998. The present analysis is based on data from the Registry of subjects receiving GH therapy (GH Registry) made up of the 918 pediatric patients (age <18 yr) with a diagnosis of GHD (excluding Prader-Willi and Turner syndromes and other conditions), diagnosed in the period January 1, 2002 - December 31, 2004. The case series has been described as regards the number of cases per year of diagnosis; the prevalence and incidence rates, calculated per 10,000 (per ten thousand) inhabitants, are given for each year of the study period., Results: The prevalence rate increases slightly from 8.62 per thousand in 2002 to 9.44 per thousand in 2004 and the incidence rates estimated were 2.49 per ten thousand, 1.86 per ten thousand and 1.97 per ten thousand in the yr 2002, 2003 and 2004, respectively., Conclusion: The Piedmont GH Registry represents the first database available in Italy and could set an example for the other Italian regions as well.

Traumatic Brain Injury (TBI) and Subarachnoid Haemorrhage (SAH) are conditions at high risk to develop hypopituitarism as pointed out by many papers in scientific literature. But most of the papers were referred to retrospective evaluations, not considering the possible evolution of the pituitary function over time. Aim of our studies was to clarify whether pituitary deficiencies and normal pituitary function recorded at short term follow-up (3 months), would improve or worsen, respectively, at long term (12 months after the brain injury). In a multicenter study protocol, in patients who suffered TBI (n = 70; 50 Males, 20 Females; age 39.31 +/- 2.4 years; BMI 23.8 +/- 0.4 kg/m(2)) or SAH (n = 32; 12M, 20F; age: 51.9 +/- 2.2 year; BMI: 24.7 +/- 0.6 kg/m(2)) we tested 3 and 12 months after the pathological events the pituitary function. In TBI patients, the 3 month evaluation had shown some degree of hypopituitarism in 32.8% and the 12 months retesting demonstrated some degree of hypopituitarism in 22.7%. Total hypopituitarism was always confirmed at 12 months while Multiple and Isolated deficits recorded at 3 months was confirmed in nearly 25% only of the patients. On the other hand, in 5.5% of TBI with normal pituitary function at 3 months Isolated deficits were recorded at 12 months testing. Moreover, in 13.3% of TBI with Isolated deficit at 3 months Multiple hypopituitarism was demonstrated at 12 months retesting. In SAH patients, the 3 months evaluation had shown some degree of hypopituitarism in 46.8% and the 12 month retesting demonstrated some degree of hypopituitarism in 37.5%. No multiple hypopituitarism recorded at 3 months was confirmed at 12 months, but 2 patients with isolated deficits at 3 months showed multiple hypopituitarism at 12 month retesting. At 12 as well as at 3 months, both in TBI and SAH patients, the most common deficit was severe GHD (>20%) followed by secondary hypogonadism and then hypoadrenalism and hypothyroidism. In all, in patients who experienced TBI or SAH the risk to develop hypopituitarism is very high; early diagnosis of total hypopituitarism is always confirmed at the long term follow-up; however pituitary function in brain injured patients may improve over time, because, isolated and even multiple pituitary insufficiencies recorded at short term can be transient; on the other hand normal pituitary function recorder at short term may, become impaired 12 months after the injury. Thus, brain injured patients must undergo neuroendocrine follow-up over time in order to monitoring pituitary function and eventually providing appropriate placement.