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Background and Aims To assess the risk of hospitalization and mortality within 1 year of severe hypoglycaemia and theirs clinical predictors. Methods and Results We retrospectively examined 399 admissions for severe hypoglycemia in adults with DM at the Emergency Department (ED) of the University Hospital of Novara (Italy) betweeen 2012-2017, and we compared the clinical differences between older (aged ≥ 65 years) and younger individuals (aged 18-64 years). A logistic regression model was used to explore predictors of hospitalization following ED access and 1-year later, according to cardiovascular (CV) or not (no-CV) reasons; 1-year all-cause mortality was also detected. The study cohort comprised 302 patients (median [IQR] age 75 [17] years, 50.3% females, 93.4% white, HbA1c level 7.6% [1.0%]). Hospitalization following ED access occurred in 16.2% of patients and kidney failure (OR .50 [95% CI 1.29-5.03]) was the only predictor of no-CV specific hospitalization; 1-year hospitalization occurred in 24.5% of patients and obesity (OR 3.17 [95% CI 1.20-8.12]) and pre-existing heart disease (OR 3.20 [95% 1.20-9.39]) were associated with CV specific hospitalization; 1-year all-cause mortality occurred in 14.9% of patients and was associated with older age (OR 1.12 [95% CI 1.07-1.18]) and pre-existing heart disease (OR 2.63 [95% CI 1.19-6.14]) Conclusions Severe hypoglycemia is associated with risk of hospitalization and mortality mainly in elderly patients and it may be predictive of future cardiovascular events in diabetic patients with pre-existing heart disease and obesity.

Purpose Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. Methods We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. Results Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73–0.94; OR 1.17, 95% CI 1.04–1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8–0.93; p Conclusion Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.

Uncertainties exist about the predictors of the severity of the clinical picture of GH deficiency (GHD) syndrome. Aim of the study was to evaluate, in adult patients with GHD, the predictors of the development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis. We retrospectively studied 327 adult patients (age 47.1 ± 17.1 years) with untreated severe GHD (mean follow-up 110.9 ± 56.8 months). GHD was defined by GHRH + arginine test using BMI cut-offs. The possible development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis was investigated by Kaplan–Meier survival analysis. For each clinical outcome, either a univariate or multivariate analysis according to the Cox proportional-hazards model was performed to identify those factors that were associated with the development of the event. GH secretion parameters were not associated with the outcomes. Hypercholesterolemia was positively and negatively predicted by a BMI ≥ 30 kg/m2 (HR 2.50, p 0.00) and the dose of l-thyroxine possibly in place (HR 0.98, p 0.02), respectively. Hypertension was positively predicted by a BMI ≥ 30 kg/m2 (HR 2.64, p 0.00) and IGF-I SDS values (HR 2.26, p 0.00). Diabetes mellitus was positively predicted by hypertension (HR 11.76, p 0.01). Osteoporosis was positively and negatively predicted by hypercholesterolemia (HR 3.25, p 0.01) and hypertension (HR 0.21, p 0.00), respectively. The severity of the impairment of GH secretion does not predict the development of the clinical picture of GHD syndrome: untreated adult GHD does not increase the development of metabolic risk factors in hypopituitaric patients.

Modern advances in oncological treatments determined a significant improvement in survival rates for several malignancies. Nevertheless, survivorship and quality of life of cancer survivors may be negatively impaired by metabolic and endocrine side effects related to anticancer treatments, including alterations of pituitary-gonadal axis function. In fact, both medical (chemo- and radiotherapy) and surgical approaches may negatively impact on gonadal function, leading to transient or permanent hypogonadism and infertility. In view of these considerations, fertility preservation (FP) should be a primary concern in all oncological patients who may potentially achieve parenthood, irrespectively from their sex and pubertal status at treatment, and adequate counselling should be provided before undergoing gonadotoxic therapy or gonadectomy. Cryopreservation of gametes, when feasible, represents the mainstay for FP in postpubertal age, while procedures involving storage of tissue specimens or stem cells should still be considered as experimental. Given the complexity of both hormonal and psychological implications in this clinical setting, a multidisciplinary approach is advisable for optimal FP and for early diagnosis and treatment of hypogonadism.

Context Erythrocytosis is one of the most common side effects occurring during testosterone replacement therapy (TRT) in male hypogonadism. It is well known that all testosterone formulations may cause Hb and hematocrit increase, especially with short-acting injectable formulations. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a new class of glucose-lowering agents that reduce hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by inhibition of renal glucose reabsorption, leading to increased urinary glucose excretion. The co-occurrence of T2DM and hypogonadism is known to be increasingly frequent. However, to date, no adverse events with the concomitant use of TRT and SGLT2is are reported. Case description We report two cases of erythrocytosis during testosterone treatment and SGLT2i in patients with hypogonadism and T2DM. Conclusion Considering that hypogonadism and T2DM are frequently associated, clinicians should carefully monitor the risk of occurrence of erythrocytosis when prescribing TRT and SGLT2i together.

Uric acid (UA) is a byproduct of the high-energy purine metabolism and is conventionally regarded as a marker of cardio-metabolic impairment. Its potential relationship with energy homeostasis is unknown to date.In a cross-sectional study on 121 otherwise healthy obese and 99 sex- and-age-matched lean subjects, UA levels were analyzed in relation to metabolic health, inflammatory markers, respiratory quotient (RQ) and resting energy expenditure (REE) as assessed by indirect calorimetry, fat mass (%FM) and fat-free mass (FFM) as determined by bioimpedance analysis. As expected, obese and lean subjects differed in BMI, glucolipid homeostasis, leptin and insulin levels, inflammatory markers, %FM and FFM (p 0.001 for all). Likewise, UA levels (p 0.001) and rates of hyperuricaemia (40.5% vs 3.0%, p 0.0001) were also higher in obese than lean controls. Further, indirect calorimetry confirmed that obesity increased REE and decreased RQ significantly (p 0.001). Beyond the expected metabolic correlates, in individual and merged groups UA levels were associated negatively with RQ and positively with REE (p 0.0001 for both). In multivariable regression analysis, significant independent predictors of UA were BMI and sex. When BMI was replaced by measures of body composition, %FM and FFM emerged as significant predictors of serum UA (p 0.0001).A potential link relates serum UA to measures of resting energy expenditure and their determinants.

Background Post-cardiotomy vasoplegic syndrome is a vasodilatory shock characterized by a decrease of vascular tone with a normal or increased cardiac output. A relative deficit in vasopressin secretion in the postoperative was hypothesized. Copeptin is secreted in equimolar ratio with vasopressin but it is more stable and easier to measure. The aim of the present study was to investigate whether perioperative copeptin was associated with post-cardiotomy vasoplegic syndrome. Methods All patients scheduled for cardiac surgery were evaluated. Exclusion criteria were age < 18 years old, corticosteroids therapy, heart transplantation, extra-circulatory life support, sepsis, preoperative use of vasoactive drugs, off-pump surgery, chronic hepatic and renal failure, paraneoplastic syndrome, lack of informed consent. Post-cardiotomy vasoplegic syndrome was defined as a mean arterial pressure < 60 mmHg, a reduction of systemic vascular resistances < 1200 dyn*s/cm 5 *m 2 and/or the need of nor-epinephrine ³ 0.1 µg/kg/min. All patients underwent a preoperative evaluation of the corticotropin stimulation test; then, before surgery (T0), on day one after surgery (T1) and after 7 days (T2) copeptin and NT-proBNP concentration were measured. Results Among 55 enrolled patients, 9 (16.3%) developed post-cardiac surgery vasoplegia. Patients with vasoplegia had higher preoperative level of copeptin (19.2 pmol/L, IQR 17.89 – 21.29 vs 11.39 pmol/L, IQR 6.33 - 14.78; p < 0.001) and NT-proBNP (1435 pg/ml, IQR 721.75 – 1836.25 vs 365.5 pg/ml, IQR 141 - 977); p = 0.006) compared to the control group. At the multivariable analysis, preoperative copeptin resulted a significant predictor of vasoplegia (OR 1.56, 95% CI 1.002-1.33) and the ROC analysis showed an accurate copeptin cut off able to identify vasoplegic patients (> 16.9 pmol/L, AUC = 0.86, 95% CI 0.73-0.94). Otherwise, a lack of response to the low dose corticotropin test was not a predictor of PCVS; no patient presented a pathological response to the standard dose test. ConclusionsIncreased preoperative copeptin and NT-proBNP levels might be associated with an increased risk to develop post-cardiotomy vasoplegic syndrome. Our results suggest that patients with a decompensated neuroendocrine control of cardiovascular function are more prone to develop postoperative vasoplegia.

The first description of Klinefelter syndrome (KS) dates back to 1942, when Harry F. Klinefelter et al. (J Clin Endocrinol 2(11):615–627, 1942) reported the occurrence of a ‘not uncommon’ syndrome characterized by small testes, tall stature, gynaecomastia and azoospermia. In 1959, Patricia A. Jacobs et al. (Nature 183(4657):302–303, 1959) identified the causal role in 47,XXY chromosomal aneuploidy, allowing its diagnosis by karyotyping.

A 53-year-old male referred to our centre because of hypergonadotropic hypogonadism detected during urological follow-up for urethral lithiasis. Physical examination showed short stature, micropenis, ambiguous external genitalia, and normal secondary sexual characteristics. Karyotype: 45 × 0/46XY. Abdominal MRI revealed the presence of uterus-like structure, right annex, and left testes without prostate. He underwent laparoscopic removal of dysgenetic tissues; histologic examination confirmed the presence of little uterus, fallopian tubes, little atrophic ovary, and vaginal tract; left testes was atrophic with sclero-jalinosis of seminal tubes and Leydig's cells hyperplasia. Testosterone replacement therapy was started after surgery and prostate became MRI visible after 2 years.

Unfortunately in the original publication, the affiliation of the author Paolo Marzullo was incorrect. The author inadvertently missed out to include his second affiliation.

Erectile dysfunction (ED) seems to be a widespread sexual issue in men affected by chronic obstructive pulmonary disease (COPD). Multiple causes appear to be involved such as hormonal imbalance, smoking habit, chronic inflammation, endothelial dysfunction, chronic hypoxia, psychiatric disorders (depression and anxiety), and medications. ED can have a significant impact on COPD men and consequently on their quality of life, which is usually already compromised. Given this situation, however, pneumologists usually do not properly care for the sexuality of COPD patients especially because men can be reluctant to talk about their intimate issues. The aim of this narrative review is to briefly summarize the evidence emerging from literature and to provide a wide point of view about sexual dysfunction in COPD men.

To evaluate early results of transsphenoidal surgery for pituitary adenomas. Retrospective evaluation of 90 consecutive patients undergoing endoscopic pituitary adenoma surgery (2007–2016) at “Maggiore della Carita” Hospital in Novara, Italy. Age at diagnosis, sex, symptoms at presentation, hormonal and radiological data, complications of surgery, and short-term follow-up information were collected. The majority of patients were male (M/F: 1.5/1, mean age at diagnosis 62.1 ± 1.5 years mean ± SEM). Most patients (91.1%) presented with a macroadenoma (27.4 mm ± 1.1 mm mean ± SEM), while 77.8% were non-functioning pituitary adenomas. Clinical presentations related to mass effect were visual impairment (74.0%) and/or hypopituitarism (55.1%). The main surgery complication was insipidus diabetes (12.2%), followed by cerebral hemorrhage (4.4%), cerebrospinal fluid (CSF) leaks (4.4%), syndrome of inappropriate antidiuresis (SIAD) (2.2%), and epistaxis (2.2%); only one patient died because of stroke. Risk of complications was not associated with tumor size (OR = 0.588, 95% CI 0.967–1.081, p = 0.443). Visual function improved in 70.6% of patients, while recovery of normal pituitary function occurred in 48.1%. Early neuroimaging studies demonstrated no residual tumor in 27.6% of patients. Invasion of cavernous sinus (OR = 3.293, 95% CI 0.897–16.738, p = 0.05) and maximum tumor diameter (OR = 6.857, 95% CI 1.039–1.309, p

Varicocele is defined as a state of varicosity and tortuosity of the pampiniform plexus around the testis caused by retrograde blood flow through the internal spermatic vein. The prevalence of clinically relevant varicocele ranges from 5 to 20% in the male population and is often associated with infertility and reduction of sperm quality. In this review, the pathophysiology and clinical aspects of varicocele are reviewed along with therapeutic options and treatment effects on sperm parameters and fertility both in adult and in pediatric/adolescent subjects. We conducted a Medline and a PubMed search from 1965 to 2018 to identify publications related to varicocele clinical aspects, treatment procedures and treatment outcomes. Keywords used for the search were: “varicocele”, “varicocelectomy”, “sclerotherapy”, “male infertility”, “subfertility”, and “semen abnormalities”. Data from a large number of studies in adolescent and adult males indicate that varicocele correction improves semen parameters in the majority of patients, reducing oxidative stress and improving sperm nuclear DNA integrity either with surgical or percutaneous approach. Varicocele repair seems to represent a cost-effective therapeutic option for all males (both adolescent and adults) with a clinical varicocele in the presence of testicular hypotrophy, worsening sperm alterations or infertility. On the other hand, some investigators questioned the role of varicocelectomy in the era of assisted reproduction. Thus, a better understanding of the pathophysiology of varicocele-associated male subfertility is of paramount importance to elucidating the deleterious effects of varicocele on spermatogenesis and possibly formulating new treatment strategies.

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

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.

Background 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. Methods This is a report of 2 cases of unusual metastases from TCV, BRAF V600E-positive. Results 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. Conclusion 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. © 2013 Wiley Periodicals, Inc. Head Neck 35: E381–E385, 2013

To assess the incidence of abnormal neuroendocrine function post-traumatic brain injuriy (TBI) in a large group of paediatric patients and its correlations with clinical parameters (Glasgow coma scale—GCS, Glasgow outcome scale—GOS, TC marshall scale, height velocity). We evaluated 70 patients [58 M, 12 F; age at the time of TBI (mean ± SEM) 8.12 ± 4.23 years] previously hospitalized for TBI at the “Regina Margherita” Hospital, in Turin and “Maggiore della Carita Hospital” in Novara, Italy, between 1998 and 2008. All patients included underwent: auxological, clinical, hormonal and biochemical assessments at recall (after at least 1 year from TBI to T0); auxological visit after 6 months (T6) and hormonal assessments at 12 months (T12) in patients with height velocity (HV) below the 25th centile. At T0, 4 cases of hypothalamus-pituitary dysfunction had been diagnosed; At T6 20/70 patients had an HV

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.

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.

Growth hormone (GH) deficiency (GHD) is a complex disease with a constellation of symptoms and signs which involve metabolism at several levels. Particular attention has been paid to glucose and insul

a Endocrinology, Department of Translational Medicine, Universita del Piemonte Orientale “A. Avogadro”, Italy b SCDU of Pediatrics, Department of Health Sciences, Universita del Piemonte Orientale “A. Avogadro”, Italy c Interdisciplinary Centre for the Study of Obesity (ICSO), Universita del Piemonte Orientale “A. Avogadro”, Novara, Italy d Endocrinology and Metabolism, University of Turin, Italy e Don Gnocchi Rehabilitation Center, Turin, Italy f General Medicine, Istituto Auxologico Italiano, Piancavallo (VB) 28923, Italy