Preliminary data on the relationship between circulating levels of Sirtuin 4, anthropometric and metabolic parameters in obese subjects according to growth hormone/insulin-like growth factor-1 status.

Background: The main components of GH/insulin-like growth factor (IGF)-1 axis and Sirtuin 4 (Sirt4), highly expressed in liver and skeletal muscle mitochondria, serve as active regulators of mitochondrial oxidative capacity with opposite functions. In obesity both GH/IGF-1 status and serum Sirt4 levels, likely mirroring its reduced mitochondrial expression, might be altered.

Objective: To evaluate the association between circulating levels of Sirt4, body composition, metabolic parameters and cardio-metabolic risk profile in obese patients according to their different GH/IGF-1 status.

Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression.

Precise control of the thyroid hormone (T3)-dependent transcriptional program is required by multiple cell systems, including muscle stem cells. Deciphering how this is achieved and how the T3 signal is controlled in stem cell niches is essentially unknown. We report that in response to proliferative stimuli such as acute skeletal muscle injury, type 3 deiodinase (D3), the thyroid hormone-inactivating enzyme, is induced in satellite cells where it reduces intracellular thyroid signaling.

The hypertension of Cushing's syndrome: controversies in the pathophysiology and focus on cardiovascular complications.

Cushing's syndrome is associated with increased mortality, mainly due to cardiovascular complications, which are sustained by the common development of systemic arterial hypertension and metabolic syndrome, which partially persist after the disease remission. Cardiovascular diseases and hypertension associated with endogenous hypercortisolism reveal underexplored peculiarities. The use of exogenous corticosteroids also impacts on hypertension and cardiovascular system, especially after prolonged treatment.

Hypovitaminosis D in adolescents living in the land of sun is correlated with incorrect life style: a survey study in Campania region.

Purpose: The aim of this study is to investigate in a population of adolescents living in Regione Campania, undergoing sun exposure at least 9 months per year the prevalence of severe deficiency (<20 ng/ml) or insufficiency (21-29 ng/ml) of 25-Hydroxyvitamin D (25(OH)D) levels and its relationship with individual body weight, use of smoking, and exercise performance.

Methods: From October 2012 to October 2013, 373 healthy subjects (153 girls, 223 boys 11-20 years) without chronic diseases were consecutively enrolled in a campaign to prevent metabolic, cardiovascular, and oncological diseases. 25(OH)D assay, BMI, and lifestyle habitudes (smoking and exercise indoor or outdoor) were assessed.

Alteration of the growth hormone axis, visceral fat dysfunction, and early cardiometabolic risk in adults: the role of the visceral adiposity index.

The aim of the study is to clarify the relationship between adipose tissue dysfunction, metabolic profile and growth hormone (GH)/insulin-like growth factor (IGF)-I secretion in healthy adult subjects. We investigated the metabolic profile in a cohort of 231 consecutive healthy subjects in relation to GH, IGF-I levels, and visceral adiposity index (VAI). Anthropometric measures, lipid profile, and glucose and insulin levels during oral glucose tolerance test, Homa-IR and ISI Matsuda, IGF-I and GH peak after GHRH plus Arginine test were analyzed.

Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy?

Purpose: Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications.

The complex relationship between obesity and the somatropic axis: the long and winding road.

Despite the considerable body of evidence pointing to a possible relationship between the state of the adipose tissue depots and regulation of the somatotropic axis, to date the relationship between obesity and low growth hormone (GH) status remains incompletely understood. The low GH status in obesity is mainly considered as a functional condition, largely reversible after a sustained weight loss. Moreover, due to the effects of the adiposity on the regulation of the somatotropic axis, the application of GH stimulation tests in obesity may also lead to an incorrect diagnosis of GH deficieny (GHD).

Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial.

Background: Many patients with acromegaly do not achieve biochemical control despite receiving high doses of the first-generation somatostatin analogues octreotide or lanreotide. In the PAOLA trial, we aimed to assess the efficacy and safety of two different doses of the somatostatin analogue pasireotide long-acting release compared with active control (octreotide or lanreotide) in patients with inadequately controlled acromegaly.

Methods: In a multicentre, randomised, phase 3 trial, we enrolled eligible patients aged 18 years or older with acromegaly who were inadequately controlled (5-point, 2 h mean growth hormone concentration >2·5 μg/L and insulin-like growth factor 1 [IGF-1] concentration >1·3 times the upper normal limit) and had received 30 mg octreotide long-acting repeatable or 120 mg lanreotide (Somatuline Autogel; Ipsen, UK) as monotherapy for 6 months or longer.

The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism.

Real-world study of everolimus in advanced progressive neuroendocrine tumors.

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs).

Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study.

Purpose: A large, randomized, double-blind, Phase III core study demonstrated that pasireotide LAR was significantly superior to octreotide LAR at providing GH <2.5 μg/L and normalized IGF-1 after 12 months' treatment in patients with acromegaly. We report the efficacy and safety of pasireotide LAR and octreotide LAR after up to 26 months' treatment.

Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

Alterations in lipid pattern and increased risk for obstetric/neonatal complications have been observed in patients with polycystic ovary syndrome (PCOS). Pregnancy leads to physiologic changes in lipoprotein metabolism, and alterations in lipid profile have been related with adverse pregnancy outcomes. Based on these considerations, the aim of the present prospective controlled clinical study was to test the hypothesis that the changes in the lipid profile in patients with PCOS during pregnancy are characteristic and potentially related to the increased risk of obstetric/neonatal complications.

Characterization of the mTOR pathway in human normal adrenal and adrenocortical tumors.

The mTOR pathway has recently been suggested as a new potential target for therapy in adrenocortical carcinomas (ACCs). The aim of the current study is to describe the expression of the mTOR pathway in normal adrenals (NAs) and pathological adrenals and to explore whether there are correlation between the expression of these proteins and the in vitro response to sirolimus. For this purpose, the MTOR, S6K1 (RPS6KB1), and 4EBP1 (EIF4EBP1) mRNA expression were evaluated in ten NAs, ten adrenal hyperplasias (AHs), 17 adrenocortical adenomas (ACAs), and 17 ACCs by qPCR, whereas total(t)/phospho(p)-MTOR, t/p-S6K, and t/p-4EBP1 protein expression were assessed in three NAs, three AHs, six ACAs, and 20 ACCs by immunohistochemistry.

Hepatic arterial embolization in patients with neuroendocrine tumors.

Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms (NENs). Presence and extension of liver metastases are considered important prognostic factors, as they may significantly impair the patient's quality of life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN liver metastases include surgical resection, liver transplantation, chemotherapy and biotherapy.

Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells.

Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60-90% of men.

Could different treatment approaches in acromegaly influence life expectancy? A comparative study between Bulgaria and Campania (Italy).

Background: Mortality in acromegaly strictly depends on optimal control of GH and IGF1 levels. Modern medical therapy with somatostatin analogs (SSAs) and GH receptor antagonists (GHRAs) is not available in many countries due to funding restrictions. This retrospective, comparative, cohort study investigated the impact of different treatment modalities on disease control (GH and IGF1) and mortality in acromegaly patients.

Low-grade chronic inflammation in pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

Context: Polycystic ovary syndrome (PCOS) and pregnancy are conditions characterized by an increased low-grade chronic inflammation state. A higher incidence of pregnancy complications has been detected in pregnant PCOS women.

Objective: The objective of the study was to test the hypothesis that the low-grade chronic inflammation state typical of PCOS patients persists during gestation and is exacerbated by pregnancy and contributes to the increased risk of obstetric/neonatal complications.

Growth hormone replacement delays the progression of chronic heart failure combined with growth hormone deficiency: an extension of a randomized controlled single-blind study.

Objectives: This study sought to evaluate the efficacy and safety of long-term growth hormone (GH) replacement therapy in GH-deficient patients with chronic heart failure (CHF).

Background: Recent evidence indicates that growth hormone deficiency (GHD) affects as many as 40% of patients with CHF, and short-term GH replacement causes functional benefit. Whether long-term GH replacement also affects CHF progression is unknown.

Pituitary tumors and pregnancy: the interplay between a pathologic condition and a physiologic status.

Pregnancy is becoming a relatively common event in patients with pituitary tumors (PT), due to the increasing availability of medical treatments, which control pituitary diseases associated with the development of PT. However, the presence of PT and its treatment may be a disturbing factor for pregnancy, and pregnancy significantly influences the course and the management of PT. This review summarizes the knowledge about the management of PT during pregnancy and the occurrence of pregnancy in patients with pre-existent PT, focusing on secreting PT characterized by hormonal excess and on clinically non-functioning PT often associated to hormone deficiency, which configure the hypopituitaric syndrome.