Francesco Tassone

Obstructive sleep apnoea syndrome impairs insulin sensitivity independently of anthropometric variables

objectives Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity and characterized by endocrine and metabolic changes including impairment of insulin sensitivity. The aim of this study was to further clarify the insulin dynamics and glucose metabolism in this condition.

Screening of Cushing's syndrome in adult patients with newly diagnosed diabetes mellitus

Objective  Recent studies have shown that a relatively high number of diabetic patients may have unsuspected Cushings syndrome (CS). The aim of the present study was to screen for CS in adult patients with newly diagnosed diabetes mellitus who were not selected for clinical characteristics, such as poor control and obesity, which may increase the pre‐test probability of CS.

Effects of glucose, free fatty acids or arginine load on the GH-releasing activity of ghrelin in humans

objective Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an n‐octanoyl ester in serine‐3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS‐R) and strongly stimulates GH secretion. In humans, ghrelin is more potent than growth hormone‐releasing hormone (GHRH) and non‐natural GHS such as hexarelin. Moreover, ghrelin shows a true synergism with GHRH, has no interaction with hexarelin and, similarly to non‐natural GHS, is partially refractory to the inhibitory effect of exogenous somatostatin (SS). Despite this evidence, the mechanisms underlying the GH‐releasing effect of ghrelin in humans have not been fully clarified.

Screening of Cushing's Syndrome in Outpatients with Type 2 Diabetes: Results of a Prospective Multicentric Study in Italy

CONTEXT Cushings syndrome may remain unrecognized among patients referred for metabolic syndrome; thus, a proactive screening has been suggested in certain patient populations with features of the disorder. However, conflicting data have been reported on the prevalence of Cushings syndrome in patients with type 2 diabetes. OBJECTIVE Our aim was to evaluate the prevalence of unsuspected Cushings syndrome among outpatients with type 2 diabetes. DESIGN AND SETTING This was a cross-sectional prospective study in 24 diabetes clinics across Italy. PATIENTS Between June 2006 and April 2008, 813 patients with known type 2 diabetes without clinically overt hypercortisolism were evaluated. Follow-up of the study was closed in September 2010. Patients were not selected for characteristics conferring a higher pretest probability of hypercortisolism. Patients underwent a first screening step with the 1-mg overnight dexamethasone suppression test. RESULTS Forty patients failed to suppress serum cortisol less than 5.0 μg/dl (138 nmol/liter) and underwent a standard 2-d, 2-mg dexamethasone suppression test, after which six patients (0.6% of the overall series) failed to suppress cortisol less than 1.8 μg/dl (50 nmol/liter), receiving a definitive diagnosis of Cushings syndrome that was adrenal dependent in five patients. Four patients were cured, being able to discontinue, or reduce, the glucose-lowering agents. CONCLUSIONS The present data do not support widespread screening of patients with type 2 diabetes for Cushings syndrome; however, the disorder is less rare than previously thought when considering epidemiology of type 2 diabetes. Our results support a case-finding approach in patients with uncontrolled diabetes and hypertension despite appropriate treatment.

Marked GH secretion after ghrelin alone or combined with GH-releasing hormone (GHRH) in obese patients.

objectives  Ghrelin is a 28‐amino‐acid peptide, predominantly produced by the stomach. It displays a strong GH‐releasing activity mediated by the hypothalamus–pituitary GH secretagogue (GHS)‐receptor (GHS‐R). There are different studies that suggest the importance of ghrelin in feeding and weight homeostasis. In obesity there is a markedly decreased GH secretion. For both children and adults, the greater the body mass index (BMI), the lower the GH response to provocative stimuli, including the response to GHRH. However, the response to the natural GH secretaogogue ghrelin is unclear at the present time. The aim of the present study was to evaluate the GH response to ghrelin alone or combined with GHRH in a group of obese patients, in order to further understand the deranged GH secretory mechanisms in obesity and to clarify the mechanism of action of ghrelin.

Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function

objective  Obstructive sleep apnoea syndrome (OSAS) is strongly associated with obesity (OB) and is characterized by several changes in endocrine functions, e.g. GH/IGF‐I axis, adrenal and thyroid activity. It is still unclear whether these alterations simply reflect overweight or include peculiar hypoxia‐induced hormonal alterations. Hormonal evaluations have been generally performed in basal conditions but we have recently reported that OSAS is characterized by a more severe reduction of the GH releasable pool in comparison to simple obesity. We aimed to extend our evaluation of anterior pituitary function to corticotroph, thyrotroph and lactotroph secretion under dynamic testing in OSAS in comparison with simply obese and normal subjects.

Glomerular Filtration Rate and Parathyroid Hormone Secretion in Primary Hyperparathyroidism

CONTEXT The recent Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism (PHPT) set 60 ml/min as the precise level of glomerular filtration rate (GFR) below which surgery is recommended because it is considered a threshold of concern in patients with PHPT. OBJECTIVE The aim of the study was to investigate the relationship between different stages of renal insufficiency and PTH levels in PHPT patients. DESIGN We conducted a cross-sectional study. PATIENTS AND METHODS We studied 294 consecutive PHPT patients. Biochemical evaluation included total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D3 levels in the fasting state. GFR was assessed with the Modification of Diet in Renal Disease Study formula. RESULTS The mean GFR of the whole group of PHPT patients was 92.3 +/- 31.6 ml/min x 1.73 m(2). The patients were divided into four groups according to National Kidney Foundation Disease Outcomes Quality Initiative (K/DOQI) guidelines: group 1 with normal or increased GRF (>90 ml/min x 1.73 m(2); n = 153); group 2 with mild decreased GFR (60-89 ml/min x 1.73 m(2); n = 90); group 3 with moderately decreased GFR (30-59 ml/min x 1.73 m(2); n = 45); and group 4 with severely decreased GFR (<30 ml/min x 1.73 m(2); n = 6). PTH levels were comparable across groups 1-3, whereas group 4 showed significantly higher PTH levels (P < 0.0001). CONCLUSION In our series of PHPT patients, only a severe impairment of GFR was characterized by a further PTH increase. These findings challenge the concept of a PTH elevation below the threshold of 60 ml/min of GFR.

Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism

Aims  An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients.

Both fasting-induced leptin reduction and GH increase are blunted in Cushing's syndrome and in simple obesity.

background  Simple obesity and Cushings syndrome (CS) are two clinical models of leptin hypersecretion coupled with GH hyposecretion. Fasting inhibits leptin while stimulating GH secretion in normal human subjects.

Silent renal stones in primary hyperparathyroidism: prevalence and clinical features.

OBJECTIVE (1) To evaluate the prevalence of silent nephrolithiasis in patients with primary hyperparathyroidism (PHPT) compared with controls, and (2) To characterize clinically PHPT patients with silent renal stones. METHODS We reviewed clinical data for 141 patients with PHPT and without symptoms or history of nephrolithiasis in whom renal ultrasonography was performed at diagnosis. A total of 141 sex- and age- matched subjects with abdomen ultrasonography obtained for reasons different from urinary symptoms served as controls. RESULTS Silent nephrolithiasis was more prevalent in PHPT patients than in controls (11.35% vs. 2.13%; P = .003). Among patients with PHPT, those with silent renal stones showed higher serum calcium and parathyroid hormone levels and met surgical criteria, regardless of nephrolithiasis, more frequently than those without renal stones. CONCLUSION The prevalence of silent nephrolithiasis is increased in patients with PHPT as compared with controls. Moreover, it seems likely that silent renal stone disease could identify a subset of PHPT patients with more severe disease. Accordingly, we suggest ultrasonographic screening of nephrolithiasis in all PHPT patients. Further studies are needed to better characterize this clinical entity.