G. Tamburrano

The long‐term efficacy of conventional radiotherapy in patients with GH‐secreting pituitary adenomas

Objective  To assess the long‐term efficacy and safety of conventional radiotherapy (RT) in the control of acromegaly according to recent stringent criteria of cure.

Glucose homeostasis in acromegaly: effects of long‐acting somatostatin analogues treatment

objective  Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty‐four active acromegalic patients were studied in order to determine the long‐term effects of octreotide‐LAR and SR‐lanreotide on insulin sensitivity and carbohydrate metabolism.

Echocardiographic evidence for a direct effect of GH/IGF-I hypersecretion on cardiac mass and function in young acromegalics

The interpretation of echocardiographic abnormalities in acromegalic patients is complicated by non‐specific age‐related diseases, many of which are commoner in acromegaly. We have therefore investigated the cause‐effect relationship between GH/IGF‐I hypersecretion and precocious cardiovascular abnormalities in a series of young acromegalic patients.

Glucose intolerance in liver cirrhosis

Abstract Glucose intolerance and hyperinsulinemia frequently occur in patients with chronic liver failure. To investigate the importance of glucose counterregulating factors, an oral glucose tolerance test was performed on 18 patients with compensated liver cirrhosis, matched for liver function tests and degree of portal hypertension, and 10 healthy controls. Blood glucose, immunoreactive insulin, C-peptide, immunoreactive glucagon, glucagon like immunoreactivity, growth hormone, cortisol and free fatty acids were determined in both groups at 30 min intervals for 240 min. Despite the similarity in the severity of liver damage five cirrhotic patients showed normal glucose tolerance, eight impaired glucose tolerance and five overt diabetes. Immunoreactive insulin was significantly higher in cirrhotic patients than in controls both before and during the oral glucose tolerance test. As basal C-peptide values were significantly higher and C-peptide/immunoreactive insulin ratio was significantly lower in cirrhotic patients than in the control subjects, both hyperproduction and hypodegradation seem to be responsible for the high insulin levels. Immunoreactive glucagon and cortisol showed no statistical differences between cirrhotic patients and control subjects whereas high basal growth hormone and free fatty acids values were observed in the cirrhotic group. Basal values and maximum increase or decrease of all the factors examined were tested by a correlation analysis with the blood glucose at 120 min and evaluated by a stepwise linear regression analysis. Only basal blood glucose, basal free fatty acids and immunoreactive insulin increment correlated significantly with blood glucose at 120 min. By the stepwise procedure these factors were found to account for 86% of the variance of the glucose level at 120 min. In chronic liver disease we failed to establish a pathogenetic role of hormones involved in the glucose counterregulating system. Free fatty acids may play an important role in glucose intolerance in chronic liver failure.

Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients

OBJECTIVE Transsphenoidal surgery results in biochemical remission of acromegaly in 45–80% of patients; however, few studies have addressed the impact of transsphenoidal surgery on cardiovascular function in acromegalic patients. The aim of this prospective study was to investigate the effects of postoperative GH/IGF‐I normalization on echocardiographic parameters and blood pressure (BP) in a series of patients with active acromegaly.

Diagnostic reliability of a single IGF-I measurement in 237 adults with total anterior hypopituitarism and severe GH deficiency

objective Within an appropriate clinical context, GH deficiency (GHD) in adults must be demonstrated biochemically by a single provocative test. Insulin‐induced hypoglycaemia (ITT) and GH‐releasing hormone (GHRH) + arginine (ARG) are indicated as the tests of choice, provided that appropriate cut‐off limits are defined. Although IGF‐I is the best marker of GH secretory status, its measurement is not considered a reliable diagnostic tool. In fact, considerable overlap between GHD and normal subjects is present, at least when patients with suspected GHD are considered independently of the existence of other anterior pituitary defects. Considering the time and cost associated with provocative testing procedures, we aimed to re‐evaluate the diagnostic power of IGF‐I measurement.

Relationship between blood pressure and glucose tolerance in acromegaly

Hypertension represents a well‐known risk factor for cardiovascular diseases. The pathogenesis of hypertension in acromegaly is commonly viewed as multifactorial, but the possible influence of metabolic disorders on blood pressure (BP) in affected patients is largely unknown.

Expression of insulin/IGF-I hybrid receptors is increased in skeletal muscle of patients with chronic primary hyperinsulinemia.

The insulin receptor (IR) shares structural and functional homology with the IGF-I receptor (IGF-IR). Hybrid receptors composed of an IR αβ-heterodimer and an IGF-IR αβ-heterodimer are formed in tissues expressing both molecules. Hybrids behave as IGF-IR rather than IR with respect to ligand binding affinity, receptor autophosphorylation, and hormone internalization and degradation. Factors regulating hybrid formation in vivo are unknown. We recently reported that in skeletal muscle of NIDDM patients, expression of hybrids is increased and correlated with a decrease in IR number and an increase in fasting insulin levels. However, it is not clear whether increased expression of hybrid receptors is a primary defect specifically associated with NIDDM or a secondary event caused by hyperinsulinemia. To address this issue, we used a quantitative microwell-based immunoassay to measure hybrid receptor abundance in skeletal muscle of 11 normal subjects and 12 patients with insulinoma, a state of primary nongenetically determined hyperinsulinemia. Total insulin binding was lower in insulinoma patients than in normal subjects (0.70 ± 0.18 vs. 4.59 ± 0.77; P < 0.0001). Total IGF-I binding did not differ between the two groups (0.81 ± 0.27 and 0.85 ± 0.10, respectively). The amount of hybrids, expressed as bound/total (B/T), was higher in patients with insulinoma than in normal subjects (0.57 ± 0.19 vs. 0.36 ± 0.03; P < 0.0006) and was inversely correlated with total insulin binding (r = −0.64, P < 0.0004). Increased abundance of hybrid receptors was positively correlated with insulin levels (r = −0.82, P < 0.0009) and inversely correlated with insulin-mediated glucose uptake (r = −0.80, P < 0.01). No correlations were observed between insulin-mediated glucose uptake and maximal specific insulin binding (r = 0.19, P = 0.64). These results indicate that insulin-induced IR downregulation may lead to the formation of a higher proportion of hybrid receptors, whose abundance is negatively correlated with in vivo insulin sensitivity. These results, therefore, support a role for insulin in the regulation of hybrid receptors formation and suggest that increased expression of hybrids in NIDDM may be a secondary event caused by hyperinsulinemia rather than a primary defect.

The efficacy and tolerability of long‐term cabergoline therapy in hyperprolactinaemic disorders: an open, uncontrolled, multicentre study

OBJECTIVE We assessed the efficacy and safety of the new, long‐acting dopamine agonist drug cabergoline during long‐term therapy of hyperprolactinaemia.

Total and individual free fatty acid concentrations in liver cirrhosis

The finding of high plasma free fatty acid (FFA) levels in cirrhotic patients has been attributed either to decreased hepatic clearance or to enhanced fat mobilization. To better clarify these hypotheses, total and individual FFA and glycerol levels were determined in 21 cirrhotic patients with different degrees of hepatocellular damage (evaluated by liver function tests), portal hypertension (evaluated by endoscopy and clinical signs), and nutritional status (evaluated by anthropometric and biohumoral parameters) and in 10 age- and sex-matched healthy subjects. Glucose tolerance and insulin and glucagon levels were determined in all individuals. Well-nourished and malnourished patients were identified within the cirrhotic group. Plasma FFA and glycerol concentrations were well correlated (r = 0.47, P less than 0.05), levels being significantly higher in cirrhotic individuals than in controls (746.6 +/- 46.29 SE v 359.22 +/- 40.82 mumol/L, P less than 0.001 for plasma FFA; 150.1 +/- 3.12 v 82.5 +/- 9.2 mumol/L, P less than 0.01 for glycerol). Plasma FFA and glycerol showed no correlation with the liver function test results or portal hypertension parameters. Interestingly, plasma levels of FFA and glycerol were influenced by the nutritional status, significantly higher FFA levels being observed in the well-nourished than in the malnourished patients (842.5 +/- 47.5 v 563.4 +/- 78 mumol/L, P less than 0.005). Furthermore, a positive correlation was found between plasma glycerol level and percentage of triceps skinfold (r = 0.45, P less than 0.05). No correlation was found between plasma levels of FFA or glycerol and glucose tolerance, insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)