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G Tamburrano

Publications and source records attributed to G Tamburrano.

At least 37 records · Page 2Linked to original sources
PubMed2001

Adrenomedullin, a new peptide, in patients with insulinoma.

BACKGROUND: It has been demonstrated that adrenomedullin, a newly discovered peptide, affects the release of insulin from pancreatic islets cells, suggesting a role in the insulin-regulating system. OBJECTIVE: To investigate whether adrenomedullin secretion is modified in patients with insulin-secreting islet cell tumours. DESIGN: The study was performed in nine patients with surgically treated insulinoma. Circulating adrenomedullin was assayed using a specific radioimmunoassay and its localization and distribution in the tumour were determined by means of immunohistochemistry. RESULTS: Adrenomedullin concentrations were significantly greater in patients with insulinoma (6.6 +/- 3.2 fmol/ml) than in controls (2.1 +/- 1.1 fmol/ml). In six patients monitored before and after surgery, plasma adrenomedullin decreased from 6.3 +/- 2.9 fmol/ml to 3.0 +/- 1.6 fmol/ml. Immunoreactive adrenomedullin was localized exclusively in the tumours cells, whereas stroma, surrounding pancreas parenchyma and major ducts were negative for the peptide. CONCLUSIONS: Our findings indicate that circulating adrenomedullin is increased in insulinoma and that this increase is related to the neoplastic phenotype.

Adenoma, Islet Cell↗
PubMed2001

Physiology and possible pathology of growth hormone secretagogues.

Growth hormone segretagogues (GHS) are artificial molecules able to stimulate growth hormone (GH) secretion. They were discovered before the hypothalamic growth hormone-releasing hormone (GHRH). These molecules had a structure devoid of opiate activity, and GHRP-6 is the most representative compound. These compounds identified a new physiological system involved in GH regulation, and their action is independent of GHRH or somatostatin. Recently an endogenous ligand for the GHS receptor, ghrelin, was discovered, suggesting that this may be the third factor in the control of GH secretion. This peptide was isolated from the stomach and is characterized by the presence of an acylated group representing a new type of molecular hormonal structure; it is able to stimulate GH secretion in vitro and in vivo in the rat. As observed for the majority of GHS, ghrelin's action is not fully specific for GH release; the acute administration of ghrelin stimulates the release of significant amounts of PRL, ACTH and cortisol. Moreover, the presence of ghrelin in rat and human placenta has been reported, suggesting a possible role of this peptide in the local modulation of GH release and in maternal and fetal pituitary secretion. Ghrelin stimulates gastric acid secretion, is able to induce adiposity by activating a central mechanism for increasing food intake and decreasing fat utilization, and ghrelin mRNA and peptide are expressed in normal and adenomatous human pituitary tissue. Possible therapeutic applications of ghrelin remain to be assessed.

Ghrelin↗
PubMed2000

Systemic hypertension and impaired glucose tolerance are independently correlated to the severity of the acromegalic cardiomyopathy.

Increased mortality from cardiovascular diseases has been reported in acromegaly. Our objective was to evaluate the impact of glucose tolerance abnormalities and/or systemic hypertension in further worsening the acromegalic cardiomyopathy. The study design was open transversal. The subjects studied were 130 consecutive naive acromegalic patients (74 women and 56 men; age, 17-80 yr). Interventricular septum (IST) and left ventricular (LV) posterior wall thickness (PWT), LV mass index (LVMi), maximal early to late diastolic flow velocity ratio (E/A), isovolumic relaxation time (IRT), and LV ejection fraction (EF) were measured by echocardiography. The results were analyzed in line with the presence of glucose tolerance abnormalities (normal in 60, impaired in 38, diabetes mellitus in 32) and the presence (in 46) or absence (in 84) of hypertension. Patients with impaired glucose tolerance and diabetes mellitus had significantly higher age (P = 0.01), and systolic (P = 0.01) and diastolic (P = 0.01) blood pressures and lower E/A (P = 0.01) and EF (P = 0.01) than those with normal glucose tolerance. Disease duration, circulating GH and insulin-like growth factor I (IGF-I) levels, IST, LVPWT, LVMi, and IRT were similar in the 3 groups. Normotensive patients had significantly lower age (P<0.001), LVPWT (P<0.001), IST (P = 0.003), LVMi (P<0.001), and IRT (P = 0.02) and significantly higher E/A (P<0.001) and EF (P<0.001) than hypertensive subjects. Disease duration, circulating GH, and IGF-I levels were similar in the 2 groups. Multiple regression analysis showed that systolic blood pressure was the strongest predictor of LVMi (P = 0.0004), followed by GH levels (P = 0.02), whereas diastolic blood pressure was the strongest predictor of LVEF reduction (P<0.0001), followed by glucose tolerance status (P = 0.02). Age was the strongest predictor of both E/A impairment (P<0.0001) and IRT (P = 0.01), followed by IGF-I levels (P = 0.02). Compared to patients with uncomplicated acromegaly, those with hypertension but without abnormalities of glucose tolerance had an increased prevalence of LV hypertrophy (75% vs. 37.2%) as well as of impaired diastolic (50% vs. 7.8%) and systolic function (18.7% vs. 3.9%), whereas patients with glucose tolerance abnormalities but without hypertension had only an increased prevalence of impaired diastolic (39.7%) and systolic function (31.7%). The subgroup of acromegalic patients suffering from hypertension and diabetes mellitus had the highest prevalence of LV hypertrophy (84.6%), diastolic filling abnormalities (69.2%), and impaired systolic function at rest (53.9%). A careful cardiac investigation should thus be performed in all acromegalic patients showing these complications.

Acromegaly↗
PubMed2000

Two-year follow-up of acromegalic patients treated with slow release lanreotide (30 mg).

Pharmacotherapy of acromegaly has been improved in recent years as new long-acting somatostatin analogs have became available; they have been suggested as an alternative treatment to pituitary surgery and radiotherapy. To avoid the inconvenience of multiple daily injections during long-term therapy, a slow release formulation of lanreotide (LAN), to be administered im at a dose of 30 mg every 7-14 days, has been introduced in the therapeutic management. The suppressive effects of a short-term LAN treatment on GH and insulin-like growth factor I (IGF-I) hypersecretion were shown to be similar to those obtained with sc octreotide. However, scant data have been reported concerning a long-term treatment with this drug. In the present study the efficacy and tolerability of a 24-month LAN treatment were evaluated in 118 active acromegalic patients; 71 had been previously operated on and treated with s.c. octreotide (operated patients), 24 previously operated on had been irradiated and treated with s.c. octreotide (irradiated patients), and the remaining 23 were newly diagnosed (de novo patients). The efficacy was considered on the basis of controlled GH (fasting, <7.5 mU/L; glucose-suppressed, <3.0 mU/L) and IGF-I (age-adjusted normal values) secretion. In the 118 patients as a whole, circulating GH and IGF-I levels were significantly decreased during the 24-month LAN treatment (P < 0.0005 at all time points vs. basal value). After 24 months of therapy, controlled GH and IGF-I levels were achieved in 64%, 37%, and 78% and in 51%, 37%, and 70% of operated, irradiated, and de novo patients, respectively. A reduction in tumor size was documented in 5 of 23 de novo patients (22%). Among the 84 operated/irradiated with evident tumor remnant, significant shrinkage was documented in 5 patients (5.9%). Treatment was well tolerated by the majority of patients. Only 2 patients (1.7%) withdrew from LAN treatment due to severe side effects. In conclusion, a 24-month treatment with slow release lanreotide (30 mg) is effective in reducing GH and IGF-I levels; furthermore, in de novo patients it induces disease control in 70% of patients and causes tumor shrinkage in 22% of them, with excellent compliance. These data suggest that LAN can be used in long-term treatment of acromegalic patients.

Acromegaly↗
PubMed1999

p16 (INK4a, MTS-1) gene polymorphism and methylation status in human pituitary tumours.

OBJECTIVE: The p16 gene, which encodes a physiological inhibitor of the cyclin D-CDK4 complex, is now considered as an important tumour-suppressor gene in a variety of tumours. A marked reduction of its expression has been reported to occur without significant genetic alterations in human pituitary adenomas, although rare point mutations of uncertain functional significance have been described. On the other hand, p16 gene silencing due to hypermethylation has been reported in several human primary tumours. The aim of this study was to further investigate the pathogenetic events leading to p16 gene inactivation in pituitary tumours. DESIGN: To screen a european series of human pituitary tumours for p16 gene alterations and possible gene hypermethylation. PATIENTS: A representative series of 31 human pituitary tumours-30 macroadenomas, including a MEN-1 non-secreting pituitary adenoma and a non-MEN-1 familial giant GH-secreting adenoma, and one FSH-secreting pituitary carcinoma-was studied. METHODS: Polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis was used to screen for p16 gene alterations in all cases. Direct sequencing of PCR-products was obtained by the di-deoxynucleotide method where suspected abnormalities of the PCR-SSCP analysis were observed. In 24 samples, a methylation-specific PCR assay (MSP-PCR) was used to determine p16 gene methylation status. RESULTS: Two sporadic cases of pituitary adenomas had a similar single A to G base substitution leading to an heterozygous Ala140Thr p16 polymorphism, which has not previously been described in such tumours, but is known to be functionally silent. No other p16 abnormality could be suspected from PCR-SSCP analysis in this series. In contrast, the presence of methylated-specific PCR products was observed in 20/24 cases (83.3%). CONCLUSIONS: This study confirms that p16 gene mutations are not involved in the pathogenesis of human pituitary tumours, although polymorphisms can be demonstrated, depending on the population considered. In contrast, the high incidence of hypermethylation of the p16 gene suggests that such an alteration occurs early in pituitary tumours, and may play a role in pituitary tumorigenesis.

Adenoma↗
PubMed1999

Comparison of six months therapy with octreotide versus lanreotide in acromegalic patients: a retrospective study.

OBJECTIVE: We analysed the effects of 6-months' treatment with octreotide s.c. and lanreotide-SR on circulating GH and IGF-I levels in acromegaly. DESIGN: Open retrospective study. PATIENTS: Thirty-eight patients with active acromegaly (plasma IGF-I levels greater than 2 standard deviations for age-matched controls and increased serum GH levels not suppressible by oral glucose load) were studied. All patients received s.c. octreotide at a dose of 150-600 microg/day for six months as first therapy and subsequently, lanreotide i.m., 30-60 mg either at 14 or 10 day intervals, for 6 months. A 3 months' washout was applied before starting lanreotide treatment. MEASUREMENTS: Mean serum GH levels (from three samples), IGF-I, and clinical examination were performed before and 30, 60, 90 and 180 days after octreotide and lanreotide treatments. Safety tests, HbA1c and, thyroid function were evaluated every three months. RESULTS: Circulating GH and IGF-I levels were significantly reduced (P < 0.001) after one, three and six months of both octreotide and lanreotide treatment. The absolute values were lower and the percent decrease in serum GH levels obtained after octreotide treatment was significantly greater, at all scheduled assessments, than after lanreotide (P < 0.01). Serum IGF-I levels during octreotide were significantly lower only after the first month of therapy (P < 0.01). CONCLUSIONS: Our study shows that octreotide s.c. is able to induce an earlier reduction in IGF-I levels and a more marked reduction in GH levels than lanreotide. However, after six months of therapy the number of patients with safe GH levels and normal IGF-I age-matched levels, was similar with both drugs. Therefore we suggest that octreotide treatment be preferentially used in the short-term presurgical treatment, while lanreotide can be used in chronic therapy when better compliance is necessary.

Acromegaly↗
PubMed1999

Alkaptonuria.

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Aged↗
PubMed1999

Cardiac effects of slow-release lanreotide, a slow-release somatostatin analog, in acromegalic patients.

Cardiac involvement, mostly characterized by left ventricular hypertrophy associated with various degrees of cardiac dysfunction, greatly contributes to the increased mortality and morbidity observed in acromegaly. Lanreotide is a new SRIF analog characterized by a slow-release (SR) formulation with the peculiarity of a 30-mg im administration every 10-14 days. In this study, 13 patients with postoperative active acromegaly (9 females, 4 males, 45.9 +/- 16.3 yr old) underwent an echo-Doppler and hormonal study before and during a 12-month period of treatment with SR-lanreotide. GH and insulin-like growth factor I plasma levels (mean +/- SD) decreased significantly throughout the study period (from 10.1 +/- 2.2 to 3.9 +/- 0.9 ng/mL for GH, P < 0.005; and from 511.0 +/- 33.0 to 305.0 +/- 34.2 ng/mL for insulin-like growth factor I, P < 0.0001). Left ventricular mass index (mean +/- SD, 137.1 +/- 7.5 g/m2 at baseline) decreased after 3 months (120.0 +/- 5.4 g/m2), 6 months (111.7 +/- 5.7 g/m2), and 12 months (110.3 +/- 5.2 g/m2) of treatment (P < 0.005 at each time-point). This reduction in left ventricular mass index was accompanied by an improvement in some indexes of left ventricular diastolic function, especially the isovolumetric relaxation time (mean +/- SD, 109.1 +/- 4.6 m/sec at baseline), which decreased after 3 months (91.9 +/- 2.8 m/sec), 6 months (92.3 +/- 3.2 m/sec), and 12 months (92.2 +/- 3.0 m/sec) of treatment (P < 0.005 at each time-point). We conclude that SR-lanreotide is able to improve cardiac morphology and functional abnormalities in acromegaly; whether such beneficial effects on cardiac parameters will contribute to improve life expectancy in these patients should be further investigated.

Acromegaly↗
PubMed1999

Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism.

As there are few data on the evaluation of the adequacy of levothyroxine (L-T4) therapy in patients with central hypothyroidism (CH), a prospective study was performed to assess the accuracy of various parameters in the follow-up of 37 CH patients. Total and free thyroid hormones, TSH, and a series of clinical and biochemical indexes of peripheral thyroid hormone action have been evaluated off and on L-T4 therapy. Samples were taken before the daily administration of L-T4. In all patients off therapy, clinical hypothyroidism and low levels of free T4 (FT4) were observed, whereas values of FT3, total T4, and total T3 were below the normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of thyroid hormone action were significantly modified after L-T4 withdrawal and exhibited significant correlation with free thyroid hormone levels. During L-T4 replacement therapy, 32 patients had circulating levels of FT4 and FT3 and indexes within the normal range with a mean L-T4 daily dose of 1.5 +/- 0.3 microg/kg BW. Despite normal serum FT4, 3 patients had borderline high values of FT3 and a clear elevation of serum-soluble interleukin-2 receptor concentrations, suggesting overtreatment. Low or borderline low FT4/FT3 levels indicated undertreatment in 2 patients. The clinical parameters lack the required specificity for the diagnosis or follow-up of CH patients. The L-T4 daily dose should be established, taking into account the weight, the age, and the presence of other hormone deficiencies or pharmacological treatment of CH patients. In conclusion, our results indicate that the diagnosis of CH is reached at best by measuring TSH and FT4 concentrations. In the evaluation of the adequacy of L-T4 replacement therapy, both FT4 and FT3 serum levels together with some biochemical indexes of thyroid hormone action are all necessary to a more accurate disclosure of over- or undertreated patients.

Adult↗
PubMed1999

Evidence for glucose/hexosamine in vivo regulation of insulin/IGF-I hybrid receptor assembly.

Hybrid receptors composed of an insulin alphabeta-hemireceptor and a type 1 IGF alphabeta-hemireceptor are formed in tissues expressing both molecules. We recently reported an increased hybrid receptor expression in skeletal muscle of type 2 diabetic patients that is inversely correlated with in vivo insulin sensitivity. It is unclear whether these changes were due to primary abnormalities or to secondary derangements acting in vivo, such as hyperglycemia. To address this, we determined abundance of hybrids in skeletal muscle from three groups of rats: controls, diabetic (90% pancreatectomy), and diabetic treated with phlorizin to normalize plasma glucose levels. We found that the abundance of hybrid receptors was higher in diabetic rats compared with control and phlorizin-treated diabetic rats (percentage of 125I-insulin bound versus total added radioactivity [B/T] = 1.8+/-0.11, 0.4+/-0.01, and 0.32+/-0.04, respectively; P < 0.0001). Fasting plasma glucose levels were positively correlated with hybrids abundance (r = 0.77, P < 0.002). Hybrid receptor protein content, assessed by immunoblotting, was 2.4-fold higher in diabetic rats as compared with control and phlorizin-treated diabetic rats. Because it has been shown that some of the regulatory effects of glucose may be mediated by the glucosamine pathway, we subsequently determined the effect of an in vivo glucosamine infusion on hybrid receptor formation. We found that abundance of hybrids was significantly higher in muscle from glucosamine-treated rats compared with control rats (B/T = 0.17+/-0.02 and 0.11+/-0.01, respectively; P < 0.009). Quantitation of hybrid content by immunoblotting revealed that their abundance was 1.9-fold higher in glucosamine-treated rats. The results demonstrate that 1) elevated glucose levels in diabetic rats are associated with increased expression of hybrid receptors in muscle, 2) correction of hyperglycemia with phlorizin completely reverses increased expression of hybrids, and 3) glucosamine infused into control rats mimics the effects of hyperglycemia on hybrid receptor formation. Thus, the results support the hypothesis that glucose acting, at least in part, through the glucosamine pathway may play an important role in regulating hybrid receptor assembly in vivo.

Animals↗
PubMed1999

Pancreatic endocrine tumours.

Gastrointestinal endocrine neoplasms are rare tumours that have been classified by the peptides they secrete and the resulting clinical syndromes. The incidence of these tumours is estimated to be less than 1-1.5 cases/100,000 of the general population. These gastrointestinal endocrine cells are characterized by similar cytochemical and ultrastructural characteristics, contain amines and they are capable of uptake of amine precursors to amines or peptides. The function of these cells is the neuroendocrine regulation of normal homeostatic mechanisms including vasomotor tone as well as carbohydrate, calcium and electrolyte metabolism. Each amine precursor uptake and decarboxylation cell normally synthesizes, stores and secretes its single amine or polypeptide and is responsive to its environment for stimulation or suppression in the related clinical syndrome.

Adenoma↗
PubMed1998

Relative contribution of glycogenolysis and gluconeogenesis to hepatic glucose production in control and diabetic rats. A re-examination in the presence of euglycaemia.

Several studies have suggested that, in non-insulin-dependent diabetes mellitus, augmented gluconeogenesis is responsible for increased endogenous glucose production (EGP) and in the end determines fasting hyperglycaemia. However, human and animal studies have been conducted by comparing euglycaemic control subjects to hyperglycaemic diabetic probands. We measured EGP and hepatic gluconeogenesis comparing control and diabetic rats in the fasting state (with diabetic animals in hyperglycaemia), re-examining them in the presence of identical euglycaemia (with diabetic rats made acutely euglycaemic through i. v. phloridzin) or during a hyperinsulinaemic clamp. All rats were infused with [3-3H]-glucose and [U-14C]-lactate; the ratio between 14C-uridine-diphosphoglucose (reflecting 14C-glucose 6-phosphate) and 2 14C-phosphoenolpyruvate specific activities (both purified by high performance liquid chromatography from liver) measured hepatic gluconeogenesis. In diabetic animals, although overall EGP ( approximately 19.5 mg x kg[-1] x min[-1]) remained unaffected by experimental euglycaemia, the contribution of glycogenolysis largely increased (from 5.4 to 11.7 mg x kg(-1) min(-1), hyper- vs euglycaemia) while gluconeogenesis decreased (from 14.0 to 8.1 mg x kg(-1) x min[-1]); both were responsible for the augmented EGP (control rats, EGP: 12.7 mg x kg(-1) x min(-1); gluconeogenesis: 5.9 mg x kg(-1) x min(-1); glycogenolysis: 6.7 mg x kg[-1] x min[-1]). Finally, during insulin clamp, gluconeogenesis and glycogenolysis were similarly decreased, and both contributed to the hepatic insulin-resistance of diabetic animals. We conclude that, in this model of non-insulin-dependent diabetes, augmented gluconeogenesis is not primarily responsible for fasting hyperglycaemia and hepatic insulin resistance. Finally, failure to accurately match the experimental conditions in which diabetic and control humans or animals are compared affects gluconeogenesis, overestimating its role in determining hyperglycaemia.

Animals↗
PubMed1998

Functioning human insulinomas. An immunohistochemical analysis of intracellular insulin processing.

Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30-100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.

Adolescent↗
PubMed1998

Expression of the two insulin receptor isoforms is not altered in the skeletal muscle and liver of diabetic rats.

Alternative splicing of the 36-base pair exon 11 of the human insulin receptor (IR) gene and of the corresponding domain of the rat IR gene results in the synthesis of two IR isoforms with distinct functional characteristics. Altered expression of these IR isoforms has been previously demonstrated in the skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM); however, this observation was not confirmed by other studies and is still a matter of debate. To assess whether the reported altered isoform expression is due to the secondary metabolic derangement of diabetes, we examined alternative splicing of IR mRNAs (IR36+ and IR36-, corresponding to human Ex11+ and Ex11-) in the skeletal muscle and liver of 6-hour fasting 90% pancreatectomized insulin-resistant diabetic and control Sprague-Dawley rats, using the reverse transcriptase-polymerase chain reaction (PCR) technique. Both diabetic and control rats showed the same pattern of IR mRNA expression: the liver exclusively expressed IR36+ mRNA, whereas only IR36- mRNA was detected in muscle. In conclusion, diabetes mellitus per se does not alter the expression of IR isoforms in the liver and skeletal muscle, and therefore, at least in this animal model of NIDDM, impaired insulin action develops independently from a relative increase in IR36+ mRNA expression in skeletal muscle.

Animals↗
PubMed1998

Visual improvement during octreotide therapy in a case of episellar meningioma.

Meningiomas of the tuberculum sellae can induce compression of the optic tract. We report the case of a 54-year-old female patient affected by a suspected pituitary macroadenoma with severe visual field defects, who experienced a significant clinical and visual improvement during short-term octreotide therapy, contrasting with the lack of neuroradiological evidence for tumor shrinkage. The patient subsequently underwent transcranial surgery with a final diagnosis of meningioma. The putative mechanisms of visual improvement during octreotide therapy are discussed.

Adenoma↗
PubMed1998

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

OBJECTIVE: 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. DESIGN: An open prospective study. PATIENTS: 20 acromegalic patients aged under 30 years, with normal blood pressure and glucose tolerance, and 20 age-matched control subjects. MEASUREMENTS: Cardiac morphological parameters and indices of systolic and diastolic function at rest were studied by Doppler echocardiography. RESULTS: Left ventricular mass (LVM) and LVM index (LVMi) were higher in acromegalics than in control subjects (215.0 +/- 15.4 g vs 140.8 +/- 8.5 g, P = 0.0002 and 109.8 +/- 5.9 g/m2 vs 82.1 +/- 3.7 g/m2, P = 0.0008, respectively), reaching values of left ventricular hypertrophy in 4 patients (20%). Both ejection fraction and fractional shortening were normal (66.4 +/- 2.1% vs 62.2 +/- 1.9% and 37.5 +/- 1.5% vs 35.8 +/- 1.3%, respectively), indicating normal left ventricular systolic function. Abnormalities of left and right diastolic ventricular filling were found, which consisted of an increased isovolumic relaxation time (99.2 +/- 2.7 ms vs 89.0 +/- 2.7 ms, P = 0.01) and impaired mitral and tricuspidal flow velocity curves. CONCLUSIONS: An increase in cardiac mass and subclinical biventricular diastolic dysfunction were observed in young acromegalic patients. These findings argue for a direct cause-effect relationship between GH/IGF-I hypersecretion and myocardial abnormalities, and indicate that careful cardiological evaluation is mandatory in all acromegalics, whatever their age.

Acromegaly↗
PubMed1998

Epidermal growth factor binding sites in human pituitary macroadenomas.

The number of epidermal growth factor (EGF) binding sites was determined by competitive binding assays in a series of 46 pituitary macroadenomas. A single concentration of 125I-EGF (1 nM) was used for all experiments. In four cases, a displacement curve was obtained by adding increasing concentrations of cold EGF, and Scatchard analysis showed the presence of two classes of EGF binding sites, with Kd1 = 0.62 +/- 0.23 nM and Kd2 = 53.8 +/- 8.2 nM for the high- and low-affinity binding sites respectively. The distribution of EGF binding sites was studied in 42 cases by a single-point assay, in the presence and in the absence of a 100-fold cold EGF excess. A non-parametric distribution of EGF binding sites was observed (median 10.2 fmol/mg membrane protein, range 0.0-332.0). EGF-receptor positivity, defined as EGF binding > or = 10.0 fmol/mg protein, was observed in 23 samples (54.8%), especially in prolactinomas (76.5%, P < 0.05 vs other tumors taken together) and in gonadotrope adenomas (62.5%). EGF binding was higher in invasive than in non-invasive adenomas (median: 12.8 vs 0.0 fmol/mg membrane protein, P = 0.047), and especially in adenomas invading the sphenoid sinus (median 26.7 fmol/mg membrane protein, P = 0.008 vs other adenomas). EGF binding also tended to increase with the grade of supra/extrasellar extension according to Wilson (P = 0.15). Sex steroid receptors (SSRs) were simultaneously determined in both cytosolic and nuclear fractions of 31 pituitary adenomas. Estrogen and progesterone receptors were determined by an enzyme-linked immunoassay and androgen receptors by a competitive binding assay with [3H]methyltrienolone. No correlation could be found between EGF binding and either the gender and gonadal status of the patients, or the expression of SSRs by the adenomas. We conclude that the EGF family of growth factors may play a role in the evolution of a significant subset of human pituitary adenomas, especially in their invasiveness, and that a high EGF binding capacity may represent an additional marker of aggressiveness for these tumors. Sex steroids do not appear to have a significant role in the regulation of EGF binding in vivo in these tumors.

Adenoma↗