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G Angeletti

Publications and source records attributed to G Angeletti.

At least 19 recordsLinked to original sources
PubMed2007

Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumours.

The widespread availability and reliability of immunohistochemical techniques in the last three decades have allowed researchers to identify cells with common neuroendocrine markers in virtually every organ. As a whole, these neuroendocrine cells form the so-called diffuse neuroendocrine system. Tumours arising from the cells of the diffuse neuroendocrine system are defined as (neuro)endocrine tumours (NETs). NETs have been increasingly described in recent years. However, despite the increase in the number of published papers focused on NET, we still lack adequate epidemiological data, particularly for non-gastroenteropancreatic (GEP) NETs. Furthermore, the real incidence of neuroendocrine differentiation for most sites is not completely known and is probably underestimated. As a consequence, data on the clinical features of many NET subgroups are not well known or confusing. For all of these reasons, we have attempted to evaluate the epidemiology of non-GEP NETs, reviewing the limited data available in the literature.

Carcinoid Tumor↗
PubMed2005

Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series.

Neuroendocrine tumors may occur in the setting of multiple endocrine neoplasia type 1 (MEN1) syndrome. Among these, a probably underestimated prevalence of well differentiated neuroendocrine thymic carcinoma (carcinoid), a neoplasm characterized by very aggressive behavior, has been described. We report characterization of the seven Italian cases in which this association occurred among a series of 221 MEN1 patients (41 sporadic and 180 familial cases; prevalence, 3.1%). All of the patients were male, and six of seven (85%) were heavy smokers. No associated hormonal hypersecretion was detected. The first diagnosis was between the second and fifth decades. Familial clusters were present in three of seven (42.8%). No genotype-phenotype correlation was found. All seven cases were associated with hyperparathyroidism. In one patient, prophylactic thymectomy revealed a small nodular lesion suggestive of a thymic carcinoid, providing evidence that preventive thymectomy might prevent additional growth of an occult thymic carcinoid. These findings confirm that thymic carcinoids are associated with a very high lethality, with a near-total prevalence in smoker males. Therefore, prophylactic thymectomy should be considered at neck surgery for primary hyperparathyroidism in MEN1 male patients, especially for smokers, and, due to the frequent familial clusters distribution of this pathology, in subjects with affected relatives presenting this feature. Thus, we recommend screening every patient affected with a neuroendocrine thymic neoplasm for MEN1 syndrome.

Adult↗
PubMed2005

Efficacy and safety of 48 weeks of treatment with octreotide LAR in newly diagnosed acromegalic patients with macroadenomas: an open-label, multicenter, non-comparative study.

The aim of the present multicentric, open-label, non-comparative study was to evaluate the role of octreotide long-acting repeatable (LAR) as primary therapy for the treatment of GH-secreting pituitary macroadenomas. The patients received octreotide LAR 20 mg every 4 weeks for 12 weeks; afterwards the dose was confirmed or adjusted at 30 mg every 4 weeks, for the remaining 12 weeks, for responder or non-responder patients, respectively. Responder patients continued the study until 48 weeks. Twenty-one naive active acromegalic patients were enrolled. In all patients, GH profile, IGF-I levels and magnetic resonance imaging (MRI) were evaluated at baseline and during treatment. The ability of octreotide LAR to decrease mean GH < 2.5 microg/I and/or normalize IGF-I levels, adjusted for age and gender, was defined respectively as total or partial success. Total success was achieved in 5/21 (23.8%), 6/20 (30%) and 4/14 (28.6%) patients after 12, 24 and 48 weeks; partial success in 7/21 (33.3%), 9/20 (45%) and 9/14 (64%) patients at 12, 24 and 48 weeks according to GH levels, while according to IGF-I levels in 7/21 (33.3%), 7/20 (35%) and 5/14 (35.7%) patients at 12, 24 and 48 week. Tumor size was notably decreased after treatment with octreotide LAR: in 16 macroadenoma patients completing the study, the tumor sizes were 1609 +/- 1288, 818 +/- 616 (49.1 +/- 23.7%) and 688 +/- 567 mm3 (54.6 +/- 24.4%) at baseline, 24 and 48 weeks. This study shows that octreotide LAR is effective in suppressing GH/IGF-I secretion and inducing tumor shrinkage in GH-secreting macroadenomas in a 48-week treatment. Octreotide LAR could be used as primary therapy in patients harbouring large pituitary tumors, who are less likely to be cured by neurosurgery.

Acromegaly↗
PubMed2003

Sertoli cell-induced adult rat islet beta-cell mitogenesis: causative pathways.

We have previously observed that in vitro co-incubation of rat pre-pubertal Sertoli cells (SC), or their dialyzed/concentrated secretory products with homologous islets, resulted in significant stimulation of the islet beta-cell mitotic index. Aim of the present work was to assess both the specificity and nature of the mechanisms underlying this phenomenon. For this purpose, first we tested astrocytes (AA), separated and purified from the rat brain cortex, where they are known to release a number of growth factors and neurotrophic cytokines, for co-incubation with the islets. However, under the same experimental conditions used for SC, AA did not induce any changes in the beta-cell life cycle, thereby confirming specificity of SC, with respect to induction of beta-cell mitogenicity. For the second purpose, we examined the products of PD-1, a gene located in the cytoplasm of SC, where it promotes spermatogenesis. By blocking the protein encoded by PD-1, under appropriate culture conditions, we observed that the SC-induced increase in beta-cell mitotic activity lost its statistical significance, which suggested a role of PD-1 with respect to SC-related mitogenic properties on beta-cells. These findings corroborate the idea that SC, by either direct contact, or by means of their secretory products, clearly affect the islet beta-cell mitotic rate. Preliminarily, PD-1 gene, located in the cytoplasm of SC, might be one of the factors involved with the induction of beta-cell mitotic activity. In conclusion, SC-induced beta-cell mitotic activity is specific, seemingly mediated by humoral factors whose acting mechanisms have started being unfolded.

Animals↗
PubMed2002

Expression of endocrine autoantibodies in chronic hepatitis C, before and after interferon-alpha therapy.

Interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (CHC) has been associated with thyroid autoimmunity and/or dysfunction. Only a few data concerning the prevalence of islet-cell or adrenal cortex autoantibodies in IFN-alpha-treated subjects are currently available. The aims of our study were to evaluate in CHC, 1) the prevalence and association of thyroid, islet-cell and adrenal autoantibodies, and 2) the appearance of endocrine dysfunction, before and after a 6 month IFN-alpha treatment. We analyzed serum samples from 203 adult patients at the time of clinical diagnosis of CHC and showed that the prevalence of thyroperoxidase (TPOAb), thyroglobulin (TGAb), TSH-receptor (TRAb), glutamic acid decarboxylase (GAD65Ab), IA-2/ICA512 (IA-2/ICA512Ab) and 21-hydroxylase (21OHAb) autoantibodies was similar to that observed among healthy control subjects of similar age and sex distribution. Among 99 patients with follow-up serum samples, 83 accepted and 16 refused IFN-alpha treatment. The IFN-alpha treatment was associated with increase of TPOAb levels in 3 subjects already positive at baseline, with progression to overt hypothyroidism in 2 of them. The de novo appearance of autoantibodies was observed in 5/80 (6%) cases for TPOAb, 1/81 (1.2%) for GAD65Ab and 2/81 (2.5%) for IA-2/ICA512Ab. Clinical or subclinical signs of either hyperthyroidism or hypothyroidism were demonstrated in 3/5 cases with de novo appearance of TPOAb. Four subjects, initially positive for either GAD65Ab or IA2/ICA512Ab, were all found negative after IFN-alpha-treatment. No subjects showed positivity for 21OHAb either at baseline or after the follow-up period. Our study suggests that, in CHC untreated patients, the prevalence of endocrine autoantibodies is similar to that observed in the general population. Furthermore, we demonstrate that IFN-alpha treatment is associated with the induction or enhancement of thyroid, but not of islet-cell or adrenal cortex autoimmunity.

Adult↗
PubMed2000

Administration of recombinant human growth hormone on alternate days is sufficient to increase whole body protein synthesis and lipolysis in growth hormone deficient adults.

OBJECTIVE: At present, the duration of the effect of recombinant human growth hormone (rhGH) on the rates of protein synthesis and lipolysis in GH deficient (GHD) adults is unknown. This study was designed to establish the frequency of rhGH administration necessary to provide the beneficial metabolic effects of the hormone in GHD adults. DESIGN AND PATIENTS: Two different studies (A and B) were performed in two groups of five GHD men. In study A, whole body protein and lipid kinetics was determined in the basal state (Bas), 12 (GH12h) and 36 (GH36h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime on alternate days. In study B, the same parameters were determined in the basal state (Bas), 60 (GH60h) and 84 (GH84h) h after the last of seven injections of rhGH (3.3 microg/kg), given at bedtime at 3 day intervals. MEASUREMENTS: The rates of protein metabolism were estimated by infusing [1-13C]leucine, and those of lipolysis by infusing [1,1,2,3, 3-D5]glycerol. RESULTS: Leucine oxidation decreased (P < 0.01) by approximately 30% after GH12h and GH36h but did not change after GH60h and GH84h. Non-oxidative leucine disposal increased after GH12h and GH36h by approximately 13% (P < 0.05) whereas it did not change after GH60h and GH84h. Glycerol appearance increased (P < 0. 01) by approximately 45% after GH12h and GH36h but did not change after GH60h and GH84h. CONCLUSIONS: The effects on protein and lipid metabolism following the injection of rhGH last longer than 36 and less than 60 h. In fact, rhGH administration on alternate days induced a sustained increase in the rates of protein synthesis and lipolysis of GHD adults, whereas a longer interval of administration (3 days) had no effect by 60 h.

Adult↗
PubMed2000

Sertoli cell-induced reversal of adult rat pancreatic islet beta-cells into fetal-like status: potential implications for islet transplantation in type I diabetes mellitus.

BACKGROUND: Clinical success of pancreatic islet allograft (TX) for the therapy of diabetes mellitus is hampered by several pitfalls, primarily including the restricted availability of donor tissue and the immune- and/or non-immune-related TX's early loss, with the latter not necessarily being prevented by the host's general immunosuppression. Finally, adult islet beta-cells normally exhibit minimal proliferation capacity, which would not permit restoration of an eventually declining TX mass. METHODS: To address the limited beta-cell growth capacity, we have examined whether in vitro co-culturing adult rat islets (I) with prepubertal homologous Sertoli cells (SC) would stimulate I beta-cell expansion. SC-derived effects on the islets were studied in vitro, both morphologically (confocal laser microscopy) and functionally (glucose-stimulated insulin release). We have also preliminarily examined the in vivo impact of microencapsulated SC + I co-cultures on TX in diabetic mice. RESULTS: In vitro, we observed that SCs promoted significant beta-cell replication, as I beta-cell mitotic activity increased from 1% to greater than 8%, which coincided with the adult elements reversing into fetal-like status. This finding was coupled with significantly greater insulin release either in basal or in response to glucose, as compared with controls. CONCLUSIONS: Addition of SC to islets promotes reversal of the adult beta-cell elements into fetal-like conditions, thereby providing a new, potentially powerful tool that could significantly enhance the functional performance of islet TX in diabetic recipients.

Animals↗
PubMed1998

A dose-response study of growth hormone (GH) replacement on whole body protein and lipid kinetics in GH-deficient adults.

This study was designed to establish the lower dose of effective GH replacement therapy in severe GH-deficient (GHD) adults. Whole body protein and lipid kinetics were determined in six GHD men in the basal state (B) and after 1 week of treatment with placebo (PL) or 3.3 (GH3.3) or 2 (GH2) micrograms/kg.day recombinant human GH (rhGH). The rates of whole body proteolysis, oxidation, and synthesis were estimated by infusing [1-13C]leucine (prime, 1 mg/kg; infusion rate, 1 mg/kg.h); those of lipolysis (measured in four of the six patients) were estimated by infusing [1,1,2,3,3-D5]glycerol (prime, 1.8 mumol/kg; infusion rate, 0.06 mumol/kg.min). Serum insulin-like growth factor I (IGF-I) concentrations (picograms per mL; mean +/- SE) similarly increased from the basal level (39 +/- 7) after 3.3 (108 +/- 18) or 2 (109 +/- 24) microgram/kg.day rhGH (P < 0.001 vs. basal), whereas they did not change with placebo (41 +/- 8). Leucine Ra was unaffected by the treatments. GH3.3 reduced by 30% the rate of leucine oxidation (P = 0.0069 vs. basal) and increased by 11% nonoxidative leucine disposal (P = 0.0095 vs. basal) and by 21% glycerol Ra (0.0035 vs. basal); GH2 and placebo had no significant effect. In conclusion, 1) at least 3.3 micrograms/ kg.day rhGH are required to increase whole body protein synthesis and lipolysis in male GHD adults; 2) 2 micrograms/kg.day rhGH normalize serum IGF-I concentrations, but do not modify protein and lipid metabolism; and 3) a normal serum IGF-I concentration does not guarantee that rhGH treatment is also effective on intermediate metabolism.

Adult↗
PubMed1998

Etiological diagnosis of primary adrenal insufficiency using an original flowchart of immune and biochemical markers.

Approximately 70-80% of cases of primary adrenal insufficiency are classified as idiopathic. An effective protocol for the etiological diagnosis of primary adrenal insufficiency is needed to ensure correct patient management. With the aim of developing an algorithm for the etiological diagnosis of primary adrenal insufficiency, we studied 56 Italian patients with nonsurgical primary adrenal insufficiency and 24 French patients with X-linked adrenoleukodystrophy (ALD) for serum levels of adrenal cortex, steroid-21-hydroxylase (21OHAb), islet cell (ICA), glutamate decarboxylase (GAD65Ab), IA2/ICA512 (ICA512Ab), thyroid peroxidase (TPOAb) autoantibodies, and plasmatic concentrations of very long chain fatty acids (VLCFA). High levels of 21OH and adrenal cortex antibodies were found in 35/42 (83%) and 17/42 (40%) Italian patients with idiopathic adrenal insufficiency, respectively. Levels of adrenal autoantibodies correlated inversely with disease duration (P < 0.0001). Elevated VLCFA were found in 4/42 (10%) idiopathic patients. A total of 34/35 (97%) idiopathic patients with a disease duration of less than 20 yr was positive for either 21OHSAb or elevated levels of VLCFA. None of 14 patients with posttuberculosis adrenal insufficiency had elevated levels of either adrenal antibodies or VLCFA. ICA, GAD65Ab, ICA512Ab, and TPOAb were found in 6/56 (11%), 8/56 (14%), 4/56 (7%), and 23/56 (41%) patients, respectively. None of 24 French ALD patients with adrenal insufficiency was positive for organ-specific autoantibodies. The measuring of 21OH antibodies and plasma VLCFA levels enabled a correct diagnosis of autoimmune (89%) and ALD (8%) in 97% of patients with idiopathic primary adrenal insufficiency of less than 20 yr of duration. The results of our study have important therapeutic and prognostic implications.

Adolescent↗
PubMed1997

Pure Leydig cell tumour (hilus cell) of the ovary: a rare cause of virilization after menopause.

A 58-year-old postmenopausal woman with high plasma testosterone levels and virilization, as demonstrated by hirsutism and alopecia, is presented. Urinary 17-ketosteroids and 17-hydroxycorticosteroids as well as the computed axial tomography scan of the adrenal glands were normal. Although no pelvic mass was detected by sonography or pelvic examination, the patient was found to have small pure Leydig cell tumour of the left ovary. Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the patient had regression of the hirsutism, and the plasma testosterone dropped to normal level.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Absence of circulating adrenal autoantibodies in adult-onset X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a frequent cause of adrenal insufficiency in young-adult patients with Addison's disease. As the contribution of an autoimmune process in the destruction of steroid cells in ALD is unclear, the aim of the present study was to evaluate the occurrence of adrenal-, thyroid- and islet-specific and non organ-specific autoantibodies in adult ALD patients. In all 5 patients, Addison's disease was the first manifestation of ALD. None of the ALD patients were positive for adrenal cortex autoantibodies in an indirect immunofluorescence assay, or for 21-hydroxylase autoantibodies in a radiobinding assay with recombinant human antigen. Similarly, we found neither non-organ specific autoantibodies (such as anti-nuclear, anti-ribosomal, anti-mitochondria, anti-smooth-muscle, anti-liver/kidney microsomal or anti-reticulin autoantibodies), nor islet-cell antibodies or glutamic acid decarboxylase (GAD65 or GAD67) autoantibodies, nor thyroglobulin autoantibodies in the sera of the 5 ALD patients. Two out of five patients were positive for thyroid microsomal autoantibodies. One of the two latter thyroid antibody-positive patients had clinical symptoms of hypothyroidism, and the other presented high levels of circulating TSH but no clinical signs or symptoms of hypothyroidism. Our study demonstrates that adult ALD is not immediately associated with the presence of adrenal autoantibodies and suggests that adrenal insufficiency is not mediated by an autoimmune process in adult ALD patients.

Addison Disease↗
PubMed1996

X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison's disease in young adult male patients.

X-Linked adrenoleukodystrophy (ALD) is a genetic disease associated with demyelination of the central nervous system, adrenal insufficiency, and accumulation of very long chain fatty acids in tissue and body fluids. ALD is due to mutation of a gene located in Xq28 that encodes a peroxisomal transporter protein of unknown function. The most common phenotype of ALD is the cerebral form (45%) that develops in boys between 5-12 yr. Adrenomyeloneuropathy (AMN) involves the spinal cord and peripheral nerves in young adults (35%). Adrenal insufficiency (Addison's disease) is frequently associated with AMN or cerebral ALD and may remain the only clinical expression of ALD (8% of cases). The prevalence of ALD among adults with Addison's disease remains unknown. To evaluate this prevalence, we performed biochemical analysis of very long chain fatty acids in 14 male patients (age ranging from 12-45 yr at diagnosis) previously diagnosed as having primary idiopathic adrenocortical insufficiency. In 5 of 14 patients (35%), elevated plasma concentrations of very long chain fatty acids were detected. None of these patients had adrenocortical antibodies. By electrophysiological tests and magnetic resonance imaging it was determined that two patients had cerebral ALD, one had adrenomyeloneuropathy with cerebral involvement, and two had preclinical AMN. Our data support the hypothesis that ALD is a frequent cause of idiopathic Addison's disease in children and adults.

Addison Disease↗
PubMed1995

Fundus abnormalities in Cushing's disease: a preliminary report.

Three patients, 2 males and 1 female, with intrasellar, hypersecretive pituitary adenoma were studied. Blood hypertension was present in all and hyperglycemia in 2 (1 male, 1 female). None had neurological signs of compression of the optic disk or chiasma. One patient showed bilateral circumpapillary and multiple retinal pigment epithelium (RPE) detachment with pooling defects and intraretinal leakage from small retinal arterioles. Another had loss of foveolar, macular and retinal reflexes in the right eye; negligible RPE changes became visible with fluorescein angiography. The third, who had developed malignant hypertension, manifested bilateral hypertensive neuroretinopathy and papilledema. The simultaneous improvement of general and ocular symptoms after removal of the pituitary tumor makes a causal relationship possible and even very likely, between the underlying disorder and fundus abnormalities.

Adenoma↗
PubMed1990

Precocious puberty and neurofibromatosis of von Recklinghausen. A clinical report.

A case of a 9-year-old boy with neurofibromatosis of von Recklinghausen and precocious puberty is reported. The patient was referred to us because of an unexplained onset of precocious puberty. Clinical manifestations of neurofibromatosis included multiple café-au-lait spots, skeletal anomalies, progressive impairment of vision and precocious sexual development. CT scan and NMR demonstrated the presence of optic gliomas. The correlation between the lesions of retino-hypothalamic projection and production of the neuroendocrinology mechanism of sexual changes is discussed.

Brain↗
PubMed1987

Effect of exogenously administered estrogens on luteinizing hormone release in a complete testicular feminization syndrome patient with very low testosterone levels, before and after gonadectomy.

The response of LH to exogenously administered estrogens was evaluated in a 63-year-old patient affected by complete testicular feminization syndrome (CTFS) with very low testosterone (T) levels, before and after gonadectomy. Prior to gonadectomy a durative fall in gonadotropin levels was observed after estrogen administration, without observing of an estrogenic positive feed-back (EPF) from LH. After gonadectomy, following an initial decrement in both gonadotropins, the characteristic. LH peak was seen, 48 h after E2B (Estradiol Benzoate) administration. This observation, together with the very low T levels that we found in this patient, prompted us to construe that absence of EPF in males is not due, as previously believed, to a direct inhibitory action of T or E2, deriving from T aromatization, on the hypothalamus, but by a still unknown gonadal factor. The hypothesis that this factor has a tubular origin is formulated and discussed.

Androgen-Insensitivity Syndrome↗