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Stefania Bonadonna

Publications and source records attributed to Stefania Bonadonna.

15 recordsLinked to original sources
PubMed2006

Functional effects of nitric oxide-releasing aspirin on vein conduits of diabetic patients undergoing CABG.

BACKGROUND: Type 2 diabetes mellitus (DM) is known to negatively affect biological properties of venous vasculature, and, particularly, to reduce endothelium-derived nitric oxide release. This condition might influence venous graft function following coronary artery bypass surgery (CABG). The aim of this study was to evaluate the functional effects of a NO-releasing aspirin (NORA) on vein grafts (VG) of diabetics and control patients undergoing elective CABG. METHODS: In 40 consecutive ischemic heart disease patients, the effects of NORA were tested on segments of saphenous vein conduits harvested during elective CABG. Twenty patients had type-2 DM (mean age 69+/-2), whereas 20 patients had no DM (NDM) and represented the control group (mean age 67+/-4). Functional responses were tested by exposing VGs to NORA and to standard vasoactive agents in an organ-bath preparation. Histological features of VGs were also assessed by light and electronic microscopy. RESULTS: Significant impairment of endothelial-dependent vasodilation (acetylcholine induced) was documented in VGs of DM subjects. NORA induced a significant and comparable vascular relaxation in all venous segments of NDM and DM patients (56+/-12% of maximal relaxation vs 61+/-11% in the control group, respectively). Histology showed variable extent of vascular layer and cellular abnormalities in VGs of diabetics (intimal hyperplasia, calcific deposition, endothelial cell degeneration) likely responsible of the endothelial functional impairment, whereas control group VG showed preserved structures. CONCLUSIONS: This preliminary study confirms the impairment of endothelium-dependent vasodilative property of VGs in DM patients. It also indicates that NORA effectively induces vasodilation of VGs which was effective also in DM patients thereby representing a promising therapy for diabetics undergoing CABG with the use of VGs, although further studies are mandatory to conclusively assess the safety and benefits of this pharmacological agent.

Acetylcholine↗
PubMed2006

Increased prevalence of radiological spinal deformities in adult patients with GH deficiency: influence of GH replacement therapy.

UNLABELLED: This cross-sectional study shows that a high number of untreated adult patients with GHD develop radiological vertebral deformities. Patients undergoing GH replacement treatment showed a significantly lower prevalence of vertebral deformities versus treated patients in the presence of similar BMD, as assessed by DXA. INTRODUCTION: In this cross-sectional study, we investigated whether the prevalence and degree of spinal deformities in adults with growth hormone deficiency (GHD) were related to the age of patients, degree of bone turnover, BMD, and recombinant human GH (rhGH) replacement therapy. MATERIALS AND METHODS: One hundred seven adult hypopituitary patients (67 males and 40 females; mean age, 47 years; range: 16-81 years) with severe GHD and 130 control subjects (39 males, 91 females; mean age: 58.9 years; range: 26-82 years) were evaluated for BMD (DXA) and vertebral deformities (quantitative morphometric analysis). At study entry, 65 patients were on replacement therapy with rhGH, whereas 42 patients had never undergone rhGH. RESULTS: Vertebral fractures were significantly more frequent in GHD patients versus control subjects (63.6% versus 37.7%; chi2 15.7; p < 0.001). The fracture prevalence, as well as the fracture number, was significantly higher in untreated versus treated patients (78.6% versus 53.8%; chi2: 6.7; p = 0.009), although the two groups of patients did not show any significant difference in median T score. In untreated GHD patients, the prevalence of vertebral deformities was correlated with T score (p = 0.002) and duration of disease (p = 0.003). In treated GHD patients, the prevalence of spinal deformities was correlated only with the timing of the beginning of rhGH replacement. CONCLUSIONS: This cross-sectional study reports high prevalence of vertebral radiological deformities in adult patients with untreated GHD. The replacement treatment of GHD leads to a significant decrease in fracture rate.

Adolescent↗
PubMed2006

Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects.

Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation, increased GH secretion and eventually pituitary acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal adenomas, and pheochromocytomas which have been reported to secrete GHRH. Acromegaly in these patients, however, is uncommon. The distinction of pituitary vs. extrapituitary acromegaly is extremely important in planning effective management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH levels fail to suppress (<1 microg/l) after an oral glucose load in all forms of acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic patients with pituitary tumors from those harbouring extrapituitary tumors. Plasma GHRH levels are usually elevated in patients with peripheral GHRH-secreting tumors, and are normal or low in patients with pituitary acromegaly. Unique and unexpected clinical features in an acromegalic patient, including respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones sometimes are helpful in alerting the physician to diagnosing non pituitary endocrine tumors. If no facility to measure plasma GHRH is available, and in the absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and abdominal ultrasound could be performed to exclude with good approximation the possibility of an ectopic GHRH syndrome. Surgical resection of the tumor secreting ectopic GHRH should be the logical approach to a patient with ectopic GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors is generally unsuccessful in controlling the activated GH axis. Somatostatin analogs provide an effective option for medical management of carcinoid patients, especially those with recurrent disease. In fact, long-acting somatostatin analogs may be able to control not only the ectopic hormonal secretion syndrome, but also, in some instances, tumor growth. Therefore, although cytotoxic chemotherapy, pituitary surgery, or irradiation still remain available therapeutic options, long-acting somatostatin analogs are now preferred as a second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.

Acromegaly↗
PubMed2006

Active acromegaly enhances spontaneous parathyroid hormone pulsatility.

In healthy subjects, parathyroid hormone (PTH) is secreted in a dual fashion, with low-amplitude and high-frequency pulses superimposed on tonic secretion. These 2 components of PTH secretion seem to have different effects on target organs. The aim of our study was to evaluate whether growth hormone excess in acromegaly may modify the spontaneous pulsatility of PTH. Five male patients with newly diagnosed active acromegaly and 8 healthy subjects were evaluated by 3-minute blood sampling for 6 hours. Plasma PTH concentrations were evaluated by multiparameter deconvolution analysis. Plasma PTH release profiles were also subjected to an approximate entropy (ApEn) estimate, which provides an ensemble measure of the serial regularity or orderliness of the release process. In acromegalic patients, baseline serum PTH values were not significantly different from those measured in the healthy subjects, as well as tonic PTH secretion rate, number of bursts, fractional pulsatile PTH secretion, and ApEn ratio. Conversely, PTH pulse half-duration was significantly longer in acromegalic patients vs healthy subjects (11.8+/-0.95 vs 6.9+/-1.6 minutes; P=.05), whereas PTH pulse mass showed a tendency (P=.06) to be significantly greater in acromegalic patients. These preliminary data suggest that growth hormone excess may affect PTH secretory dynamics in patients with acromegaly. Potentially negative bone effects of the modifications of PTH secretory pattern in acromegaly should be investigated.

Acromegaly↗
PubMed2005

Primary empty sella.

CONTEXT: The term primary empty sella (PES) refers to a number of endocrine and/or neurological disturbances that may be caused by the herniation of subarachnoid space within the sella. SETTING: The records of all patients with a diagnosis of empty sella between 1985 and 2002 seen at the Catholic University of Rome and University of Brescia were examined retrospectively. PATIENTS: We have observed 171 female and 42 male patients affected by PES (over 4:1 sex ratio). The mean age at diagnosis in our subjects was 51.8 +/- 2.1 yr. Mean body mass index was 27.3 +/- 3.5 kg/m2. MAIN OUTCOME MEASURE: All the patients have been analyzed first either with sellar computed tomography scan or magnetic resonance imaging. All patients underwent neurological, ophthalmological, and baseline endocrine evaluation (appropriate stimulation tests were performed when hypopituitarism was suspected). RESULTS: In the overall population, 40 of 213 patients had documented endocrine abnormalities, specifically 31 females and nine males. Twenty-two patients (10.3% of total patients; 18 women, 10.5% of all women, with a mean age of 38.6 +/- 1.1 yr and four males, with a mean age 46.5 +/- 3.52 yr) presented with hyperprolactinemia. Global anterior hypopituitarism was confirmed in nine patients. Eight patients presented an isolated GH deficiency. One hundred thirty-eight of our patients presented a so-called partial empty sella at computed tomography scan/magnetic resonance imaging, and 75 had total PES. CONCLUSIONS: PES may be associated with variable clinical conditions ranging from mild endocrine disturbances to severe intracranial hypertension and rhinorrhea. The need for treatment of hyperprolactinemia as well as for replacement hormone therapy must be assessed in PES. Symptomatic intracranial hypertension makes cerebrospinal fluid shunting procedures necessary.

Adult↗
PubMed2005

Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women.

UNLABELLED: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. INTRODUCTION: We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. MATERIALS AND METHODS: Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. RESULTS: Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosis, and 42.9% were osteopenic). In contrast, 41.7% of women whose fractures were associated with active disease had a normal T score (>-1.0 SD), whereas osteopenia and osteoporosis were found only in 33.3% and 25.0% of them, respectively. CONCLUSIONS: This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. Furthermore, our study shows that, in patients with active acromegaly, vertebral fractures occur even in the presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD.

Acromegaly↗
PubMed2005

The somatostatin subtype-2 receptor antagonist, BIM-23627, improves the catabolic effects induced by long-term glucocorticoid treatment in the rat.

BIM-23627 is a synthetic peptide with "in vitro" and "in vivo" properties consistent with a pure sst2 antagonist. The aim of the present study was to evaluate the effects of long-term administration of BIM-23627 and the combined effects of BIM-23627 and dexamethasone (DEX) on the somatotropic axis, including growth, epididymal fat accumulation, glucose homeostasis and insulin activity, in young male rats. Beginning on day 23 of age, 16 animals were treated daily with saline or DEX (40 microg/kg/daily). Each group was subdivided into two paired groups and treated with either vehicle or BIM-23627 (0.5 mg/kg, t.i.d.). The treatment period lasted 31 days. The animals were killed by decapitation; trunk blood and pituitaries were collected for the determination of hormone concentrations and GH mRNA expression, respectively. Based on plasma GH and IGF-I concentrations and GH mRNA expression in the pituitary, BIM-23627 was able to counteract the inhibitory effects of DEX on the somatotropic axis; however, only a partial reversal of somatic growth inhibition was observed. DEX-treated rats remained euglycemic, but their insulin levels were significantly increased, indicating an incipient insulin resistance. Although BIM-23627 itself tended to increase insulin concentration in saline-treated rats, its administration to DEX-treated rats reduced insulin levels (saline: 25+/-3; DEX: 55+/-16*; DEX+BIM-23627: 34+/-5; BIM-23627: 38+/-7 microIU/ml; *P<0.05 vs. saline), apparently improving the degree of insulin sensitivity. DEX administration significantly reduced circulating ghrelin, whereas the sst2 antagonist had no significant effect. An inverse correlation was found between ghrelin concentrations and plasma insulin levels. Both rats receiving DEX and rats receiving BIM-23627 had decreased plasma concentration of total testosterone (P<0.05); however, the effects of DEX and BIM-23627 were not additive. In conclusion, BIM-23627 may represent a new pharmacological agent to reduce the suppression of the GH-IGF-I axis in long-term GC treated patients and enhance insulin sensitivity. Further studies are required in order to fully optimize the SSTR-2 antagonist-induced reversal of DEX-induced somatic growth inhibition.

Animals↗
PubMed2005

Cardiac and metabolic effects of chronic growth hormone and insulin-like growth factor I excess in young adults with pituitary gigantism.

Chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess is associated with considerable mortality in acromegaly, but no data are available in pituitary gigantism. The aim of the study was to evaluate the long-term effects of early exposure to GH and IGF-I excess on cardiovascular and metabolic parameters in adult patients with pituitary gigantism. Six adult male patients with newly diagnosed gigantism due to GH secreting pituitary adenoma were studied and compared with 6 age- and sex-matched patients with acromegaly and 10 healthy subjects. Morphologic and functional cardiac parameters were evaluated by Doppler echocardiography. Glucose metabolism was assessed by evaluating glucose tolerance and homeostasis model assessment index. Disease duration was significantly longer (P<.05) in patients with gigantism than in patients with acromegaly, whereas GH and IGF-I concentrations were comparable. Left ventricular mass was increased both in patients with gigantism and in patients with acromegaly, as compared with controls. Left ventricular hypertrophy was detected in 2 of 6 of both patients with gigantism and patients with acromegaly, and isolated intraventricular septum thickening in 1 patient with gigantism. Inadequate diastolic filling (ratio between early and late transmitral flow velocity<1) was detected in 2 of 6 patients with gigantism and 1 of 6 patients with acromegaly. Impaired glucose metabolism occurrence was higher in patients with acromegaly (66%) compared with patients with gigantism (16%). Concentrations of IGF-I were significantly (P<.05) higher in patients with gigantism who have cardiac abnormalities than in those without cardiac abnormalities. In conclusion, our data suggest that GH/IGF-I excess in young adult patients is associated with morphologic and functional cardiac abnormalities that are similar in patients with gigantism and in patients with acromegaly, whereas occurrence of impaired glucose metabolism appears to be higher in patients with acromegaly, although patients with gigantism are exposed to GH excess for a longer period.

Acromegaly↗
PubMed2005

Growth hormone response to growth hormone-releasing hormone is reduced in adult asthmatic patients receiving long-term inhaled corticosteroid treatment.

BACKGROUND: Some studies have demonstrated that the function of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis is significantly impaired in patients with oral corticosteroid (CS)-induced osteoporosis. The aim of study was to investigate the effects of long-term therapy with inhaled CSs (ICSs) on the hypothalamic-pituitary-GH axis by the GH response to GH-releasing hormone (GHRH), as well as bone turnover, in adult asthmatic patients. DESIGN: Cross-sectional study. PATIENTS: Twenty-seven adult subjects with mild-to-moderate persistent asthma (long-term ICS therapy [ie, > 1 year], 20 patients; naive to ICS treatment, 7 patients) and 10 control subjects. MEASUREMENTS: Each subject underwent testing with an IV bolus (1 mug/kg) injection of human GHRH, and samples of GH were taken 15 min before the GHRH injection, at 0 min (ie, at the time of GHRH injection), and at 15, 30, 45, 60, and 90 min after injection to obtain values for peak GH and DeltaGH. At baseline, samples of serum IGF-1 and blood-urine were collected for bone turnover markers. RESULTS: The GH response to GHRH was significantly reduced in asthmatic patients receiving ICSs (peak GH, p < 0.05; and DeltaGH, p < 0.01) in comparison with control subjects and asthmatic patients who were naive to ICS therapy (peak GH and DeltaGH, p < 0.01). Baseline IGF-1 levels were similar in the three groups. Serum osteocalcin, a marker of bone formation, was significantly reduced (p < 0.01) and correlated with GH peak (r(2) = 0.34; p = 0.007) in asthmatic patients who were treated with ICSs. CONCLUSIONS: We conclude that GH secretion in response to GHRH is significantly reduced in adult asthmatic patients receiving therapy with ICS and that such inhibition could play a negative role in bone metabolism.

Administration, Inhalation↗
PubMed2005

Chronic glucocorticoid treatment alters spontaneous pulsatile parathyroid hormone secretory dynamics in human subjects.

OBJECTIVE: Spontaneous parathyroid hormone (PTH) secretory dynamics include tonic and pulsatile components. It is not known how glucocorticoids might alter these secretory dynamics. DESIGN: The aim of our study was to evaluate spontaneous fluctuations in serum PTH levels in six adult male patients (aged 31-64 years) receiving chronic (>6 months) therapy with glucocorticoids (daily dosage >7.5 mg of prednisone or dose equivalent of other corticosteroid) as compared with a control group of 10 age- and sex-matched normal subjects. METHODS: Peripheral venous blood sampling was performed every 3 min for 6 h from 0900 to 1500 h. Plasma PTH release profiles were subjected to deconvolution analysis, a method that resolves measured hormone concentrations into secretion and clearance components, and to an approximate entropy (ApEn) estimate, that in turn provides an integrated measure of the serial regularity or orderliness of the release process. RESULTS: In the glucocorticoid-treated group, the PTH tonic secretory rate was reduced (4.3+/-0.74 vs 8.8+/-1.4 pg/ml per min in controls, P = 0.017). There was, however, an increase in the fractional pulsatile PTH secretion (42+/-8.2 vs 18.3+/-3.9 pg/ml per min, P = 0.006) in glucocorticoid-treated vs normal subjects. Mean overall PTH concentration, as well as mean integrated area, was similar among normal and glucocorticoid-treated subjects. CONCLUSIONS: These results demonstrate, for the first time, that chronic glucocorticoid treatment induces a redistribution of spontaneous PTH secretory dynamics by reducing the amount released in tonic fashion and increasing the amount released as pulses.

Adult↗
PubMed2004

Clinical review: Growth hormone and cardiovascular risk factors.

The aim of this article is to review the lessons on the relationship between GH and the principal metabolic cardiovascular risk factors that we learned from studies of GH deficiency (GHD) in the adult. The lesson that "organic" GHD has taught us is that primary impairment in the GH/IGF-I axis may lead to a high-risk cardiovascular profile that is partially reversible during GH replacement. Waiting for the definitive demonstration that GH substitution may reduce cardiovascular mortality in these patients, we find that data so far reported are encouraging and indicate in the beneficial cardiovascular effects of GH one of the major factors supporting this type of treatment in hypopituitary GHD adults. Moreover, enough evidence from GHD studies has been produced to suggest a physiological role for the GH/IGF-I axis in the control and regulation of several metabolic cardiovascular risk factors.

Cardiovascular Diseases↗
PubMed2004

Acromegalic patients show the presence of hypertrophic remodeling of subcutaneous small resistance arteries.

Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.

Acromegaly↗
PubMed2003

Transformation of a MGUS to overt multiple myeloma: the possible role of a pituitary macroadenoma secreting high levels of insulin-like growth factor 1 (IGF-1).

We present a female patient with monoclonal gammopathy of undetermined significance who has remained stable for five years but evolved to overt myeloma in strict temporal relationship with the diagnosis of GH-secreting pituitary macroadenoma. IGF-I serum levels correlated with serum and urine M component. Since the in vitro role of IGF-I on proliferation and survival of normal and neoplastic plasma cells has been recently emphasized, the pathogenetic link between acromegaly and transformation of gammopathy to overt myeloma in this case is discussed.

Adenoma↗