Biomedical subjects

Paolo Marzullo

Publications and source records attributed to Paolo Marzullo.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of a multisensor armband in estimating energy expenditure in obese individuals.

OBJECTIVE: To examine the reliability and validity of the SenseWear Pro 2 Armband (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect calorimetry (IC) in obese individuals. RESEARCH METHODS AND PROCEDURES: Energy expenditure was assessed during rest with the SWA and IC in 142 obese adults (37 men and 105 women, BMI = 42.3 +/- 7.0) and in 25 lean and overweight adults (BMI = 25.3 +/- 3.2) who were used as a comparison group. Twenty-nine of the obese adults also participated in three separate short exercise sessions including cycle ergometry, stair stepping, and treadmill walking. RESULTS: The repeatability of SWA estimates in obese subjects was high (r = 0.88, p < 0.001). The SWA generally underestimated the resting energy expenditure (REE) (1811 +/- 346 vs. 1880 +/- 382 kcal/d) and highly overestimated the energy expenditure during the exercise sessions in obese individuals. REE estimations by SWA were significantly correlated with fat-free mass (r = 0.88, p < 0.001). Bland-Altman plots based statistical analysis for the estimated REE, and measured IC showed a low agreement (Total Error > 20% but Systematic Error < 5%) between the two methods in obese subjects, although they showed a high correlation and a very good agreement in lean and overweight patients. DISCUSSION: The SWA is an easy to handle, practical, new portable device for measuring energy expenditure. The accuracy of the SWA appeared to be poor in the obese subjects we examined, especially those with high REE both in rest and exercise. We believe that it is necessary to incorporate new, obesity-specific algorithms in the relative software.

Adult↗

PubMed2006

Cardiac imaging improves risk stratification in high-risk patients undergoing surgical revascularization.

OBJECTIVE: In patients with ischaemic left ventricular dysfunction, multivessel disease and dominance of necrotic myocardium, perioperative mortality due to coronary artery bypass grafting is still a rather unclear issue. The aim of this study was to analyse the impact of different imaging variables in predicting perioperative mortality. METHODS: We selected a group of 259 patients who had preoperatively been defined as 'high-risk patients' and who showed a mostly necrotic myocardium as detected by thallium-201 myocardial scintigraphy. RESULTS: Mean ejection fraction was 0.26 +/- 0.07. In a 16-segment model, the mean number of scintigraphic necrotic myocardial segments was 5.07 +/- 1.09, echocardiographic end-diastolic diameter was 29.41 +/- 2.38 mm/m2 and wall motion score index was 2.29 +/- 0.19. Perioperative mortality increased along with the increase in the number of necrotic segments: 5/105 (5%), 4/63 (6%), 8/52 (15%) and 8/39 (20%) patients with four, five, six and seven necrotic segments, respectively. The analysis of additional variables in survived vs. deceased patients demonstrated a significant difference in echocardiographic end-diastolic diameter (27 +/- 8 vs. 31.9 +/- 1.9 mm/m2, P < 0.001) and in wall motion score index (2.2 +/- 0.1 vs. 2.4 +/- 0.2, P < 0.001). CONCLUSIONS: In high-risk patients, the extension of scintigraphic myocardial scar has a significant impact on perioperative mortality. For similar values of ejection fraction at rest, additional imaging variables, such as echocardiographic end-diastolic diameter and wall motion score index, may contribute to select those patients in whom mortality may exceed 15%.

Chi-Square Distribution↗

PubMed2005

The impact of growth hormone/insulin-like growth factor-I axis and nocturnal breathing disorders on cardiovascular features of adult patients with Prader-Willi syndrome.

CONTEXT: Adult patients with Prader-Willi syndrome (PWS) are prone to develop obesity, GH deficiency (GHD), and their related complications, with cardiopulmonary failure explaining more than half of PWS fatalities. OBJECTIVE AND STUDY PARTICIPANTS: This study was undertaken to examine the effect of GHD and sleep breathing disorders on cardiovascular risk factors and heart features of 13 PWS (age 26.9 +/- 1.2 yr) and 13 age-, gender-, and body mass index-matched obese individuals (age 26.2 +/- 0.8 yr). RESULTS: Compared with controls, PWS patients had lower GH response to arginine+GHRH, IGF-I levels, triglycerides, total and LDL-cholesterol, insulin, and insulin resistance measured by a homeostatic model approach. Dual-energy x-ray absorptiometry, abdominal computed tomography scans, and polysomnography revealed a greater fat mass, similar abdominal fat, but greater sleep breathing disorders in PWS than obese subjects. Echocardiography showed no systolic or diastolic alteration, although PWS had lower left ventricle (LV) mass (135.7 +/- 7.7 vs. 163.5 +/- 8.4 g, P < 0.05) and near significantly lower values of LV end-diastole diameter (P = 0.08), compared with obese controls. Baseline radionuclide angiography documented comparable values of systolic and diastolic values between groups. However, adrenergic stimulation with dobutamine caused a lower increase of LV ejection fraction (71.9 +/- 1.9 vs. 76.3 +/- 1.2%, P < 0.05) and heart rate (103 +/- 6.9 vs. 128 +/- 2.8 beats/min, P < 0.05) in PWS than obese individuals. By multivariate analysis, nocturnal oxygen desaturation and IGF-I levels were main significant predictors of LV mass and heart rate in PWS patients. CONCLUSIONS: PWS differs from simple obesity by a healthier metabolic profile, impaired nocturnal breathing, decreased heart geometry, and systolic and chronotropic performance. GHD and the predictive role of IGF-I on structural and functional heart parameters suggest a GH/IGF-I-mediated control of cardiac risk in PWS.

Adipose Tissue↗

PubMed2005

Extension of myocardial necrosis differently affects MIBG retention in heart failure caused by ischaemic heart disease or by dilated cardiomyopathy.

PURPOSE: This study aims to investigate the relationship between cardiac sympathetic nervous function (CSNF) and myocardial perfusion/function in patients with heart failure (HF) due to dilated cardiomyopathy (DCM) or ischaemic heart disease (CAD). METHODS: Twenty patients (10 DCM, 10 CAD, 17 males, age 69+/-5 years) with NYHA class IIIb HF were studied. CSNF was evaluated by early/delayed (123)I-metaiodobenzylguanidine (MIBG) uptake and regional washout (WO). Myocardial perfusion and function were evaluated by (99m)Tc-tetrofosmin gated single-photon emission tomography (G-SPECT) using a 20-segment model for 400 segments. In each segment, regional MIBG WO was computed as (count density in early images-count density in delayed images/count density in early images)x100. RESULTS: DCM and CAD showed similar summed rest perfusion score (6.7+/-5 vs 9.5+/-5, p=NS) and mean ejection fraction values (29+/-7% vs 30+/-9%, p=NS). By contrast, the summed thickening score was higher in DCM than in CAD patients (26+/-7 vs 17+/-6, p<0.05). QGS analysis identified akinesis/dyskinesis in 129/137 (94%) severely hypoperfused segments which were considered as damaged. According to the underlying aetiology of HF, marked differences in regional MIBG WO were observed. In fact, within the CAD group, regional MIBG WO was lower in reference than in damaged segments (38+/-21% vs 46+/-19%, p<0.05). By contrast, in DCM patients, regional MIBG WO was faster in reference than in damaged segments (49+/-18% vs 41+/-30%, p<0.05). When the two groups were directly compared, regional MIBG WO from damaged areas was similar irrespective of the underlying disease, while it was faster in DCM than in CAD patients from reference segments. CONCLUSION: These data confirm the hypothesis that the presence of myocardial necrosis in HF due to CAD and the consequent loss of neuronal endings cause alterations in regional MIBG WO different from those observed in DCM.

3-Iodobenzylguanidine↗

PubMed2005

Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study.

BACKGROUND: Botulin toxin (BTX) has been proposed as a potential obesity treatment. METHODS: In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35-57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m(2); range 38.2-56.7 kg/m(2)) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region. RESULTS: No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism. CONCLUSIONS: BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely.

Adult↗

PubMed2005

A fast and effective method to assess myocardial necrosis by means of contrast magnetic resonance imaging.

PURPOSE: Contrast magnetic resonance (CMR) can identify myocardial necrosis after gadolinium administration as a hyperenhanced (HE) area. Yet there are no software tools that can effectively quantify such an area. The aim of this study is to develop a robust and effective algorithmic method for defining the extent of myocardial necrosis evidenced through CMR. METHOD: Fifteen patients with previous myocardial infarction underwent nitrate Tetrofosmin G-SPECT and CMR. A software tool was developed, allowing semiautomatic detection of endocardial and epicardial borders and the automatic detection of HE regions. The accuracy of the proposed quantitative method of analysis has been tested with G-SPECT analysis that it is less than an ideal method for assessing myocardial viability, but at present is accepted and widely used in the clinical arena. RESULTS: Segmental (SEHE) and global extension of HE were evaluated. HE was present in 161 of the 255 analyzed segments. Of the 161 HE segments, the mean SEHE was 36 +/- 30%. The operator independence (intraobserver: r = 0.97, p < 0.0001, interobserver: r = 0.95, p < 0.0001) was good and significant, with noticeable time savings with respect to manual analysis. There was strong and inverse correlation between SEHE and scintigraphic regional uptake reduction (r = -0.66, p < 0.0001), and also a positive correlation between SEHE and SPECT defect extension (r = 0.75, p < 0.0001). When assessing the global extent of necrosis, the correlation between the two techniques was strong (r = 0.79, p = 0.0004). CONCLUSIONS: The proposed method of quantifying myocardial necrosis by CMR is highly reliable, reproducible, and operator-independent for quantifying.

Algorithms↗

PubMed2005

Effect of gender and gonadal status on the long-term response to somatostatin analogue treatment in acromegaly.

UNLABELLED: :GH and IGF-I secretion is related to gender and age. OBJECTIVE: To evaluate the impact of gender and gonadal status on the long-term sensitivity to the somatostatin analogues depot octreotide long-acting release (OCT-LAR) and lanreotide (LAN). PATIENTS: Seventy-three patients with active acromegaly (37 women, median age 34 years; 36 men, median age 38 years) who had not previously been treated with somatostatin analogues were studied: 24 women and 23 men were newly diagnosed; 22 men (61.1%) and 17 women (45.9%) had hypogonadism (P=0.28). Exclusion criteria were age >45 years, follow-up less than 12 months, mixed GH/PRL-secreting adenomas. Study design Observational, analytical, retrospective. Outcome measures (1) Disease control measured as serum GH< 2.5 microg/l and IGF-I normal for age and gender; (2) reduction in tumour volume graded as absent (< 25%), mild (25-50%) and notable (>50%). Results Basal GH, but not IGF-I, levels were higher in women than in men both in the entire series and in 'de novo' patients (97.8+/- 42.2 vs. 71.1+/- 32.6 microg/l, P=0.021). After 12 and 24 months of treatment, respectively, disease control was achieved similarly in men (57.1 and 86.7%) and women (48.6 and 86.7%). Hypogonadal men had longer disease duration than eugonadal men (P=0.022), without any difference in the other parameters. No difference was found between eugonadal and hypogonadal women. Eugonadal men had a smaller tumour volume at baseline than eugonadal women (1396+/- 794 vs. 2896+/- 2871 mm(3), P=0.025). In men undergoing testosterone replacement and withdrawal, there was no change in GH and IGF-I levels after 12 and 24 months of treatment with either LAR or LAN. In the seven women receiving oestro-progestinic replacement, after 24 months of LAR or LAN treatment GH levels were higher during replacement than at withdrawal and IGF-I levels were lower during replacement than withdrawal. Tumour volume decreased significantly in both women and men without any difference between them: the percentage tumour shrinkage in men and women was similar either after 12 (34.4+/-24.4 vs. 40.7+/-22.5%, P=0.38) or 24 months of treatment (58.5+/- 17.4 vs. 56.1+/- 23.6%, P=0.75). Similarly, there was no difference in tumour volume between hypogonadal and eugonadal women and men. CONCLUSIONS: The results of this study demonstrate that long-term responsiveness to OCT-LAR is similar in women and men. Care should be taken in women with acromegaly and hypogonadism treated with somatostatin analogues and oral oestro-progestinic as in this case GH levels are higher while IGF-I levels are lower than after the somatostatin analogues alone.

Acromegaly↗

PubMed2005

Coronary microcirculatory vasoconstriction is heterogeneously distributed in acutely ischemic myocardium.

The classical model of coronary physiology implies the presence of maximal microcirculatory vasodilation during myocardial ischemia. However, Doppler monitoring of coronary blood flow (CBF) documented severe microcirculatory vasoconstriction during pacing-induced ischemia in patients with coronary artery disease. This study investigates the mechanisms that underlie this paradoxical behavior in nine patients with stable angina and single-vessel coronary disease who were candidates for stenting. While transstenotic pressures were continuously monitored, input CBF (in ml/min) to the poststenotic myocardium was measured by Doppler catheter and angiographic cross-sectional area. Simultaneously, specific myocardial blood flow (MBF, in ml.min(-1).g(-1)) was measured by 133Xe washout. Perfused tissue mass was calculated as CBF/MBF. Measurements were obtained at baseline, during pacing-induced ischemia, and after stenting. CBF and distal coronary pressure values were also measured during pacing with intracoronary adenosine administration. During pacing, CBF decreased to 64 +/- 24% of baseline and increased to 265 +/- 100% of ischemic flow after adenosine administration. In contrast, pacing increased MBF to 184 +/- 66% of baseline, measured as a function of the increased rate-pressure product (r = 0.69; P < 0.05). Thus, during pacing, perfused myocardial mass drastically decreased from 30 +/- 23 to 12 +/- 11 g (P < 0.01). Distal coronary pressure remained stable during pacing but decreased after adenosine administration. Stenting increased perfused myocardial mass to 39 +/- 23 g (P < 0.05 vs. baseline) as a function of the increase in distal coronary pressure (r = 0.71; P < 0.02). In conclusion, the vasoconstrictor response to pacing-induced ischemia is heterogeneously distributed and excludes a tissue fraction from perfusion. Within perfused tissue, the metabolic demand still controls the vasomotor tone.

Acute Disease↗

PubMed2005

Baseline/postnitrate tetrofosmin SPECT for myocardial viability assessment in patients with postischemic severe left ventricular dysfunction: new evidence from MRI.

UNLABELLED: The aim of this study was to compare (99m)Tc-tetrofosmin SPECT with contrast-enhanced MRI (ceMRI), a new direct sign of myocardial fibrosis. METHODS: We studied 21 patients (age, 60 +/- 11 y; 19 male) with previous myocardial infarction and severe left ventricular dysfunction (ceMRI EF, 29% +/- 6%). All patients underwent resting and postnitrate (intravenous isosorbide dinitrate) (99m)Tc-tetrofosmin gated SPECT as well as ceMRI. Scintigraphic analysis was performed using quantitative perfusion SPECT (QPS), providing the percentage radiotracer uptake and defect severity in a 20-segment model. Hyperenhancement was defined by the increase of ceMRI signal intensity 20 min after intravenous injection of gadolinium-diethylenetriaminepentaacetic acid and its regional extension as the percentage of the total segment area. RESULTS: In ceMRI dysfunctional segments, the correlation between the extent of hyperenhancement and both (99m)Tc-tetrofosmin uptake and defect severity was significantly better after nitrate administration rather than at rest (P < 0.0001). Using a ceMRI cutoff below 40%, 102 of 196 (52%) segments were viable, whereas 94 (48%) segments were not viable. According to receiver-operating characteristic curve analysis, diagnostic accuracies were higher for postnitrate (99m)Tc-tetrofosmin uptake as well as perfusion defect severity than using resting data (0.84 vs. 0.71, P < 0.001; 0.89 vs. 0.76, P < 0.001, respectively). CONCLUSION: After nitrate administration, (99m)Tc-tetrofosmin uptake and perfusion defect severity were closely related to ceMRI, demonstrating, in vivo, the existence of an inverse correlation between the transmural distribution of fibrosis and tracer delivery to the myocardium.

Adult↗

PubMed2004

Nuclear imaging after cell implantation.

Since no currently available method is able to determine engraftment into the myocardium or stem cell differentiation in a living patient, the evidence of stem cell therapy efficacy is in all cases indirect.

Cardiomyopathies↗

PubMed2004

Systemic complications of acromegaly: epidemiology, pathogenesis, and management.

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are advantageously benefitted by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.

Acromegaly↗

PubMed2004

Acromegalic axial arthropathy: a clinical case-control study.

Arthropathy is the major cause of morbidity in acromegaly. To feature the spinal involvement, 54 patients with active acromegaly (27 men, 27 women; age range, 21-69 yr) and 54 sex-, age-, and body mass index-matched healthy controls were enrolled in this observational analytical prospective case-control study. A questionnaire to describe onset, duration, and severity of articular symptoms; rheumatological examination, including vertebral and chest mobility, Schober test, thorax expansion, and axial radiological study; and IGF-I, GH, insulin, and glucose level measurement (baseline and after an oral glucose tolerance test) was used to investigate the prevalence of arthropathy and correlate these findings with hormonal parameters. Axial arthropathy was found in 28 patients (52%) and 12 controls (22%; chi(2) = 8.9; P = 0.003). In detail, spinal mobility was reduced in 30 patients (56%) and 10 controls (18%; chi(2) = 14.3; P < 0.0001), thoracic cage was involved in six patients (11%), alterations of spinal profile were observed in 37 patients (68%) and 15 controls (28%; chi(2) = 16.3; P < 0.0001), and increased L2 vertebra diameters were observed in 34 patients (63%) and none of the controls (chi(2) = 46.7; P < 0.0001). Narrowing and widening of L2-L3 disk space were found in 20 (37%) and seven (13%) patients, respectively. Features of diffuse idiopathic skeletal hyperostosis (DISH) were found in 11 patients (20%) and none of the controls (chi(2) = 10.1; P < 0.001). Disease duration was correlated with vertebral body height (P = 0.001) or intervertebral space height (P = 0.02), and lumbar mobility with thorax expansion (P = 0.004); DISH severity was correlated with basal (P = 0.04) and peak (P = 0.01) glucose levels after glucose load. In conclusion, chronic GH and IGF-I excess typically affects the axial skeleton with development of severe alterations of spine morphology and function until features of DISH occur. An early diagnosis of acromegaly is mandatory to reduce the severity of spine abnormalities as they were significantly higher in patients with longer disease duration.

Acromegaly↗

PubMed2004

The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure.

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.

Adult↗

PubMed2003

Reversal of acromegalic cardiomyopathy in young but not in middle-aged patients after 12 months of treatment with the depot long-acting somatostatin analogue octreotide.

BACKGROUND: Cardiovascular disease is the most frequent cause of death of patients with acromegaly. AIM: To investigate whether young patients with a presumed short disease duration are more likely to reverse the acromegalic cardiomyopathy than older patients with longer disease duration. DESIGN: An open prospective design. PATIENTS: Ten young (aged < 40 years), and 12 middle-aged (41-59 years) patients with active acromegaly well controlled after 12 months of treatment with the depot formulation of octreotide (OCT-LAR); 22 sex- and age-matched healthy subjects as controls. METHODS: Left ventricular (LV) mass (LVM) by echocardiography and performance by equilibrium radionuclide angiography were measured before and after 12 months of OCT-LAR treatment. RESULTS: At study entry, none of the controls and 14 patients (63.4%) of whom six were young (chi2 = 17.7; P < 0.0001) had LV hypertrophy (LVH); none of the controls and four patients of whom one was young had insufficient LV ejection fraction (LVEF) at rest (< 50%); one control and 13 patients (59.1%) of whom five were young (chi2 = 12.7; P < 0.0001) had inadequate LVEF at peak exercise (deltaLVEF; < 5% increase of baseline). After 12 months, no change in haemodynamic and diastolic parameters was observed in both groups, except for a significant decrease in heart rate at peak exercise in young patients (P < 0.0001). The LVM index decreased significantly in both young (124.4 +/- 5.8 vs. 103.4 +/- 3.9 g/m2; P = 0.01) and middle-aged patients (140.9 +/- 7.9 vs. 117.8 +/- 6.6 g/m2; P = 0.03). LVH disappeared in 10 of 14 patients (71.4%): all six young and four of eight middle-aged patients (50%). LVEF at rest and at peak exercise increased significantly in both groups but deltaLVEF increased significantly only in young patients (1.5 +/- 2.9 vs. 13.7 +/- 5.2%, P = 0.04); it normalized in nine of 13 patients (69.2%), four of five young (80%) and four of eight middle-aged patients (50%). Exercise capacity (82.5 +/- 5.3 vs. 110.0 +/- 5.5 W, P = 0.005) and duration (7.3 +/- 0.3 vs. 9.9 +/- 0.4 min, P = 0.0003) also increased only in young patients. CONCLUSIONS: The acromegalic cardiomyopathy is reversed in most young patients with short disease duration and achieving disease control after OCT-LAR treatment for 12 months, indicating that early diagnosis and effective treatment are essential.

Acromegaly↗

PubMed2003

High prevalence of cardiac valve disease in acromegaly: an observational, analytical, case-control study.

To characterize mitral and aortic valve abnormalities we performed M-mode, two-dimensional, and pulsed Doppler echocardiography in 42 patients with active acromegaly, 22 patients cured of acromegaly, and 64 controls pair-matched with the patients for sex and age. The overall prevalence of valve abnormalities was higher in both the active patients (86% vs. 24%; P < 0.0001) and the cured patients (73% vs. 9%; P < 0.0001) than in controls. Left ventricular hypertrophy was higher in active (81% vs. 29%; P < 0.0001), but not in cured (41% vs. 14%; P = 0.09) patients than in controls. Cardiac valve abnormalities were associated with left ventricular hypertrophy in both patients and controls, without any difference between them. Conversely, among subjects without left ventricular hypertrophy, mitral and aortic abnormalities were only present in the patients (75% of active and 54% of cured), but not in controls (3% of active controls and 0% of cured controls). In conclusion, patients with active acromegaly and those cured of the disease have a high prevalence of mitral and aortic abnormalities. The persistence of valve disease in patients with cured acromegaly is likely to be correlated with the persistence of left ventricular hypertrophy, which should be carefully and continuously monitored as an aspect of the risk of cardiac dysfunction in these patients.

Acromegaly↗

PubMed2003

Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly.

OBJECTIVE: To evaluate the role of age, gender, duration and control of acromegaly on the reversibility of arthropathy. PATIENTS AND DESIGN: 30 de novo patients with active acromegaly, 30 cured patients and 30 healthy subjects were studied in a tranverse and an open longitudinal study design. METHODS: Shoulder, wrist and knee thickening was measured by ultrasonography at study entry in all 90 subjects and after 12 Months of treatment with octreotide-LAR (OCT-LAR) at a dose of 10-40 mg every 28 days in the 30 de novo patients. RESULTS: Thickness at all joint sites was greater in the active than in the cured patients and controls (P<0.001), and was greater in the cured patients than in the controls (P<0.001). There was no gender difference, but joint thickness was less in the patients with disease duration >10 Years. Age significantly correlated with wrist (r=-0.55; P<0.001), right knee (r=-0.45; P=0.01), and left knee thickness (r=-0.42; P=0.02) in patients with active disease, and with wrist thickness (r=0.88; P<0.0001) in controls. Twelve Months of OCT-LAR treatment led to disease control in 18 patients (60%). There was a decrease in the thickness of the shoulder (15.1+/-3.2%), wrist (20.5+/-3.1%), right knee (22.2+/-3.4%) and left knee (18.2+/-2.8%) in all patients but the reduction in joint thickness at all sites was greater in the patients with controlled disease after OCT-LAR treatment than in the uncontrolled patients (P<0.01). Shoulder and right knee thickening normalized in respectively 11 (61.1%) and 16 (88.9%) well-controlled patients. CONCLUSIONS: Growth hormone and insulin-like growth factor-I (IGF-I) suppression by 12 Months' OCT-LAR treatment is accompanied by a significant decrease in the thickness of both weight-bearing and non-weight-bearing joints (mainly in patients whose disease is controlled) regardless of disease duration. These findings suggest that tIssue hypertrophy in the context of the acromegalic arthropathy can be improved by suppressing IGF-I levels.

Acromegaly↗

PubMed2002

Severe impairment of bone mass and turnover in Cushing's disease: comparison between childhood-onset and adulthood-onset disease.

BACKGROUND: Osteoporosis is an important, frequently unrecognized consequence of hypercortisolism. OBJECTIVE: To evaluate whether the age of onset of hypercortisolism influences its effects on bone mass and turnover. SUBJECTS: 10 with childhood-onset (co) and 18 with adulthood-onset (ao) Cushing's disease (CD); 28 age-, sex- and body mass index (BMI)-matched healthy subjects served as controls. STUDY DESIGN: Open, cross-sectional controlled. MEASUREMENTS: Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC), and urinary N-telopeptides of type I collagen (Ntx) levels. RESULTS: BMD at lumbar spine was significantly lower in all CD patients than in controls (Z score, -2.3 +/- 0.1 vs. -0.2 +/- 0.01; P < 0.001). co-CD and ao-CD patients had similar values of bone mass when expressed as Z score (-2.6 +/- 0.4 vs. -2.1 +/- 0.2; P = 0.27) or as BMD (0.728 +/- 0.03 vs. 0.78 +/- 0.03 g/cm2; P = 0.25). In particular, osteoporosis was observed in 16 patients (57.1%) [eight adolescents (80%) and eight adults (44.4%)] and none of the controls; osteopenia was found in two co-CD patients (20%) and none of the healthy adolescents, 10 ao-CD patients (55.6%) and four healthy adults (14.3%) (chi2 = 7.87, P < 0.01; chi2 = 2.99, P = 0.09, respectively). In co-CD and ao-CD patients, serum OC levels were similar and significantly lower than in controls (P < 0.01); urinary Ntx levels were significantly higher than in controls (P < 0.001) and were significantly higher in co-CD than in ao-CD patients (P < 0.001). No significant correlation was found between urinary cortisol levels, serum cortisol and age and lumbar Z score values, while a significant correlation was found between Ntx levels and disease duration (r = 0.434; P = 0.021) and plasma cortisol (r = 0.440; P = 0.019). CONCLUSIONS: Cushing's disease causes bone loss and abnormalities of bone turnover both in childhood-onset and in adulthood-onset patients. A strict follow-up of bone mass and turnover is mandatory in all patients with Cushing's disease to prevent fractures later in life and specific treatment for bone loss is strongly suggested.

Adolescent↗

PubMed2002

Leptin concentrations in GH deficiency: the effect of GH insensitivity.

Disorders of GH secretion are known to impair the physiological lipostat and to affect the secretion of leptin, a sensitive marker of regional fat accumulation and total body composition. In both children and adults with GH deficiency (GHD), leptin levels are increased proportionately with enhanced adiposity. In GHI, mutations of the GH receptor gene result in a phenotype similar to GHD, with increased adiposity and unfavorable lipid profiles. To examine the impact of different forms of growth disorders on leptin production, we measured leptin levels in 22 GHI patients homozygous for the E180 splice mutation (15 females and 7 males, aged 8-37 yr) and compared results with those obtained in 20 subjects heterozygous for the mutation (11 females and 9 males, aged 7-54), 17 idiopathic GHD patients (6 females and 11 males, aged 3-34), and 44 normal subjects (25 females and 19 males, aged 7-45). After the baseline evaluation, all subjects received two 7-d GH treatments at doses of 0.025 and 0.050 mg/kg x d in random order. Leptin, IGF-I, and IGF-binding protein-3 (IGFBP-3) were assayed by specific immunoassays. IGF-I and IGFBP-3 levels were significantly lower (P < 0.0001) in homozygous GHI and GHD patients compared with either controls or GHI heterozygotes. Circulating leptin levels were significantly higher in homozygous GHI patients than in normal controls (20.7 +/- 4.2 vs. 8.7 +/- 1.4 microg/liter) as well as when compared with heterozygous GHI subjects (14.4 +/- 3.4 microg/liter) and GHD patients (9.8 +/- 1.6 microg/liter; P < 0.01). Similar results were obtained when leptin was normalized for body mass index. When subjects were subgrouped by gender, leptin levels were significantly higher (P < 0.05) in GHI females than in females of all other groups and were significantly increased in GHD males (P < 0.01 vs. control males). Within the study groups, females had significantly higher leptin levels than males in controls (12.7 +/- 2 vs. 3.3 +/- 1 microg/liter; P < 0.001) and homozygous GHI patients (28.7 +/- 5.3 vs. 6.9 +/- 2.3 microg/liter; P < 0.05), but not in heterozygous GHI (20.1 +/- 5.4 vs. 7.3 +/- 2.4 microg/liter; P < 0.06) and GHD (10.9 +/- 2.6 vs. 9.2 +/- 2.1 microg/liter) patients. By multivariate analysis, log-normalized leptin levels were best predicted by gender and body mass index in homozygous GHI patients as well as in normal subjects. During the 1-wk courses of GH therapy, serum IGF-I and IGFBP-3 levels significantly increased (P < 0.0001) in GHD patients, heterozygous GHI patients, and control subjects at both GH doses. Inversely, leptin levels did not change significantly during either course of GH administration in the groups examined. These data demonstrate that leptin is increased in patients affected with long-standing homozygous GHI, probably reflecting abnormalities of body composition and metabolism typical of this condition.

Adolescent↗