Biomedical subjects

P Marzullo

Publications and source records attributed to P Marzullo.

At least 19 recordsLinked to original sources

PubMed1998

Prostatic hyperplasia: an unknown feature of acromegaly.

This study was designed to investigate whether GH and insulin-like growth factor I (IGF-I) excess could lead to the development of benign prostatic hyperplasia and/or prostatic carcinoma. Prostatic diameters and volume as well as the occurrence of prostatic diseases were studied by ultrasonography in 10 untreated acromegalic patients less than 40 yr of age and 10 age- and body mass index-matched healthy males. Serum GH, IGF-I, PRL, testosterone, dihydrotestosterone, prostate-specific antigen, and prostatic acid phosphatase levels were assessed. All patients had secondary hypogonadism, as diagnosed by low testosterone levels, and 4 of 10 patients had hyperprolactinemia. After 1 yr of treatment with octreotide (0.3-0.6 mg/day), ultrasound scan and hormone parameters were repeated. The 4 hyperprolactinemic acromegalics were treated with octreotide and cabergoline (1-2 mg/week) to suppress PRL levels. Symptoms due to prostatic, seminal vesicle, and/or urethral disorders or obstruction were experienced by neither acromegalics nor controls. Digital rectal examination revealed no occurrence of prostatic nodules or other abnormalities. Compared to healthy subjects, a remarkable increase in transversal prostatic diameter and volume was observed in acromegalics. In healthy subjects, prostate volume ranged from 15.1-21.8 mL, whereas in acromegalics it ranged from 21.8-41.8 mL. Similarly, an increased median lobe was observed. In fact, the transitional zone diameter was just detectable in 5 of 10 controls, whereas it was measurable in all acromegalics (18 +/- 1.2 vs. 2.8 +/- 0.3 mm; P < 0.001). The prevalence of periurethral calcifications was more than doubled in acromegalics (50%) compared to that in controls (20%). Treatment with octreotide for 1 yr produced normalization of circulating GH and IGF-I levels in 7 of 10 patients. In these 7 patients, ultrasound evaluation showed a significant reduction of the antero-posterior diameter (26.1 +/- 1 vs. 28.9 +/- 1.6 mm; P < 0.01), the transversal diameter (44.9 +/- 2 vs. 48 +/- 2 mm; P < 0.01), and the cranio-caudal diameter (36.5 +/- 1 vs. 41.3 +/- 1.5 mm; P < 0.001), whereas the transitional zone diameter was unchanged (16.4 +/- 1.5 vs. 17.4 +/- 1.7 mm). As a consequence, a significant decrease in prostate volume was recorded (22.1 +/- 1.1 vs. 29.8 +/- 2.5 mL; P < 0.001). Prostate volume increased in 2 of the 3 patients who did not achieve normalization of GH and IGF-I after octreotide treatment. Finally, after treatment, serum testosterone levels were significantly increased (from 1.5 +/- 0.3 to 3.5 +/- 0.3 microg/L), whereas dihydrotestosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, 17beta-estradiol, prostate-specific antigen, and prostatic acid phosphatase were unchanged. Serum PRL levels were suppressed after cabergoline treatment in all 4 hyperprolactinemic patients throughout the study period. In conclusion, prostate enlargement occurs in young acromegalics with a higher than expected prevalence of micro- and macrocalcifications. This suggests that a careful prostate screening should be included in the work-up and follow-up of acromegalic males.

Acromegaly↗

PubMed1998

Reversibility of joint thickening in acromegalic patients: an ultrasonography study.

Axial and peripheral arthropathy affects the majority of patients with acromegaly, being a leading cause of morbidity and functional disability. Treatment with octreotide (OCT) improves symptoms and signs of acromegalic arthropathy, but objective detection of structural changes in bone and cartilage has not been reported to date. This open prospective study was designed to evaluate the effect of a long term treatment with OCT on acromegalic arthropathy assessed by ultrasonography examination. Articular cartilage thicknesses of shoulder, wrist, and knee as well as sizes of heel tendons were measured in 30 acromegalic patients (18 with active and 12 with inactive disease) and 18 sex-, age-, and body mass index-matched healthy subjects. The thicknesses of shoulder, wrists and knees articular cartilages and that of heel tendons were significantly increased in patients with active acromegaly compared to those in healthy subjects (P < 0.01). With the exception of shoulder cartilage, significant increases in wrist and knee cartilages (P < 0.01) and right and left heel tendon sizes (P < 0.05) were found in patients with active compared to those with inactive disease. After 6 months of OCT treatment, a significant decrease in shoulder, wrist, and left knee articular cartilage was found (P < 0.001). No significant change was recorded in right knee cartilage or heel tendon size. The decrease in thickness of shoulder and wrist cartilages was more pronounced than that measured at the level of left knee (26.3 +/- 3.3% and 27.2 +/- 4.2% vs. 14.2 +/- 4.2%, respectively; P < 0.05). Ultrasonography is able to reveal articular involvement in acromegalic patients and may be useful to monitor the effect of treatment.

Acromegaly↗

PubMed1998

Perfusion-contraction mismatch during inotropic stimulation in hibernating myocardium.

UNLABELLED: The aims of this study were to assess the value of dobutamine echocardiography in identifying myocardial hibernation versus stunning and to elucidate the underlying pathophysiological mechanism of the contractile impairment. METHODS: Twenty-one patients with isolated stenosis of the left anterior descending artery were evaluated 1 mo after thrombolysed acute anterior infarction. Regional function and blood flow were measured using echocardiography and PET at rest and during dobutamine administration (10 microg/kg/min). RESULTS: Defined by [18F]fluorodeoxyglucose uptake, 36 of 102 dyssynergic segments were necrotic, and 66 were viable. The latter segments were subdivided according to their [13N]ammonia flow distribution: 30 hibernating regions with perfusion defects (flow of <80% of maximum) and 36 stunned areas with preserved resting perfusion (flow of > or =80% of maximum). Resting flows were similar in necrosis and hibernation (0.43 +/- 0.18 versus 0.47 +/- 0.16 ml x min(-1) x g(-1); not significant), and both resting values were lower than those seen in stunning (0.79 +/- 0.24; p < 0.05). Flow response to dobutamine was markedly reduced in necrosis (dobutamine/resting flow = 1.16 +/- 0.27), whereas it was maintained in hibernation (1.65 +/- 0.54) and stunning (1.42 +/- 0.57). Dobutamine improved function in a higher number of stunned (55%) than hibernating (16%) or necrotic (11%) segments. CONCLUSION: Dobutamine improves function mainly in stunned myocardium and does not reliably identify hibernation. The lack of functional response in hibernation is not related to an exhausted vasodilating capacity.

Cardiotonic Agents↗

PubMed1997

Flow-function relation in patients with chronic coronary artery disease and reduced regional function. A positron emission tomographic and two-dimensional echocardiographic study with coronary vasodilator stress.

OBJECTIVES: We sought to elucidate the flow-function relation in chronic postischemic dysfunction during vasodilator stress. BACKGROUND: In patients with ischemia and regional dysfunction, stress echocardiography can elicit three responses in the dysfunctioning segments: no change, improvement or worsening. The physiology underlying these responses is unclear. METHODS: Seventeen patients with ischemia and left ventricular dysfunction underwent evaluation of regional function by two-dimensional echocardiography and myocardial blood flow by positron emission tomography and 13N-ammonia. Flow (ml/min per g) and function (regional wall motion score [RWMS] from 1 = normal to 4 = dyskinetic) were evaluated both at rest and after dipyridamole (0.56 mg/kg body weight over 4 min). RESULTS: In 45 normal segments, rest to dipyridamole flow increased from 0.83 +/- 0.22 (mean +/- 1 SD) to 1.87 +/- 0.90 (p < 0.01) with a hyperkinetic contraction pattern. Among dysfunctioning segments, responders (n = 11) showed an upsloping flow-function curve during stress (i.e., increased function [RWMS rest 2.5 +/- 0.5 vs. dipyridamole 1.2 +/- 0.4] and increased flow [rest 0.69 +/- 0.30 vs. dipyridamole 1.89 +/- 1.43, p < 0.01]); nonresponders (n = 20) had a flat flow-function curve during dipyridamole (i.e., fixed function [RWMS rest and dipyridamole 2.6 +/- 0.5] and no flow increase [rest 0.64 +/- 0.24 vs. dipyridamole 0.87 +/- 0.51, p = NS): Ischemic segments (n = 9) exhibited a downsloping flow-function curve during dipyridamole (i.e., worsened function [RWMS rest 2 +/- 0.5, dipyridamole 3.1 +/- 0.6] and no significant flow change [rest 0.67 +/- 0.29 vs. dipyridamole 0.79 +/- 0.23, p = NS]). CONCLUSIONS: Myocardial segments with rest dysfunction and a contractile reserve elicitable by a vasodilator stress more often exhibit residual flow reserve, whereas segments with a fixed or worsening mechanical response during stress show a flat flow response.

Aged↗

PubMed1997

Increased prevalence of colonic polyps and altered lymphocyte subset pattern in the colonic lamina propria in acromegaly.

OBJECTIVE: The balance of evidence suggests that acromegaly is a risk factor for colonic neoplasia. We have evaluated the prevalence of colonic polyps in acromegalics from Southern Italy and characterized the lymphocyte subsets in the colonic lamina propria in order to analyze differences in the colonic immunological environment. DESIGN: All the patients and controls were submitted to pancolonoscopy. Ten per-endoscopic biopsies of the intestinal mucosa surrounding polyps were carried out to evaluate lymphocyte subsets. PATIENTS: Fifty acromegalics and 318 sex- and age-matched controls entered this study. Colonic lamina propria lymphocyte subsets were studied in 34 patients and 34 controls. RESULTS: Colonic polyps were resected in 23 acromegalics (46%) and 42 controls (13.2%; P < 0.0001); hyperplastic polyps were found in 24% and 6.3%, adenomatous polyps in 22 and 6.9%, (P < 0.01), adenocarcinoma in 2 and 1.2% while synchronous polyps occurred in 18% and 2.5% (P < 0.01), respectively. The number of polyps was significantly correlated with age both in acromegalics (r = 0.422, P < 0.005) and in controls (r = 0.865, P < 0.001). However, polyp prevalence was greater in patients aged below 40 yrs (r.r = 1.9) and in patients with two or more skin tags (r.r = 1.2). A significant decrease of CD20, CD19, CD16, gamma/delta, CD4@leu8- and increase of CD3 and CD4+/leu8+ was found in the lamina propria lymphocyte subsets. CONCLUSIONS: The results of this study confirm that acromegalics are at increased risk of colonic polyps compared to the healthy population. The increased prevalence of premalignant polyps, namely the adenomatous type, suggests that acromegalics should undergo a careful screening and follow-up by pancolonoscopy. An impairment of mucosal immune surveillance seems to exist in acromegaly although a causal effect in the polyp formation cannot be ruled out.

Acromegaly↗

PubMed1997

Effect of growth hormone on cardiac function.

At present, there is a growing body of evidence implicating growth hormone (GH) and/or insulin-like growth factor-I (IGF-I) in the intricate cascade of events connected with the regulation of heart development and hypertrophy. In addition, advanced clinical manifestations of abnormal GH levels almost always include impaired cardiac function, which may reduce life expectancy. This finding is related both to a primary impairment of heart structure and function and to metabolic changes such as hyperlipidaemia, increased body fat and premature atherosclerosis. Acromegalic cardiomyopathy is better correlated with disease duration than with GH or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often result in increased right and left ventricular mass concentric hypertrophy. Conversely, patients with childhood or adult-onset GH deficiency (GHD) have a reduced left ventricular mass (LVM) and ejection fraction (EF) and the indices of left ventricular systolic function remained markedly depressed during exercise. Cardiac function is reported to improve during octreotide and GH replacement treatment in acromegaly and GHD, respectively. The evidence that GH can increase cardiac mass suggests its use in the treatment of idiopathic dilated cardiomyopathy. In a recent study on such patients, the administration of recombinant GH (rGH) was demonstrated to increase myocardial mass and reduce the size of the left ventricular chamber, resulting in improved haemodynamics, myocardial energy metabolism and clinical status.

Acromegaly↗

PubMed1997

Effect of octreotide pretreatment on surgical outcome in acromegaly.

Pretreatment with octreotide (OCT) in acromegaly has been reported to improve surgical outcome. The objective of this study was to analyze retrospectively the effects of a 3- to 6-month presurgical treatment with OCT in acromegalics focusing on electrocardiographic (ECG) records, blood pressure levels, glucose and lipid profile, tumor size and consistency, easy tumor removal at surgery, and morphological findings at pathology. Fifty-nine patients with acromegaly who were undergoing surgical treatment were studied randomly before surgery; 37 patients were untreated, and 22 were treated with OCT at doses ranging 150-600 micrograms/day for 3-6 months. At study entry, untreated and OCT-treated patients had similar circulating GH and insulin-like growth factor I (IGF-I), glucose, and cholesterol levels as well as prevalence of overt diabetes mellitus, hypertension, and ECG abnormalities. In untreated and OCT-treated patients, respectively, radiological imaging documented microadenoma in 0 and 1, intrasellar macroadenoma in 10 and 6, intra- and suprasellar macroadenoma in 18 and 11, invasive macroadenoma in 9 and 4 patients. Before surgery, serum GH and IGF-I levels significantly decreased in the 22 OCT-treated acromegalics, and in 5 of them, a significant shrinkage was documented. ECG abnormalities disappeared in 7 of 11 (63.6%) OCT-treated patients. In 3 of the 7 patients with diabetes mellitus, treatment with OCT together with low carbohydrate intake normalized blood glucose levels, whereas in 2 patients, insulin could be replaced by oral antidiabetics, and in 2 patients, the insulin dose was reduced. Presurgical blood glucose, total cholesterol and triglyceride levels, as well as systolic (145.2 +/- 3.4 vs. 132.9 +/- 2.5 mm Hg; P < 0.01) and diastolic (94.3 +/- 1.7 vs. 84.3 +/- 1.6 mm Hg; P < 0.001) blood pressure levels were significantly higher in untreated than in OCT-treated patients. Two weeks after surgery, circulating GH and IGF-I levels were normalized in 11 untreated (29.7%) and 12 OCT-treated (54.5%) patients (P < 0.005, by chi 2 test). Macroscopically, no difference was found between untreated and OCT-treated adenomas, whereas at pathology, a significant increases in cellular atypia (31.6% vs. 19.2%; P < 0.05) was found in OCT-treated adenomas. One patients in the untreated group died from cardiorespiratory arrest during the early postoperative period. Finally, the average duration of hospitalization after operation was longer in untreated than in OCT-treated patients (8.6 +/- 0.7 vs. 5.6 +/- 0.5 days). We conclude that a 3- to 6-month treatment with OCT before surgery for GH-secreting adenoma improved clinical conditions and surgical outcome and reduced the duration of hospitalization after operation.

Acromegaly↗

PubMed1997

Effect of different dopaminergic agents in the treatment of acromegaly.

Medical treatment of acromegaly with dopamine agonists possesses 2 main advantages: the oral administration and the low costs. In this study, we reported on the results of chronic treatments with quinagolide (CV 205-502), cabergoline (CAB) and long-acting depot preparation of bromocriptine (BRC-LAR) in 34 acromegalics. Patients were divided into three groups on the basis of different treatment: CV 205-502 given to 16 patients at the dose of 0.3-0.6 mg/day for 6 months; CAB given to 11 patients at the dose of 1.0-2.0 mg weekly for 6 months; and BRC-LAR injected into 7 patients at the dose of 100 mg/month for 6-12 months. Basal and oral glucose tolerance test-stimulated serum GH levels, basal and TRH-stimulated PRL levels, plasma insulin-like growth factor I (IGF-I) levels, computed tomography scan, and/or magnetic resonance imaging were assessed before and quarterly during treatments. The chronic administration of CV 205-502, CAB, and BRC-LAR caused a significant decrease of circulating GH, IGF-I, and PRL levels (P < 0.005). Normalization of circulating GH and IGF-I levels was obtained in 7 of 16 (43.8%) patients treated with CV 205-502. Serum GH response to oral glucose tolerance test (oGTT) significantly improved (P < 0.005), and PRL levels were significantly suppressed during treatments. No correlation was found between basal and TRH-stimulated PRL levels and GH suppression during different therapies. Immunohistochemical staining revealed 19 GH-positive and 10 GH + PRL-positive adenomas. A significant association was found between GH/PRL staining and responsiveness to chronic treatments (chi 2 = 7.985, P < 0.005). Three patients had significant adenoma shrinkage. Slight nausea and hypotension which spontaneously disappeared within therapy progression, were referred by 5/16 patients during CV 205-502 and 2/7 during BRC-LAR. The results of this study indicate that CAB and BRC-LAR cannot be considered as useful medical approaches for acromegalics, whereas CV 205-502 normalized circulating GH and IGF-I levels in 47.8% of patients.

Acromegaly↗

PubMed1997

Is growth hormone bad for your heart? Cardiovascular impact of GH deficiency and of acromegaly.

At present, there is growing evidence implicating GH and/or IGF-I in the intricate cascade of events connected with the regulation of heart development and hypertrophy. Moreover, GH excess and/or deficiency have been shown to include in their advanced clinical manifestations almost always an impaired cardiac function, which may reduce life expectancy. This finding is related both to a primitive impairment of heart structure and function and to metabolic changes such as hyperlipidemia, increase of body fat and premature atherosclerosis. Patients with childhood or adulthood-onset GH deficiency have a reduced left ventricular mass and ejection fraction and the indexes of left ventricular systolic function remain markedly depressed during exercise. Conversely, in acromegaly the cardiac enlargement, which is disproportionate to the increase in size of other internal body organs, has been a rather uniform finding. The severity of the acromegalic cardiomyopathy was reported to be correlated better with the disease duration than with circulating GH and/or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often results in concentric hypertrophy of both ventricles. The treatment of GH deficiency and excess improved cardiac function. Interestingly, based on the evidence that GH increases cardiac mass, recombinant GH was administered to patients with idiopathic dilated cardiomyopathy. It increased the myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement of hemodynamics, myocardial energy metabolism and clinical status. These promising results open new perspectives for the use of GH in heart failure.

Acromegaly↗

PubMed1996

Cardiovascular aspects in acromegaly: effects of treatment.

Patients with acromegaly have significant morbidity and mortality, associated with cardiovascular disease. Acromegaly is often complicated by other diseases such as diabetes mellitus, hypertension, and coronary artery disease, so the existence of acromegalic cardiomyopathy remains uncertain. Cardiac performance was investigated in patients with uncomplicated acromegaly. A subgroup of hypertensive acromegalics was also studied. In addition, the effects of chronic octreotide therapy or surgery on cardiac structure and function in acromegaly were studied. Twenty-six patients and 15 healthy controls underwent gated blood-pool cardiac scintigraphy and echocardiography at rest and during exercise. Echocardiography was repeated after 6 months of octreotide therapy (n = 11). Cardiac scintigraphy was repeated after 12 and 24 months of octreotide therapy (n = 10) or 12 to 24 months after surgery (n = 8). ECG, blood pressure, and heart rate were monitored during cardiac scintigraphy. Left ventricular mass (LVM) was calculated from the findings of the echocardiography. Serum growth hormone (GH) levels and plasma insulin-like growth factor-1 (IGF-1) levels were monitored. LVM index was significantly higher (P < .003) in acromegalics than controls and in hypertensive acromegalics than normotensives, but all other indices of cardiac function were similar. Chronic octreotide decreased GH and IGF-1 levels and improved the structural abnormalities as measured by echocardiography. Chronic octreotide or surgery did not alter cardiac function parameters. Thus, important changes in cardiac structure and function occur in uncomplicated acromegaly, and improvements can be demonstrated after chronic octreotide therapy. Heart disease in acromegaly appears to be secondary to high circulating GH levels.

Acromegaly↗

PubMed1996

Vasopressin levels in Cushing's disease: inferior petrosal sinus assay, response to corticotrophin-releasing hormone and comparison with patients without Cushing's disease.

BACKGROUND: Higher vasopressin (AVP) levels have been found in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one, suggesting a potential pathogenetic role of AVP in Cushing's disease. DESIGN: In order to investigate AVP release, plasma ACTH and AVP concentrations were assayed in the inferior petrosal sinuses and in the peripheral blood before and after CRH stimulation. PATIENTS: Twenty patients with Cushing's disease and 12 with other pituitary diseases were subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Ten healthy sex and age-matched subjects served as control for peripheral AVP values. MEASUREMENTS: Plasma ACTH concentrations were measured by RIA using commercial kits. Plasma AVP concentrations were assayed by RIA in acetone extracts of 1-2 ml plasma. RESULTS: Plasma AVP levels in the inferior petrosal sinuses were significantly higher in Cushing's disease than in patients with other pituitary diseases (P < 0.05) and in both groups AVP levels were higher in the inferior petrosal sinuses than in the peripheral blood (P < 0.01). In Cushing's disease, ACTH, but not AVP levels, were higher in the inferior petrosal sinus ipsilateral to the adenoma than in the contralateral one (P < 0.01). Seven patients showed a significant ACTH and AVP increase (greater than 50% of baseline) after CRH stimulation in the inferior petrosal sinus ipsilateral to the adenoma. Conversely, no change was found in AVP levels in the remaining 13 patients. When AVP values were analyzed in relation to surgical cure, higher inferior petrosal sinus levels (P < 0.05) were found in 6 patients with poor outcome: 4 of these patients had significantly decreased plasma AVP concentrations (by 32-43% of baseline) after CRH bolus. Peripheral AVP levels were similar in healthy subjects and patients with Cushing's disease whereas they were significantly reduced in patients with other pituitary diseases (P < 0.002). CONCLUSIONS: The results of this study show that patients with Cushing's disease and poor surgical outcome had the highest AVP levels in our series. CRH administration caused different effects on AVP levels: it increased them in 35% of patients whereas there was no response in the remaining patients. On the basis of these findings, it is hypothesized that AVP might be involved in the persistence of ACTH hypersecretion in a subset of patients poorly responsive to surgery.

Adenoma↗

PubMed1996

Cyclic variation in myocardial gray level as a marker of viability in man. A videodensitometric study.

Experimental and human studies have shown that a preserved cyclic (diastolic-to-systolic) echoreflectivity variation, assessed by radiofrequency sampling of backscatter signal with non-commercially available prototypes, identifies viability in a myocardial segment with a resting dyssynergy. The objective of this study was to assess whether a videodensitometric analysis of myocardial gray level variation during cardiac cycle might identify viable but dyssynergic myocardium in a clinical setting. Thirty-four patients with a resting dyssynergy (akinesis in 26, marked hypokinesis in eight) in the septum and/or inferno-posterior wall were evaluated by videodensitometry. All echo studies were performed with commercially available instruments in the long axis parasternal view, with quantitative analysis of gray levels performed off-line on digitized images. Segmental wall motion was assessed with a 16 segment model of the left ventricle, each scored from 1, normal, to 4, dyskinetic. A follow-up echo study was obtained in all patients > 4 weeks after successful revascularization (in 22 by angioplasty, in 12 by bypass surgery). Two groups of segments were identified: 18 viable segments (contractile improvement of 1 grade or more in resting function after revascularization); 16 necrotic segments (no contractile improvement in resting function after revascularization). The % cyclic variation was higher in viable vs necrotic segments (26 +/- 16 vs 1 +/- 13%, P < 0.01), in spite of similar % systolic thickening (5 +/- 5 vs 4 +/- 6%, P = ns) and end-diastolic thickness (10 +/- 2 vs 10 +/- 2 mm, P = ns). When individual patient analysis was performed, % cyclic variation was below the 95% confidence limits obtained from normal control regions (n = 34; % cyclic variation = 38 +/- 14) in two out of 18 viable and in 14 out of 16 necrotic segments. A cut-off of > or = 9.4% cyclic variations in a dyssynergic segment yielded 89% sensitivity and 88% specificity for predicting functional recovery following successful revascularization. In conclusion, viable dyssynergic myocardial segments show a cyclic gray level variation at rest, which can be detected by simple videodensitometric analysis, much less technologically demanding than radiofrequency backscatter evaluation.

Cell Survival↗

PubMed1996

Corticotropin-releasing hormone administration increases alpha-melanocyte-stimulating hormone levels in the inferior petrosal sinuses in a subset of patients with Cushing's disease.

The effect of corticotropin (ACTH)-releasing hormone (CRH) administration on alpha-melanocyte-stimulating hormone (alpha-MSH), ACTH and beta-endorphin (beta-EPH) was evaluated in the inferior petrosal sinuses and in the periphery of 30 patients affected with Cushing's disease subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Baseline PRL levels, sensitivity to dexamethasone and surgery outcome were compared to alpha-MSH response. CRH bolus did not modify alpha-MSH concentrations either in the inferior petrosal sinuses or in the periphery in the 30 patients considered as a whole. In 7 of 30 patients, however, a greater than 50% increase over baseline alpha-MSH levels (from 50 to 115.5%) was recorded in the inferior petrosal sinus ipsilateral to the adenoma (from 42.9 +/- 1.7 to 76.4 +/- 4.6 ng/l; p < 0.001), whereas no change was found in the contralateral inferior petrosal sinus or in the periphery. Conversely, as expected, ACTH and beta-ELI significantly increased in all the patients after CRH both in the inferior petrosal sinuses and in the periphery (particularly in the inferior petrosal sinus ipsilateral to the adenoma). No difference in sensitivity to dexamethasone (urinary cortisol percent decrease: 66.4 +/- 4.9 vs. 67.8 +/- 3.4) and surgery outcome (chi 2 test: p = 0.7) was found between patients with alpha-MSH response to CRH and patients without such a response. By contrast, baseline PRL levels, although being normal in both groups, were significantly higher in patients with alpha-MSH response to CRH (18.1 +/- 1.6 vs. 10.1 +/- 0.7 micrograms/l; p < 0.001). In conclusion, the results of the present study suggest that in a subset of patients with Cushing's disease (23.3% of our series) alpha-MSH may be released after the administration of CRH together with ACTH and beta-EPH by adenomatous corticotrophs. In this subset of patients, PRL levels may be in the upper normal range.

Adolescent↗

PubMed1996

Prediction of efficacy of octreotide therapy in patients with acromegaly.

Octreotide (OCT) administration provides a biochemical cure in most acromegalic patients. This drug, however, causes several side effects and is very expensive. Acute testing has been reported to predict chronic responsiveness to OCT administration. The aim of this retrospective study was to evaluate which test, if any, among acute testing, short-term (1 month) administration, and 111In-pentetreotide (111In-DTPA-Phe-D-OCT) scintigraphy, is best in predicting response to long-term OCT treatment. Sixty-eight patients with active acromegaly were studied. An acute test (100 micrograms sc OCT) was performed as usual: a GH decrease greater than or equal to 50% of baseline was considered a positive response. GH and insulin-like growth factor I (IGF-I) were then assayed after 1 month (300 micrograms daily) and 3 months (150-600 micrograms daily) of OCT administration. GH was considered normalized when decreased less than or equal to 5 micrograms/L. Twenty-six of 68 patients were subjected to 111In-pentetreotide scintigraphy. Linear correlation analysis of the results was performed. Sensitivity, specificity, and positive and negative predictive values of the three tests were also calculated. Thirty-eight of 68 patients (56%) responded to the acute test. Among these 38 patients, 20 experienced normalization of GH and IGF-I levels during long-term therapy, as did 8 patients who did not respond to the acute test. No significant correlation was found between GH percent decrease during acute testing and long-term therapy (r = 0.11). Seven patients who responded to the acute test and 2 who did not respond had adenoma shrinkage during therapy. Conversely, GH and IGF-I decrease after short-term treatment significantly correlated with long-term treatment (r = 0.76 and 0.64, P < 0.01). Of the 26 patients subjected to 111In-pentetreotide scintigraphy, 13 had significant tracer uptake: normalization of GH and IGF-I was obtained in 8 patients. A significant correlation was found between tracer uptake and GH/IGF-I inhibition after 3 months of therapy (r = 0.6; P < 0.05). In the whole population, the positive predictive value of acute testing, short-term OCT administration, and 111In-penetreotide scintigraphy was 53%, 70%, and 73%, respectively, when the GH normalization (< 5 micrograms/L) after 3 months of therapy was considered. Moreover, 111-In-pentetreotide scintigraphy had the highest specificity (100% in patients with baseline GH values below 50 micrograms/L) compared with that of acute testing and short-term OCT administration. The acute test cannot be considered as a valuable index to identify patients' responsiveness to long-term OCT therapy, but it can be useful to test tolerability. By contrast, 1 month of OCT administration or the in vivo imaging of somatostatin receptors by 111-In-pentetreotide might better indicate the patients who might effectively benefit from this treatment.

Acromegaly↗

PubMed1996

Thallium-201 reverse redistribution at reinjection imaging correlated with coronary lesion, wall motion abnormality and tissue viability.

UNLABELLED: Previous studies based on standard stress-redistribution 201TI scintigraphy provided conflicting results about the clinical significance 201Tl reverse redistribution. Recent observations indicate that the majority of these defects normalize following reinjection reflecting viable myocardium. METHODS: In this study, the meaning of reverse redistribution occurring at reinjection imaging, its relation to standard 4-hr redistribution, coronary lesion, abnormal wall motion and tissue viability were assessed. A region with normal activity in the stress image was considered as having reverse redistribution if 201Tl activity at reinjection imaging was definitely abnormal with a decrease in relative tracer uptake >15% of the peak. From a series of 270 patients, 29 showed reverse redistribution. Of these 29 patients, 27 had evidence of previous myocardial infarction. Coronary lesions were detected in all but 1 patient. Average ejection fraction was 0.38 +/- 0.11. RESULTS: On a segmental basis, 50/377 regions showed the pattern of reverse redistribution. A significant coronary lesion (> or = 50%) was found in 78% of these regions; occlusion rate was 50%, and collateral circulation was found in 35% of occluded vessels. Hypokinesis or akinesis was present in 72% of segments. Tissue viability, defined as an uptake >55% of the peak, was found in 44% of these segments. The 50 segments showing reverse redistribution were divided into two groups according to an abnormal uptake also at 4-hr redistribution (group 1, 25 segments) or appearing only following reinjection (group 2,25 segments). Despite segments of group 1 showing a higher degree of coronary stenosis (80 +/- 32 versus 59 +/- 43%, p < 0.01), a similar rate of coronary occlusion, ventricular dysfunction and maintained viability was found in the two groups. CONCLUSION: Reverse redistribution in chronic coronary artery disease is frequently associated with significant coronary lesion, collateral-dependent dysfunctioning myocardium and preserved tissue viability. The occurrence of reverse redistribution following reinjection expands the indication for viability imaging to all patients with known coronary artery disease and regional wall motion abnormalities who undergo diagnostic and prognostic 201TI scintigraphy.

Coronary Angiography↗

PubMed1995

Microvascular dysfunction in collateral-dependent myocardium.

OBJECTIVES: The aim of this study was to evaluate myocardial blood flow regulation in collateral-dependent myocardium of patients with coronary artery disease. BACKGROUND: Despite great clinical relevance, perfusion correlates of collateral circulation in humans have rarely been estimated by quantitative methods at rest and during stress. METHODS: Nineteen patients with angina and isolated occlusion of the left anterior descending (n = 14) or left circumflex (n = 5) coronary artery were evaluated. Using positron emission tomography and nitrogen-13 ammonia, we obtained flow measurements at baseline, during atrial pacing-induced tachycardia and after intravenous administration of dipyridamole (0.56 mg/kg body weight over 4 min). Flow values in collateral-dependent and remote areas were compared with values in 13 normal subjects. RESULTS: Flow at rest was similar in collateralized and remote myocardium (0.61 +/- 0.11 vs. 0.63 +/- 0.17 ml/min per g, mean +/- 1 SD), and both values were lower than normal (1.00 +/- 0.20 ml/min per g, p < 0.01). During pacing, blood flow increased to 0.83 +/- 0.25 and 1.11 +/- 0.39 ml/min per g in collateral-dependent and remote areas, respectively (p < 0.05 vs. baseline); both values were lower than normal (1.86 +/- 0.61 ml/min per g, p < 0.01). Dipyridamole induced a further increase in perfusion in remote areas (1.36 +/- 0.57 ml/min per g, p < 0.01 vs. pacing) but not in collateral-dependent regions (0.93 +/- 0.37 ml/min per g, p = NS vs. pacing); again, both values were lower (p < 0.01) than normal (3.46 +/- 0.78 ml/min per g). Dipyridamole flow in collateral-dependent myocardium was slightly lower in patients with poorly developed than in those with well developed collateral channels (0.75 +/- 0.29 vs. 1.06 +/- 0.38 ml/min per g, respectively, p = 0.06); however, the former showed higher flow inhomogeneity (collateral/control flow ratio 0.58 +/- 0.10 vs. 0.81 +/- 0.22, respectively, p < 0.02). A linear direct correlation was observed between flow reserve of collateral-dependent and remote regions (r = 0.83, p < 0.01). CONCLUSIONS: Despite rest hypoperfusion, collateral-dependent myocardium maintains a vasodilator reserve that is almost fully utilized during increases in oxygen consumption. A global microvascular disorder might hamper adaptation to chronic coronary occlusion.

Adult↗

PubMed1995

Residual coronary reserve identifies segmental viability in patients with wall motion abnormalities.

OBJECTIVES: The aim of this study was to determine whether the presence of residual coronary reserve can in itself identify viable segments. BACKGROUND: Experimental data suggest that despite hypoperfusion at rest, viable myocardium may exhibit persistence of coronary reserve. Preliminary observations in patients show that in basally dyssynergic areas, a residual vasodilator capability is present despite hypoperfusion at rest and that a flow-mediated increase in regional wall motion identifies residual viability. METHODS: Fourteen patients with evidence of previous myocardial infarction, infarct-related single-vessel coronary artery disease and impaired regional ventricular function at rest underwent positron emission viability imaging by fluorine-18 deoxyglucose. In addition, blood flow at rest and vasodilator capability were regionally evaluated in all patients by means of nitrogen-13 ammonia. RESULTS: Of a total of 252 segments, 133 were dyssynergic at rest. Of these 133 segments, 60 (group 1) showed normal metabolic activity and only mild reduction in myocardial blood flow. The other 73 segments showed a marked reduction in flow; of these, 25 (group 2, viable) had persistent metabolic activity, whereas 48 (group 3, necrotic) did not. Despite similar levels of hypoperfusion at rest, group 2 segments showed a preserved coronary reserve that was virtually absent in necrotic segments (2.6 +/- 1.3 vs. 1.3 +/- 0.5, p < 0.01). This value was similar to that observed in viable group 1 segments (2.5 +/- 1.6, p = NS). CONCLUSIONS: In addition to characterizing myocardium at risk, imaging of coronary flow at baseline and after dipyridamole by positron emission tomography provides helpful information on myocardial viability that may integrate the "static" viability information obtained with the baseline flow/metabolic approach.

Aged↗

PubMed1995

Comparison among different dopamine-agonists of new formulation in the clinical management of macroprolactinomas.

BACKGROUND: In the last decade, the treatment of macroprolactinomas has been significantly improved by the introduction in the clinical practice of new drugs with dopamine-agonist properties. In particular, the availability of different forms of bromocriptine (BRC) with long duration of action and slow absorption, suitable for injectable (BRC-LAR) or oral (BRC-SRO) administration, has allowed one to obtain a more constant bromocriptinemia than with standard BRC, thus reducing adverse reactions. Moreover, a selective action on dopamine D2 receptors has been achieved using a new non-ergot derivative: the quinagolide (CV 205-502). The aim of this study was to evaluate the effects of BRC-LAR, BRC-SRO and CV 205-502 in 34 patients with macroprolactinoma. PROTOCOL OF THE STUDY: BRC-LAR was given at the monthly dose of 50-100 mg for 6-24 months to 8 patients whose PRL levels were 150-700 micrograms/l. BRC-SRO was given at the daily dose of 5-20 mg for 1-24 months to 10 patients whose PRL levels were 120-900 micrograms/l. CV 205-502 was given at the daily dose of 0.075-0.6 mg for 6-12 months to 16 patients whose PRL levels were 250-2,050 micrograms/l. CT and/or MRI scans were performed before and during treatment to evaluate tumor shrinkage. Data are presented as Mean +/- SD. RESULTS: Serum PRL levels normalized in 8/8 with BRC-LAR, 7/10 with BRC-SRO and 12/16 patients with CV 205-502. A significant shrinkage of tumor mass was obtained in 7/8 with BRC-LAR, 9/10 with BRC-SRO and 16/16 patients with CV 205-502, with consequent improvement of visual-field defects. Overall, the drugs were rather well tolerated: no patient stopped BRC-LAR or BRC-SRO and only 2 stopped CV 205-502. In particular, nausea, vomiting, headache, hypotension that disappeared spontaneously were observed in 5/8 with BRC-LAR, 4/10 with BRC-SRO and 4/16 with CV 205-502. CONCLUSIONS: The medical approach with long-acting BRC preparations and CV 205-502 which selectively binds D2 receptors allows one to obtain rapid normalization of PRL levels and shrinkage of macroprolactinomas in a large series of patients. These drugs are rather well tolerated also by patients proven to be untolerant to standard BRC.

Administration, Oral↗