Biomedical subjects

D Ferone

Publications and source records attributed to D Ferone.

At least 73 records · Page 4Linked to original sources

PubMed1997

Different sensitivity to sodium valproate in healthy, non-tumoral and tumoral hyperprolactinemic subjects.

GABAergic drugs affect PRL secretion in both rat and man. Sodium valproate (SV) inhibits GABA transaminase so increasing the endogenous GABAergic tone. The aim of this study was to evaluate the effects of SV at low and high doses on PRL release in healthy subjects and hyperprolactinemic patients. Fifteen patients with prolactinomas, 8 patients with non-tumoral hyperprolactinemia and 10 healthy subjects were studied: in non consecutive days, all subjects received placebo and SV at the dose of 400 and 800 mg po. Serum PRL levels were assessed 30, 15 and 5 min before and every 30 min for 4 hours after administration. SV at the dose of 400 mg induced a significant decrease of serum PRL in healthy subjects (p < 0.05), whereas no effect was noted in both tumoral and non-tumoral hyperprolactinemia. The administration of 800 mg SV induced a significant decrease of PRL levels in healthy subjects and in patients with non-tumoral hyperprolactinemia (p < 0.05). Conversely, in prolactinomas a paradoxical increase of serum PRL concentration (p < 0.05) was observed 120 min after the administration of the drug. These data confirm the inhibitory activity of SV on PRL release in healthy subjects, and suggest the existence of a partial resistance to GABA in non-tumoral hyperprolactinemia. In prolactinomas, the paradoxical PRL increase after high dose of SV suggests the existence of a complete pituitary resistance to GABA. This finding might be explained by the appearance of the stimulatory effect of GABA at hypothalamic level that could have been unmasked by the lack of pituitary GABA effects on adenomatous lactotrophs.

Adolescent↗

PubMed1997

Fixity of vocal cords and laryngocele in acromegaly.

Acromegalic patients have a reduced life expectancy mainly due to cardio-, cerebrovascular and respiratory disorders and increased prevalence of neoplasias. Particularly, the pathogenesis of respiratory disorders in acromegalics is debated. Laryngeal abnormalities are not yet well clarified even if they are frequently involved in the occurrence of respiratory insufficiency. In this study, we report on a 65 year-old acromegalic male suffering from frequent and severe dyspnea attacks and clinical findings of respiratory upperway obstruction, besides the common acromegalic features. At the external examination of the larynx, a bilateral painless and soft mass, located in the laterocervical region under the hyoid bone, was detected. Fiberoptic laryngoscopy, showed bilateral swelling between the aryepiglottic fold and the false vocal cords, whose size increased during the expiration and the phonation, fixity of the vocal cords in paramedian position, with a marked reduction of the respiratory space and increase in arytenoid cartilage size and mucosal edema. Neck and mediastinum CT scan showed the presence of an air containing bilateral swelling, crossing the thyrohyoid membrane. Bilateral cricoarytenoidal joint chondrocalcification, associated to a mixed-type bilateral laryngocele, was diagnosed. Laryngoceles were both surgically removed and a left monolateral arytenoidectomy was performed, using fiberoptic microlaryngoscopy with CO2 laser. The clinical evaluation, one month later, confirmed the complete disappearance of dyspnea and a partial improvement of phonation. Three months later, laryngoscopy showed the bilateral restoration of vocal cords motility and a significant improvement of phonation. This case presents an uncommon and severe respiratory problem in acromegaly such as the fixity of vocal cords associated to laryngocele. Circulating GH and IGF-I hypersecretion caused edema and laxity of laryngeal mucosa as well as bilateral ankylosis of cricoarytenoidal joints. The use of CO2 laser technique via micro-laryngoscopy successfully resolved laryngeal abnormalities.

Acromegaly↗

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

Acute administration of hexarelin stimulates GH secretion during day and night in normal men.

OBJECTIVE: Hexarelin is a synthetic hexapeptide with potent GH-releasing activity in both animals and men. The aim of this study was to investigate the effect of a bolus injection of hexarelin given in the morning during wakefulness and during nocturnal sleep in a group of normal adult men. DESIGN AND SUBJECTS: Eight normal men, aged 21-33 years, of normal height and within 10% of ideal body weight were studied. All subjects received in random order saline or hexarelin (2 micrograms/kg) in the morning between 0800 and 0900 h after they had fasted overnight. The same experiments were performed during nocturnal sleep in the same subjects. Saline or hexarelin were injected within 30 minutes after the onset of sleep between 2300 and 2400 h. Sleep was recorded by visual inspection. MEASUREMENTS: In all four test sessions blood samples were taken 30, 15 minutes and immediately before the injection of saline or hexarelin and then every 15 minutes for 2 hours. GH was measured by an immunoradiometric assay. All values are expressed as peak GH levels or as area under the curve (AUC) calculated by trapezoidal integration. RESULTS: Mean peak GH concentrations after hexarelin during the morning (58.2 +/- 4.7 micrograms/l) (GH micrograms/l l x 2 = mU/l) were not different from those observed during sleep (61.2 +/- 4.3 micrograms/l). The rate of disappearance of GH from plasma was slower during sleep (t1/2 = 64.9 +/- 14.8 min) than during morning hours (t1/2 = 24.9 +/- 1.4 min, P < 0.01). Mean AUC responses to hexarelin during sleep (1466 +/- 145 micrograms.min/l) were significantly higher than during morning hours (903 +/- 94 micrograms.min/l, P < 0.001). CONCLUSIONS: These results show that GH responsiveness to a growth hormone releasing peptide is preserved during the night. This could be exploited for diagnostic and/or therapeutic purposes.

Adult↗

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

Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment.

Cabergoline (CAB), a new, potent, and long-lasting PRL-lowering agent, was shown to be effective in tumoral hyperprolactinemia. The aim of this study was to investigate the effectiveness of CAB in patients with prolactinoma proven to be resistant to bromocriptine (BRC) and quinagolide (CV 205-502). Twenty-seven patients (19 macro- and 8 microprolactinomas) were treated with CAB at a weekly dose of 0.5-3 mg for 3-22 months. All patients were previously shown to be resistant to BRC, and 20 of them were resistant to CV 205-502 as well. Basal serum PRL levels before CAB treatment ranged from 108-3500 micrograms/L in macroprolactinomas and from 64-205 micrograms/L in microprolactinomas. Gonadal failure was present in all patients, whereas symptoms of tumor expansion, such as visual field defects and headache, were present in 10 of 27 patients. Eight macroprolactinomas had previously undergone surgery and/or radiotherapy. CAB treatment normalized serum PRL levels in 15 of 19 macroprolactinomas and in all 8 microprolactinomas. In 3 of the remaining 4 patients it caused a notable decrease in prolactinemia (89%, 80.5%, and 68.7% of the baseline). Only 1 patient was withdrawn from CAB therapy after 3 months at the weekly dose of 2 mg due to the absence of any significant clinical, hormonal, or radiological improvement. Gonadal function was restored in 18 of 27 patients, galactorrhea disappeared in 5 of 6 women, and headache improved in 7 of 8 patients. A significant tumor shrinkage was detected by computed tomography and/or magnetic resonance imaging in 9 macroprolactinomas and 4 microprolactinomas. CAB was well tolerated by all patients, except 6 who referred slight and short-lasting nausea, postural hypotension, abdominal pain, dizziness, and sleepiness at the beginning of treatment. In particular, CAB was well tolerated by 19 patients previously shown to be poorly tolerant to BRC and CV 205-502. In conclusion, CAB may represent, at the moment, the only successful therapy for prolactinoma-bearing patients resistant to BRC and CV 205-502, as it normalized PRL levels in 22 of 27 patients, reduced tumor size in 13 of 27 patients, and improved clinical symptoms in 25 of 27 patients in the present study.

Adolescent↗

PubMed1997

Acromegaly.

Explore the source record for details and available documents.

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

Tumor necrosis factor-alpha increases after corticotropin-releasing hormone administration in Cushing's disease. In vivo and in vitro studies.

The aim of this study was to evaluate the effect of acute human corticotropin (ACTH)-releasing hormone (CRH) administration (100 micrograms, as i.v. bolus) on tumor necrosis factor-alpha (TNF alpha) levels in the inferior petrosal sinuses and in the peripheral blood of 7 patients with Cushing's disease subjected to diagnostic inferior petrosal sinus sampling. Blood samples for ACTH, beta-endorphin (beta-EPH) and TNF alpha were collected from inferior petrosal sinuses and periphery simultaneously. In addition, TNF alpha concentrations were measured after CRH administration (10 nmol/l, 100 nmol/l and 1 mumol/l) in culture medium from primary cultures obtained in 3 of 7 patients. At baseline, plasma ACTH and beta-EPH levels were significantly higher in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one and in the periphery (p < 0.001) whereas no significant difference was found as far as serum TNF alpha levels were concerned. CRH administration caused a significant increase of ACTH (p < 0.001), beta-EPH (p < 0.01) and TNF alpha (p < 0.01) levels greater in the ipsilateral inferior petrosal sinus than in the contralateral one and in the periphery. In addition, CRH increased ACTH, beta-EPH and TNF alpha levels in the culture medium of three ACTH-secreting tumors at the doses of 100 nmol/l and 1 mumol/l (greater than 300, 200 and 110% of baseline pretreatment incubation levels, respectively). These data suggest that CRH may increase TNF alpha concentrations in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma and in the peripheral blood as well. In addition, it stimulated TNF alpha release both in vivo and in vitro. These findings suggest the possibility that an imbalanced intrapituitary TNF alpha production can be detected in ACTH-secreting adenomas.

Adenoma↗

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↗

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↗

PubMed1995

CV 205-502 treatment in therapy-resistant acromegalic patients.

The growth hormone (GH) inhibitory effect of CV 205-502 was evaluated during acute and 3-month administration, alone or in combination with octreotide, in 12 therapy-resistant acromegalic patients. Although these patients previously had undergone surgery and received chronic therapy with octreotide at 0.3-0.6 mg/day, they still had high GH and insulin-like growth factor I (IGF-I) levels. CV 205-502 (0.15 mg), octreotide (0.1 mg) and placebo were tested acutely. CV 205-502 at the dose of 0.15 mg caused a decrease of GH level (from 34.9 +/- 15.1 to 2.7 +/- 0.3 micrograms/l) in 4/12 (33.3%) and completely inhibited prolactin (PRL) secretion in all the patients. Octreotide caused a decrease of GH level (from 37 +/- 6.7 to 15.9 +/- 3.0 micrograms/l) without any change of PRL level. The GH and PRL levels were not changed during placebo administration. CV 205-502 at the dose of 0.3 mg/day (chronic test) normalized GH and IGF-I levels in five patients (41.6%: the four responders to the acute test and an additional patient who was a poor responder to acute CV 205-502 administration). The remaining seven patients were subjected to CV 205-502 (0.6 mg/day) and octreotide (0.6 mg/day) in combination for 3 months. In 2/7 patients the combined therapy induced a greater inhibition of GH and IGF-I levels than did each drug when administered alone. The drug was well-tolerated by the 12 patients. In conclusion, CV 205-502 is able to normalize GH and IGF-I levels and to improve clinical symptoms in certain acromegalic patients resistant to other therapeutic approaches.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1995

Technetium-99m pentavalent dimercaptosuccinic acid imaging in patients with pituitary adenomas.

We studied the tumor-seeking agent technetium-99m-labeled pentavalent dimercaptosuccinic acid ([99mTc](V)DMSA) to visualize 21 growth hormone (GH)-, nine prolactin (PRL)-, two mixed GH/PRL-, six adrenocorticotrophin (ACTH)-secreting and 15 clinically non-functioning pituitary adenomas, three craniopharyngiomas and one dysgerminoma of the sella. All non-adenomas and 31 out of 53 adenomas were studied before treatment: 22 after surgery and/or radiotherapy. Eight cases of acromegaly were studied before and after chronic treatment with octreotide, whereas three cases of acromegaly, one of prolactinoma and two of non-functioning adenoma were imaged before and after adenomectomy. As a control group, 27 patients without any clinical evidence of pituitary adenoma were studied: 10 of them were operated on previously and treated with iodine-131 for metastatic thyroid carcinoma, 10 had brain tumors and the remaining seven patients had functional pituitary hypersecretion (four Klinefelter's syndrome, two primary hypothyroidism and one Addison's disease). The scintigraphy was repeated after testosterone in Klinefelter's syndrome, L-thyroxine in primary hypothyroidism and cortisone administration in Addison's disease. Seventeen GH-secreting (81%), seven PRL-secreting (78%), three ACTH-secreting (50%), 15 non-functioning (100%) and one (50%) mixed adenoma significantly concentrated [99mTc](V)DMSA, showing elevated tumor-to-background (T/B) ratios. The T/B ratios were similar in untreated and surgically treated adenomas (11.2 +/- 5.6 vs 11.8 +/- 6.2). Radiotherapy significantly lowered the [99mTc](V)DMSA uptake to 5.1 +/- 2.8 (p < 0.1 vs untreated patients). Non-adenomatous lesions of the sella turcica did not concentrate [99mTc](V)DMSA in the pituitary as well as brain tumors and 8 out of 10 metastatic thyroid cancers. The treatment with octreotide normalized GH and insulin-like growth factor I levels and reduced [99mTc](V)DMSA from 15.7 +/- 4.8 to 13.5 +/- 3.9 (p < 0.05). Conversely, adequate substitutive therapy completely inhibited the uptake of the radiotracer in Klinefelter's syndrome, in primary hypothyroidism and in Addison's disease. The [99mTc](V)DMSA scintigraphy showed an overall sensitivity of 81% (43/53) in detecting pituitary adenomas, which was increased to 95% for lesions greater than 10 mm in size. High-quality images with minimal total body radiation were obtained, enabling a good in vivo characterization of viable adenomatous tissue as well as an accurate monitoring of the effects of different therapeutic regimens.

Addison Disease↗