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N Panza

Publications and source records attributed to N Panza.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cisplatin, gemcitabine, and paclitaxel in locally advanced or metastatic non-small-cell lung cancer: a phase I-II study. Southern Italy Cooperative Oncology Group.

PURPOSE: Because both cisplatin-paclitaxel and cisplatin-gemcitabine combinations are generally considered to be among the most active regimens in non-small-cell lung cancer (NSCLC) patients, this study aimed to determine the maximum-tolerated dose (MTD) of paclitaxel when combined with fixed doses of cisplatin and gemcitabine in advanced NSCLC patients and aimed to define the therapeutic activity of this new regimen. PATIENTS AND METHODS: From October 1996 to September 1998, 75 patients with stage IIIB-IV NSCLC, who were either chemotherapy-naive (65 patients) or who had been pretreated (10 patients), received fixed doses of cisplatin (50 mg/m(2)) and gemcitabine (1,000 mg/m(2)) and escalating doses of paclitaxel in a 1-hour infusion, all on days 1 and 8, every 3 weeks. RESULTS: Five different paclitaxel doses were tested, for a total of 275 cycles delivered. The escalation was stopped at the paclitaxel dose of 75 mg/m(2) in pretreated patients, whereas it continued to 150 mg/m(2) in chemotherapy-naive patients. A total of 65 chemotherapy-naive patients were treated. A paclitaxel dose of 125 mg/m(2) was recommended for phase II, and a total of 39 patients were treated at this level, for a total of 158 cycles delivered. No treatment-related deaths occurred. Five patients were hospitalized because of sepsis, and packed RBC transfusion was required in 13 patients. Grade 4 neutropenia and thrombocytopenia occurred in 23 (31%) and eight (11%) patients, respectively. Overall, 74 of the 75 patients were assessable for response. Four complete (CR) and 38 partial (PR) responses were recorded, for an overall response rate (ORR) of 57%. Three of the ten pretreated patients achieved a PR, compared with four CRs and 35 PRs in the 64 chemotherapy-naive patients (ORR, 61%). Thirty-eight of 39 patients included in phase II were assessable for response and quality of life (QOL) (one patient's disease was not measurable). Two CRs and 24 PRs were recorded in this group, for an ORR of 68% (95% confidence interval, 51% to 82%). The QOL score improved in 27 of 38 (71%) patients. The median survival time was 15 months in the 65 chemotherapy-naive patients, but it had not yet been reached in the 39 patients included in phase II, for whom the 1-year projected survival was 70%. CONCLUSION: The cisplatin-gemcitabine-paclitaxel combination is a feasible and well-tolerated approach in advanced NSCLC patients. Both a major response and a QOL improvement can be obtained in a high proportion of patients, with a median survival time exceeding 1 year. A phase III trial comparing this combination with other effective regimens is under way.

Adult↗
PubMed1999

Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism.

Although subclinical hypothyroidism is frequently diagnosed, the decision to institute a substitutive therapy with L-T4 remains controversial. Because the cardiovascular system is considered a main target for the action of thyroid hormone, we investigated whether subclinical hypothyroidism induces cardiovascular abnormalities. Twenty-six patients (mean age, 36 +/- 12 yr) were evaluated by Doppler-echocardiography, whereas a subgroup of 10 patients, randomly selected, were reevaluated after 6 months of L-T4 substitutive therapy (mean dose, 68 microg daily). Thirty subjects (matched for age, sex, and body surface area) served as controls. Mean plasma TSH was significantly higher in patients (P < 0.001), whereas mean serum free T4 and free T3 concentrations, although in the normal range, were significantly lower (P < 0.001 and P < 0.005, respectively). Blood pressure and heart rate did not differ from control values. Echocardiogram examination showed no abnormalities of the left ventricular morphology and a slight, but not significant, reduction in the systolic function in the patient group. In contrast, Doppler-derived indices of diastolic function showed significant prolongation of the isovolumic relaxation time (94 +/- 13 vs. 84 +/- 8 msec; P < 0.001), increased A wave (55 +/- 13 vs. 48 +/- 9 cm/sec; P < 0.05), and reduced early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.4 +/- 0.3 vs. 1.7 +/- 0.3; P < 0.001). In the subgroup of 10 patients, thyroid hormone profile was normalized by 6 months of L-T4 substitutive therapy, whereas no changes were observed in the left ventricular morphology. Systolic function was significantly enhanced, as compared with pretreatment values (P < 0.01) but did not differ from control values. Also, systemic vascular resistance was significantly decreased by L-T4 replacement therapy. Assessment of diastolic function showed significant shortening of isovolumic relaxation time (77 +/- 15 vs. 91 +/- 8; P < 0.05), reduction of A wave (51 +/- 13 vs. 60 +/- 12; P < 0.01), and increase of early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.7 +/- 0.4 vs. 1.3 +/- 0.3; P < 0.001). These indices, however, were comparable with those of control subjects. These findings indicate that subclinical hypothyroidism affects diastolic function and that this abnormality may be reversed by L-T4 substitutive therapy.

Adult↗
PubMed1999

Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials.

Lung cancer represents the major cause of cancer-related death in Europe and North America, accounting for 28% of all cancer deaths. Seventy to 80% of all lung cancers are non-small cell lung cancers (NSCLCs), and approximately 75 % of these patients present with locally advanced or disseminated disease. Even though chemotherapy is now recommended in the majority of cases of unresectable NSCLC, it still fails to substantially modify the fate of these patients. In recent years, several active cytotoxic drugs (paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan) have been developed, showing an overall response rate (ORR) <20% in NSCLC. Phase II/III trials testing these new agents in combination with cisplatin have been carried out in recent years with inconsistent results. Large randomized trials testing cisplatin-paclitaxel, carboplatin-paclitaxel, and cisplatin-gemcitabine regimens have been reported showing no substantial superiority of these combinations over standard treatments. The ORR remained well below 50%, and the median survival times were quite far from one year. These data could suggest that the addition of a single new agent to a platinum compound could be insufficient to substantially improve the prognosis of advanced NSCLC patients. In view of these disappointing data, the Southern Italy Cooperative Oncology Group has tried to improve the fate of patients with advanced NSCLC by testing new triplet combinations, which combined cisplatin with two rather than one of the newest chemotherapy agents. To avoid an unacceptable increase in toxicity and/or a marked decrease in dose intensity, the standard schedules of administration of the three agents used in these studies were changed, and the schedule changes were evaluated in phase I trials aimed at determining the maximum tolerated dosages of the drugs. Subsequently, phase II and III trials were conducted. The present paper summarizes the results of the clinical trials either completed or under way and aims to evaluate whether this strategy will result in a substantial prognostic improvement.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia.

The toxicity and therapeutic activity, including the effect on quality of life, of the carboplatin-oral etoposide combination, given with an intrapatient dose escalation, was tested in 38 non-small cell lung cancer (NSCLC) patients aged over 70 years, and in 8 younger patients with a performance status of 2. In the absence of grade 3-4 toxicity, doses were escalated as follows: first course (carboplatin AUC 4; etoposide 50 mg twice daily orally days 1-14); second course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-14); third course (carboplatin AUC 5; etoposide 50 mg twice daily orally days 1-21). A total of 141 chemotherapy cycles were delivered. The treatment was, in general, well tolerated and no toxic deaths occurred. More than 60% of patients received 100% of the planned dose intensity. Transient grade 4 neutropenia or thrombocytopenia occurred in 6 and 2 patients, respectively, but only 2 patients had to be hospitalised because of fever. All patients were evaluated for activity on an 'intention to treat basis'. Ten partial responses and 20 stable disease were recorded, for an overall response rate of 22% (95% confidence interval (CI) = 11-36). 9/38 (24%; 95% CI = 12-41) elderly patients obtained a partial response. The median response duration was 4 months. A quality of life improvement was observed in 19 of the 46 enrolled patients (41%; 95% CI = 27-57), and 15/46 (33%; 95% CI = 19-48) showed a performance status improvement. The quality of life score improved in 17/38 (45%) elderly patients. 8/10 responders and 11/20 patients with stable disease showed a concomitant improvement in quality of life. At a median potential follow-up of 16 months (range 2-21), 31 patients had had progression of disease and 23 had died, for a median time to progression (TTP) and overall survival (OS) of 5 and 10 months, respectively. The median survival time was 11 months in the elderly patients. The median time to subjective impairment (TSI) was 6 months (7 months in the elderly group). One-year estimated TTP, TSI and OS rates were 22, 29 and 41%, respectively. At multivariate Cox analysis, a > 25% improvement in the quality of life score was more predictive of a better survival outcome than the response achievement.

Administration, Oral↗
PubMed1998

Bone marker and bone density responses to dopamine agonist therapy in hyperprolactinemic males.

The aim of this prospective study was to evaluate the bone mineral density (BMD) at lumbar spine and femoral neck levels and biochemical parameters of bone turnover in 20 consecutive hyperprolactinemic males before and after an 18-month treatment with different dopamine agonists. Six patients received bromocriptine at a dose of 2.5-10 mg/day; 7 patients received quinagolide at a dose of 0.075-0.3 mg/day; 7 patients received cabergoline at a dose of 0.5-1.5 mg/week. BMD, serum PRL, testosterone, dihydrotestosterone, and osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured before and every 6 months during treatment. At study entry, BMD values were lower in patients than controls at both lumbar spine (0.82 +/- 0.03 vs. 1.18 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.85 +/- 0.02 vs. 0.92 +/- 0.02 g/cm2; P < 0.05) levels. Osteopenia or osteoporosis was diagnosed in 16 patients at the lumbar spine and in 6 of them at the femoral neck level. A significant inverse correlation was found between lumbar spine and femoral neck BMD values and both PRL levels and disease duration (P < 0.01). In the 20 patients, serum OC levels were significantly lower (2.1 +/- 0.1 vs. 9.3 +/- 2.4 microg/L; P < 0.01), whereas Ntx levels were significantly higher (157.8 +/- 1.1 vs. 96.4 +/- 7.4 nmol bone collagen equivalent/mmol creatinine; P < 0.001) than control values. A significant inverse correlation was found between serum PRL and OC (P < 0.01), but not Ntx, levels. After 18 months of treatment, serum PRL levels were suppressed, and gonadal function was restored in all 20 patients, as shown by the normalization of serum T (from 2.2 +/- 0.2 to 5.0 +/- 0.2 microg/L) and dihydrotestosterone (0.3 +/- 0.02 vs. 0.5 +/- 0.01 nmol/L) levels, without any significant difference among groups. A progressive significant increase in serum OC levels together with a significant decrease in Ntx levels were observed after 6, 12, and 18 months of treatment in the 3 groups of patients. A slight, although significant, increase in BMD values was recorded in all patients after 18 months of bromocriptine, quinagolide, and cabergoline treatment, serum OC levels were normalized after treatment, whereas neither urinary Ntx levels nor BMD values were normalized by 18 months of treatment with dopaminergic agents. In conclusion, treatment with bromocriptine, quinagolide, and cabergoline for 18 months, although successfull in suppressing serum PRL levels and restoring gonadal function, was unable to restore lumbar spine and femoral neck BMD and normalize Ntx levels. However, BMD was slightly increased during treatment, suggesting that additional bone loss was prevented after treatment of hyperprolactinemia.

Adult↗
PubMed1997

Cisplatin, gemcitabine and vinorelbine in locally advanced or metastatic non-small-cell lung cancer: a phase I study.

PURPOSE: The objective of this study was to determine the maximally tolerable doses (MTDs) of vinorelbine (VNR) and gemcitabine (GEM) when combined with a fixed dose of cisplatin (CDDP). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer (NSCLC) received a fixed dose of CDDP (50 mg/m2) and escalating doses of VNR (starting from 20 mg/m2) and GEM (starting from 800 mg/m2) on days 1 and 8, every three weeks. The single escalation of GEM alone, by 200 mg/m2 at each step, was initially planned up to a dose of 1,200 mg/m2, to be followed by increments of the VNR dose of 5 mg/m2 at each step. RESULTS: Thirty-one patients were enrolled at five different dose levels. The escalation was stopped at level 4 (GEM 1,200 mg/m2 and VNR 25 mg/m2) since two of six patients of this cohort showed dose-limiting neutropenia at treatment cycle 1. Two different dose levels, GEM 1,200 mg/m2 + VNR 20 mg/m2, and GEM 1,000 mg/m2 + VNR 25 mg/m2 were fairly well tolerated. No treatment-related deaths occurred. Neutropenia was the main toxic effect, occurring in 76% of the total of 116 cycles delivered, and in 24% of them was of grades 3 or 4. A total of eight patients (26%) experienced grade 4 neutropenia lasting more than seven days; in five of them it occurred in the first course. Neutropenic fever was observed in four cases. Grade 4 thrombocytopenia occurred in only two patients. Non-hematologic toxicity was a minor problem in all patients but was never dose-limiting. No complete responses were obtained, but sixteen out of 31 (52%) patients achieved partial responses. The median duration of response was 20 (range 6-56+) weeks, while at a nine-month median follow-up, the median survival time has not yet been reached. To date, 18 patients are still alive. The one-year projected survival for all patients was 51%. CONCLUSIONS: Our results show that CDDP, VNR and GEM can be safely given together without substantial reductions in their individual dose intensities. In our opinion, the dose level of GEM 1,000 mg/m2 + VNR 25 mg/m2 given in combination with CDDP 50 mg/m2 on days 1 and 8 of a three-week cycle can be recommended for phase II trials, since it provides a better balance in dose intensity of GEM and VNR. A phase II randomised study is underway to establish the activity of this new regimen (at the above-cited dose level) in chemo-naive NSCLC patients.

Adult↗
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

Diagnosis and radioguided surgery with 111In-pentetreotide in a patient with paraneoplastic Cushing's syndrome due to a bronchial carcinoid.

In a 28-year-old man with Cushing's syndrome, studies investigating a hypophyseal and/or adrenal origin of the disease, including computed tomography and magnetic resonance imaging, were negative. In agreement with reports showing somatostatin receptors on the cell membrane of ectopically secreting ACTH tumours, scintigraphy was performed after intravenous injection of 111 MBq 111In-pentetreotide (OCT). The radiolabelled OCT scan showed a small focal area of intense uptake at the inferior lobe of the right lung. Subsequent radioguided surgery located and defined a small mass (1.8 x 1.4 x 1.6 cm). The probe pinpointed the mass to the right inferior chest lobe, with a tumour/normal tissue count ratio of 6:1 and tumour/hilar normal lymph node ratio of 12:1, thus permitting the complete excision of the tumour to exclude lymph node and/or parietal involvement. A lung carcinoid was diagnosed at histology. The patient is still alive and disease-free 24 months after surgery. 111In-OCT was found to be useful for localizing the ACTH-secreting tumour and also permitted rapid non-invasive differential diagnosis between an ACTH-secreting pituitary adenoma and malignancy causing ectopic ACTH syndrome. This study also showed the clinical usefulness of radioguided surgery in the treatment of bronchial carcinoid.

Adult↗
PubMed1996

Langerhans cell histiocytosis, diabetes insipidus, hyperprolactinemia and empty sella: a four-fold association. Report of two cases.

Two cases of Langerhans cell histiocytosis (LCH) expressing as Hand-Schuller-Christian syndrome with diabetes insipidus, hyperprolactinemia and empty sella are here reported. Up-to-date this four-fold association is lacking in world literature and it is here discussed in the light if LCH is a cancer or the clinical expression of an immunologic disorder.

Adult↗
PubMed1996

Partial substitution of cisplatin with carboplatin in combination with etoposide in advanced non-small cell lung cancer (NSCLC): a multicentric randomised phase II trial.

Seventy previously untreated patients with advanced NSCLC were randomised, after stratification for stage (IIIB vs. IV) and Performance Status (0-1 vs. 2), to receive either treatment A: CDDP 40 mg/m2 + VP16 100 mg/m2 day 1-3 (37 patients); or treatment B: CBDCA 250 mg/m2 day 1 + CDDP 30 mg/m2 day 2, 3 + VP16 100 mg/m2 day 1-3 (33 patients). Therapy was recycled on day 29 in both arms. The two arms were well balanced for the main pretreatment characteristics. Sixty-six patients (32 with Stage IIIB and 34 with Stage IV disease) were evaluable for toxicity and response (arm A = 34, arm B = 32), while four ineligible patients were excluded from analysis. Acute toxicity was assessed at recycling. Non-hematologic toxicity was higher in arm A. However, the reduction of nephrotoxicity (9% vs. 23%) in arm B was lower than expected. Leukopenia (15 vs. 5 patients) or thrombocytopenia (7 vs. 0 patients) of any grade affected more patients of arm B. Moreover, Grade 3-4 leukopenia (six patients) or thrombocytopenia (four patients) was observed only in arm B. Seventeen patients responded: 11/34 (32%; 95% C.I. = 17-50%) in arm A, and 6/32 (19%; 95% C.I. = 7-36%) in arm B. Median survival times of 40 and 34 weeks, respectively, were reported in arm A and B. Stage IIIB and squamous cell histology were associated with a higher probability of response. In conclusion, the partial replacement of CDDP with CBDCA in combination with VP16 slightly improves the tolerance of the treatment in terms of nephro- and neurotoxicity; however, it induces a significant increase in hematologic toxicity. In view of this unfavourable toxicologic profile and of the discouraging response rate observed, this regimen cannot be recommended as standard treatment in advanced NSCLC.

Adult↗
PubMed1996

Cisplatin/carboplatin + etoposide + vinorelbine in advanced non-small-cell lung cancer: a multicentre randomised trial. Gruppo Oncologico Campano.

A multicentre randomised phase III trial in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) was undertaken to compare the therapeutic activity and toxicity of a cisplatin/carboplatin-etoposide-vinorelbine combination with that of a cisplatin-etoposide regimen. Patients with advanced (stage IIIB-IV) NSCLC were randomised, after stratification for stage (IIIB-IV) and performance status (0-1 and 2), to receive either (A) CDDP 40 mg m-2 + VP16 100 mg m-2 on days 1-3 as standard treatment or (B) CBDCA 250 mg m-2 on day 1 + CDDP 30 mg m-2 on days 2 and 3 + VP16 100 mg m-2 on days 1-3 + NVB 30 mg m-2 on day 1. Therapy was recycled on day 29 in both arms. We hypothesised a 15% minimum increment in the response rate with the experimental regimen over the 25% expected activity rate of the standard regimen. A two-stage design was chosen, which permitted the early termination of the trial (after the accrual of 52 patients in each arm) if the difference in response rates between the two regimens was less than 3% at the end of the first stage. A total of 112 patients (arm A = 57, arm B = 55) were enrolled in the study (53 with stage IIIB and 59 with stage IV), of which 105 eligible patients were evaluable for response on an "intention to treat' basis. Seven patients were excluded because they did not fulfil the inclusion criteria. Fifteen responses were observed in arm A (28%, 95% CI = 17-42) and 13 (one complete) in arm B (25%, 95% CI = 13-37). On multivariate logistic analysis, treatment did not affect the response rate, while stage IV and performance status 2 were significantly associated with a lower probability of response. Median survivals were similar in the two arms (31 vs 27 weeks). The experimental regimen was associated with an extremely poor median survival in patients with poor performance status (21 weeks). On Cox analysis, treatment failed to show a significant impact on survival: stage IV (relative risk = 1.6. CI = 1.0-2.6, P = 0.036) was the only prognostic variable significantly associated with a worse survival outcome and, although poor performance status adversely affected survival, this effect did not reach the level of statistical significance (relative risk = 1.6, CI = 0.98-2.5; P = 0.063). There were no significant differences in non-haematological toxicities between the two arms, although three patients in the control arm had to discontinue the treatment because of the persistence of severe nephrotoxicity (two patients) or neurotoxicity (one patient). In contrast, a significant increase in both neutropenia and thrombocytopenia was observed in the experimental arm. Four treatment-related deaths were registered in arm B (two due to neutropenic sepsis, one to myocardial failure and one to acute renal failure) compared with one toxic death (acute renal failure) in arm A. In view of these results, the trial was stopped and the null hypothesis (< 15% increase in response rate with the experimental regimen) has been accepted. Therefore, our combination does not deserve further evaluation as first-line treatment in advanced NSCLC patients. As our data suggest that an aggressive chemotherapy might have a negative impact on survival of patients with poor performance status, trials to evaluate the activity of new regimens should be conducted separately for each subset of patients with different performance status.

Adenocarcinoma↗
PubMed1995

Auditory brainstem responses in thyroid diseases before and after therapy.

The aim of this study was to evaluate through the auditory brainstem responses (ABRs) the electrical events generated along the auditory pathway in 56 adult patients affected with hyper- and hypothyroidism. Twenty-four normal-hearing hyperthyroid patients affected with Graves' disease and 32 normal-hearing hypothyroid patients (9 with subclinical and 23 with overt hypothyroidism) were subjected to standard (clicks at 21 pps) and sensitized ABR with masking wide-band (masking noise). In addition, thyroid scintiscan and ultrasonography, free T3 and T4, total T3 and T4, TSH, antimicrosomal and antithyroglobulin antibodies, audiogram and impedance tests were performed in all the patients. This study was repeated after 6-12 months of treatment in conditions of euthyroidism. The results showed changes of ABRs both in the standard procedure as well as in the sensitized test in 6 hyperthyroid (25%) and 8 hypothyroid patients (25%). All the patients with abnormal ABRs had overt hypothyroidism (8/23; 34.7%). The ABRs became normal in 5 out of 6 Graves' patients after 6-12 months of methimazole treatment. ABRs remained abnormal in all the hypothyroid patients despite their having been on L-thyroxine treatment for 6-12 months and were euthyroid for at least 5 months before the study was repeated. These findings suggest that ABR abnormalities are indicative only of a nonspecific injury in the bulbo-ponto-mesencephalic centers. Alterations of ABRs in thyroid diseases are not specific in relation to hyper- or hypothyroidism. Lastly, there is a relationship between ABR abnormalities and the degree of hypothyroidism, even if ABR alterations are not always reversible after long-term therapy.

Adult↗
PubMed1995

Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine: beneficial effect of beta-blockade.

Thyroid-stimulating hormone (TSH) suppressive therapy with levothyroxine (L-T4) may cause adverse cardiac effects such as rhythm disturbances and ventricular hypertrophy. The latter is a predisposing condition to diastolic dysfunction. Thus, this study was designed to assess the effect of long-term TSH suppressive therapy on cardiac diastolic function. Because beta-blockade is known to reduce ventricular hypertrophy in patients on L-T4 therapy, we also tried to determine whether the addition of a beta-blocker to L-T4 improved diastolic function. Twenty-five patients (21 female and 4 male; mean age 41 +/- 10 yr) on TSH suppressive therapy for 3-9 yr (9 for differentiated carcinoma and 16 for nontoxic goiter) and 20 control subjects were studied. A subgroup of 10 patients, selected for the presence of symptoms and signs of adrenergic overactivity, was treated for 4 months with the beta-blocker bisoprolol (4.25 +/- 1.2 mg/day), and their maintaining L-T4 therapy was unchanged. In the patient group, left ventricular mass was significantly increased (P < 0.001), isovolumic relaxation time was prolonged (P < 0.001), and early diastolic filling velocity was markedly reduced (P < 0.001), whereas late diastolic filling was increased (P < 0.005). Consequently, the early-to-late diastolic flow velocity ratio was markedly decreased (P < 0.001). These alterations were more pronounced in the subgroup of patients with evidence of adrenergic overactivity. In these patients, beta-blockade induced a significant regression of cardiac hypertrophy and improved diastolic dysfunction. In particular, isovolumic relaxation time decreased (P < 0.01) and the early-to-late flow velocity ratio increased significantly (P < 0.01). Both indices reached values after beta-blockade that were no longer different from those of asymptomatic patients. It is concluded that long-term L-T4 therapy increases myocardial mass and causes relevant diastolic dysfunction, particularly in those patients with evidence of mild hyperthyroidism and adrenergic overactivity. Both myocardial hypertrophy and diastolic dysfunction are significantly improved by adrenergic beta-blockade.

Adult↗
PubMed1995

Indium-111 octreotide in Graves' disease and in the evaluation of active exophthalmos.

Thyroid Associated Ophthalmopathy (TAO) is an autoimmune disorder generally associated with Graves' disease (GD). The aim of our study was to evaluate the uptake of indium-111 Octreotide (111In-OCT), a somatostatin (SS) analogue able to bind specific SS receptors, at the level of the thyroid and orbits in patients with TAO. Seven patients with exophthalmos were investigated: six had GD while one was affected with a non small cell lung cancer (NSCLC). One patient with GD had undergone total thyroidectomy (TT) for a thyroid cancer. At the time of the study two patients were hyperthyroid, four were euthyroid and one was hypothyroid. 111 MBq of 111In-OCT were i.v. injected and two 30-minute scans were performed at 4 and 24 hours; 5 minute planar images were also obtained at 25, 60 and 120 minutes. A 180 degrees SPECT was carried out 5 hours after the injection in one patient. A qualitative analysis was performed, comparing these images with those obtained in 7 control patients without thyroid illness or exophthalmos. Moreover, in the TAO patients thyroid, orbit and brain counts were evaluated in comparison with background (BK) and blood activity (BA), measured at the level of the venous longitudinal sinus. In GD intense thyroid uptake was demonstrated independently of the functional state, with highest ratio compared to BK seen at 24 hours. Low uptake in the patient with NSCLC, no activity in the patient with GD that underwent TT, and slight or absent thyroid uptake in the controls were observed. Intense uptake was seen in the orbits of the patient who clinically had the most severe ophthalmopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Follicular thyroid carcinoma and mediastinal goiter in a case of situs inversus viscerum.

A 55-year-old woman with total situs inversus viscerum was subjected to total thyroidectomy for a well-differentiated follicular thyroid carcinoma. After surgery the patient remained euthyroid for two months and serum TSH did not rise. A whole body scan with iodine-131 (131I) showed mediastinal uptake. A chest computed tomography visualized a sequestered substernal goiter. Upon the patient's refusal to undergo surgery, she was treated with 150 mCi of 131I. A further dose of 100 mCi of 131I was administered six months later. Ten years after treatment, the patient is still alive and disease-free.

Adenocarcinoma, Follicular↗
PubMed1995

111In-octreotide in the evaluation of autoimmune thyroid diseases.

Aim of our study was to evaluate the uptake of Indium-111 Octreotide (OCT) at the level of thyroid and orbits in autoimmune thyroid diseases. Nine patients with Graves' disease (GD) who were also affected with thyroid associated ophthalmopathy (TAO) and four patients with Hashimoto's thyroiditis (HT) were evaluated. A patient with lung cancer, presenting ophthalmopathy did not related to autoimmune dysthyroidism, was also studied. All patients with ophthalmopathy were evaluated by a Clinical Activity Score and an A-scan standardized echography. Multiple planar images were acquired over a 24-hour period after i.v. injection of 111 MBq of 111In-OCT. A SPECT study was also obtained in 7 patients five hours after the injection. A qualitative analysis was performed. Semiquantitative ratios comparing the counts on the thyroid with respect to background (T/BK) and on the orbits and brain with respect to the blood-pool were also obtained. Thyroid uptake of OCT was higher in GD with respect to HT, and was not related to the functional state of the gland. The highest T/BK ratio was observed at the 24 hour control. Intense orbital uptake was observed only in case where a clinically active ophthalmopathy was present.

Adult↗
PubMed1994

CV 205-502 in the treatment of tumoral and non-tumoral hyperprolactinemic states.

CV 205-502 (octahydrobenzol[g]quinoline), a non-ergot dopamine agonist drug, was administered to 40 patients with hyperprolactinemic syndrome: 16 patients with macroprolactinoma, 14 with microprolactinoma and 10 with non-tumoral hyperprolactinemia. Twenty-four out of 40 patients had previously been treated by surgery and/or bromocriptine, with variable results. All had gonadal dysfunction and 22 patients had galactorrhea. Eight patients with macroprolactinoma had defects of the visual field. Pre-treatment serum PRL levels ranged from 60 to 2050 micrograms/l. The daily dose of CV 205-502 used in this trial ranged from 0.075 to 0.600 mg. After 6-12 months of treatment, serum PRL level decreased in all the patients reaching normoprolactinemia in 31 of them (77.5%) who demonstrated restoration of menses and disappearance of galactorrhea. The remaining nine patients (22.5%) had only a decrease of PRL levels without reaching normoprolactinemia and without any clinical effect. In 12 out of 16 patients with macroprolactinoma not previously surgically treated, a significant tumor shrinkage was shown by means of Computed Tomography and/or Magnetic Resonance Imaging. The disappearance of visual defects was obtained in four out of eight patients. CV 205-502 was tolerated satisfactorily: mild side-effects occurred in four patients in the first week of treatment and spontaneously disappeared, whereas six patients (15%) needed to withdraw the therapy after 6 months because of side-effects. In conclusion CV 205-502 is a potent and well-tolerated drug in the treatment of tumoral and non-tumoral hyperprolactinemic states and is an effective alternative to other dopamine agonists in use today.

Adult↗