Biomedical subjects

M Ferdeghini

Publications and source records attributed to M Ferdeghini.

At least 19 recordsLinked to original sources

PubMed2006

Long-term quiescence of ectopic Cushing's syndrome caused by pulmonary neuroendocrine tumor (typical carcinoid) and tumorlets: spontaneous remission or therapeutic effect of bromocriptine?

In 1990, a 55-yr-old woman was admitted to the Medical Department of our hospital for severe hypercortisolism complicated by secondary diabetes mellitus and serious hypokalemia. Although inferior petrosal sinus sampling did not show any significant difference between central and peripheral ACTH concentration, suggesting an ectopic source of ACTH secretion, diagnostic imaging was negative and Cushing's disease due to hyperplasia of the pituitary intermediate lobe was suspected. Medical treatment with bromocriptine and cyproheptadine led to a rapid and stabile normalization of adrenal function, so that after two months cyproheptadine was stopped and bromocriptine was tapered to a smaller dose. An attempt to discontinue medical treatment, carried out 3 yr later, was followed by a quick increase of ACTH and cortisol levels, which were normalized by the resumption of the bromocriptine. Adrenal function remained normal until 1994 when hypercortisolism relapsed despite the treatment. Chest radiography and computed tomography (CT) scan detected a 6 mm nodule in the middle lobe of the lung which proved to be a neuroendocrine tumor, with immunohistochemical positivity for ACTH. Nests of neuroendocrine cells (tumorlets) were also demonstrated in the surrounding lung tissue. After the lobectomy, the patient recovered completely from Cushing's syndrome and no symptoms and/or signs of recurrence have been observed over the subsequent follow-up period. Although cyclical spontaneous Cushing's syndrome could not be excluded, there was strong evidence that medical treatment with bromocriptine might have played a key role in long-lasting remission. To our knowledge, this is the second case described in literature of Cushing's syndrome caused by neuroendocrine lung tumor responsive to bromocriptine.

ACTH Syndrome, Ectopic↗

PubMed2006

Carcinoid crisis induced by receptor radionuclide therapy with 90Y-DOTATOC in a case of liver metastases from bronchial neuroendocrine tumor (atypical carcinoid).

SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days.

Aged↗

PubMed2006

Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma.

About 40% of nonfunctioning pancreatic endocrine carcinomas (NF-PEC) cannot be cured by surgery due to advanced stage disease. Somatostatin analogues have been proposed as first line therapy in these cases. We performed a prospective phase IV study to assess the efficacy of octreotide in advanced NF-PEC and identify factors predictive of response to therapy. Twenty-one consecutive patients with octreoscan-positive advanced-stage well-differentiated NF-PEC were treated with long-acting release octreotide 20 mg i.m. at diagnosis. The immunohistochemical expression of somatostatin receptor 2 (SSTR2) and the quantitative mRNA analysis of SSTR2 and SSTR5 were assessed in 12 tumours. The tumour proliferative fraction was assessed by immunohistochemistry for Ki-67. Eight patients (38%) had stable disease (SD) after a median follow-up of 49.5 months. Thirteen patients (62%) developed progression after a median of 18 months. Tumour progression correlated with a proliferative index>or=5% (P=0.016), weight loss (P=0.006) and absence of abdominal pain (P=0.003) at diagnosis. Other clinical (age, gender and primary tumour resection) or pathological parameters (site, size and liver metastasis) lacked significant correlation with tumour progression. No difference in the amount of SSTR2 mRNA and protein or SSTR5 mRNA was found between tumours that were stable (n=5) and seven tumours that progressed (n=7). Treatment with long-acting release octreotide was associated with stabilization of disease and a good quality of life in 38% of patients. A Ki-67 index>or=5% and/or the presence of weight loss may justify more aggressive therapy without waiting for radiologically proven progression of disease.

Aged↗

PubMed2004

Oxidative and genotoxic damage after radio-iodine therapy of Graves' hyperthyroidism.

PURPOSE: To evaluate genetic damage and oxidative stress following a single therapeutic dose of 131I in Graves' disease patients monitored up to 180 days after treatment. MATERIALS AND METHODS: Genetic damage induction was estimated as the increase in micronuclei in peripheral lymphocytes of patients. As indicators of radiogenic oxidative stress, vitamin E and lipoperoxide levels were assessed in the plasma of patients, as well as the release of plasmic clastogenic factors measured by the induction of micronuclei in vitro in peripheral lymphocytes of a healthy donor. RESULTS: Vitamin E depletion lasted at least 3 days and the basal level was restored within 7 days. No statistically significant variations were observed in lipoperoxide plasma levels. A sharp increase of micronuclei in the peripheral lymphocytes of patients was correlated (p < 0.001) with the release of clastogenic factor in the plasma. The highest micronucleus value was negatively correlated (p < 0.03) with the lowest vitamin E level observed in each patient. CONCLUSIONS: Micronuclei induction was the direct consequence not only of the energy deposition of 131I on the genetic material, but also of oxidative stress, likely via the release of clastogenic factor.

Adult↗

PubMed2001

A new human chromogranin 'A' immunoradiometric assay for the diagnosis of neuroendocrine tumours.

We investigated whether plasma chromogranin A (CgA), measured by a new immunoradiometric assay, may be a sensitive and specific marker of phaeochromocytoma and of other neuroendocrine tumours. This study involved 121 patients of whom 20 with phaeochromocytoma, 28 with other neuroendocrine tumours (19 gastroenteropancreatic tumors, 3 medullary thyroid and 6 small cell lung carcinomas), 25 with solid nonfunctioning adrenocortical tumours and 48 with essential hypertension. In addition, 130 normal subjects were taken as controls. Plasma catecholamines were measured by using high-performance liquid chromatography, and CgA by a two-site sandwich immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245) of human CgA. Plasma CgA in controls (49.0 +/- 3.1 ng ml(-1), mean +/- SE) and in essential hypertensives (50.8 +/- 3.5 ng ml(-1)) was lower (P< 0.0001) than in adrenocortical tumours (91.8 +/- 13.2 ng ml(-1)), in phaeochromocytomas (254 +/- 49 ng ml(-1)) and in patients with other neuroendocrine tumours (469 +/- 84 ng ml(-1)). Plasma CgA and catecholamines identified 13 and 18 out of 20 phaeochromocytomas with sensitivity of 65% and 90%, respectively. Combined measurement of both markers improved sensitivity up to 100%. In the other neuroendocrine tumours, CgA was abnormal in 23/28 cases (sensitivity 82%) and in 6 it was the only circulating marker of disease. In gastroenteropancreatic tumours, CgA measurement identified all cases (sensitivity 100%). Specificity of CgA in patients with essential hypertension was 98%. In conclusion, CgA determination showed high sensitivity in identifying gastroenteropancreatic tumours and, in association with catecholamines, in detecting patients with phaeochromocytoma. CgA sometimes appeared to be the only circulating marker of disease. Since the specificity of CgA proved to be excellent, this assay may be useful for diagnosis both of functioning and non-functioning neuroendocrine tumours.

Adolescent↗

PubMed2000

Final height, gonadal function and bone mineral density of adolescent males with central precocious puberty after therapy with gonadotropin-releasing hormone analogues.

UNLABELLED: Few data are available on the outcome of boys with central precocious puberty (CPP) treated with gonadotropin-releasing hormone (GnRH) analogues. We report on final height, endocrine and exocrine testicular function, and bone mineral density (BMD) in nine males (age 16.7 +/- 1.5 years) treated with GnRH analogues from the age 6.0 +/- 1.8 years for a mean period of 5.6 +/- 2.4 years. The following parameters were evaluated: final height, serum gonadotropin and gonadal steroid levels, spermarche, semen analysis, area and volumetric BMD. Final height (-0.4 +/- 1.1 SDS) was significantly higher than pre-treatment predicted adult height (-2.0 +/- 1.2 SDS) and not significantly different than midparental height (-0.1 +/- 0.8 SDS). Pubertal response of gonadotropins to GnRH test occurred within 1.5 years (mean 0.7 +/- 0.4 years) and spermarche (n = 7) from 0.7 to 3 years (1.8 +/- 0.9 years) after the discontinuation of GnRH analogue therapy. No alteration in semen analysis was found (n = 6, sperm count, 10(6)/ml: 52.0 +/- 18.7; normal motility (%): 49.5 +/- 18.7; atypical morphology (%): 44.5 +/- 11.4). Area and volumetric BMD were not reduced (0.2 +/- 1.0 SDS and -0.1 +/- 0.9 SDS, respectively). CONCLUSION: Long-term treatment with gonadotropin-releasing hormone analogues improves final height in boys with central precocious puberty. Post-therapy data demonstrating normal endocrine and exocrine testicular function support the safety of gonadotropin-releasing hormone analogues on reproductive function. Long-term pharmacological suppression of testicular function in childhood does not impair bone mineral density in late adolescence.

Adolescent↗

PubMed2000

Octreotide acetate long-acting release in patients with metastatic neuroendocrine tumors pretreated with lanreotide.

BACKGROUND: In the present study we investigated the efficacy and tolerability of i.m. octreotide acetate (octreotide LAR) in patients with metastatic neuroendocrine tumors (NETs) previously treated and failed on i.m. lanreotide. PATIENTS AND METHODS: Fifteen patients (8 females, 7 males, median age 67 years, range 28-81 years) with metastatic NETs (8 endocrine pancreatic tumors, 7 midgut carcinoids) were enrolled in the study. All patients were in progressive disease (objective: 11 patients, symptomatic: 10 patients, biochemical: 11 patients) after treatment with slow release lanreotide, 30 mg every 14 days for a median time of 8 months (range 3-19 months). All patients had measurable disease; 12 patients had elevated serum and/or urine markers and 11 were symptomatic. Octreotide scintigraphy was positive in 13 of 15 patients. Octreotide LAR was administered as i.m. injection at the dose of 20 mg every four weeks until disease progression. RESULTS: An objective partial response (PR) was documented in one patient (7%), no change (NC) in six (40%), and progressive disease (PD) in eight patients (53%). The PR was observed in one patient with non-functioning endocrine pancreatic tumor with progressive liver and lymph node metastases after 16 months of i.m. lanreotide therapy. The median duration of disease stabilization was 7.5 months (range 6-12+ months). The overall biochemical response rate was 41%, including CRs (33%) and PRs (8%); biochemical responses were observed in carcinoids as well as in endocrine pancreatic tumors; the median duration of response was 5 months for CRs and 7.5 months for PRs. The overall symptomatic response rate was 82%. The median duration of response for diarrhoea, abdominal pain, or both was 6.5 months (range 3-12+ months). Improvement in performance status (PS) was obtained in 5 of 11 patients with PS of 1 at study entry. Median duration of octreotide LAR treatment was seven months (range 3-12+ months). No serious adverse events were reported; mild side effects were reported in 26% of patients. CONCLUSIONS: Octreotide LAR 20 mg shows significant efficacy in terms of objective response rate (PR + SD), biochemical and symptomatic control in patients with metastatic NETs of the GEP system pretreated and progressing on slow release lanreotide.

Adult↗

PubMed2000

Clinical experience with recombinant human thyrotrophin (rhTSH) in the management of patients with differentiated thyroid cancer.

The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.

Adenocarcinoma, Follicular↗

PubMed2000

Long-acting depot lanreotide in the treatment of patients with advanced neuroendocrine tumors.

Long-acting depot forms of somatostatin analogs administered by intramuscular injections are now available for the treatment of neuroendocrine tumors (NETs). In the present study, we investigated the efficacy and tolerability of a slow-release form of lanreotide in patients with advanced NETs. From July 1996 to January 1999, 25 patients with advanced NETs (12 carcinoids, 13 endocrine pancreatic tumors) were enrolled in the study. Thirteen patients were pretreated with subcutaneous octreotide, chemotherapy, or hepatic metastasis alcoholization. All the patients had measurable disease. Seventeen patients were symptomatic and 20 patients had elevated serum and/or urine markers. Octreotide scintigraphy was positive in 23 of 25 patients. Lanreotide was administered as intramuscular injections at the dose of 30 mg every 2 weeks until there was objective, biochemical, or symptomatic tumor progression. Objective partial responses (PRs) were documented in 2 patients (8%), whereas 10 patients (40%) had tumor stabilization. The PRs were observed in patients with midgut carcinoids, of whom one was pretreated with subcutaneous octreotide. The response duration was 21+ and 24+ months in responding patients; the median duration of disease stabilization was 8.5 months (range, 4-21+). The overall biochemical response rate was 42%, including 2 complete responses (CRs) (10.5%) and 6 PRs (31.5%); all biochemical responses were observed mostly in patients with carcinoid tumors; the duration of response was 18+ and 30+ months for CRs; the median duration of biochemical response was 7 months (range, 4-18+) for PRs. The overall symptomatic response rate was 70% with a median duration of 7.5, 18, and 18+ months for diarrhea, abdominal pain, and flushing, respectively. Median duration of lanreotide treatment was 10 months (range, 2-30+). No significant side effects were reported. Depot lanreotide 30 mg shows significant efficacy in terms of objective response rate and in biochemical and symptomatic control, in pretreated patients as well as nonpretreated patients with advanced NETs. Tolerability is good, with good patient compliance.

Abdominal Pain↗

PubMed2000

Renal function and serum concentration of five tumor markers (TATI, SCC, CYFRA 21-1, TPA, and TPS) in patients without evidence of neoplasia.

The aim of this study was to evaluate the relationship between renal function and the blood level of some tumor markers that are low molecular weight proteins, that is, tumor-associated trypsin inhibitor (TATI), squamous cells carcinoma antigen (SCC), cytokeratin 19 fragments (CYFRA 21-1), tissue polypeptide antigen (TPA), and M3-specific epitope of tissue polypeptide antigen (TPS). In 41 adult patients without evidence of neoplastic disease, glomerular filtration rate (GFR) and the blood levels of creatinine and of the tumor markers were determined. The decrease in GFR was accompanied by an increase in serum levels of TATI, SCC, CYFRA 21-1, and TPA. The serum level of tumor markers increased particularly when GFR fell below 40 ml/min. On the basis of these results, the renal function must be taken into account for the clinical evaluation of the studied tumor markers.

Adolescent↗

PubMed1999

Endothelin-1 release from atherosclerotic plaque after percutaneous transluminal coronary angioplasty in stable angina pectoris and single-vessel coronary artery disease.

To assess the effects of percutaneous transluminal coronary angioplasty on endothelin-1 (ET-1) release, we assessed ET-1 concentrations at different sites of the coronary circulation in patients submitted to elective procedures. ET-1 levels immediately downstream from the plaque and ET-1 aortocoronary gradient increased significantly after the procedure, which was related to mechanical wall stress in patients only receiving balloons, but not in those undergoing stent percutaneous transluminal coronary angioplasty. No changes were found in the coronary sinus; these results suggest ET-1 release from the plaque rather than an ischemia/reperfusion-related production from the distal myocardium.

Aged↗

PubMed1999

GH, IGFBP-1, and IGFBP-3 response to oral glucose tolerance test in perimenopausal women: no influence of body mass index.

OBJECTIVES: an increasing interest is being focused on the role of the somatotropic axis in the modulation of body weight and fat distribution, particularly in climacteric women. The influence of the glycometabolic state on the somatotropic axis in postmenopausal and in obese subjects has not been investigated. The aim of the present study is to evaluate whether menopause and body mass index (BMI) affect the response of growth hormone (GH), insulin-like growth factor-binding protein-1 (IGFBP-1) and -3 (IGFBP-3) to the oral glucose tolerance test (OGTT). METHODS: the study included 24 women, aged 45-55 years, categorized into 4 groups, premenopausal pre-obese (BMI = 28.5 +/- 0.8 Kg/m2) and normal body weight (BMI = 22.2 +/-1.1 Kg/m2), and postmenopausal pre-obese and normal body weight. All women underwent: (1) a biophysical evaluation with determination of waist/hip ratio; (2) an assessment of fat and lean tissue mass and body fat distribution by total body DEXA; and to (3) an OGTT. RESULTS: in response to OGTT plasma GH levels significantly decreased in all groups, but the relative decrease was more prominent in the lean subjects. A significant decrease of IGFBP-1 levels in response to OGTT was observed in all women, regardless of menopausal age and BMI, while IGFBP-3 levels did not significantly change in either group. CONCLUSIONS: in conclusion, the impact of both BMI and menopausal condition on GH, IGFBP-1, and -3 response to OGTT is limited to a blunted GH response in overweight women compared with normally-weighing ones. These findings appear to rule out the hypothesis that a common glycometabolic derangement may affect both the modifications of body weight and of the somatotropic axis observed in perimenopausal women.

Body Composition↗

PubMed1999

Effect of somatostatin infusion on the somatotrope responsiveness to growth hormone-releasing hormone in patients with anorexia nervosa.

BACKGROUND: According to the existence in anorexia nervosa (AN) of peripheral growth hormone (GH) resistance, low circulating insulinlike growth factor I (IGF-I) levels may be coupled with GH hypersecretion; however, there is also evidence for alterations in the neural control of GH secretion. In fact, reportedly GH secretion is partially refractory to the inhibitory effect of muscarinic cholinergic antagonists as well as to the stimulatory effect of muscarinic cholinergic agonists, which act via opposite modulation of hypothalamic somatostatin (SS) release. Thus, somatostatinergic activity could be impaired in AN. This could be due to an impaired hypothalamic SS release or, alternatively, an altered somatotroph sensitivity to SS. METHODS: We studied in 10 women with AN in acute phase (AN, age, mean +/- SEM: 18.7 +/- 0.8 years) the effect of exogenous SS1-14 (25 and 75 micrograms/hour i.v., infused from +15 to +75 min), at doses that had previously been shown capable of increasing circulating SS levels within the physiological range, on the GH response to GH-releasing hormone (GHRH) (1 microgram/kg i.v. at 0 min). The same study protocol was performed in 8 normal age-matched women (NW, 22.9 +/- 1.0 years). RESULTS: In AN patients, IGF-I levels were lower (p < .01) than those in NW, while basal GH levels were similar in both groups. The GHRH-induced GH rise in AN was higher (p < .01) than that in NW. In AN, the exaggerated GH response to GHRH was inhibited to the same extent by both SS doses (p < .05) and became similar to that after GHRH alone in NW. In NW both 25 and 75 micrograms/hour SS decreased the GHRH-induced GH response; however, the inhibitory effect of the lower dose did not attain statistical significance, whereas the higher dose did (p < .02). During SS infusion, the GHRH-induced GH response in NW was persistently lower (p < .02) than that in AN. The percent inhibitory effect of SS on the somatotroph responsiveness to GHRH was similar in both groups at each dose. CONCLUSIONS: Our present findings demonstrate that the sensitivity of somatotroph cells to exogenous SS given at physiological doses is preserved in patients with AN. It is noteworthy that, during the infusion of physiological SS doses, the GH response to GHRH in AN overlaps on that to GHRH alone under physiological conditions. Thus, in AN, the sensitivity of somatotroph cells to SS apparently being preserved, an impairment of somatostatinergic neurons cannot be ruled out.

Adolescent↗

PubMed1999

Assessment of the prognostic relevance of serum anti-p53 antibodies in epithelial ovarian cancer.

The objective of this study was to assess the prognostic relevance of preoperative serum anti-p53 antibodies in epithelial ovarian cancer. These autoantibodies were detected with a new generation enzyme-linked immunosorbent assay in blood samples preoperatively drawn from 86 patients with this malignancy. Serum anti-p53 antibodies were found in 3 (10.0%) of the 30 patients with stage I-II and 15 (26.8%) of the 56 patients with stage III-IV epithelial ovarian cancer (P = 0.09). We assessed in detail 44 patients with stage III-IV disease who underwent six cycles of first-line platinum-based chemotherapy. A pathological complete response at second-look was achieved by none of the 15 patients with serum anti-p53 antibodies compared to 24.1% of the 29 patients without autoantibodies (P = 0.09). However, the preoperative serum anti-p53 antibody status had no prognostic relevance for progression-free survival and survival. In conclusion, the assessment of preoperative serum anti-p53 antibodies seems to have a limited clinical value in the management of patients with advanced epithelial ovarian cancer.

Autoantibodies↗

PubMed1999

Relation of fetal growth to maternal responses to oral glucose tolerance test throughout gestation.

Fetal growth is dependent on transplacental supply of fuels. We aimed to assess the effect of serial changes in maternal glucose tolerance and insulin secretion with advancing pregnancy on maternal-fetal outcomes. Sixty-nine healthy pregnant women were studied over the course of gestation for glucose tolerance, by oral glucose tolerance test (OGTT), and hemoglobin A(1c) (HbA(1c)), fetal intrauterine growth (by ultrasound) and pregnancy outcome. Seven women had an abnormal OGTT in the third trimester developing gestational diabetes mellitus (GDM), but none of the 12 mothers of large babies (> 3.9 kg) had GDM: the former had the highest post-load glycemic increment, despite an apparently 'normal' insulin secretory response, the latter showed the lowest post-load glucose increase in the face of the lowest insulinemic response. Neonatal body weight correlated with maternal gestational weight gain, placental weight, third trimester ratio of incremental plasma insulin and glucose integrated areas under the curve and first and second trimester HbA(1c) levels. Fetal growth indices (femur length, biparietal diameter and abdominal circumference) were correlated with both HbA(1c) and 2h OGTT. Fetal growth rate is confirmed as being associated with maternal glycemic equilibrium, but one of the main determinants of high infant birthweight seems to be an enhanced maternal insulin sensitivity, accompanied by remarkable gestational weight gain.

Adult↗

PubMed1999

Local insulin infusion stimulates expression of plasminogen activator inhibitor-1 and tissue-type plasminogen activator in normal subjects.

PURPOSE: Plasma levels of plasminogen activator inhibitor-1 are increased in obesity, hypertension, and diabetes. Their correlation with insulin levels supports the hypothesis that hypofibrinolysis may affect the development of atherosclerotic complications in patients with insulin resistance. To investigate the effect of insulin on fibrinolysis, we evaluated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) antigens during insulin infusion in the forearm vascular beds of 8 healthy subjects. MATERIALS AND METHODS: Insulin was infused in the brachial artery of each subject to raise local venous concentrations to approximately 100 microU/mL. Blood samples were obtained from the brachial artery and vein at baseline, after 30, 60, 90, and 120 minutes of infusion, and 30 minutes after the end of the infusion. RESULTS: Following intra-arterial infusion of insulin, forearm blood flow (mean +/- SD) increased progressively from 2.7 +/- 0.6 to 4.0 +/- 0.6 mL/dL/min (P <0.01) and did not return to baseline after the end of the infusion. Plasminogen activator inhibitor-1 balance increased (345 +/- 160 versus 8 +/- 152 fmol/dL/min, P <0.02) at 60 minutes, reaching baseline levels after the end of the infusion. After 90 minutes, tPA balance increased (40 +/- 26 versus 7 +/- 29 fmol/dL/min, P <0.01) with a profile similar to forearm blood flow. CONCLUSIONS: Local hyperinsulinemia induces regional vasodilation and expression of PAI-1 and tPA antigens. An alteration of this physiological process could be involved in the development of hypofibrinolysis and atherosclerosis in states of insulin resistance.

Adult↗

PubMed1999

Can insulin action induce myocardial texture alterations in essential hypertension?

The prevalence of hyperinsulinemia/insulin resistance in hypertensive individuals, as well as the effects of insulin on myocytic and fibroblastic growth, are well known in both epidemiologic and animal models. To check whether there are any links between ultrasonic myocardial texture parameters and insulin level in essential hypertensives, we compared 18 essential hypertensive men (Group 1, H) with 18 age- and gender-matched healthy controls (Group 2, C) (age, 57 +/- 10 years). For all study subjects we performed ambulatory blood pressure monitoring (ABPM); conventional 2-D Doppler echocardiography for the assessment of the left ventricular mass index (LVMi) and function; quantitative analysis of digitized echocardiographic images for evaluation of cyclic variation (CVI) of mean gray level (MGL) at the septum and posterior wall levels; and 75-g 3-h oral glucose tolerance test (OGTT) for analysis of area under glycemic curve (AUGC, g/min/dL) and insulinemic curve (AUIC, mU/min/mL), as well as serum glucose and insulin peaks. Both the daily mean blood pressure (H: 109 +/- 4.6 v C: 94.6 +/- 4.6, P < .0001) and LVMi (adjusted for body surface) (H: 133 +/- 24 v C: 97 +/- 21 g/m2, P < .0001) were significantly higher in hypertensives. Values for AUIC were significantly higher in hypertensives (10.37 +/- 5.53 v 6.33 +/- 5.28), P < .032); CVI was also significantly higher in group C, for both septum (C: 40.2 +/- 16.9 v H: 15.9 +/- 18.1, P < .0001) and posterior wall (C: 44.5 +/- 19.6 v H: 20 +/- 17.5; P < .0001). There was a significant inverse correlation between AUIC and CVI for both septum (r: -0.57, P < .001) and posterior wall (r: -0.50, P < .002). The significantly higher impairment of myocardial ultrasonic texture and the higher level of the AUIC insulinemia in hypertensives, as well as the significant inverse relationship between CVI and hyperinsulinemia, are our major findings. Hyperinsulinemia/insulin resistance could cause an altered collagen/muscular ratio, which could potentially explain, at least in part, the CVI alterations detected in hypertensive patients.

Adolescent↗

PubMed1999

Effect of 1-year treatment with interferon-beta1b on thyroid function and autoimmunity in patients with multiple sclerosis.

OBJECTIVE: Interferon-beta (IFN-beta) is a widely used therapy for multiple sclerosis (MS), a demyelinating disease of the central nervous system. This study has evaluated the effect on thyroid function and autoimmunity of a 1-year treatment with IFN-beta1b in patients with MS. PATIENTS: We studied 31 patients (age 34+/-7 years, 21 women) with relapsing-remitting MS during IFN-beta1b treatment of 1 year duration. Systematic thyroid assessment and measurements of serum interleukin-6 (IL-6) levels were performed at baseline and every 3 months during treatment. RESULTS: Sixteen percent of the patients had autoimmune thyroiditis before IFN-beta1b, all positive for anti-peroxidase antibodies. The overall incidence of thyroid dysfunction was 33% over 1 year (10% hyperthyroidism, 23% hypothyroidism). Thyroid autoimmunity developed in 5/26 patients (19%), in one case without dysfunction. In addition to autoantibody positivity at baseline, female gender and the presence of an ultrasound thyroid pattern suggestive of thyroiditis were identified by multiple logistic regression as additional risk predictors for the development of thyroid dysfunction. During IFN-beta1b treatment, serum IL-6 levels rose in a consistent biphasic pattern; there was, however, no difference between patients with or without incident thyroid abnormalities. CONCLUSIONS: We conclude that IFN-beta1b therapy can induce multiple alterations in thyroid function, some of which are unrelated to thyroid autoimmunity. IL-6 measurement is not useful to identify patients prone to develop thyroid abnormalities. Though thyroid dysfunction is generally subclinical and often transient, systematic thyroid assessment should be performed during IFN-beta1b treatment.

Adjuvants, Immunologic↗