Patrizia Gargiulo

The long‐term efficacy of conventional radiotherapy in patients with GH‐secreting pituitary adenomas

Objective  To assess the long‐term efficacy and safety of conventional radiotherapy (RT) in the control of acromegaly according to recent stringent criteria of cure.

Metformin decreases platelet superoxide anion production in diabetic patients

Patients with type 2 diabetes mellitus are usually treated with oral antidiabetic agents but it is still not known whether these drugs have antioxidant effects in humans.

Atypical Celiac Disease as Cause of Increased Need for Thyroxine: A Systematic Study

OBJECTIVE Replacement T4 dose in hypothyroid patients bearing both chronic autoimmune thyroiditis and atypical celiac disease (CD) has been analyzed. DESIGN Replacement T4 dose has been analyzed in 35 hypothyroid patients with Hashimotos thyroiditis (HT) and atypical CD, as defined by the American Gastroenterological Association. We have evaluated the ability of the same dose of T4 to reach target TSH in 21 patients before and during gluten-free diet (GFD). In the remaining 14 patients, noncompliant with GFD, we analyzed replacement T4 dose and compared it with that in a similar group consisting of 68 patients with hypothyroid HT but no evidence of celiac sprue or other conditions interfering with T4 absorption. RESULTS In patients with isolated HT, the desired serum TSH (median=1.02 mU/liter) was reached in all patients after 5±2 months of treatment at a median T4 dose of 1.31 μg/kg·d. After a similar period and dose of T4, higher levels of TSH (median=4.20 mU/liter) were observed in patients with HT and CD. In 21 CD patients, target TSH (median TSH=1.25 mU/liter) has been attained after 11±3 months of GFD without increasing T4 dose (1.32 μg/kg·d). In the remaining 14 patients, who were noncompliant with GFD, target TSH has also been achieved but at a higher T4 dose (median=1.96 μg/kg·d; +49%; P=0.0002) than in hypothyroid patients without CD. CONCLUSIONS Atypical CD increases the need for T4. The effect was reversed by GFD or by increasing T4 dose. Malabsorption of T4 may provide the opportunity to detect CD that was overlooked until the patients were put under T4 therapy.

Anti-endomysial antibody of IgG1 isotype detection strongly increases the prevalence of coeliac disease in patients affected by type I diabetes mellitus

A strong association between type 1 insulin‐dependent diabetes mellitus (IDDM1) and coeliac disease (CD) is well documented, but it is known that prevalence values are underestimated. Serum anti‐endomysial antibodies (EMA), considered diagnostic for CD because of their high sensitivity and specificity, belong to the IgA class, but the existence of EMA of IgG1 isotype in the presence or absence of IgA deficiency was reported. In order to re‐evaluate the occurrence of CD in IDDM1 patients we performed a screening in IDDM1 patients using EMA of both isotypes. Ninety‐four adults affected by IDDM1 (unaffected by CD before enrolling) were enrolled and 83 blood donors as controls. All subjects were on a gluten‐containing diet. Histology and biopsy culture were performed. EMA IgA and IgG1 in sera and culture supernatants were detected. Serum EMA were positive in 13 of 94 IDDM1 patients (13·8%). Six of 13 presented IgA‐EMA, seven of 13 presented IgG1‐EMA. No EMA were found in the control population. Total intestinal atrophy was found in all six patients with serum IgA‐EMA and in five of seven with serum IgG1‐EMA. Diagnosis of CD was confirmed by histology and organ culture in all 13 patients with serum EMA. The prevalence of CD in the patients affected by IDDM1 was 6·4% for IgA‐EMA‐positive and 7·4% for IgG1‐EMA‐positive patients. We confirmed the prevalence of CD in the IDDM1 population obtained with IgA‐EMA screening only (6·4%). This prevalence value increases dramatically to 13·8% when IgG1‐EMA are also used in the screening. We conclude that IgG1‐EMA should also be sought whenever an IDDM1 patient undergoes screening for CD.

Qualitative and quantitative studies of autoantibodies to phospholipids in diabetes mellitus

Diabetes mellitus is associated with vascular and neurological complications. We have investigated the presence of antibodies to phospholipids and to phospholipid binding plasma proteins in blood samples collected from 68 clinically and biochemically characterized type I and type II diabetic patients and from 252 healthy blood donor controls. Each sample was analysed for antibodies to three phospholipids (cardiolipin, phosphatidylserine and phosphatidylethanolamine), the antibody isotypes (IgA, IgG and IgM), and whether antibody activity was plasma protein‐dependent. Patients were considered to have anti‐phospholipid antibodies when one or more of these 18 tests was found above predetermined control values. The results of these experiments revealed an increased incidence of anti‐phospholipid antibodies in diabetic patients compared with control subjects. The incidence of IgA isotype to phosphatidylethanolamine was higher than the incidence of other isotypes to other phospholipids, and their reactivities were independent of phospholipid‐associated proteins. In addition, these antibody findings were studied for associations with prothrombin degradation products, activated factor VII and activated protein C, and with the incidence of diabetic complications. The anti‐phosphatidylethanolamine antibody association with proliferative retinopathy was significant.

Insulin-anti-insulin complexes in diabetic women and their neonates

SummaryIt is known that insulin does not cross the placenta, whereas maternal anti-insulin antibodies do. We have therefore investigated insulin antibodies and insulin-anti-insulin complexes both in pregnant diabetic women during pregnancy and in umbilical cord blood from their new-born infants. Forty-seven diabetic pregnant women and 23 new-born infants of these diabetic women were studied. All the pregnant patients were studied at the end of pregnancy and, in 27, at least on one other occasion during pregnancy. All the patients were treated with insulin during pregnancy: 26 had Type 1 (insulin-dependent) diabetes, 14 Type 2 (non-insulin-dependent) diabetes and seven had gestational diabetes. Insulin antibodies were found in 62% of the Type 1 diabetic patients, in 71% of the Type 2 diabetic patients and in 43% of the gestational diabetic patients. They were present in 48% of the infants studied. Insulin-anti-insulin complexes were found in 37% of the women with Type 1 diabetes, in 21% of those with Type 2 diabetes and in 14% of those with gestational diabetes. Complexes were found in 38% of the new-born infants. The presence of these complexes in the babies was more strongly correlated with their occurrence in their mothers at the beginning than at the end of pregnancy. Insulin-anti-insulin complexes are thus present in the neonatal circulation. They may differ from those in their mothers and they may have patho-physiological and clinical importance.

Is acetazolamide effective in the treatment of diabetic macular edema? A pilot study

Aim: To investigate whether acetazolamide, already found to be helpful in decreasing cystoid macular edema in patients with retinitis pigmentosa, was also effective in the treatment of diabetic macular edema in nonproliferative retinopathy. Methods:Two randomized age- and sex-matched groups (cases and controls) of 12 diabetics (five Type 1 and seven Type 2) were selected for this pilot study and graded for retinopathy (Early Treatment of Diabetic Retinopathy Study – Airlie House Classification). Cases were treated with acetazolamide for three months according to a standard protocol. The Early Treatment of Diabetic Retinopathy Study chart was used for assessing far-best corrected visual-acuity, and fluorescein angiography was performed using the Heidelberg Retina Angiograph. The Amsler grid-test and computerized-perimetry (Octopus 2000R) were also performed. Results: Fluorescein-angiographic findings and perimetric data improved significantly (p < 0.01) in the acetazolamide-treated cases compared to the controls while visual-acuity varied only slightly (p > 0.01). The Amsler grid-test resulted insignificant in our study (p > 0.05). No adverse effects or significant variations in laboratory tests were recorded. Conclusion: Further clinical investigations involving larger numbers of patients and a longer follow-up are required to confirm these preliminary results. However, the present study seems to suggest that acetazolamide could be effective in reducing fluorescein-angiographic findings and improving perimetric data in diabetics with macular edema, even though the mechanism of action remains obscure. Visual-acuity varied only slightly.

Long-term treatment of somatostatin analog-refractory growth hormone-secreting pituitary tumors with pegvisomant alone or combined with long-acting somatostatin analogs: a retrospective analysis of clinical practice and outcomes

BackgroundPegvisomant (PEGV) is widely used, alone or with somatostatin analogs (SSA), for GH-secreting pituitary tumors poorly controlled by SSAs alone. No information is available on specific indications for or relative efficacies of PEGV?+?SSA versus PEGV monotherapy. Aim of our study was to characterize real-life clinical use of PEGV vs. PEGV?+?SSA for SSA-resistant acromegaly (patient selection, long-term outcomes, adverse event rates, doses required to achieve control).MethodsA retrospective analysis of data collected in 2005–2010 in five hospital-based endocrinology centers in Rome was performed. Sixty-two adult acromegaly patients treated ≥6 months with PEGV (Group 1, n?=?35) or PEGV?+?SSA (Group 2, n?=?27) after unsuccessful maximal-dose SSA monotherapy (≥12 months) were enroled. Groups were compared in terms of clinical/biochemical characteristics at diagnosis and before PEGV or PEGV?+?SSA was started (baseline) and end-of-follow-up outcomes (IGF-I levels, adverse event rates, final PEGV doses).ResultsGroup 2 showed higher IGF-I and GH levels and sleep apnea rates, higher rates residual tumor tissue at baseline, more substantial responses to SSA monotherapy and worse outcomes (IGF-I normalization rates, final IGF-I levels). Tumor growth and hepatotoxicity events were rare in both groups. Final daily PEGV doses were similar and significantly increased with treatment duration in both groups.ConclusionsPEGV and PEGV?+?SSA are safe, effective solutions for managing SSA-refractory acromegaly. PEGV?+?SSA tends to be used for more aggressive disease associated with detectable tumor tissue. With both regimens, ongoing monitoring of responses is important since PEGV doses needed to maintain IGF-I control are likely to increase over time.

Immunology in diabetic pregnancy: activated T cells in diabetic mothers and neonates.

SummaryLymphocytes bearing surface antigens indicating early and full activation have been evaluated, in addition to T cell subsets, in blood samples from diabetic pregnant patients, neonates from diabetic mothers and control groups. The type of diabetes and the trimester of pregnancy were taken into account. Monoclonal antibodies were used to enumerate total T cells, helper/inducer, cytotoxic/suppressor T lymphocytes and activated mononuclear cells using antibodies binding lymphocyte surface antigens as markers of early lymphocyte activation, and MHC Class II surface antigens as markers of late activation. A decrease in T-helper cells during the third trimester of pregnancy in Type 1 (insulin-dependent) and gestational diabetic patiens (p<0.02) and a decrease in T-suppressor cells in Type 2 (non-insulin-dependent) diabetic pregnant patients during the third trimester (p<0.01) were observed in relation to normal values. As in normal pregnancy, 4F2-positive cells were increased in 48% of diabetic pregnant patients during the second and third trimesters of gestation. Class II-positive cells were increased in almost 60% of Type 1 and gestational diabetic patients during the last trimester of pregnancy in comparison with normal pregnant women and control subjects. A decrease in T-helper cells (p<0.02) and a clear increase in 4F2-positive cells (p<0.001) and Class II-positive lymphocytes (p<0.005) were observed in the infants of diabetic mothers in comparison with control subjects. The maternal cellular immune system, actively alerted in pregnancy, is fully activated in a number of Type 1 and gestational diabetic pregnant patients. Activated lymphocytes are even found in the neonates of diabetic mothers, but these do not trigger the events leading to the onset of diabetes in the short term.

Coagulation pathways and diabetic retinopathy: abnormal modulation in a selected group of insulin dependent diabetic patients

AIMS To investigate whether diabetic retinopathy (DR), already associated with microvascular alterations, ischaemia, and endothelial dysfunction, was also characterised by abnormal modulation of coagulation pathways. METHODS Plasma samples, collected from 67 type 1 diabetics comparable for age, duration of disease (DD), and metabolic control (MC), were processed for prothrombin degradation products (F1+2) and factor VII coagulant activity (FVII:c). 50 normal subjects served as a control group. The ETDRS-Airlie House Classification of DR was used. RESULTS A significant correlation between FVII:c and F1+2 plasma concentrations was observed (p <0.05). FVII:c (p <0.005) and F1+2 (p <0.0001) levels were higher in diabetics than in controls, especially in patients with proliferative DR (FVII:c p <0.0001; F1+2 p<0.005). However, cases without retinal lesions and healthy subjects did not differ significantly (FVII:c and F1+2 p >0.05). CONCLUSIONS These findings pointed out the presence of a hypercoagulable state associated with endothelial dysfunction in patients with insulin dependent diabetes mellitus (IDDM), demonstrated both by increased FVII:c and F1+2 plasma levels. Moreover, the observation of different DR related degrees of procoagulant activity, despite comparable DD and MC, strengthens the hypothesis of multiple risk factors in the pathogenesis of DR.