Improving the prediction of malignancy in cytologically suspicious thyroid nodules.

BACKGROUND: Fine needle cytology aspirates (FNA) classified as THY4 are a heterogeneous group suspicious for malignancy [papillary thyroid cancer (PTC)], which is confirmed in 50-80% of cases after surgery. AIM: To better stratify THY4 FNA specimens for the relative risk of malignancy. METHODS: We retrospectively analyzed 78 thyroid nodules classified as THY4 because of the presence of atypical cells, hypercellular trabeculae and/or intranuclear inclusions (ICI), in the absence of papillae. Two subgroups were identified: group 1 (38 nodules), showing ICI with (no.=17) or without (no.=21) trabeculae and cellular atypia, and group 2 (40 nodules), showing trabeculae and atypia but without ICI. RESULTS: PTC was detected at histology in 56/78 of the patients (71.8%). Malignancy occurred in 36/38 (94.7%) of the patients in group 1 and in 20/40 (50.0%) of the patients in group 2. Therefore, the positive predictive value (PPV) for PTC was 97.3% in the ICI+ specimens (group 1), with a sensitivity of 64.3% and specificity of 95.2%. When only ICI was present, without atypia and trabeculae, the PPV and specificity were similar (95.0 and 95.2%, respectively), but the sensitivity was decreased (48.7%). In specimens without ICI (group 2), the PPV was only 50.0%; however, combined with young age (<40 yr) and male gender, it reached a value similar to that of group1. CONCLUSIONS: In ICI+ specimens compared to ICI-, the risk of PTC is nearly doubled, since PPV increases from 50.0% to 97.3%. This observation suggests that surgery should be considered mandatory in all lesions classified THY4 at FNA, although the relevant difference in terms of cancer risk between ICI- vs ICI+ nodules might be an useful information for both the clinician and the patient.

Contraception in diabetic women: an Italian study.

Over 1 year, a survey on contraception and obstetric history was performed on a cohort of 667 Caucasian fertile diabetic women (446, type 1 and 201, type 2) living in Italy. RESULTS: Of these women, 30.4% used hormonal contraceptives, 12.0% intra-uterine device (IUD), 10.7% declared they used no contraception, 47.0% only utilised barrier and/or natural methods. However, irrespective of their previous contraceptive strategy, 7.2% of all the studied population was surgically sterilized during caesarean section. HORMONAL CONTRACEPTION: Of these women, 60.4% was prescribed by a gynaecologist, 11.2% by a diabetologist, 15% by both of them and 13.4% by others. The proportion using oral contraception was similar among types 1 and 2 women (29.4% versus 27.8%, chi(2) = ns). SMOKING HABITS: Of women taking hormonal contraception, 30.0% were smokers. EDUCATIONAL LEVEL: University graduates (37.1%), high school leaves (32.2%), secondary school (28.2%) and primary school leaves (15.5%) used oral contraceptives (OC). OBSTETRIC HISTORY: The mean number of deliveries was 1.14 +/- 1.1, of miscarriages was 1.3 +/- 0.7 and of induced abortions 0.17 +/- 0.5. Planning of at least one pregnancy was reported in 29.4% of patients.

Low-dose bedtime NPH insulin in treatment of secondary failure to glyburide.

Secondary failure to oral hypoglycemic agents (OHAs) is a possible outcome for non-insulin-dependent diabetes mellitus (NIDDM) patients and poses a serious therapeutic problem. In this study, we evaluated the effect of adding a single bedtime low-dose NPH insulin injection to the previous ineffective sulfonylurea therapy in 23 NIDDM patients with true secondary failure to OHAs. This treatment schedule was conducted for 3 mo by 18 patients (78%) who completed the study. In these patients, the addition of NPH insulin (0.2 +/- 0.01 IU/kg body wt) greatly decreased fasting and postprandial plasma glucose (P less than .001) and glycosylated hemoglobin (P less than .005). No weight gain was observed in any of the patients studied. Five patients dropped out: 2 patients (9%) due to insufficient compliance, 2 patients (9%) due to the multiple insulin injections required to achieve good metabolic control, and 1 patient (4%) due to recurrent hypoglycemic episodes. No correlation was observed between glucagon-stimulated C-peptide values and amelioration of metabolic control. In conclusion, most NIDDM patients with secondary failure to OHAs may be successfully treated with the addition of a single low-dose bedtime NPH insulin injection, and residual beta-cell function evaluation is not able to predict the effectiveness of the combined treatment.

Comparison of combined therapies in treatment of secondary failure to glyburide.

OBJECTIVE: To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment. RESULTS: Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients. CONCLUSIONS: The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.

Direct effects of biguanides on glucose utilization in vitro.

The effect of the biguanides metformin and phenformin on glucose utilization in isolated cells was studied with IM-9 human lymphocytes. Both agents stimulated glucose consumption from the incubation media. Detectable effects of metformin were seen at 33 mumol/L and detectable effects of phenformin were seen at 1.7 mumol/L. Both agents, at similar concentrations, also stimulated [3H] 2-deoxy-D-glucose uptake. Studies with phenformin indicated that biguanides increase the Vmax of uptake without changing the Km. In contrast to the biguanides, IM-9 cells insulin did not influence either glucose consumption or [3H] 2-deoxy-D-glucose uptake. These data provide evidence, therefore, that biguanides may directly influence the cellular utilization of glucose.

Incidence of type I diabetes in the district of Catania, Sicily.

The incidence of type I (insulin-dependent) diabetes was determined in the district of Catania (eastern Sicily) in children under 15 years of age over a 3-year period (1 January 1989 to 31 December 1991). Two independent sources of information were used. The primary source was contact with all medical services in the province, and the secondary source was the personal identification cards issued to all diabetic patients by the National Health System necessary for obtaining free medical care. The information obtained was 99.6% complete. The overall incidence was 10.2/10(5) per year. This study provides the first standardized data on the incidence of type I diabetes in Sicily and is consistent with the possibility of regional deviations from the proposed north to south gradient.

Identification of a novel HLA-DPB1 allele, DPB1*02014, by sequence-based typing.

In this report we describe the identification of a novel DPB1 allele, DPB1*02014, found in an Italian Caucasian individual. The new allele was detected during routine HLA sequence-based typing (SBT) for an individual undergoing bone marrow transplantation. DPB1*02014 was identical to DPB1*02012 except for a single nucleotide substitution in codon 72 (GTG-->GTT). This nucleotide change represents a synonimous mutation, as both triplets code for a valine. This new allele has been submitted to GenBank and assigned the accession number AF326565. The WHO Nomenclature Committee has officially assigned the name DPB1*02014.

Treatment of NIDDM patients with secondary failure to glyburide: comparison of the addition of either metformin or bed-time NPH insulin to glyburide.

In this study we compared, in 12 NIDDM patients with secondary failure to glyburide, the effect of adding either a single, low-dose bed time NPH insulin injection (0.2 U/Kg) or an oral metformin administration (500 mg x 3) to the previously ineffective sulfonylurea treatment. The addition of both insulin and metformin treatment significantly improved fasting plasma glucose, post-prandial plasma glucose and %HbA1. The effect of both combined therapies was already evident and maximal after 2 weeks of treatment. The addition of bed-time NPH insulin caused a greater decrease of fasting plasma glucose, although the difference with the addition of metformin was not significant. In contrast, the average post-prandial plasma glucose decrease was significantly greater after metformin addition. The addition of bed-time NPH insulin caused a significant increase in average body weight, while after metformin addition, average body weight was unchanged; no change in the average cholesterol and triglyceride level was observed after either combined therapies.

A ten-year (1989-1998) perspective study of the incidence of Type 1 diabetes in the district of Catania (Sicily) in a 0-14 year age group.

The aim of this report was to evaluate the incidence of Type 1 diabetes mellitus (T1DM) in the district of Catania (eastern Sicily) in children under 15 yr of age over a ten-yr period (01/01/1989 - 31/12/1998) in relation to age, sex, monthly-seasonal variability, calendar yr and spatial clustering. The estimated completeness of our register was 99.2%. The overall incidence rate was 12.38 per 100,000 during the period of the study. Twenty-four percent of cases were 0-4 yr at diagnosis, 42% were 5-9 yr and 34% were 10-14 yr. More males (no. 148) than females (no. 125) were newly diagnosed with a male/female ratio similar to the base population ratio in the range 0-14 yr and within age groups. The study revealed a non-random spatial distribution of T1DM incidence in children not accounted for by known demographic factors. A significant seasonal pattern and temporal trend of incidence were also detected.

Efficacy of combined treatments in NIDDM patients with secondary failure to sulphonylureas. Is it predictable?

The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments.