The incidence of Hashimoto's disease in nodular goitre: the concordance in serological and cytological findings.

OBJECTIVE: To determine the incidence of Hashimoto's disease in nodular goitre and to ascertain the degree of the concordance between serological and cytological findings. METHODS: We retrospectively reviewed data from 188 patients who underwent a fine needle aspiration biopsy of the thyroid for uninodular or multinodular goitre with a documented serological level of antithyroid peroxidase (TPO) antibodies. AntiTPO antibodies were measured by immunochemiluminescent assay (Quest Diagnostics, Madison, NJ, USA). RESULTS: The study cohort consisted of 170 female and 18 male patients with a mean (+/- SD) age of 47.8 +/- 14.9 years. AntiTPO antibodies were positive in 74 (39.36%) of the individuals and negative in 114 (60.63%). The cytodiagnoses were as follows: 5 (2.6%) cancerous, 18 (9.5%) suspicious, 12 (6.3%) inadequate, 92 (48.9%) benign and 61 (32.4%) consistent with chronic lymphocytic thyroiditis (CLT). For further analysis, we excluded all inadequate specimens. Based on the final sample of 176 patients, the sensitivity and specificity of antiTPO antibody test to detect CLT in nodular goitre were estimated to be 76.38% and 94.23% respectively. The prevalence of CLT in nodular goitre based on cytological criteria was (35.46%) compared with (31.97%) goitre based on positive antiTPO titres only. CONCLUSION: There is a high degree of concordance between serological and cytological findings of CLT in people with nodular goitres. The high prevalence of CLT in nodular goitre justifies the use of antiTPO antibodies as part of the workup in this population.

The effect of healthcare provider education on diabetes management of hospitalised patients.

BACKGROUND: The importance of optimising blood glucose (BG) control in hospitalised patients is widely accepted. To determine whether focused education of physicians and nurses would result in measurable changes in glycaemic control, the effect of a diabetes-focused educational programme on point of care (POC) BG measures was monitored. METHODS: This programme included 2 h symposium and 2 h interactive session. The POC BG measures were determined at 2-month period prior to implementing the programme and the ensuing 7 months after. Outcome parameters included the mean BG values, the incidence of hyperglycaemia (BG > 180 mg/dl) and hypoglycaemia (BG < 60 mg/dl). The outcome parameters were analysed by comparing the Internal Medicine (target service) to other such as Neurology and Surgical Trauma where no programme was offered. RESULTS: On Internal Medicine, the mean BG decreased soon after implementing the programme and stayed lower than the baseline values over 7 months. The changes were significant at the third, fourth, seventh and the ninth month of the study. Hyperglycaemia decreased significantly (p < 0.05) on the third, fourth, seventh and eighth month, while hypoglycaemia increased following the education programmes. On Neurology and Surgical Trauma, the mean BG values were significantly higher, and hypoglycaemia was significantly lower during the same time frame. CONCLUSIONS: Implementing an educational programme for healthcare providers had significant effects on the lowering of mean BG values and the incidence of hyperglycaemia, but increased the risk of hypoglycaemia. The merits of such programmes need to be tested before their widespread implementation.

Serum leptin response to endogenous hyperinsulinemia in aging rats.

To determine if aging is associated with altered serum leptin response to diet-induced changes in endogenous hyperinsulinemia, male Fisher 344 (F344) rats at different age groups were studied while on regular rat chow and following 10 days of experimental diets consisting of 60% of the weight as fructose or glucose. The serum leptin concentration (ng/ml) gradually increased from basal levels of 2.5+/-0.1 at age of 4 months to 3.7+/-0.1, 6.9+/-0.9, 9. 4+/-0.3 and 8.9+/-1.1 at 6, 12, 18 and 24 months of age, respectively (P<0.001). Hyperinsulinemia associated with 60% fructose diet was associated with increased serum leptin levels in 4, 12, and 24 month old rats to 5.1+/-0.8, 6.7+/-1.2, and 8.6+/-1.1, respectively (P<0.001). Feeding 60% glucose diet also was associated with increased serum leptin levels in 4, 12 and 24 month old rats to 7.6+/-0.6, 7.2+/-0.7, and 9.1+/-1.1, respectively (P<0.001). Restricting dietary intake to 60% of the calories consumed by control rats for 10 days resulted in a decrease in serum leptin to 1.0+/-0.02 in 4 month old rats and 2.5+/-0.4 in 24 month old rats (P<0.01). It is concluded that aging in F344 rats is associated with increased serum leptin concentrations. However, diet-related hyperinsulinemic effect on leptin is blunted in aging rats although leptin response to caloric restriction is maintained. The inability of aging rats to mount hyperleptinemic response to dietary changes may contribute to the age-related increase in adiposity.

A rational approach to drug therapy of type 2 diabetes mellitus.

Several new pharmacological agents have recently been developed to optimise the management of type 2 (non-insulin-dependent) diabetes mellitus. The aim of this article is to briefly review the various therapeutic agents available for management of patients with type 2 diabetes mellitus and to suggest a potential approach to drug selection. There are three general therapeutic modalities relevant to diabetes care. The first modality is lifestyle adjustments aimed at improving endogenous insulin sensitivity or insulin effect. This can be achieved by increased physical activity and bodyweight reduction with diet and behavioural modification, and the use of pharmacological agents or surgery. This first modality is not discussed in depth in this article. The second modality involves increasing insulin availability by the administration of exogenous insulin, insulin analogues, sulphonylureas and the new insulin secretagogue, repaglinide. The most frequently encountered adverse effect of these agents is hypoglycaemia. Bodyweight gain can also be a concern, especially in patients who are obese. The association between hyperinsulinaemia and premature atherosclerosis is still a debatable question. The third modality consists of agents such as biguanides and thiazolidinediones which enhance insulin sensitivity, or agents that decrease insulin requirements like the alpha-glucosidase inhibitors. Type 2 diabetes mellitus is a heterogeneous disease with multiple underlying pathophysiological processes. Therapy should be individualised based on the degree of hyperglycaemia, hyperinsulinaemia or insulin deficiency. In addition, several factors have to be considered when prescribing a specific therapeutic agent. These factors include efficacy, safety, affordability and ease of administration.

Malondialdehyde binding of rat cerebral proteins is reduced in experimental hypothyroidism.

To determine the effect of thyroid hormones (TH) on cerebral tissue malondialdehyde (MDA) content and accumulation of MDA-bound proteins, hyperthyroid rats and hypothyroid rats were compared to euthyroid controls. Hyperthyroidism was induced by daily injection of l-3,5, 3'-triiodothyronine (15 ug (100 g)-1) intraperitoneally daily for 10 days. Hypothyroidism was induced with 0.025% methimazole in the drinking water for 4 weeks. Immunoblot analysis of cerebral and plasma proteins was carried out using a specific anti-MDA-protein antiserum. MDA was measured as thiobarbituric acid reactive substance. Hypothyroidism was associated with significant reduction in MDA-proteins of plasma (59.3+/-9.5% vs. 99.8+/-23.0% of control p<0.05) and cerebral tissue (17.6+/-19.9% vs. 100.2+/-29.0% of control p<0.001). Hyperthyroidism did not significantly alter MDA-protein distribution. These changes did not correlate with cerebral tissue or plasma MDA concentration. It is concluded that hypothyroidism in rats is associated with significant decrease in MDA-bound proteins. This may have some clinical and biological implications.

Age-related changes in thyroid hormone effects on glucose transporter isoforms of rat heart.

To determine the age-related changes in thyroid hormone (TH) effects on cardiac glucose transporter one (GLUT-1) and four (GLUT-4) isoforms, male Fischer 344 rats at 4, 12, and 25 months of age were studied at euthyroid, hyperthyroid and hypothyroid conditions. Hyperthyroidism was induced with daily intraperitoneal injections of triiodothyronine (15 microg/100 gm) for 10 days. Hypothyroidism was achieved with 0.025% methimazole in the drinking water for 4 weeks. Immunoblot analysis indicated that at euthyroid basal conditions GLUT-1 protein was not significantly altered with age while GLUT-4 protein was significantly reduced in 25 month old rats (82.0 +/- 28.8% of a 4 month old rat p <0.01). In 4 months old rats, GLUT-1 was increased in both hypothyroidism (432.5 +/- 208.7% of age-matched euthyroid control) and to a lesser extent in hyperthyroidism (242.0 +/- 93.3% of control) p<0.01. In 25 month old rats, hyperthyroidism was also associated with increased GLUT-1 mass (190.8 +/- 117.6% of age-matched euthyroid control) p<0.01. Hypothyroidism in this age group was not associated with significant change in GLUT-1 protein. The cardiac GLUT-4 protein was increased during both hypothyroidism and hyperthyroidism. The changes of GLUT-4 in aged rats were similar to those found in young rats. It is concluded that TH effect on GLUT-1 expression in the heart is altered with age while TH effects on GLUT-4 are age independent.

Implications of the UK prospective diabetes study: questions answered and issues remaining.

The UK Prospective Diabetes Study (UKPDS) provides the first conclusive proof for the importance of intensifying diabetes control in individuals with type 2 diabetes mellitus. However, reduction in cardiovascular disease risk with intensive therapy was modest and did not reach statistical significance. Metformin therapy in obese individuals with type 2 diabetes mellitus was associated with reduced cardiovascular death. These observations should be re-evaluated to determine whether various therapeutic agents available for treatment of type 2 diabetes mellitus have different effects on cardiovascular complications of diabetes. The addition of alpha-glucosidase inhibitor, acarbose, improved glycaemic control irrespective of concomitant therapy for diabetes, although compliance with this agent was poor. The tight blood pressure control study embedded in UKPDS reaffirms the importance of lowering the blood pressure below 150/85 to reduce microvascular and macrovascular complications of diabetes.

Monosaccharide-enriched diets cause hyperleptinemia without hypophagia.

To determine the effect of monosaccharide-enriched diets on plasma leptin and food consumption, body weight, food intake, and serum glucose, insulin, and leptin concentrations were measured in rats maintained on a 10-d course of 60% glucose or 60% fructose diet. The serum leptin concentration in rats fed a high-glucose diet (7.60 +/- 0.6 ng/mL) or a high-fructose diet (5.12 +/- 0.8 ng/mL) was significantly increased compared with that in control rats (2.45 +/- 0.10 ng/mL; P < 0.001). To ascertain that the observed effect was related to hyperinsulinemia, a group of rats were infused with exogenous insulin or rendered insulin resistent with a high-fat diet. When hyperinsulinemia was induced with exogenous infusion, the serum leptin was increased (5.56 +/- 0.23 ng/mL; P < 0.001). High-fat feeding was associated with increased serum leptin (12.1 +/- 1.4 ng/mL) and insulin levels. The increased serum leptin concentration was not associated with decreased food intake. We conclude that monosaccharide-enriched diets, probably through hyperinsulinemia or relative or absolute insulin resistance, cause hyperleptinemia, which does not appear to change feeding behavior.

Effect of select antioxidants on malondialdehyde modification of proteins.

To determine whether commonly used antioxidants alter malondialdehyde (MDA) modification of proteins, a known mechanism of free radical-related tissue injury, we studied the effect of adding 1 mg/mL of pycnogenol, 5 mM of alpha-tocopherol, 5 mM of ascorbate, and 0.2 mg/mL of an ethanol equivalent of red and white wine on MDA-protein content of endothelial cells in culture. The addition of pycnogenol but not of the other antioxidants was associated with significant reduction in MDA-protein content compared with controls (0.521 +/- 0.041 in arbritrary units versus 1.011 +/- 0.021, P < 0. 001). To determine whether the observed effect occurs distal to MDA generation, the effect of these antioxidants on the modification of bovine serum albumin with MDA generated in a cell-free system was studied. In this cell-free assay, pycnogenol but not the other antioxidants reduced MDA-BSA generation by approximately 50%. It is concluded that pycnogenol may reduce MDA modification of proteins at a step distal to MDA generation. This may be an additional mechanism of protective effects of pycnogenol against oxidative stress.

Role of repeated fine-needle aspiration of thyroid nodules with benign cytologic features.

OBJECTIVE: To determine the role of repeated fine-needle aspiration (FNA) biopsy in the evaluation of thyroid nodules initially classified as benign. METHODS: We retrospectively reviewed data on 235 patients with clinically palpable thyroid nodules who underwent a repeated FNA biopsy after an initially benign diagnosis. All the nodules were evaluated and biopsies were obtained by the same endocrinologist. Cytodiagnoses were divided into four major categories: inadequate, benign, suspicious, or malignant. RESULTS: The study cohort consisted of 211 female and 24 male patients with a mean age of 47.1 years. The repeated FNA cytodiagnoses were as follows: 204 (86.8%) remained benign and 19 (8.1%), 11 (4.7%), and 1 (0.4%) became inadequate, suspicious, and malignant, respectively. All patients with benign or inadequate cytologic results on repeated FNA who underwent thyroid surgical resection had benign histologic findings (N = 23). The mean follow-up period between the initial and the last benign FNA cytodiagnosis in the 186 patients without surgical intervention was 1,078 days (2.95 years). Nine of 11 patients with suspicious cytologic results underwent a thyroid surgical procedure, which revealed a benign lesion in 7 and malignant disease in 2 (18%). The other two patients with suspicious cytologic findings had a 13-year clinical follow-up without any clinical evidence of a thyroid malignant lesion. The only patient with malignant cytologic findings on repeated FNA (a 76-year-old woman) refused surgical treatment and was lost to follow-up. CONCLUSION: Although the yield of finding a malignant lesion on repeated FNA biopsy in the follow-up of a presumably benign thyroid nodule may be low, rebiopsy reduces the rate of false-negative diagnosis from an average of 5.2% to <1.3%.

Delayed recovery of thyrotropin responsiveness after radioactive iodine therapy for hyperthyroidism.

BACKGROUND: After radioactive iodine therapy for hyperthyroidism, an expected lag in the responsiveness of thyrotropin (TSH) is 60 to 90 days. In our experience, however, many patients seemed to have a more prolonged lag in TSH recovery. METHODS: A retrospective chart review was performed in 58 patients who underwent radioactive iodine therapy for hyperthyroidism (52 with Graves disease, 5 with toxic nodular goiters, and 1 with a toxic adenoma). RESULTS: Forty-nine patients (84%) had appropriate responses of TSH for their level of serum thyroid hormone. Thirty-one became hypothyroid, 12 became euthyroid, and 6 remained hyperthyroid. Nine patients (16%) had a lag in their TSH responsiveness. The TSH remained low for 3 months in 5 patients, for 9 months in 3 patients, and 1 patient had low levels of serum TSH for at least 12 months. CONCLUSIONS: After radioactive iodine therapy for hyperthyroidism, decisions upon further therapy must be based upon the clinical status as well as the serum levels of TSH and thyroid hormones.

Dose-response profile of acarbose in older subjects with type 2 diabetes.

OBJECTIVE: To examine the dose-response relationship of acarbose, an alpha-glucosidase inhibitor, in older subjects with type 2 diabetes. RESEARCH DESIGN: Fourteen subjects with type 2 diabetes who were over 65 years old were studied. Five subjects had been treated with diet alone and 9 were receiving a sulfonylurea. The subjects underwent a meal tolerance test in the presence of varying doses of acarbose (0, 25, 50, and 100 mg) on 4 occasions, each 1 week apart. The test meal was chosen to include food items commonly consumed during breakfast in the United States. The 483-kcal meal consisted of 51% of calories in the form of carbohydrates, 14% protein, and 35% fat. The serum glucose, insulin, and triglyceride levels were measured at 0, 1, and 2 hours after the meal. RESULTS: The postprandial hyperglycemic response to the test meal was significantly reduced with 25 mg of acarbose compared with baseline values. Increasing doses of acarbose to 50 or 100 mg had no significant additional ameliorating effects on postprandial hyperglycemia. Postprandial insulin or triglyceride levels were not significantly altered with single dose acarbose treatment. CONCLUSIONS: It is concluded that the acute efficacy of acarbose is near maximal at 25 mg when the meal size does not exceed 483 kcal and contains only 61 gm of carbohydrates.

Supplementation of pre-oxygenation in morbidly obese patients using nasopharyngeal oxygen insufflation.

During apnoea following induction of anaesthesia, morbidly obese patients may suffer a rapid decrease in oxygen saturation. This study compares pre-oxygenation alone with pre-oxygenation followed by nasopharyngeal oxygen insufflation on the onset of desaturation occurring during the subsequent apnoea. A randomised controlled trial was performed in 34 morbidly obese patients undergoing gastric bypass or gastric band surgery. Seventeen patients received nasopharyngeal oxygen supplementation following pre-oxygenation (Study group, body mass index = 41.8 (6.9) kg.m(-2)), and the other 17 patients received pre-oxygenation alone (Control group, body mass index = 42.7 (5.4) kg.m(-2)). Time from the onset of apnoea until S(p)o(2) fell to 95% was compared between the two groups with a cut-off of 4 min. In the control group, the S(p)o(2) fell from 100% to 95% during the subsequent apnoea in 145 (27) s, with a significantly negative correlation (r(2) = 0.66, p < 0.05) between the time to desaturation to 95% and the body mass index. In the study group, the S(p)o(2) was maintained in 16 of 17 patients at 100% for 4 min when apnoea was terminated. In conclusion, nasopharyngeal oxygen insufflation following pre-oxygenation in morbidly obese patients delays the onset of oxyhaemoglobin desaturation during the subsequent apnoea.

Age-related changes in the thyroid hormone effects on malondialdehyde-modified proteins in the rat heart.

To determine the age-related changes in thyroid hormone (TH) effects on malondialdehyde (MDA)-modified proteins in cardiac tissue, rats at 4, 12, and 25 months of age were studied. Hyperthyroidism was induced with daily injection of L-triiodothyronine (15 microg/100 g) intraperitoneally for 10 days. Hypothyroidism was induced with 0. 025% methimazole in the drinking water for 4 weeks. MDA proteins were measured with immunoblots using a specific anti-MDA antiserum. MDA was measured as thiobarbituric acid reactive substance. Hypothyroidism in 4-month-old rats was associated with significant reduction in MDA proteins compared to euthyroid rats (13.4 +/- 5.9% vs. 99.8 +/- 10.4% of controls P < 0.001). Hyperthyroidism did not result in a significant change of MDA proteins. In aged rats, neither hypothyroidism nor hyperthyroidism was associated with significant changes in cardiac MDA proteins. The changes in MDA proteins did not correlate with cardiac MDA concentrations. In young rats, the MDA concentrations (nmol/mg) were significantly reduced in hypothyroidism (2.71 +/- 0.21) and were increased in hyperthyroidism (8.19 +/- 0.78) compared to euthyroid values (5.06 +/- 0.71) P < 0. 01. In aged rats, cardiac MDA content was significantly increased during both hyperthyroidism and hypothyroidism. We conclude that alterations in MDA protein content is yet another potential biochemical effect of TH in cardiac tissue. This particular effect is significantly blunted with age.

Age-related changes in plasma leptin binding activity in rats: A comparison of a simple acid-ethanol precipitation technique with column chromatography.

A novel assay for measuring the free leptin fraction was developed and validated against a chromatographic technique. The assay used acid-ethanol extraction (AEE) for separation of bound/free leptin moieties. The interassay coefficient of variation was 3.9%. The specificity for leptin binding was confirmed by incubation with 1 microg of unlabeled rat leptin that effectively competed with radiolabeled leptin whereas human growth hormone and interleukin-6 were ineffective in competing with radiolabeled leptin binding. Scatchard analysis of competitive binding experiments with rat plasma demonstrated a linear relationship with a binding affinity of 0.3-0.6 x 109 M-1. This novel assay was used to determine if age-related insensitivity to leptin action is secondary to altered serum leptin binding. Rats at various age groups were studied for changes in body adiposity and serum total and free leptin concentrations. Serum free leptin concentrations (ng/ml mean +/- SEM) were significantly increased in 24-month-old rats (5.56 +/- 0. 21) compared with 18-month-old rats (4.76 +/- 0.17) (P < 0.01) despite similar body weight and adiposity of the two age groups. The increase in plasma free leptin concentrations in 12-month-old rats (3.86 +/- 0.28) and 6-month-old rats (2.05 +/- 0.06) relative to 3-month-old rats (1.37 +/- 0.06) (P < 0.001) was out of proportion to the increase in body adiposity in aging rats. It is concluded that aging in rats is associated with relative insensitivity to leptin. This change cannot be attributed to increased plasma binding or to a reduction in the leptin free fraction.

Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia.

BACKGROUND: Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. METHODS: One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 microg nalmefene, or 25 microg nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation. RESULTS: The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nahmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nahmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h. CONCLUSION: Compared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine.