Thyroid hormones modulate uric acid metabolism in patients with recent onset subclinical hypothyroidism by improving insulin sensitivity.

Some evidence suggests a relationship between thyroid dysfunction and uric acid (UA) metabolism, but the potential influential role of thyroid hormones on UA metabolism is still debated. This report was designed to evaluate the influential role of levothyroxine (L-T4) replacement therapy on circulating levels of UA in patients with recent onset post-thyroidectomy subclinical hypothyroidism. Circulating levels of thyroid hormones, UA and other metabolic parameters were assessed in 155 recently thyroidectomized patients (131 females, mean age 51.1 ± 12.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with L-T4. At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 8.2 ± 5.1 mU/mL, FT3 2.1 ± 0.7 pg/mL, FT4 9.2 ± 3.4 pg/mL). The mean serum UA concentration was 5.0 ± 1.3 mg/dL, while the prevalence of hyperuricemia, defined by serum UA levels > 6 mg/dL, was 22.6%. Serum UA levels at baseline were significantly correlated with HOMA-IR index (r = 0.475, p < 0.0001). After 2 months under the replacement therapy with L-T4, both serum UA levels (- 1.2 ± 0.9 mg/dL, p < 0.0001 vs. baseline) and HOMA-IR (- 0.3 ± 1.5 mmol/L, p = 0.0328 vs. baseline) significantly decreased. Multivariate regression analysis revealed that changes in HOMA-IR explained 23% of the variations of serum UA levels under L-T4 replacement therapy (ß = 0.295, p < 0.0001, R2 = 0.230). Our study suggests that thyroid hormones could modulate UA metabolism in patients with recent onset subclinical hypothyroidism likely by improving insulin sensitivity.

Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-κB nuclear binding and increase in PPARγ expression.

It is now well accepted that oxysterols play important roles in the formation of atherosclerotic plaque, involving cytotoxic, pro-oxidant and proinflammatory processes. It has been recently suggested that tomato lycopene may act as a preventive agent in atherosclerosis, although the exact mechanism of such a protection is not clarified. The main aim of this study was to investigate whether lycopene is able to counteract oxysterol-induced proinflammatory cytokines cascade in human macrophages, limiting the formation of atherosclerotic plaque. Therefore, THP-1 macrophages were exposed to two different oxysterols, such as 7-keto-cholesterol (4-16 µM) and 25-hydroxycholesterol (2-4 µM), alone and in combination with lycopene (0.5-2 µM). Both oxysterols enhanced pro-inflammatory cytokine [interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor α) secretion and mRNA levels in a dose-dependent manner, although at different extent. These effects were associated with an increased reactive oxygen species (ROS) production through an enhanced expression of NAD(P)H oxidase. Moreover, a net increment of phosphorylation of extracellular regulated kinase 1/2, p-38 and Jun N-terminal kinase and of nuclear factor kB (NF-κB) nuclear binding was observed. Lycopene prevented oxysterol-induced increase in pro-inflammatory cytokine secretion and expression. Such an effect was accompanied by an inhibition of oxysterol-induced ROS production, mitogen-activated protein kinase phosphorylation and NF-κB activation. The inhibition of oxysterol-induced cytokine stimulation was also mimicked by the specific NF-κB inhibitor pyrrolidine dithiocarbamate. Moreover, the carotenoid increased peroxisome proliferator-activated receptor γ levels in THP-1 macrophages. Taken all together, these data bring new information on the anti-atherogenic properties of lycopene, and on its mechanisms of action in atherosclerosis prevention.

Efficacy of the combined cabergoline and octreotide treatment in a case of a dopamine-agonist resistant macroprolactinoma.

Prolactinomas in males can be voluminous macroadenomas invading the surrounding structures. Medical therapy with dopamine agonists (the treatment of choice for these tumours) may be ineffective in the case of pharmacological resistance. In such cases, even surgical and/or radiation therapy cannot be curative due to the invasive potential of the adenoma. Hence, the appropriate therapeutic approach for these tumours is still a relevant clinical problem for endocrinologists. We report the history of an adolescent male who was diagnosed with a large invasive macroprolactinoma in 2002. He had severe bitemporal hemianopsia and hypopituitarism; prolactin levels at diagnosis were higher than 8,000 ng/ml. Medical therapy with cabergoline was initiated and resulted in decreased prolactin levels but not complete normalisation (maximal tolerated dose 3 mg/day). However, due to the worsening of the visual defect, the patient was operated in July 2004 through the trans-nasal approach and 2 years later through both the transcranial and the transphenoidal approaches. After the second surgery, a significant reduction of tumour mass was obtained. Immunohistochemistry for somatostatin receptors (sstr) subtypes showed a positive staining with the anti-sstr5 antibody. A scintigraphy with 111In-pentetreotide (Octreoscan) revealed a very intense tracer uptake in the sellar region. The administration of long-acting octreotide was initiated. After 12 months of therapy, prolactin levels normalised for the first time. Pituitary MRI did not reveal any tumor progression during a 2-year follow-up. This is a case of an invasive dopamine-resistant macroprolactinoma that was successfully controlled by extensive surgery and combined treatment with cabergoline and octreotide. The expression and functionality of sstr should be investigated in these tumours since a combined therapy with cabergoline and octreotide may be a good therapeutic course of action for select cases.

Tumor necrosis factor-alpha antagonism improves vasodilation during hyperinsulinemia in metabolic syndrome.

OBJECTIVE: Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha. We assessed the effects of TNF-alpha neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome. RESEARCH DESIGN AND METHODS: Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab. RESULTS: Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab. CONCLUSIONS: TNF-alpha neutralization ameliorates vascular reactivity in metabolic syndrome during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients.

Effect of the opioid blockade on the feeding-induced growth hormone response to growth hormone-releasing hormone in women with polycystic ovary syndrome.

OBJECTIVE: To investigate the effect of naloxone, an opioid receptor antagonist, on the release of growth hormone (GH) induced by the growth hormone-releasing hormone (GHRH) in normal-weight and obese women with PCOS in relation to feeding. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Seventeen women with PCOS (10 who were normal weight and 7 who were obese) and 14 control women (7 who were normal weight and 7 who were obese). INTERVENTION(S): A GHRH test (50 microg i.v.) and, on a different day, a GHRH test during a naloxone infusion (1.6 mg/h) during fasting. The same tests were repeated after a standard meal. MAIN OUTCOME MEASURE(S): GH response to GHRH (expressed as the area under the curve [AUC]) in different experimental conditions. RESULT(S): All normal-weight women showed a significantly higher AUC-GH compared with obese women in the fasting state. Normal-weight controls had a decrease in GH response to GHRH after feeding, and naloxone did not reverse the decrease. In obese controls, feeding increased the GH response but naloxone induced a decrease in the AUC. In fasting, normal-weight women with PCOS, naloxone significantly decreased the AUC-GH; in these patients, food intake induced an inhibition of GH response to GHRH, reversed by naloxone infusion. In obese PCOS patients, GH levels did not increase significantly after GHRH stimulation, either in the fasting state or after a meal, and naloxone did not affect these responses. CONCLUSION(S): Factors other than obesity and insulin may be involved in disruption of GH secretion in women with PCOS.

Naloxone decreases insulin secretion in hyperinsulinemic postmenopausal women and may positively affect hormone replacement therapy.

OBJECTIVE: To evaluate the influence of the opioid system on glyco-regulation in postmenopausal women before and after hormone replacement therapy (HRT). DESIGN: Prospective nonrandomized clinical study. SETTING: Academic research environment. PATIENT(S): Twenty-one healthy normo- or hyperinsulinemic postmenopausal women. INTERVENTION(S): Oral glucose tolerance test (OGTT) (saline study), OGTT with IV injection of naloxone (naloxone study), and hyperinsulinemic euglycemic clamp performed before treatment, after 12 weeks of estrogen replacement therapy (ERT), and after 12 additional weeks of estro-progestin combined therapy (i.e., HRT). MAIN OUTCOME MEASURE(S): Glucose, insulin, and c-peptide plasma levels assessed in fasting condition and during the two OGTTs (area under the curve [AUC]). Evaluation of fractional hepatic insulin extraction (FHIE) and peripheral sensitivity to insulin. RESULT(S): At baseline, there is a greater increase of the FHIE and a more significant reduction of the insulin AUC in the hyperinsulinemic patients during the naloxone study compared with the saline study. In these women, ERT enhanced the c-peptide AUC and improved the FHIE; naloxone infusion mainly increased these two parameters. HRT did not induce any further change. CONCLUSION(S): Endogenous opioid peptides are involved in the modulation of carbohydrate metabolism in menopause in hyperinsulinemic patients more than in other patients. The favorable changes of the glyco-insulinemic metabolism induced by HRT may be partially due to the induction of the opioidergic activity.

Prolactin/cortisol ratio in rheumatoid arthritis.

Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. PRL/cortisol ratio, and IL-1beta and TNF-alpha levels were determined in patients with RA and in control subjects at 0600, 1000, 1400, 1800, 2200, and 0200 hours. In patients with RA we observed higher PRL/cortisol ratio at 0200 hours, whereas IL-1beta and TNF-alpha reached their highest serum levels at 0200 and 0600 hours. In patients with RA we observed an imbalance in favor of proinflammatory hormones as opposed to levels of antiinflammatory hormones during nocturnal hours together with increased levels of IL-1beta and TNF-alpha of the diurnal rhythm of disease activity.

Estrogen treatment and body fat distribution are involved in corticotropin and cortisol response to corticotropin-releasing hormone in postmenopausal women.

To assess the effect of transdermal estrogen substitution on the hypothalamic-pituitary-adrenal (HPA) axis responsiveness/sensitivity and the impact of the antrophometric characteristics on these parameters, 20 postmenopausal women seeking treatment for the relief of postemenopausal symptoms were studied. They received transdermal 50 microg/d estradiol for 12 weeks (estrogen replacement therapy [ERT]). Patients were classified as low waist-to-hip ratio (WHR) (peripheral fat distribution women; n = 12) and high WHR (central fat distribution women; n = 8) according to the cut-off value of 0.85. Plasma hormone and lipid concentration were assessed at baseline and after 12 weeks of treatment. Results were compared with a group of 8 placebo-treated patients who served as controls. Corticotropin (ACTH) and cortisol (F) were expressed as fasting values, area under the curve (AUC), and time course over 90 minutes after corticotropin-releasing hormone (CRH) intravenous (IV) bolus (1 microg/kg body weight [BW]). Adrenal sensitivity to CRH stimulus was expressed as time course over 90 minutes and AUC of the F/ACTH molar ratio. The plasma F levels in response to ACTH stimulation did not change after ERT; however, a highly significant improvement of adrenal sensitivity was observed (P <.01). In fact, estrogen treatment significantly decreased the amount of ACTH produced after CRH stimulation, both as absolute time course and AUC (P <.01). No significant change was observed in controls. Considering body fat distribution, the high WHR group showed higher ACTH (P <.01), lower F/ACTH values, and superimposable F plasma values compared with the low WHR group. Estrogen treatment induced a significant ACTH reduction after CRH (P <.01) only in the high WHR group, whereas cortisol response was similar in both groups both before and after treatment. A significant negative correlation was found between WHR and adrenal sensitivity before treatment. ERT significantly improved adrenal sensitivity only in the low WHR group (P <.01). These data suggest that different mechanisms can prevail in the control of the HPA axis in menopause. Estrogens could exert different effects on the hypothalamic-pituitary axis, as well as on adrenal function, and these changes seem to be partially dependent on the pattern of body fat distribution.

Incidência de rotavírus no Hospital Infantil Menino Jesus (SP): ELISA, um método prático e eficaz para sua detecçäo / Incidence of rotavirus in the Menino Jesus Pediatric Hospital, Säo Paulo, Brazil: ELISA, a simple and efficient method for its detection

Utilizando-se o método ELISA (Enzyme Linked Immuno Sorbent Assay) para detecçäo de rotavírus em fezes de crianças com "doença diarréica aguda infecciosa" internadas na enfermaria de diarréia do Hospital Infantil Menino Jesus (SP), obtivemos 12 casos positivos para rotavírus em 70 crianças estudadas no período de março de 1983 a junho de 1984 (17,1% de positividade para o rotavírus). Além desses casos, encontramos o rotavírus em dois casos associados com bactéria enteropatogênica (Shighella). A idade das crianças positivas para o rotavírus variou de 2 meses a 4 anos e meio. Todas as crianças positivas para o rotavírus apresentaram vômitos e febre, e a relaçäo com infecçäo de vias aéreas superiores foi significante (dois casos). A maioria dos casos positivos foi colhida em dias de clima frio ou temperado. Apenas uma criança era eutrófica