Endocrine

The ovaries' innervation arrives via the superior ovarian nerve, which originates from the celiac ganglion. Using True Blue as an antidromic marker, the present study analyzed the changes in the anatomical relation between each ovary and the prevertebral celiac-superior mesenteric ganglia during the estrous cycle. The number of labeled neurons increased from the day of diestrus 1 to the day of proestrus. The largest number of labeled cells was observed when tracer was injected into the left ovary on proestrus. The number of labeled cells was significantly higher when the tracer was injected into the left ovary on proestrus than when it was done in the right one. When tracer was injected into the left ovary, the average labeled area of cells increased significantly from diestrus 1 to proestrus, and declined at estrus. In contrast, when True Blue was injected into the right ovary, the average labeled area was similar in diestrus 1 and diestrus 2, and the values increased in proestrus and estrus. The results indicate an apparent asymmetry in the activity of neural connections between ovaries and the prevertebral celiac-superior mesenteric ganglia, and that the number of active neurons of these connections varies during the estrous cycle.

Breast cancer is the most common malignancy among women worldwide. There is extensive literature on the relationship between body weight and breast cancer risk but some doubts still remain about the role of adipokines per se, the role of insulin and glucose regardless of obesity, as well as the crosstalk between these players. Thus, in this study, we intend to determine the relation between body mass index (BMI), glycaemia, insulinemia, insulin-resistance, blood adipokine levels and tumour characteristics in a Portuguese group of pre- and postmenopausal overweight/obese women with breast cancer. We evaluated clinical and biochemical data in 154 participants, divided in 4 groups: (1) control with BMI <25 kg/m(2), n = 29 (CT); (2) control with BMI >25 kg/m(2), n = 48 (CTOb); (3) breast cancer with BMI <25 kg/m(2), n = 30 (BC); and (4) breast cancer with BMI >25 kg/m(2), n = 47 (BCOb). In women with breast cancer, we also performed tumour characterization. We found that BCO...

Purpose Pancreatic neuroendocrine neoplasms (PNENs) are a group of clinically rare and heterogeneous tumors of the pancreas. Currently there are no studies investigating the gender difference in PNEN susceptibility. Thus, the purpose of this study was aimed at examining how gender shapes risk factors, clinicopathological features, and comorbidities in PNENs. Methods The study design consisted of an Italian multicenter, retrospective study. The study included all consecutive patients with PNENs followed at the participating centers. Two hundred and twenty-nine patients (105 males,124 females, age 54 ± 0.98 years) with PNENs were enrolled at the participating centers. The clinicopathological features (age, gender, BMI, histology, tumor size, tumor grade, distant metastasis, hormonal function, and diagnostic circumstances), comorbidities (cardiovascular diseases (CVD), pancreatitis, type 2 diabetes (T2DM), and potential risk factors (smoking and drinking) were included in the analysis. Results Females were slightly prevalent (54.15%). PNENs were diagnosed at younger age in females compared to males (p = 0.04). The prevalence of CVD was significantly higher in males than in females (p = 0.006). In the female group, the presence of T2DM was significantly associated with higher tumor grade (p = 0.04) and metastatic disease (p = 0.02). The proportion of smokers and alcohol drinkers was significantly higher in the male group (p < 0.001). No significant gender differences were detected regarding the other parameters included in the analysis. Conclusions This study has identified gender differences of PNENs in terms of age at diagnosis, associated comorbidities, and potential risk factors. A gender-tailored approach could become a potential strategy to better understand the natural history of PNENs and improve the effectiveness of PNENs clinical management.

Objective. Polycystic ovary syndrome may be associated with an increased risk of endometrial hyperplasia and endometrial cancer, but substantial evidence for this remains to be established. We investigated the prevalence of endometrial hyperplasia and endometrial cancer in a well characterized group of women with polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism. Design. Retrospective observational trans-sectional study. Setting.

The purpose of this study was to investigate the effects of resistance training (RT) on novel cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). We enrolled 52 overweight/obese, type 2 diabetic patients, with inadequate glycemic control (HbA1c [ 6.5 %), but without overt diabetic vascular complications. Participants were randomly assigned into two equivalent groups (n = 26): (1) Resistance exercise group: subjects underwent a supervised RT program (3-times/week, 60 min/session, 2-3 sets of 8 machine-weight exercises, 60-80 % of onerepetition maximum). (2) Control group (CG): at study entrance, they received a structured exercise counseling to increase daily physical activity. Clinical parameters, cardiorespiratory capacity, glycemic and lipid profile, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), Lipoprotein(a) [Lp(a)], insulin resistance (HOMA-IR), highsensitivity CRP (hsCRP), fibrinogen were measured before and after 3 months. RT significantly reduced glycemic indexes, insulin resistance and systolic blood pressure, compared to CG (p \ 0.05). Moreover, exercise-treated patients conferred a remarkable downregulation in ApoB levels (from 135.92 ± 30.97 mg/dL to 85.9 ± 26.46 mg/dL, p \ 0.001) as compared to CG (from 126.33 ± 36.59 mg/dL to 116.23 ± 27.52 mg/dL, p = 0.872) (p \ 0.001). Similarly, ApoB/ApoA-I ratio was considerably decreased in REG rather than CG (-0.32 ± 0.09 vs 0.02 ± 0.01, p \ 0.001). Notably, ApoA-I, Lp(a), hsCRP, fibrinogen, the rest of lipid parameters, body weight and exercise capacity remained unaltered in both groups (p [ 0.05). Among variables, HOMA-IR reduction was found to be an independent predictor of changes in ApoB/ApoA-I ratio (R 2 = 0.406, p = 0.041) in REG. Long-term RT ameliorated glycemic control, insulin sensitivity and ApoB/ApoA-I ratio in individuals with T2DM. Although we did not observe significant benefits in the rest of cardiovascular risk factors, our results indicate a merely beneficial impact of RT.

The present study is an evaluation to determine the toxicity level of benzene and ethanol extracts of Citrus medica seeds in the endocrine organs of female albino Swiss albino mice (Mus musculus) at the dose level of 200mg and 400mg/kg body weight for 15 days. The results exposed that the (administered of extract of C. medica seeds to female mice observed) changes in the gain/loss of body weight, organ weight (Liver, Kidney, Adrenal, Ovary and Uterus) morphological and behavioural studies. The detection of haematotoxicity, haemoglobin concentration, total RBC, WBC counts and total differential count were evaluated. The biochemical (Blood Sugar, Serum Cholesterol, Total Protein and Blood Urea Nitrogen) and histological changes in the liver, ovary and uterus were also determined. All the parameters of benzene extract treated mice were found to be within normal range, when compare to control. The data suggest that the ethanol extract of C. medica seeds at both the dose level administration for 15 days little effective and shown almost significant level of toxicity on liver as well as reproductive organs.

We propose that excessive fructose intake (>50 g/d) may be one of the underlying etiologies of metabolic syndrome and type 2 diabetes. The primary sources of fructose are sugar (sucrose) and high fructose corn syrup. First, fructose intake correlates closely with the rate of diabetes worldwide. Second, unlike other sugars, the ingestion of excessive fructose induces features of metabolic syndrome in both laboratory animals and humans. Third, fructose appears to mediate the metabolic syndrome in part by raising uric acid, and there are now extensive experimental and clinical data supporting uric acid in the pathogenesis of metabolic syndrome. Fourth, environmental and genetic considerations provide a potential explanation of why certain groups might be more susceptible to developing diabetes. Finally, we discuss the counterarguments associated with the hypothesis and a potential explanation for these findings. If diabetes might result from excessive intake of fructose, then simple public health measures could have a major impact on improving the overall health of our populace. (Endocrine Reviews 30: 96 -116, 2009)

HIV-infected patients on highly active antiretroviral therapy (HAART) have increased prevalence of a number of chronic metabolic disorders of multifactorial but unclear etiology. These include disorders of lipid metabolism with or without lipodystrophy, insulin resistance, and an increased prevalence of impaired glucose tolerance, diabetes mellitus and cardiometabolic syndrome. While much attention has been focused on the lipid and cardiovascular disorders, few investigations have attempted to characterize the prevalence, incidence, etiology, mechanisms and management of glycemic disorders in HIV patients. In this review, we have focused specifically on a comprehensive assessment of dysglycemia in the context of HIV infection and HAART.

Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro-or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treat-ment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.

The purpose of this study was to determine the influence of endogenous circulating testosterone (T) on muscle androgen receptor (AR) responses to acute resistance exercise (RE). Six healthy men (26 ± 4 years; 176 ± 5 cm; 75.8 ± 11.4 kg) performed a knee extension exercise protocol on two occasions separated by 1-3 weeks. Rest preceded one trial (i.e., control [CON] trial) and a high-volume upper-body RE protocol designed to increase circulating T preceded the other trial (i.e., high T [HT] trial). Serial blood samples were obtained throughout each trial to determine circulating T concentrations. Biopsies of the vastus lateralis were obtained pre-RE (REST), 10-min post-RE (+10), and 180-min post-RE (+180) to determine muscle AR content. Circulating T concentrations remained stable during CON. Alternately, HT significantly (p ≤ 0.05) increased T concentrations above resting values (+16%). Testosterone area-under-the-time curve during HT exceeded CON by 14%. AR content remained stable from REST to +10 in both trials. Compared to the corresponding +10 value, muscle AR content at +180 tended to decrease during CON (−33%; p = 0.10) but remained stable during HT (+40%; p = 0.17). Muscle AR content at +180 during the HT trial exceeded the corresponding CON value. In conclusion, acute elevations in circulating T potentiated muscle AR content following RE.

The physiology of erection has received intense clinical and basic research scrutiny over the past two decades. This massive effort has led to a much clearer understanding of the macroscopic aspects of erection as well as identification of the prominent features of the etiology of erectile dysfunction (ED). However, it is clear that the devil is in the details of the erectile process. Therefore, to truly understand the precise mechanistic basis for erection and ED, much more still must be learned about how the biochemical cascades in the corporal smooth muscle cells are integrated to produce a normal erection, or how they are altered to result in ED. The ultimate goal of these basic research and clinical efforts will be to provide a rational scientific basis for mechanism-based, patient-specific therapies for ED. This article reviews fundamental aspects of the physiology of erection and summarizes the most recent information available concerning the putative biochemical correlates o...

Secondary hypertension affects a small but significant number of the hypertensive population and, unlike primary hypertension, is a potentially curable condition. The determinant for workup is dependent on the index of suspicion elicited during patient examination and treatment. Specific testing is available and must be balanced depending on the risk and cost of the workup and treatment with the benefits obtained if the secondary cause is eliminated. This article reviews common manifestations, workup, and the current treatments of the common causes of secondary hypertension.

THE development of sexual maturity and reproductive function in the male is dependent upon appropriate secretion of hormones that orchestrate the sophisticated relationship between the hypothalamus, pituitary, and testes -the hypothalamic-pituitary-gonadal (HPG) axis. A state of hypogonadism, i.e. inadequate testicular function, is manifested by deficiencies in secretion of androgens, with a wide range of effects on a number of physiological processes, including gametogenesis. Any dysfunction in the HPG axis can result in hypogonadotrophic hypogonadism, where a decrease in endocrine and/or gametogenic function of the testes results in retardation of puberty and reproductive insufficiency .

There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.

The gastrointestinal tracts (GIT) of fish and other vertebrates are challenged with a diversity of functional demands caused by changes and differences in dietary inputs and environmental conditions. This contribution reviews how hormonal regulation plays an essential role in modulating the GIT functions of fish to match changes in functional demands. Exemplary is how hormones produced by the GIT, the associated organs (e.g., pancreas), and other sources (e.g., hypothalamus, adrenal cortex, thyroid, gonads) modulate the digestive processes (motility, secretion, and nutrient absorption) in response to dietary inputs. Hormones regulate the other GIT functions of osmoregulation (secretion and absorption of electrolytes and water), immunity, endocrine secretions, metabolism, and the elimination of toxic metabolites and environmental contaminants to match changes in environmental conditions and physiological states. Although the regulatory molecules and associated signaling pathways have been conserved during evolution of the vertebrate GIT, the specific responses often vary among fish with different feeding habits and from different environments, and can differ from those described for mammals. D

This study estimates diagnostic performance of late-night salivary cortisol (LNSC) as measured by automated electrochemiluminescence immunoassay (ECLIA), evaluates the clinical implication of two consecutive LNSC measurements, and compares its accuracy with enzymelinked immunosorbent assay (ELISA) and serum cortisol after low-dose dexamethasone suppression test (DST) in obese and overweight patients referred for suspected Cushing's syndrome (CS). One hundred twenty three consecutive obese and overweight referred patients and 98 healthy volunteers provided two saliva samples collected at 23:00 using a Salivette (Sarstedt, Germany), assayed by ECLIA (Cobas e601) and ELISA. The patients underwent DST and were further evaluated until CS was pathologically confirmed (n = 45) or excluded. Diagnostic performance of LNSC was evaluated by receiver operating characteristic (ROC) analysis. The total areas under the curve (AUC) were calculated to compare the different tests. We found that a cut-off value of 9.4 nmol/l can differentiate CS among obese and overweight patients with sensitivity of 84.4 % (95% CI 71.2-92.2), specificity of 92.3 % (95% CI 84.2-96.4), and diagnostic odds ratio of 65.1 (95% CI 20.4-207.6). No difference was found between AUCs from the first, second, and the mean from the two LNSC measurements (ECLIA), LNSC (ELISA), or DST. The single LNSC (ECLIA) and DST improved the sensitivity and specificity for concordant results up to 100 and 97.4 %, respectively. In conclusion, due to its automation and its comparable diagnostic performance, ECLIA is preferable as a first-line LNSC screening test for CS. The initial use of single LNSC followed by DST provides better diagnostic performance for concordant results.

Clinicians use nodule size to determine which thyroid nodules should receive cytological evaluation. The American Thyroid Association (ATA) has recommended against cytological evaluation for nodules &lt;1 cm. It is unknown, however, if nodule size can accurately discriminate lesions that will represent tumors with favorable versus unfavorable prognosis. Also, the characteristics of thyroid cancers that would not be diagnosed if a strict 1 cm size cut off is used as the threshold for biopsy of intrathyroidal nodules are not well established. Using the Rochester Epidemiology Project, a population-based cohort, we identified all thyroid nodules in Olmsted County residents from 2003-2006. To assess the presence of favorable or unfavorable features for each nodule size cutoff, each patient found to have thyroid cancer was risk-stratified using the ATA risk score, which predicts risk of recurrence and persistent disease. Thyroid cancer cases in which a biopsy was done for factors other th...

Early Descriptions of Diabetes Ancient records up to 3000 years old describe a disease in youth that was sudden in onset, resulted in acute metabolic decompensation, and culminated in death. Although this clinical picture described millennia ago was likely that of diabetes, the first accepted description of diabetes as a disorder associated with increased urine output came from ancient Egypt (the Ebers papyrus) around 1550 B.C. It was not until the second century B.C. that the term ''diabetes'' was used. Credit for coining ''diabetes'' is given to Demetrios of Apamaia who derived the term from the Greek word diabeinein, meaning ''siphon'' or ''pass through.'' Aretaeus of Cappadocia reported the first clinical description of the disease in the second century A.D. using the term ''diabetes.'' Focusing on the polyuric aspect of diabetes, he wrote of the ''melting down of flesh and limbs into urine'' and stated that the disease was infrequent. Diabetes was recognized in Indian medicine in the fifth and sixth centuries as a disorder associated with the production of sweet urine that attracted insects. The term diabetes did not appear in an English text until 1425. In 1674, Thomas Willis, physician to England's King Charles II, became the first European to discover the sweetness in the urine of those afflicted with diabetes. Perhaps the first English diabetes epidemiologist, Thomas, also noted the importance of lifestyle in the development of diabetes. He noted that the prevalence of diabetes was increasing because of ''good fellowship and gusling down chiefly of unalloyed wine.'' A century later, Matthew Dobson proved that the sweetness in urine was caused by sugar and was associated with sugar in the blood. John Rollo was the first person to coin the term ''diabetes mellitus'' (mellitus from Latin for honey) and distinguished this disease from another disease of polyuria, ''diabetes insipidus'' (insipidus from Latin for tasteless) around the turn of the 18th century.

Several epidemiological, pathophysiologic and clinical data demonstrate the interrelationship between upper and lower airways, and common features between inflammatory pathways and disorders of the nasal and bronchial mucosa have been emphasized both in the clinic (ARIA guidelines [1]) and in basic science, and reflected by numerous reviews on this topic. In contrast, detailed comparative analysis of basic defence mechanisms in upper versus lower airways and its clinical relevance is lacking.

Recently, hyperketonemia induced by fasting or ketogenic diet calls attention because of the possibilities for various clinical applications. Animal species comparisons and biochemical data show that all fetuses can develop by using ketogenic energy through a pathway which seems to have been maintained. We hypothesized that 3-β-hydroxybutyrate (β-HB) could be the fuel for the basic engine that produces energy in all terrestrial species. However, ATP production from glucose-pyruvic acid pathway seems to be added as a dominant system in human. We hypothesize the establishment of TCA cycle in mitochondria and enough oxygen supply since two billion years ago would be the key events to promote this change. The efficacy of ATP production from β-oxidation product is 10 ATP molecules, while it is 12.5 molecules from pyruvic acid. So, evolution should select glucose burning system as a booster engine for energy production. The liver and kidney are major ketone producing organs which contain abundant glycogen particles. So, a close relationship between ketone and glucose burning system may be present. This explains why certain level of glucose is steadily maintained even in the hyperketogenic state. Ketogenic diets efficiently treat with gestational diabetes. Placenta is the ketogenic tissue which reflects high concentration of ketones in umbilical cord blood. In addition to the role of energy source, β-HB shows various pharmacological effects on disease prevention, such as cardiovascular disease, Alzheimer’s disease, epilepsy, etc. Inhibition of histone deacetylase, stimulation of FOXO, resistance to oxidative stress, protection of mitochondria, stimulation of adiponectin release, suppression of inflammasome, etc. are included. The contribution of intestinal microbiota to ketone body production should open a new field of medicine. Altogether, the above data suggest that longer-term human studies are necessary to exclude risks of unbalanced diet and to confirm the best combination of fuels for
energy production, disease prevention and medical treatment.

Disease affecting the avian endocrine system is discussed: neoplasia, goiter, hypothyroidism, hyperparathyroidism, hypocalcemia syndrome, adrenal conditions and diabetes mellitus. Clinical diagnostic procedures such as TSH and ACTH stimulation tests and the use of plasma insulin and glucagon concentrations are reviewed.

Type 2 diabetes and other non-communicable diseases (NCD) are a growing public health challenge globally. An estimated 285 million people, corresponding to 6.4 % of the world's adult population has diabetes. This is expected to reach 552 million by 2030, 7.8 % of the adult population, with the African region expected to experience the greatest increase. A much larger segment of the world's population, approximating 79 million individuals in the US alone, has prediabetes. Multiple factors including genetic predisposition, insulin resistance, increased insulin secretory demand, glucotoxicity, lipotoxicity, impaired incretin release/action, amylin accumulation, and decreased b-cell mass play a causative role in the progressive b-cell dysfunction characteristic of prediabetes. Interventions preventing progression to type 2 diabetes should therefore delay or prevent b-cell failure. This article will first review the principal pathophysiological mechanisms underlying prediabetes and subsequently address treatment considerations based on these in the prevention of type 2 diabetes. In view of long-standing safety data with demonstrated efficacy and cost-effectiveness in the prevention of type 2 diabetes in high-risk individuals, metformin should be considered as initial therapy for those unable to comply with or lifestyle modification or where the latter has been ineffective in decreasing progression to type 2 diabetes.

Resumen La glándula tiroides, es uno de los órganos endocrinos encargado de la regulación de diferentes procesos metabólicos, sintetiza las hormonas tiroideas, tiroxina y triyodo-tironina, necesarias para el funcionamiento del organismo. El hipotiroidismo, es una condición en la cual la glándula tiroides no puede producir la suficiente cantidad de hormonas tiroideas necesarias para cumplir con el requerimiento tisular, es el desor-den más común de la tiroides y una de las principales alteraciones endocrinas. Las causas más comunes son la deficiencia de yodo y la tiroiditis autoinmune linfocítica crónica. El cuadro clínico del hipotiroidismo es bastante amplio afectando diferentes órganos y sistemas. El manejo de esta patología se hace con reemplazo hormonal, para ello levotiroxina es la indicación. El hipertiroidismo por su parte, hace referencia al incremento sostenido de las hormonas tiroideas debido al aumento de biosíntesis y secreción de la tiroides. Entre las principales causas se encuentra la enfermedad de Graves Basedow (EG). Su presentación clínica es amplia y varía de asintomática a una tormenta tiroidea que compromete la vida del paciente. El tratamiento está ba-sado en medicamentos antitiroideos pero también se han diseñado otras alternativas como yodo radioactivo y tiroidectomía. También las enfermedades que afectan direc-tamente la tiroides, como el cáncer, son de gran importancia; la evidencia obtenida en numerosos estudios sugiere que los polimorfismos genéticos influencian el riesgo de carcinogénesis y que la susceptibilidad genética es un factor importante para el desarrollo del cáncer. Los avances genéticos en esta patología han permitido una compresión mas a fondo de las diferencias en el comportamiento de los trastornos tiroideos entre una persona y otra, así mismo han generado un nuevo punto de partida para el tratamiento farmacológico.

The findings in hyperthyroid patients with Graves' orbitopathy (GO) of antibodies against antigens shared between the thyroid and orbit, such as the TSHreceptor (TRAb) and a novel protein G2s (G2sAb), suggested a possible common therapeutic strategy. However, the gold therapeutic standard for hyperthyrodism in these patients remains still unsettled and is mainly based on personal experience. Studies on the effect of total thyroidectomy (TT) alone or followed by radioiodine ablation (RAI) of thyroid remnants showed often conflicting results. This longitudinal study was aimed at evaluating the influence of TT alone or followed by post-surgical RAI with respect to methimazole treatment on the activity and severity of GO in patients with hyperthyroidism and GO. Sixty consecutive patients with Graves' disease and mild/ moderate GO were studied and grouped as follows: group 1, including 25 patients (16F, 9M) undergoing TT alone; group 2, including 10 patients (8F, 2M) undergoing TT followed by RAI for histological evidence of differentiated thyroid cancer; group 3, including 25 patients (18F, 7M) euthyroid under methimazole therapy, studied as controls. Clinical study of ophthalmopathy and measurements of TRAb and G2sAb were performed in all patients at start of the study (time of TT for group 1 and RAI after TT for group 2 and of the first finding of euthyroidism under methimazole treatment for group 3) and after 6, 12, 24 months. Patients of both groups 1 and 2 showed an early significant decrease and a further progressive reduction of the activity and severity of GO with a disappearance of TRAb and a decrease of G2sAb levels during the followup, without statistically significant differences between the two groups. Patients in group 3 showed a much later and less marked improvement of GO with persistence of TRAb and G2sAb positivity, even if with reduction of TRAb levels at 12 and 24 months. Our results suggest that in Graves' patients with large goiter or relapse of hyperthyroidism and mild/moderate GO, TT alone could be an advisable choice to treat hyperthyroidism also improving GO with reduction of cost/benefit ratio.

Alpha II-spectrin (alpha-fodrin) is a demonstrated endogenous substrate for caspase-3 in neurons undergoing unscheduled apoptotic death. We have previously identi®ed the caspase cleavage site that yields the distinctive 120 kDa spectrin breakdown product (SBDP120) as (DSLD 1478 ÃSVEAL). Here, by using a synthetic peptide (NH 2 -SVEALC) mimicking the neo-N-terminal of SBDP120 as antigen, we report the development of chicken antibodies that speci®cally recognize the SBDP120 generated by in vitro caspase-3 digestion of bovine alpha-spectrin on Western blot. These anti-SBDP120 antibodies recognize SBDP120 generated by two apoptotic challenges (staurosporine, EGTA) to human neuroblastoma SH-SY5Y cells. Yet they neither react with intact alpha-spectrin nor its other fragments on Western blots. These anti-SBDP120 work equally well in detecting SBDP120 generated in rat cerebellar granule neurons undergoing potassium withdrawal-induced apoptosis. In immunocytochemical studies, these antibodies also speci®cally stained apoptotic SH-SY5Y or CGN's undergoing apoptosis in a caspase-inhibitor-sensitive manner. These anti-SBDP120s might become powerful markers for apoptotic neurons in various neurological or neurodegenerative conditions in vivo. 7

In the present study, we investigated the protein levels and phosphorylation status of the insulin receptor and insulin receptor substrates (IRS-1, IRS-2, and IRS-3) as well as their association with PI(3)-kinase in the rat adipose tissue of two models of insulin resistance: dexamethasone treatment and aging. AKT and atypical PKC phosphorylation detection were also performed. Both models showed decreased insulin-induced IRS-1 and IRS-2 tyrosine phosphorylation, accopanied by reduced protein levels of IRS-1 and IRS-2. Nevertheless, IRS-3 protein level was unchanged in aging but increased in dexamethasone-treated rats. PI(3)-kinase association with IRS-1 was reduced in aged rats, whereas dexamethasone-treated rats showed a reduced IRS-2/PI(3)-kinase association. However, IRS-3 association with PI(3)-kinase was reduced in both models, as well as insulin-induced AKT and PKC phosphorylation. The alterations described in the present study show that the action of insulin is differently impaired depending on the origin of insulin resistance. These differences might be directly linked to the singular metabolic features of the models we tested.

In the last decades, a surprising increased incidence of differentiated thyroid cancer (DTC), along with a precocious diagnosis of ''small'' tumors and microcarcinomas have been observed. In these cases, better oncological outcomes are expected, and a ''tailored'' and ''less aggressive'' multimodal therapeutic protocol should be considered, avoiding an unfavorable even if minimal morbidity following an ''overtreatment.'' In order to better define the most suitable surgical approach, its benefits and risks, we discuss the role of surgery in the current management of DTCs in the light of data appeared in the literature. Even if lymph node metastases are commonly observed, and in up to 90 % of DTC cases micrometastases are reported, the impact of lymphatic involvement on longterm survival is still argument of intensive research, and indications and extension of lymph node dissection (LD) are still under debate. In particular, endocrine and neck surgeons are still divided between proponents and opponents of routine central LD (RCLD). Considering the available evidence, there is agreement about total thyroidectomy, therapeutic LD in clinically node-positive DTC patients, and RCLD in ''high risk'' cases. Nevertheless, indications to the best surgical treatment of clinically node-negative ''low risk'' patients are still subject of research. Considering on the one hand, the recent trend toward routine central lymphadenectomy, avoiding radioactive treatment, and on the other hand, the satisfactory results obtained reserving prophylactic LD to ''high risk'' patients, we think that further prospective randomized trials are needed to evaluate the best choice between the different surgical approaches.

Resumen El síndrome de Pendred es un trastorno típicamente caracterizado por la asociación entre pérdida auditiva y bocio. En la mayoría de las personas con este síndrome, la pérdida auditiva es severa y profunda causada por cambios en el oído interno (pérdida auditiva neurosensorial) y está presente desde el nacimiento. En otros casos, la pérdida auditiva no se desarrolla hasta más tarde en la infancia o la primera infancia. Presentamos un adolescente de 14 años con sordera congénita e hiperplasia multinodular coloidea. El estudio genético confirmó que se trata de un síndrome de Pendred. Palabras Claves: Síndrome de Pendred, bocio, sordera Summary. Pendred syndrome is a disorder typically characterized by the association between hearing loss and goiter. In most people with this syndrome, hearing loss is severe and profound caused by changes in the inner ear (sensorineural hearing loss) and is present from birth. In other cases, hearing loss does not develop until later in infancy or early childhood. We present a 14-year-old adolescent with congenital deafness and multinodular colloid hyperplasia. The genetic study confirmed that it is a Pendred syndrome.

Diabetes mellitus is a heterogeneous, multifactorial, chronic disease characterized by hyperglycemia owing to insulin insufficiency and insulin resistance (IR). Recent epidemiological studies showed that the diabetes epidemic affects 382 million people worldwide in 2013, and this figure is expected to be 600 million people by 2035. Diabetes is associated with microvascular and macrovascular complications resulting in accelerated endothelial dysfunction (ED), atherosclerosis, and cardiovascular disease (CVD). Unfortunately, the complex pathophysiology of diabetic cardiovascular damage is not fully understood. Therefore, there is a clear need to better understand the molecular pathophysiology of ED in diabetes, and consequently, better treatment options and novel efficacious therapies could be identified. In the light of recent extensive research, we re-investigate the association between diabetes-associated metabolic disturbances (IR, subclinical inflammation, dyslipidemia, hyperglyc...

With an ever-growing population of obese people as well as comorbidities associated with obesity, finding effective weight loss strategies is more imperative than ever. One of the challenges in curbing the obesity crisis is designing successful strategies for long-term weight loss and weight-loss maintenance. Currently, weightloss strategies include promotion of therapeutic lifestyle changes (diet and exercise), pharmacological therapy, and bariatric surgery. This review focuses on several pharmacological targets that activate central nervous system pathways that normally limit food intake and body weight. Though it is likely that no single therapy will prove effective for everyone, this review considers several recent pre-clinical targets, and several compounds that have been in human clinical trials.

Regulation of GnRH Secretion by AGD/Lee et al. groups compared to controls independent of season or reproductive status. PRL concentrations were also increased (p < 0.05) following treatment with AGD. These results suggest that inhibition of pulsatile LH release induced by AGD is modulated by alterations in frequency of hypothalamic discharges of GnRH. Furthermore, changes in the inhibitory actions of AGD may contribute to the seasonal regulation of hypothalamic GnRH secretion in the ewe.

tumors and pituitary tumors in 93, 53, and 41% of cases, respectively. Thirty-nine subjects, belonging to affected pedigrees positive for a MEN1 mutation, were asymptomatic at clinical and biochemical screening. Age at diagnosis of multiple endocrine neoplasia type 1 probands was similar for both familial and simplex cases (mean age 47.2 ± 15.3 years). In familial cases, diagnosis of multiple endocrine neoplasia type 1 in relatives of affected probands was made more than 10 years in advance (mean age at diagnosis 36.5 ± 17.6 years). Conclusions The analysis of Italian registry of multiple endocrine neoplasia type 1 patients revealed that clinical features of Italian multiple endocrine neoplasia type 1 patients are similar to those of other western countries, and confirmed that the genetic test allowed multiple endocrine neoplasia type 1 diagnosis 10 years earlier than biochemical or clinical diagnosis.

Interactions between testosterone, estradiol, and inhibin in the control of gonadotrophin secretion in males are poorly understood. Castrated rams were treated with steroid-free bovine follicular fluid (bFF), testosterone, or estradiol and for 7 d (2 x 2 x 2 factorial design). Given independently, none of the exogenous hormones affected follicle-stimulating hormone (FSH) concentrations, but the combination of one or both steroids with bFF reduced FSH secretion. Testosterone and estradiol reduced luteinizing hormone (LH) pulse frequency (there was no synergism), and bFF had no effect. Plasma prolactin concentrations were not affected by any treatment. To locate the central sites of steroid action, castrated rams were bilaterally implanted in the preoptic area (POA), ventromedial nucleus (VMH), or arcuate nucleus (ARC). These implants did not affect FSH or prolactin concentrations, or LH pulse amplitude. The frequency of the LH pulses was not affected by testosterone in any site. Estradiol located in the ARC, but not the POA or VMH, decreased LH pulse frequency. In summary, FSH secretion is controlled by synergistic interactions between inhibin and estradiol or testosterone, whereas GnRH/LH pulse frequency is controlled by testicular steroids. Estradiol acts partly, at least, in the ARC, but the central site of action, testosterone remains unknown.

Regular consumption of fruit and vegetables is associated with reduced risks of cancer, cardiovascular disease and other aging-related diseases. Convincing evidence exists suggesting that an increased fruit, vegetables, and grains consumption is a relatively easy and practical strategy to significantly reduce the incidence of chronic diseases. Cancer chemoprevention intends to interrupt the carcinogenesis process, which includes initiation, promotion and progression of otherwise normal cells to reduce cancer. Despite the failure of β-carotene clinical trial to prevent lung cancer, the development of diet-derived constituents represents one of the major goal in cancer chemoprevention. A key question is whether a purified phytochemical has the same protective effects as does the whole food or mixture of foods in which the phytochemical is present. Putative chemopreventive agents are identified on the basis of epidemiological and in vitro and in vivo studies. All these compounds present tumor-suppressing properties in animal models of carcinogenesis, and they interfere with cellular processes involved in tumor formation, such as suppression of NF-kB and AP1 activation, induction of apoptosis, downregulation of β-catenin expression and activation of ARE/EpRE-dependent gene expression. Phase I clinical trials have been completed only for few of these phytochemicals, and pilot phase II-III trials are planned. In this review, we will begin by describing the different methodological approaches in studying chemopreventive agents, followed by the description of the mechanisms by which these compounds act. Finally, we will review more in details data concerning well-known and promising chemopreventive phytochemicals.

Indeterminate thyroid nodules (ITN) constitute the gray zone of thyroid fine-needle aspiration cytology (FNAC). About 70-80 % of ITN are later diagnosed as benign; therefore, it is very important to identify the predictors of malignancy. Aim of the study was to summarize published data about clinical risk factors for malignancy in patients with ITN and thereby provide more robust estimates of the effect of these risk factors. Sources comprised studies published through December 2012. Original articles that investigated clinical parameters as potential predictors of malignancy in ITN were identified. Two authors performed the data extraction independently. A meta-analysis of 19 relevant studies was conducted that included 3,494 patients with ITN according to FNAC. The pooled prevalence of malignancy was 28 % (95 % CI 23-33), 26 % in females and 34 % in males. The pooled OR was 1.51 (95 % CI 1.2-1.83) for males and 0.68 (95 % CI 0.53-0.88) for females. Regarding the nodule's size, the pooled OR was 2.10 (95 % CI 1.26-3.50) for nodules [4 cm in diameter. Analysis of the patient age as a risk factor was not feasible because of marked difference found between the studies. In patients with indeterminate thyroid nodules diagnosed at FNAC, the pooled rate of malignancy from 19 studies was 28 %. Patients that are male and have ITN greater than 4 cm in diameter should be considered at higher risk of cancer.

A link between stressful life events and development or exacerbation of depression has been established via a large body of evidence. An alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has also been associated with an increase in cortisol secretion. As arginine-vasopressin (AVP) plays an important role in the activation of HPA axis during stress, the present study investigated ACTH and cortisol secretory response induced by an AVP-related with the clinical response to venlafaxine treatment, which offers a dual antidepressant action. Depressive patients with no other psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAMD) in order to follow-up the response to venlafaxine. After 1 wk of treatment, 60% of patients reduced their initial HAM-D score to at least 25%; this group was classified as early responders. The other group (40%) started to reduce significantly their HAM-D score after 3 wk of treatment and was classified as late responders. After 6 wk of treatment both groups have reduced HAM-D score to at least 25% of the baseline score. Prior to the pharmacological treatment, both early and late responders showed salivary cortisol rhythm and urinary free cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe differences in basal ACTH secretion, showing that the late responder group had higher basal ACTH than both early responders and controls. The ddAVP challenge promoted a robust secretion of ACTH only in late responders, suggesting a different sensitivity of pituitary vasopressin receptor. The differences in clinical response to venlafaxine among depressive patients seem to be related to endocrinological parameters.

A detailed investigation was carried out to evaluate the occurrence, persistence and fate of a range of micropollutants at different processing points at a full-scale water recycling plant (WRP) in Queensland, Australia. The WRP, which combines an advanced water treatment plant (AWTP) with a wastewater treatment plant (WWTP), produces high quality recycled water for industrial users. The concentrations of 11 pharmaceuticals from various therapeutic categories and two endocrine disrupting chemicals were examined in full-scale microfiltration and reverse osmosis membrane facilities. Salicylic acid was the most abundant analyte in the WWTP influent, with a concentration range of 11 to 38 µg/L, followed by bisphenol A with concentrations ranging from 6 to 23 µg/L. The concentration of all analytes decreased on average by one order of magnitude following primary and secondary treatment. Gemfibrozil, primidone and carbamazepine were found to have lower removal efficiencies (74-78%) than other compounds during these stages, which could indicate lower biodegradability. The microfiltration and reverse osmosis systems were found to further lower the pollutant concentrations by an order of magnitude. The overall removal efficiencies in the final recycled water were above 97 %, resulting in product water concentrations of lower than 0.1 µg/L for most compounds. An exception to this finding was observed for bisphenol A, which was detected in concentrations up to 0.5 µg/L in the final recycled water.

Over the last three to four decades, it has been observed that the average total hours of sleep have decreased to less than seven hours per person per night. Concomitantly, global figures relating to obesity and diabetes mellitus have increased in an alarming fashion in adults and children, and it has been hypothesized that neuro-hormonal changes accompanying this behavioral sleep deprivation may lead to insulin resistance and, subsequently, to diabetes mellitus. Sleep deprivation has been associated with multiple physiological changes, including increased cortisol and ghrelin levels, decreased leptin levels and impaired glucose metabolism. Experimental studies have also shown an increase in inflammatory and pro-inflammatory markers, which are indicators of body stress, under sleep deprivation. This review elaborates further on this hypothesis, exploring the molecular basis for the link between both entities and the underlying pathophysiology that results in insulin resistance and diabetes mellitus. We review the results of experimental and epidemiological studies, specifically examining the relationship between sleep duration and the immune and endocrine systems.