Thyroid function and thyroid disorders during pregnancy: a review and care pathway.

PURPOSE: To review the literature on thyroid function and thyroid disorders during pregnancy. METHODS: A detailed literature research on MEDLINE, Cochrane library, EMBASE, NLH, ClinicalTrials.gov, and Google Scholar databases was done up to January 2018 with restriction to English language about articles regarding thyroid diseases and pregnancy. RESULTS: Thyroid hormone deficiencies are known to be detrimental for the development of the fetus. In particular, the function of the central nervous system might be impaired, causing low intelligence quotient, and mental retardation. Overt and subclinical dysfunctions of the thyroid disease should be treated appropriately in pregnancy, aiming to maintain euthyroidism. Thyroxine (T4) replacement therapy should reduce thyrotropin (TSH) concentration to the recently suggested fixed upper limits of 2.5 mU/l (first and second trimester) and 3.0 mU/l (third trimester). Overt hyperthyroidism during pregnancy is relatively uncommon but needs prompt treatment due to the increased risk of preterm delivery, congenital malformations, and fetal death. The use of antithyroid drug (methimazole, propylthiouracil, carbimazole) is the first choice for treating overt hyperthyroidism, although they are not free of side effects. Subclinical hyperthyroidism tends to be asymptomatic and no pharmacological treatment is usually needed. Gestational transient hyperthyroidism is a self-limited non-autoimmune form of hyperthyroidism with negative antibody against TSH receptors, that is related to hCG-induced thyroid hormone secretion. The vast majority of these patients does not require antithyroid therapy, although administration of low doses of ß-blocker may by useful in very symptomatic patients. CONCLUSIONS: Normal maternal thyroid function is essential in pregnancy to avoid adverse maternal and fetal outcomes.

Polycystic ovary syndrome, adipose tissue and metabolic syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD). METHODS: A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulin resistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included. RESULTS: PCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle. CONCLUSION: The high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.

Organ-specific antibodies in LADA patients for the prediction of insulin dependence.

AIM OF THE STUDY: The aim of the present study was to define the frequency of organ-specific and non-organ-specific autoantibodies in a cohort of Latent Autoimmune Diabetes in Adults (LADA) patients and to test whether multiple antibodies positivity could be a predictor of early insulin dependence. MATERIALS AND METHODS: We enrolled 210 LADA and 210 type 2 diabetes mellitus (T2D) patients. In all subjects anti-islet antigen-2 (IA-2Ab), anti-thyroperoxidase (TPOAb), anti-zinc transporter 8 (ZnT8Ab), anti-nuclear (ANA), anti-parietal cell (APCA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-liver kidney microsomes (LKM), and anti-reticulin (ARA) circulating antibodies were assessed. RESULTS: The frequency of TPOAb, ZnT8Ab, APCA, and IA-2Ab positivity was, respectively, detected in 40.0%, 32.4%, 24.7%, and 9.5% of LADA patients, whereas their frequency was significantly lower in T2D patients (11.4%, 1.9%, 9.5%, and 0.0%, respectively, p < 0.001). The frequency of ANA was the same in both groups whereas the frequency of ASMA, ARA, AMA, and LKM was very low (range 0.0-3.3%). The presence of TPOAb associated with ZnT8Ab, IA-2Ab, or APCA allows one to predict the progression of disease with a high specificity but low sensibility. CONCLUSIONS: LADA patients show an increased frequency of organ- and non-organ-specific antibodies. Consequently, a screening is worthwhile in these patients. The simultaneous presence of TPOAb with ZnT8, IA-2Ab, or APCA may help differentiate clinical phenotypes and predict faster insulin dependence in LADA patients.

Serum free thyroxine levels are positively associated with arterial stiffness in the SardiNIA study.

OBJECTIVE: Thyroid dysfunction may accelerate atherosclerosis. Aortic pulse wave velocity (PWV) is an early index of arterial stiffness and an important risk factor for cardiovascular disease and might therefore be linked to changes in thyroid activity. We investigated the relationship between thyroid function and carotid-femoral PWV, as an index of arterial stiffness. DESIGN: Cross-sectional cohort study. PATIENTS: Participants from the SardiNIA study. Those being treated for thyroid diseases were excluded, yielding a sample of 5875 aged 14-102. MEASUREMENTS: Clinical parameters, blood tests including serum TSH and serum FT4, and carotid-femoral PWV were measured. RESULTS: After adjusting for confounders, a direct and linear association between FT4 and PWV was shown (multiple regression analysis). The model containing age, mean blood pressure, body mass index, heart rate, FT4, hypertension, diabetes and dyslipidaemia accounted for 55% of the variation in PWV. CONCLUSIONS: Like several other known risk factors, serum FT4 levels are associated with carotid-femoral PWV, suggesting that high FT4 levels have a detrimental effect on aortic stiffness and may contribute to ageing process of the vascular system. This finding may help to understand the pathogenesis of cardiovascular disease and contribute to improve prevention therapy.

A case of thyroid metastasis from pancreatic cancer: case report and literature review.

BACKGROUND: Thyroid metastases are clinically rare, and usually occur in patients with a history of prior malignancy and when there are metastases elsewhere. Metastases of pancreatic carcinoma to the thyroid are extremely rare, with only three cases reported in the literature. CASE PRESENTATION: We report a patient who had a pancreatic carcinoma with metastasis to the thyroid as initial clinical presentation of the disease. A 63-year-old man with a history of weight loss and fatigue presented with cervical lymphadenopathies and a large nodule in the right lobe of the thyroid. A fine needle aspiration of the nodule gave inconclusive cytological results for the origin of the neoplastic cells. An ultrasound-guided core biopsy revealed the presence of a poorly differentiated adenocarcinoma infiltrating the thyroid with atrophic thyroid follicles. Immunohistochemical staining of the lesion was strongly positive for Cytokeratin 19 suggesting a pancreatic origin of the metastasis. A contrast CT scan demonstrated an enlargement of the pancreatic body, dilatation of the pancreatic duct, diffuse retroperitoneal, paraaortic and cervical lymphadenopathy and secondary lesions in the liver. CONCLUSION: Metastases to the thyroid from pancreatic carcinoma are extremely rare. A core biopsy of the lesion excluded a thyroid carcinoma and permitted the diagnosis of the primary neoplasm.

Gastrointestinal symptoms and Helicobacter pylori infection in school-age children residing in Porto Torres, Sardinia, Italy.

BACKGROUND: Helicobacter pylori infection is typically acquired in childhood, and following the acute event, it is thought that most infections remain asymptomatic. H. pylori has been suggested to protect against diarrhea in childhood. AIM: To examine the role of H. pylori in gastrointestinal symptoms in children. MATERIALS AND METHODS: A cross-sectional sero-epidemiologic study was conducted in Porto Torres, Sardinia, Italy. Demographic information, socioeconomic factors, and the frequency of upper gastrointestinal symptoms during the previous 3 months (e.g., abdominal pain, diarrhea, nausea, heartburn, halitosis, slow digestion, belching, and weight loss) were evaluated by a questionnaire. H. pylori status was determined by ELISA. RESULTS: Approximately 95% (N = 1741) of school children between the age of 6 and 15 years from Porto Torres participated. The sero-prevalence of H. pylori infection was 13.3% (229/1727) and similar in boys (13%) and girls (14%) (p = .57). Nausea/vomiting (odds ratio (OR) = 2.2 (95% CI = 1.2-5.1)) and diarrhea (OR = 2.1 (95% CI = 1.3-2.8)) were each significantly associated with H. pylori infection, and these associations remained significant after controlling for other study variables. There was no significant association between H. pylori and abdominal pain or heartburn (p > .25). CONCLUSIONS: The study does not support either a role of H. pylori infection in abdominal pain in children or a protective role against diarrheal illnesses or nausea/vomiting.

Absence of an opioid stimulatory tone on growth hormone secretion in women with microprolactinoma.

INTRODUCTION: Literature data suggest that prolactinoma is a tumor with a complex pathogenesis and that its growth is the result of changes at the pituitary and/or hypothalamic level. Abnormal release of hypothalamic factors (including endogenous opioid peptides) may contribute to prolactinoma development. An increased endogenous opioid tone (EOT) occurs in patients with prolactinoma, and seems to play an important role in pituitary secretion, as suggested by the ability of the opiate receptor antagonist naloxone to stimulate luteinizing hormone pulsatile secretion in these patients. OBJECTIVE: To investigate the effect of the EOT on growth hormone (GH) secretion in women with prolactinoma. DESIGN: Eleven women aged 30.4+/-6.7 years (range 20-41), with an established diagnosis of microprolactinoma, were studied. GH-releasing hormone (GHRH), 100 microg as an intravenous (i.v.) bolus, was administered with and without preadministration of i.v. naloxone, an opioid receptor antagonist, 2 mg as a bolus followed by a constant infusion of 1.6 mg/h. Blood samples were taken for 120 min after GHRH administration. RESULTS: Naloxone did not affect the GH response to GHRH, measured as single times, mean peak values, or as integrated concentrations. CONCLUSION: Our data suggest that an opioid stimulatory tone on GH secretion in women with prolactinoma is absent.

Liquid chromatography-mass spectrometry assay for quantification of Gluten Exorphin B5 in cerebrospinal fluid.

A sensitive, precise and accurate method for the quantification of the alimentary opioid peptide Gluten Exorphin B5 (GE-B5, Tyr-Gly-Gly-Trp-Leu) in cerebrospinal fluid (CSF) was developed using liquid chromatography-mass spectrometry (LC-MS). Aliquots (10 microL) of sheep CSF were injected into a LC-MS instrument equipped with a reversed-phase C12 column at a flow rate of 250 microL/min. The mobile phase consisted of Eluent A water with 0.01% acetic acid as an ion-pairing reagent, and Eluent B acetonitrile. The LC-MS system was programmed to divert column flow to waste for 3.5 min after injection, after which time flow was directed into the mass spectrometer that operated in positive ion mode. DADLE (Tyr-D-Ala-Gly-Phe-D-Leu) was used as Internal Standard. No significant interfering peaks were detected at the retention times of GE-B5 in CSF blanks. The calibration curves were linear in the range of 0.39-78.00 ng/mL. The lower limit of detection and the lower limit of quantitation values for GE-B5 in CSF were established at 0.30 and 0.78 ng/mL, respectively. The intra-day and inter-day precision values were <12% relative standard deviation. The intra-day and inter-day accuracy were 99.46-100.86% and 98.95-100.02%, respectively. Recovery of GE-B5 in CSF samples was greater than 80%. Stability studies indicate that GE-B5 in CSF undergoes significant degradation (>55% after 600 min), which is reduced by the addition of protease inhibitors. This is the first reported method for the quantification of GE-B5 in CSF.

Subclinical hypothyroidism, lipid metabolism and cardiovascular disease.

Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism.

Thyroid hormone analogs for the treatment of dyslipidemia: past, present, and future.

OBJECTIVE: Treatment of dyslipidemia is a major burden for public health. Thyroid hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR), but the use of thyroid hormone to treat dyslipidemia is not indicated due to its deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been conceived to selectively activate TR in the liver, thus reducing potential side-effects. METHODS: The authors searched the PubMed database to review TR and the action of thyromimetics in vitro and in animal models. Then, all double-blind, placebo controlled trials that analyzed the use of thyroid hormone analog for the treatment of dyslipidemia in humans were included. Finally, the ongoing research on the use of TR agonists was searched, searching the US National Institutes of Health Registry and the WHO International Clinical Trial Registry Platform (ICTRP). RESULTS: Thyromimetics were tested in humans for the treatment of dyslipidemia, as a single therapeutic agent or as an add-on therapy to the traditional lipid-lowering drugs. In most trials, thyromimetics lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides, but their use has been associated with adverse side-effects, both in pre-clinical studies and in humans. CONCLUSIONS: The use of thyromimetics for the treatment of dyslipidemia is not presently recommended. Future possible clinical applications might include their use to promote weight reduction. Thyromimetics might also represent an interesting alternative, both for the treatment of non-alcoholic steatohepatitis, and type 2 diabetes due to their positive effects on insulin sensitivity. Finally, additional experimental and clinical studies are needed for a better comprehension of the effect(s) of a long-term therapy.

Thyroid Hormones, Metabolic Syndrome and Its Components.

Metabolic syndrome is a clustering of various metabolic parameters, which include diabetes, low high-density lipoprotein cholesterol, elevated triglycerides, abdominal obesity, and hypertension. It has merged as a worldwide epidemic and a major public health care concern. However, due to the different criteria used for the assessment, the frequency of metabolic syndrome in the general population is variable but it is more common in the older people. Metabolic syndrome is closely linked to cardiovascular risk and increases cardiovascular outcomes and all-cause mortality. Recent evidences showed that alterations of the thyroid function could have an impact on the components of the metabolic syndrome, suggesting that thyroid hormones have a variety of effects on energy homeostasis, lipid and glucose metabolism, and blood pressure. In this review, we summarize available data on the action of thyroid hormone on the components of metabolic syndrome.

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults.

Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D) with the presence of islet cell antigens detected in type 1 diabetes (T1D). Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA) that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP) as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity.

Is there a role for gut microbiota in type 1 diabetes pathogenesis?

Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by insufficient insulin production due to the destruction of insulin secreting ß-cells in the Langerhans islets. A variety of factors, including chemicals, viruses, commensal bacteria and diet have been proposed to contribute to the risk of developing the disorder. In the last years, gut microbiota has been proposed as a main factor in T1D pathogenesis. Several alterations of gut microbiota composition were described both in animal model and in humans. The decrease of Firmicutes/Bacteroides ratio was the most frequent pattern described, in particular, in human studies. Furthermore, Bacteroides, Clostridium cluster XIVa, Lactobacillus, Bifidobacterium, and Prevotella relative abundances were different in healthy and affected subjects. Dysbiosis would seem to increase intestinal permeability and thus promote the development of a pro-inflammatory niche that stimulates ß-cell autoimmunity in predisposed subjects. Preliminary studies on animal models were realized to investigate the role of gut microbiota modulation as therapy or prevention approach in predisposed animals: promising and stimulating results have been reported. Key message Dietary antigens and microbiota-derived products might act as triggers of T1D by causing a pro-inflammatory and metabolic dysfunctional environment.

Leptin Levels and Insulin Dependence in Latent Autoimmune Diabetes in Adults.

Latent autoimmune diabetes in adults (LADA) is an autoimmune type of diabetes accounting for up to 10% of all cases of diabetes initially diagnosed as type 2 diabetes mellitus. It has been demonstrated that LADA patients with a lower body mass index (BMI) undergo a faster depletion of beta cell function and require insulin therapy earlier. In this study, we assayed a panel of adipokines (leptin, adiponectin, omentin, resistin, visfatin) and proinflammatory cytokines (interleukin 2, interleukin 6, tumor necrosis factor-α) in 71 LADA patients and tested the association with a number of clinical and immunological features. Among men, leptin was positively and significantly correlated with BMI and fat mass (r = 0.487 and r = 0.664, respectively), resistin was positively and significantly correlated with total and low-density lipoprotein cholesterol (r = 0.644 and r = 0.746, P < 0.0001) and with interleukin 2 (r = 0.688, P < 0.01). Omentin showed an inverse correlation with systolic blood pressure in women (r = -0.359, P < 0.001) and a positive correlation with interleukin 2 in both genders (r = 0.395, P < 0.01). The Cox regression analysis showed that leptin levels were inversely and significantly related with the risk of early insulin dependence. Higher leptin secretion may exert a direct effect on beta cell function leading to more insulin sensitivity.

Quantification of Gluten Exorphin A5 in cerebrospinal fluid by liquid chromatography-mass spectrometry.

In the present work, for the first time, a method for the quantification of the alimentary opioid peptide Gluten Exorphin A5 (GE-A5; Gly-Tyr-Tyr-Pro-Thr) in cerebrospinal fluid (CSF) was developed. Aliquots (5 microL) of CSF were injected into a liquid chromatography-mass spectrometry (LC-MS) instrument equipped with a reversed-phase C18 column at a flow-rate of 0.4 mL/min. The mobile phase consisted of Eluent A water with 0.6% acetic acid as an ion-pairing reagent and Eluent B acetonitrile/methanol (75:25, v/v). The LC-MS system was programmed to divert column flow to waste for 4 min after injection, after which time flow was directed into the mass spectrometer that operated in positive ion mode. No significant interfering peaks were detected at the retention times of GE-A5 in CSF blanks. The lower limit of detection and the lower limit of quantitation values for GE-A5 in CSF were established at 0.60 and 1.50 ng/mL, respectively. The intra- and inter-day precision values were <5% relative standard deviation. The intra- and inter-day accuracy were 99.6-102.8% and 100.0-101.9%, respectively. The reported assay employs extremely small volumes of CSF, thus allowing the analysis of GE-A5 from both small and large animal models.

Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients.

Implication of Cytotoxic Helicobacter pylori Infection in Autoimmune Diabetes.

Background. Type 1 diabetes (T1D) and type 2 diabetes (T2D) have been linked to Helicobacter pylori infection, although results are conflicting. No previous study addressed a possible link between H. pylori infection and latent autoimmune diabetes in adults (LADA). In this study, a correlation among H. pylori infection and the risk of autoimmune diabetes in comparison with T2D was investigated. Methods. Sera from 234 LADA patients, 105 patients with late-onset T1D, and 156 patients with T2D were analyzed for anti-H. pylori and the cytotoxin-associated antigen (CagA) IgG antibodies. Results. H. pylori seroprevalence was comparable in LADA (52%), late-onset T1D (45%), and T2D (49%) with no gender differences. The seroprevalence of CagA IgG was significantly higher in autoimmune diabetes (late-onset T1D: 45%, LADA: 40%) compared to T2D (25%; p < 0.028). Conclusions. Although H. pylori seroprevalence was similar in LADA, T1D, and T2D, anti-CagA positivity was significantly increased among patients with autoimmune diabetes, suggesting that more virulent H. pylori strains might be a trigger for immune mechanisms involved in their pathogenesis.

Menopause modulates the association between thyrotropin levels and lipid parameters: The SardiNIA study.

OBJECTIVE: Thyroid hormone influences lipoprotein metabolism. The role of menopausal status in this association has not been extensively studied. The aim of the present study is to evaluate the association between lipid parameters and mild elevations of thyrotropin (TSH), and whether menopause influences this relationship. STUDY DESIGN: A cross-sectional study was conducted with a sample of 2,914 women (aged 14-102 years) from the SardiNIA study. MAIN OUTCOME MEASURES: The association of TSH with blood lipid levels was examined using regression analyses, according to menopausal status. RESULTS: Postmenopausal women had lower serum TSH concentrations and higher levels of total cholesterol, low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and triglycerides than did premenopausal women (p=0.001 or less for all). In premenopausal women, after adjusting for the confounders age, BMI, smoking, insulin and glycaemia, TSH showed a direct relation to the levels of total cholesterol (ß=0.046, p=0.010), LDLc (ß=0.044, p=0.016) and triglycerides (ß=0.085, p<0.001), but no association with HDLc level. In the postmenopausal group, TSH was directly associated only with triglyceride levels (ß=0.103, p=0.014). CONCLUSIONS: The association between mild elevation of TSH and lipid levels is influenced by menopausal status. Further research is needed to clarify this finding.

Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier.

Gluten exorphin B5 (GE-B5) is a food-derived opioid peptide identified in digests of wheat gluten. We have recently shown that GE-B5 stimulates prolactin (PRL) secretion in rats; this effect is abolished by preadministration of the opioid receptor antagonist naloxone. However, since the structure of naloxone allows it to cross the blood-brain barrier (BBB) and antagonize opioid effects centrally as well as peripherally, it could not established, on the basis of those data, if GE-B5-induced PRL release is exerted through sites located inside or outside the BBB. In this study, we sought to determine the site of action of GE-B5 on PRL secretion, by pretreating male rats with naloxone methobromide (NMB), an opioid antagonist that does not cross the BBB. Four groups of rats were given the following treatments: 1) intravenous vehicle; 2) intravenous GE-B5 (3 mg kg(-1) body weight); 3) intraperitoneal NMB (5 mg kg(-1) body weight), followed by vehicle; 4) NMB, followed by GE-B5. Blood samples for PRL were taken at intervals for 40 minutes after vehicle or GE-B5 administration. GE-B5 stimulated PRL secretion; the effect was statistically significant at time 20. NMB preadministration completely abolished PRL response. Our experiment indicates that GE-B5 stimulates PRL secretion through opioid receptors located outside the BBB. Since opioid peptides do not exert their effect on PRL secretion directly, but via a reduced dopaminergic tone, our data suggest that GE-B5 can modify brain neurotransmitter release without crossing the BBB.

Screening for celiac disease in patients with autoimmune thyroid disease: from research studies to daily clinical practice.

Screening procedures performed in research-setting studies have shown that the prevalence of celiac disease in patients with autoimmune thyroid disease is approximately 4-15 times higher than the general population, thus suggesting that patients with autoimmune thyroid disease should be routinely screened for celiac disease. However, the performance of these screening programs has never been evaluated in everyday, clinical-practice setting. We invited newly diagnosed patients with autoimmune thyroid disease, seen at our Hospital, to participate in a serological screening for celiac disease. Two-hundred and thirty-one patients, female to male ratio 8.89:1, mean age 41.3 +/- 18.1 years, range 7.1-80.5 years were included. The number of diagnosed celiac disease was 0. Our results do not support the usefulness of a screening for celiac disease in patients with autoimmune thyroid disease in daily practice, despite the favorable results obtained in research-setting studies. Since screening is a resource-consuming activity, for both patients and clinicians, we suggest that a careful evaluation of the yield of a screening is always warranted before its adoption in the clinical practice.