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Background and Aims Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus (DM), mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO). Renin-angiotensin-aldosterone system inhibitors (RAASis) [angiotensin converting enzyme inhibitors (ACEis) and angiotensin II receptor antagonists (ARBs)] are recommended in these conditions to decrease proteinuria, slow CKD progression and reduce cardiovascular risk. The interactions between RAAS and the kynurenine pathway and the potential effects of RAASis have been reported in few experimental models but whether these drugs influence kynurenine levels in humans is unknown. We performed a single-centre cross-sectional observational study to evaluate tryptophan and kynurenine serum levels and IDO activity in CKD patients with and without type 2 DM, their correlations with markers of renal dysfunction, and their relationship with RAAS-inhibiting therapy. Method We enrolled 72 consecutive adult patients with CKD, of which 38 had DM, who were admitted to the Unit of Nephrology and Dialysis of our Hospital. Of them, 55 were receiving RAASis whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography) analysis with an UltiMateTM 3000 chromatograph (Thermo Fisher Scientific, 168 Third Avenue Waltham, MA, USA); kynurenine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (Catalogue n. K 7728; Immundiagnostik AG, Bensheim, Germany); IDO activity was calculated with the formula (kynurenine/tryptophan) x 100. Results Patients receiving RAASis and patients not under therapy only differed for frequency of arterial hypertension (100% vs 76.47%; P=0.002) and kynurenine levels, the latter being significantly lower in the treated group compared to the untreated one (1.56 ± 0.79 vs 2.16 ± 1.51 µmol/l; P=0.0378). Kynurenine did not correlate with estimated glomerular filtration rate (eGFR), proteinuria or albuminuria in the whole study cohort. Conversely, in patients not receiving RAASis it was inversely related to eGFR (r=-0.4862; P=0.0478) and directly related to proteinuria (ρ=0.493; P=0.0444) and albuminuria (ρ=0.542; P=0.0247); moreover, it varied across classes of albuminuria, being lower in patients with normoalbuminuria (0.98 ± 0.55 µmol/l) and higher in those with micro- (2.63 ± 1.53 µmol/l) and macroalbuminuria (3.09 ± 1.61 µmol/l) at the ANOVA test (F=4.008; P=0.042). In the same group, the relationship between IDO activity and eGFR was significant (ρ=-0.554; P=0.0210) and IDO activity differed across classes of albuminuria (F=3.702; P=0.05). Moreover, IDO activity was higher in patients with history of cardiovascular disease compared to those with no such history [10.22 (8.39 to 22.92) vs 7.57 (4.76 to 8.09) %; P=0.0343] whereas tryptophan had an opposite behaviour (17.00 ± 2.06 vs 22.00 ± 3.78 µmol/l; P=0.0036). Conclusion We observed lower kynurenine levels in CKD patients treated with RAASis compared to untreated patients, independently of the presence of DM, and a significant association between kynurenine and markers of renal damage only in the group not receiving RAASis. We could hypothesize that kynurenine may play a role in the pathophysiology of renal damage, as already suggested, and that drugs interfering with RAAS activation may act also by reducing kynurenine levels, in addition to their already known effects at the renal level. Indeed, kynurenine synthesis results to be higher in states of inflammation and RAAS has pro-inflammatory and pro-fibrotic actions; accordingly, RAASis could reduce the enzymatic activity responsible for kynurenine increase and this could be one of the mechanisms mediating the beneficial effects of RAAS inhibition on CKD progression. This may be relevant because kynurenine has shown pro-thrombotic effects and is emerging as a potential new biomarker of CKD.

Electrolytes disturbances are commonly observed in clinical practice. However, magnesium (Mg) disorders are often poorly considered. Our primary aim was to update the prevalence and the incidence of hypomagnesemia and hypermagnesemia in a real-life scenario. The secondary aim was to investigate the association of Mg disturbances with age and gender. Data from patients whose Mg serum levels were measured between January 2015 and December 2017 at our University Hospital were recorded. Hypomagnesemia was defined by Mg levels 3.8 mg/dL. Hypo and hypermagnesemia cases were considered according to age, gender, year of observation and setting of subjects including outpatients and inpatients. In particular, inpatients were recruited from a total of 25 Hospital Divisions (i.e. Cardiology, Endocrinology, Geriatrics, Hematology, Intensive Care, Internal Medicine, Infectious Disease, Nephrology, Neonatal Intensive Care, Neurology, Neuropsychiatry, Neuroradiology, Oncology, Pulmonology, Pediatrics, Psychiatry, Rheumatology and Surgical Area that included 8 Units). Over the observation period, we recognized 12,696 patients whose Mg levels were checked. Prevalences of hypomagnesemia and hypermagnesemia were 8.43% (n=1071) and 1.78% (n=226) respectively. Hypomagnesemia was encountered more frequently in female [53.3% (n=560)] rather than in male patients [47.7 % (n=511)] (χ2= 4.03, p

Background: The possible relationships between breast and thyroid diseases have been reported in the literature. The purpose of our study was to evaluate the occurrence of histologically verified thyroid pathologies in women who were diagnosed with breast cancer and, after mastectomy/quadrantectomy complemented by oncological treatment, were thyroidectomized based on their periodic thyroid evaluation. Patients and Methods: Our series consist of 31 women with a mean age of 62.9 ± 10.9 years (range, 45–81) treated for breast cancer (18 right-sided, 11 left-sided, and 2 bilateral), of whom 29 were thyroidectomized, since two women who developed Graves’ disease refused thyroidectomy. These 31 women belong to a cohort of 889 women who referred to the Breast Surgery Unit of our university hospital during the period January 2010 through December 2020. Results: The mean time interval between breast cancer and thyroid pathologies was 48.1 ± 23.4 months (range, 12–95). The final diagnosis at histopathology was infiltrating ductal breast carcinoma in 26 women (with 2/26 patients having bilateral carcinoma) and infiltrating lobular breast carcinoma in the other 5 women. Ten of the twenty-nine thyroidectomized women (34.5%) had a thyroid malignancy on histology: five papillary carcinomas, three papillary micro-carcinomas and two follicular carcinomas. Two of the five women with papillary carcinoma also had histological evidence of chronic lymphocytic thyroiditis/Hashimoto’s thyroiditis, which was also detected in another five women with benign thyroid diseases. Conclusions: We suggest that breast cancer survivors should be made aware of the possible increased risk of thyroid pathologies (including thyroid malignancy) so that they can undergo screening and follow-up.

BACKGROUND AND OBJECTIVES The heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) has been postulated as an autoantigen of psoriasis, but correlation between serum levels of anti-hnRNP-A1 autoantibodies and the severity of disease has not been investigated. We aimed to assess the frequency of anti-hnRNP-A1 autoimmunity in patients with moderate to severe psoriasis and in healthy controls, and to determine the correlation between serum levels of anti-hnRNP-A1 autoantibodies and disease severity. PATIENTS AND METHODS We performed a case-control study on 40 adult psoriatic patients with a PASI (Psoriasis Area and Severity Index) of > 10 and 40 healthy controls matched for age and gender. Immunoblotting was used to assess serum levels of anti-hnRNP-A1 autoantibodies. RESULTS Anti-hnRNP-A1 autoantibodies were found in 9/40 psoriatic patients (22.5 %) but in no healthy controls. The PASI was significantly higher in anti-hnRNP-A1-positive patients than in anti-hnRNP-A1-negative patients (40.33 ± 3.24 vs 26.06 ± 9.28, p = 0.0001). In patients positive for anti-hnRNP-A1, serum levels of such autoanti-bodies were correlated with the PASI (R = 0.89, p = 0.001). CONCLUSIONS Consistent with reports in the literature, our results suggest a role of anti-hnRNP-A1 autoimmunity in psoriasis, although probably not as the primary cause or initial/fundamental event. Unlike previously published reports, our results also suggest that anti-hnRNP-A1 autoimmunity is particularly frequent among psoriatic patients with more severe disease. Further studies are necessary with a larger number of patients.

Hintergrund und ziele Das heterogene nukleare Ribonukleoprotein A1 (hnRNP-A1) wurde als Autoantigen bei Psoriasis vorgeschlagen; eine mogliche Korrelation zwischen dem Serumspiegel von Anti-hnRNP-A1-Antikorpern und dem Schweregrad der Erkrankung wurde bislang nicht untersucht. Unser Ziel war es, die Haufigkeit der Anti-hnRNP-A1-Autoimmunitat bei Patienten mit masig schwerer bis schwerer Psoriasis und gesunden Kontrollpersonen zu bestimmen und festzustellen, ob eine Korrelation zwischen dem Anti-hnRNP-A1-Autoantikorper-Serumspiegel und dem Schweregrad der Erkrankung besteht. Patienten und methoden Wir fuhrten eine Fallkontrollstudie an 40 erwachsenen Psoriasispatienten mit einem Psoriasis Area and Severity Index (PASI) von > 10 und 40 gesunden Kontrollpersonen mit ahnlicher Alters- und Geschlechtsverteilung durch. Die Bestimmung des Serumspiegels von hnRNP-A1-Autoantikorpern erfolgte mit Immunoblots. Ergebnisse Anti-hnRNP-A1-Autoantikorper wurden bei 9 von 40 Psoriasispatienten (22,5 %) nachgewiesen, jedoch bei keiner der gesunden Kontrollpersonen gefunden. Der PASI-Wert war bei Anti-hnRNP-A1-positiven Patienten signifikant hoher als bei Anti-hnRNP-A1-negativen Patienten (40,33 ± 3,24 vs. 26,06 ± 9,28, p = 0,0001). Bei Anti-hnRNP-A1-positiven Patienten korrelierte der Serumspiegel der Autoantikorper mit dem PASI-Wert (R = 0,89, p = 0,001). Schlussfolgerungen Ubereinstimmend mit Berichten aus der Literatur legen unsere Ergebnisse nahe, dass Anti-hnRNP-A1-Autoimmunitat bei Psoriasis eine Rolle spielt, wenn auch moglicherweise nicht als primare Ursache oder als initiales oder grundlegendes Ereignis. Anders als bei fruheren Publikationen weisen unsere Daten auch darauf hin, dass Autoimmunitat gegen Anti-hnRNP-A1 unter Patienten mit schwererer Erkrankung besonders haufig ist. Weitere Studien mit einer groseren Anzahl von Patienten sind erforderlich.

In recent studies, an improvement of the response rate to therapy has been reported with corticosteroids and mycophenolic acid in patients with Graves’ ophthalmopathy (GO). In GO, retro-orbital cells (fibroblasts, preadipocytes, and extraocular muscle cells) secrete Th1 and Th2 chemokines stimulated by cytokines. Until now, no studies are present in literature regarding the effect of corticosteroids and mycophenolic acid on the secretion of chemokines in GO orbital cells. For this reason, the effect of increasing concentrations of mycophenolic acid or corticosteroids on the secretion of either the Th1 (CXCL10) and Th2 (CCL2) chemokines was tested in primary cultures of myoblasts, preadipocytes and fibroblasts obtained from GO patients. CXCL10 was undetectable in the supernatants of the retro-orbital cells in primary cultures; its release was induced dose-dependently by IFNγ, while TNFα alone had no effect. On the contrary CCL2 release (that was produced in low amounts basally) was dose-dependently induced by TNFα, while IFNγ alone had no effect. In both cases the combination of TNFα and IFNγ had a significant synergistic effect on CXCL10 and CCL2 secretion. The release of these chemokines was dose-dependently inhibited by increasing concentrations of mycophenolic acid, or corticosteroids (in a pharmacological range), in presence of IFNγ and TNFα stimulation. Moreover, the association of corticosteroids and mycophenolic acid (in presence of IFNγ and TNFα) had a stronger inhibitory effect on the chemokines release. In conclusion, in GO orbital cells, mycophenolic acid and/or corticosteroids (in a pharmacological range) have an inhibitory role on the secretion of both Th1 (CXCL10) and Th2 (CCL2) chemokines. This suggests a possible therapeutic role of these drugs.

Some natural compounds decrease serum levels of thyroid autoantibodies, but results are inconsistent and thyroid function has been evaluated infrequently; moreover, the effects of Aloe on thyroid autoimmunity and function have been examined in very few studies. This study stems from the observation of one co-author, who has Hashimoto’s thyroiditis (HT)-related subclinical hypothyroidism (SCH). Upon checking her biochemical thyroid panel when taking daily Aloe barbardensis Miller juice (ABMJ) for thyroid-unrelated reasons, she noticed a decrease in serum thyroperoxidase autoantibodies (TPOAb) and thyrotropin (TSH) and an increase in serum free thyroxine (FT4). Based on this observation, we enrolled 30 consecutive HT women with levothyroxine-untreated SCH and high TPOAb levels. All of them took ABMJ (50 ml daily) for nine months and were tested for serum TSH, FT4, free triiodothyronine (FT3) and TPOAb. Measurements were performed at baseline and at months 3 and 9. TSH, FT4 and TPOAb improved significantly already at month 3 and further (−61%, +23% and −56%) at month 9. However, FT3 decreased significantly at month 3 (−16%) with no further decrease at month 9, so that the FT4:FT3 ratio increased significantly (+33% and + 49%). At baseline, 100% of women had TSH > 4.0 mU/L and TPOAb > 400 U/ml, but frequencies fell to 0% and 37%, respectively, at month 9. In contrast, a control group (namely, 15 untreated SCH women of comparable age and baseline levels of TSH, FT4, FT3 and TPOAb) had no significant changes in any index. We conclude that the daily intake of 100 ml ABMJ for 9 months in women with HT-related SCH decreases the burden of thyroid autoimmune inflammation. In addition, ABMJ rescues thyrocyte function, with decreased need for conversion of the prohormone T4 into the more active T3 through ABMJ-induced inhibition of T4 deiodination. Keywords: Aloe vera, Subclinical hypothyroidism, Thyroid autoimmunity, Thyroid function

After encountering two women with serum thyrotropin (TSH) levels greater in periovulatory phase than in other days of the menstrual cycle, we hypothesized that TSH levels could be sensitive to changes in circulating estrogens in women.The objective of this study was to evaluate whether serum TSH increases after an induced acute increase of serum estradiol, and compare serum TSH increase with that of prolactin (PRL) which is a classic estradiol-upregulated pituitary hormone.In this retrospective study, we resorted to stored frozen sera from 55 women who had undergone the GnRH agonist (buserelin)-acute stimulation test of ovarian steroidogenesis. This test, that is preceded by dexamethasone administration to suppress adrenal steroidogenesis, had been performed to show an increased buserelin-stimulated response of 17-hydroxyprogesterone, a response that is frequent in polycystic ovary syndrome. Fifty-five women had enough serum volume at pertinent times (first observation early in the follicular phase and all times of the test) to permit assay of serum estradiol, TSH and PRL.Before dexamethasone administration, estradiol averaged 26.4 ± 15.5 pg/ml (reference range 23–139, follicular phase), TSH 1.78 ± 0.86 mU/L (reference range 0.3–4.2) and PRL 409.4 ± 356 mU/L (reference range 70.8–556) (mean ± SD).Serum estradiol, TSH and PRL averaged 47.2 ± 27 pg/ml, 0.77 ± 0.48 mU/L and 246.4 ± 206.8 mU/L just prior to the buserelin injection, but they peaked at 253.4 ± 113.5 pg/ml (nv 83–495, midcycle), 3.30 ± 1.65 mU/L and 540.3 ± 695.2 mU/L after injection. The responses to buserelin of estradiol, TSH and PRL were of wide magnitude. There was a significant correlation between TSH peak and serum estradiol peak, betweeen AUC0-24 h-TSH and AUC0-24 h-estradiol, or between PRL peak and estradiol peak and AUC0-24 h -PRL and AUC0-24 h-estradiol in only a subgroup of women.Therefore, women with estradiol-dependent increase in serum TSH do exist. Reference bands of serum TSH dependent on the phases of the menstrual cycle should be available. Keywords: Thyrotropin, Prolactin, Menstrual cycle, Estradiol, Polycystic ovary syndrome, Buserelin

Background Graves’ is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of thyroid stimulating hormone (TSH) and stimulates the thyroid hormone receptor (TSHR), which results in hyperthyroidism (overactive thyroid gland) and goiter. Methimazole (MMI) is used for hyperthyroidism treatment for patients with Graves’ disease. Methods We have developed a model using a system of ordinary differential equations for hyperthyroidism treatment with MMI. The model has four state variables, namely concentration of MMI (in mg/L), concentration of free thyroxine - FT4 (in pg/mL), and concentration of TRAb (in U/mL) and the functional size of the thyroid gland (in mL) with thirteen parameters. With a treatment parameter, we simulate the time-course of patients’ progression from hyperthyroidism to euthyroidism (normal condition). We validated the model predictions with data from four patients. Results When there is no MMI treatment, there is a unique asymptotically stable hyperthyroid state. After the initiation of MMI treatment, the hyperthyroid state moves towards subclinical hyperthyroidism and then euthyroidism. Conclusion We can use the model to describe or test and predict patient treatment schedules. More specifically, we can fit the model to individual patients’ data including loading and maintenance doses and describe the mechanism, hyperthyroidism→euthyroidism. The model can be used to predict when to discontinue the treatment based on FT4 levels within the physiological range, which in turn help maintain the remittance of euthyroidism and avoid relapses of hyperthyroidism. Basically, the model can guide with decision-making on oral intake of MMI based on FT4 levels. Electronic supplementary material The online version of this article (doi:10.1186/s12976-017-0073-6) contains supplementary material, which is available to authorized users.

We observed local homology between human pendrin and sodium/iodide symporter (NIS), that was absent in the NIS-homologous sodium/monocarboxylate transporter or apical iodide transporter (AIT) which, however, does not transport iodide. Thus, we analyzed the full proteins. They shared 63 identical and 66 similar residues (overall homology 14.4%, but 21% when omitting intervening sequences of 15 or more residues). Pendrin was more homologous to NIS (25%) than AIT (20%), particularly in the STAS domain (sulfate transporter and antisigma factor antagonist). Homology was concentrated in 11 segments, with 3/11 involving the STAS domain. In 9/11, homology was greater with NIS (45-58.3%) than with AIT (8.3-42.3%); in 4 of these 9 segments, homology was comparable to or greater than that between NIS and AIT (8.3-52.6%). Pendrin residues which are mutated in Pendred's syndrome are identical to those in the aligned position of NIS and AIT. Hypothyroidism-associated pendrin mutations almost always fall within 4/11 segments. These are the first data that show homology between pendrin and NIS, and topographic relationships between pendrin mutations and the hypothyroid phenotype of PDS.

Ingestion of coffee (which is a mixture of over 1000 hydrosoluble substances) is known to protect from type-2 diabetes mellitus and its complications, and other chronic disorders associated with increased oxidative damage in blood and tissues. This protection is generally attributed to polyphenols and melanoidins. Very few studies were conducted on the amelioration of classic blood markers of oxidative stress induced after a few days of caffeine administration, but results vary.To assess whether caffeine per se could account for antioxidant properties of coffee in the short-term, we tested the ability of pure caffeine ingestion (5â¯mg/kg body weight/day in two daily doses for seven consecutive days) to improve plasma levels of six biochemical indices in healthy male volunteers (nâ¯=â¯15). These indices were total antioxidant capacity (TAC), glutathione (GSH), oxidized glutathione (GSSG), GSH to GSSG ratio, lipid hydroperoxides (LOOH) and malondialdehyde (MDA).We found that all indices changed significantly (Pâ¯

Testis was considered unresponsive to thyroid hormone for a long time. However, like in animals, the presence of thyroid hormone receptors in different testicular cell types was demonstrated also in humans. Accordingly, thyrotoxicosis and hypothyroidism have remarkable effects on testicular function and more extensively on fertility.Thyrotoxicosis and hypothyroidism are associated with changes affecting the endocrine, sexual, or reproductive functions. Particularly, compared with controls, hyperthyroid patients have higher serum SHBG and lower free and bioavailable testosterone concentrations, a higher rate of astheno-zoospermia, oligo-zoospermia, and terato-zoospermia, and a higher prevalence of sexual disturbances, such as premature ejaculation. In hypothyroid patients, hormonal changes are in the opposite direction compared with hyperthyroid patients. Thyroid hormone regulates a number of functions in the testis, such as proliferation and differentiations of non-germ cells, steroidogenesis, and sperm motility. Furthermore, thyroid hormone regulates testicular redox status. Consequently, thyroid hormone excess or deficiency can affect testicular function at different levels.In view of the high prevalence of thyrotoxicosis and hypothyroidism, a considerable part of infertile patients may harbor overt or subclinical thyroid disease. Identification and management of thyrotoxicosis/hypothyroidism associated infertility needs the collaboration of andrologists, endocrinologists, gynecologists, and general practitioners.

Context Postpartum thyroiditis (PPT) is defined as the occurrence of de novo autoimmune thyroid disease accompanied by thyroid dysfunction in the first year postpartum. However, hormonal changes resembling the typical pattern of PPT have been reported to occur even in women with pregestational Hashimoto’s thyroiditis (HT) on levothyroxine (LT4). Objective To evaluate the risk of PPT in women with HT antedating pregnancy. Design/Setting Retrospective chart review of pregnant women with HT antedating pregnancy seen in a university hospital (2008-2017), who were followed from preconception up to 1 year after delivery. Patients 167 women preconceptionally diagnosed with HT and classified as hypothyroid HT (hypo-HT; n = 98) or euthyroid HT (eu-HT; n = 69), according to their thyroid status at the time of diagnosis. Outcome Measures PPT occurrence and associated clinical characteristics/risk factors. Results PPT occurred in 65/167 women, with a rate statistically greater in the eu-HT than in the hypo-HT group (68.1% vs 18.4%; odds ratio [OR] 9.49, 95% confidence interval [CI] 4.62-19.49). Most of the women experiencing PPT in both groups were euthyroid at the time of first-trimester evaluation (39/47 eu-HT [83%] and 16/18 hypo-HT [88.9%]). Multivariate regression analysis showed eu-HT group and first-trimester euthyroidism to be positively associated with PPT occurrence (ORs 10.71 and 3.89, respectively). Conclusion PPT may occur in hypo-HT women on LT4 therapy, although significantly less frequently than in eu-HT women. The 4-fold higher risk of PPT in HT women maintaining euthyroidism at first -trimester of gestation suggests that the risk of PPT could be related to the amount of unaffected thyroid tissue.

Many papers evaluated the effect of the environmental, or occupational endocrine disruptors (ED), on the thyroid gland, that can lead to thyroid autoimmunity. A higher prevalence of autoimmune thyroid diseases (AITD) was observed in people living in polluted areas near to petrochemical plants, and in petrochemical workers, but also in area contaminated with organochlorine pesticides, or with polychlorinated biphenyls, or near aluminum foundries. The exposure to Hg in chloralkali workers, or in swordfish consumers has been also found to increase AITD prevalence. Vanadium has been shown to increase the inflammatory response of thyrocytes. A beneficial effect of omega-3 fatty acids, and of myo-inositol and selenomethionine have been shown to counteract the appearance of AITD in subjects exposed to environmental or occupational ED. More large studies are needed to investigate the potential roles of ED in the induction of AITD, and of agents or habits that are able to prevent them.

Cadmium (Cd) damages the thyroid gland. We evaluated the effects of myo-inositol (MI), seleno-L-methionine (Se) or their combination on the thyroids of mice simultaneously administered with Cd chloride (CdCl2). Eighty-four male mice were divided into 12 groups (seven mice each). Six groups (controls) were treated with 0.9% NaCl (vehicle), Se (0.2 mg/kg/day), Se (0.4 mg/kg/day), MI (360 mg/kg/day), MI+Se (0.2 mg/kg) and MI+Se (0.4 mg/kg). The other six groups were treated with CdCl2 (2 mg/kg), CdCl2+MI, CdCl2+Se (0.2 mg/kg), CdCl2+Se (0.4 mg/kg), CdCl2+MI+Se (0.2 mg/kg) and CdCl2+MI+Se (0.4 mg/kg). An additional group of CdCl2-challenged animals (n= 7) was treated with resveratrol (20 mg/kg), an effective and potent antioxidant. All treatments lasted 14 days. After sacrifice, the thyroids were evaluated histologically and immunohistochemically. CdCl2 reduced the follicular area, increased the epithelial height, stroma, and cells expressing monocyte chemoattractant protein-1 (MCP-1) and C-X-C motif chemokine 10 (CXCL10). CdCl2+Se at 0.2/0.4 mg/kg insignificantly reversed the follicular and stromal structure, and significantly decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI significantly reversed the thyroid structure and further decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI+Se, at both doses, brought all indices to those of CdCl2-untreated mice. MI, particularly in association with Se, defends mice from Cd-induced damage. The efficacy of this combination was greater than that of resveratrol, at least when using the follicular structure as a read-out for a comparison. We suggest that the use of these nutraceuticals, more specifically the combination of MI plus SE, can protect the thyroid of Cd-exposed subjects.

Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and it is less than 2% of thyroid carcinomas (TCs). The standard treatment of ATC includes surgical debulking, accelerated hyperfractionated external beam radiation therapy (EBRT), and chemotherapy, in particular with cisplatin or doxorubicin, achieving about 10 months of median survival. Since ATC is a rare and aggressive tumor, it is still challenging to predict the patient clinical therapy responsiveness. Several genetic mutations have been described in ATC, involved in different molecular pathways linked to tumor progression, and novel therapies acting on these molecular pathways have been investigated, to improve the quality of life in these patients. Here we review the new targeted therapy of ATC. We report interesting results obtained with molecules targeting different pathways: angiogenesis (vandetanib, combretastatin, sorafenib, lenvatinib, sunitinib, CLM94, CLM3, etc.); EGFR (gefitinib, docetaxel); BRAF (dabrafenib/trametinib, vemurafenib); PPARγ agonists (rosiglitazone, pioglitazone, efatutazone); PD-1 and PD-L1 (pembrolizumab); TERT. To escape resistance to monotherapies, the evaluation of combination strategies with radiotherapy, chemotherapy, or targeted drugs is ongoing. The results of clinical trials with dabrafenib and trametinib led to the approval from FDA of this combination for patients with BRAF V600E mutated ATC with locally advanced, unresectable, or metastatic ATC. The anti-PD-L1 antibody immunotherapy, alone or combined with a BRAF inhibitor, has been shown also promising in the treatment of ATC. Furthermore, to increase the therapeutic success and not to use ineffective or even harmful treatments, a real tailored therapy should be pursued, and this can be achieved thanks to the new available genomic analysis methods and to the possibility to test in vitro novel treatments directly in primary cells from each ATC patient. Exploring new treatment strategies is mandatory to improve the survival of these patients, guaranteeing a good quality of life.

Nutraceuticals are defined as a food, or parts of a food, that provide medical or health benefits, including the prevention of different pathological conditions, and thyroid diseases, or the treatment of them. Nutraceuticals have a place in complementary medicines, being positioned in an area among food, food supplements, and pharmaceuticals. The market of certain nutraceuticals such as thyroid supplements has been growing in the last years. In addition, iodine is a fundamental micronutrient for thyroid function, but also other dietary components can have a key role in clinical thyroidology. Here, we have summarized the in vitro, and in vivo animal studies present in literature, focusing on the commonest nutraceuticals generally encountered in the clinical practice (such as carnitine, flavonoids, melatonin, omega-3, resveratrol, selenium, vitamins, zinc, and inositol), highlighting conflicting results. These experimental studies are expected to improve clinicians’ knowledge about the main supplements being used, in order to clarify the potential risks or side effects and support patients in their use.

Background: Measurement of serum thyroperoxidase autoantibodies (TPOAb) during gestation as a classical marker for the risk of postpartum thyroiditis (PPT) predicts PPT in 1/3 to 1/2 of women. Very few studies have measured serum thyroid hormone Ab (THAb) during gestation, and none as a possible marker for PPT. Methods: In 412 women who were followed up from 7 to 11 weeks of gestation through 12 months after delivery, we measured THAb (T3.IgM, T3.IgG, T4.IgM, T4.IgG), thyroglobulin autoantibodies (TgAb) and TPOAb at study entry (7–11 week of gestation). Results: Sixty-three women (15.3%) developed PPT, which progressed to permanent hypothyroidism (PH) in 34/63 (54%). THAb+ve were 21/412 women (5.1%), the frequency being greater in those who then developed PPT (12/63 [19.0%] vs. 9/349 [2.6%], P = 4.6 × 10−8), and in the PH subgroup (26.5% [9/34] vs. 10.3% [10/29], P = 0.12). THAb positivity occurred in 9/76 women (11.8%) who were TgAb and/or TPOAb+ve compared to 12/336 women who were TgAb and TPOAb negative (3.6%, P = 0.0031). Of these 9 THAb+ve, TgAb and/or TPOAb+ve women, all (100%) developed PPT compared to 3/11 (27.3%, P = 0.0011) THAb+ve, TgAb and/or TPOAb negative women. Of these 9 and 3 PPT women, 8 and 1 progressed to PH (88.9% and 33.3%, respectively, P = 0.12). Conclusions: Gestational positivity of THAb enhance enormously the predictivity for PPT of gestational positivity of TPOAb/TgAb. However, their low frequency (5.1%) and their sensitivity (17.5% [21/63]) go against their application in lieu of TPOAb/TgAb. Keywords: Thyroid autoimmunity, Thyroid hormone autoantibodies, Pregnancy, Postpartum, Postpartum thyroiditis

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves’ disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves’ disease, Hashitoxicosis can also be triggered by stressful life events.

The two main clinical presentations of autoimmune thyroid disorders (AITD) are Graves’ disease (GD) and autoimmune thyroiditis (AT). The associations between thyroid disorders and other organ specific, or systemic autoimmune diseases in the same patient has been suggested, albeit discordant results have been reported in the literature. We focused on the association between GD and other autoimmune syndromes by searching in the literature. Moreover, we have carried out a prospective study investigating about the prevalence of other autoimmune disorders in 3209 GD patients [984 of whom with Graves’ ophthalmopathy (GO)], with respect to 1069 healthy controls, or 1069 with multinodular goiter, or 1069 patients with AT. Patients and controls were matched by age and gender, come from the same area, and had a similar iodine intake. A significant increase of the prevalence of autoimmune disorders in GD patients, with respect to the controls, has been observed. In particular, the most frequently observed associations were: vitiligo (2.6%), chronic autoimmune gastritis (2.4%), rheumatoid arthritis (1.9%), polymyalgia rheumatica (1.3%), multiple sclerosis (0.3%), celiac disease (1.1%), type 1 diabetes (0.9%), systemic lupus erythematosus and sarcoidosis (

The aim of the study was to evaluate the effects on serum insulin and serum thyroid profile of a dietary supplement, myo-inositol, given alone or in combination with melatonin to women during menopausal transition.Forty women aged 45-55 years and at least 6 months of amenorrhea were enrolled in this study. They were randomly assigned to two groups of 20 each. One group took myo-inositol (myo-Ins) (2 g twice a day) and the other group took 2 g/d myo-Ins plus 3 g/d melatonin before sleeping. At the beginning of the study and after 6 months, all women were evaluated for the following indices: waist circumference, body mass index, blood pressure, endometrial thickness, as well as serum concentrations of TSH, FT3, FT4 and insulin.Both at baseline and at 6 months, the two groups were statistically similar for each of the considered indices. If percent changes (Δ%, 6 months over baseline) are contrasted in the two groups, serum TSH decreased in the myo-Ins group but increased in the latter, while serum insulin decreased in both groups.The combination of myo-Ins plus melatonin seems to affect positively glucose metabolism, while myo-Ins only seems to improve thyroid function.

Papillary thyroid carcinoma (PTC) has a good prognosis with a 10-yr survival greater than 90%. Recently, a micro-papillary pattern with hobnail appearance (MPHC) in PTC has been indicated as associated with poor prognosis, but this suggestion is based only on a few cases from geographical areas different from ours. Two-hundred ninety-nine consecutive PTC cases were collected between the years of 1992 and 2014 at our institution. The corresponding histologic sections (at least 6 for each case) were stained with hematoxylin and eosin and reviewed independently by two pathologists to reach a consensus on the identification and quantification of the MPHC. As done in other cohorts, parallel serial sections were stained with antisera for thyroglobulin, epithelial membrane antigen, thyroid-transcription-factor-1 and Ki 67. BRAF gene mutation at codon 600 and RET/PTC1 gene rearrangements were searched. A comparative statistical analysis was done between the present series and previously published series. Of the 295 PTC, 124 (42.5%) were follicular, 104 (35%) classic, 34 (11.5%) sclerosing, 15 (5%) tall cells, 10 (3.4%) Warthin-like, and 8 (2.7%) MPHC. Four MHPC cases (50%) harbored the BRAF V600E variant, while one was positive for RET/PTC1 rearrangement. Our rate of MPHC-PTC (2.7%) is 2X to 8X greater than those reported previously for cohorts from North America + North Italy, Korea and Mexico. MPHC prognosis appears to be better compared to other cohorts, probably due to not only to the lower rate of the vascular invasion, but also to the smaller size of the MPHC-PTC nodule.

Hashimoto’s thyroiditis is an autoimmune disorder of the thyroid gland. In Hashimoto disease, the immune system damages the follicular cells of the thyroid gland through humoral and cellular-mediated responses which result in diminishing production of thyroid hormones in the blood over time. Using a patient-specific model of Hashimoto’s thyroiditis, we describe the natural history of Hashitoxicosis in genetically susceptible individuals. Hashitoxicosis means a sudden leakage of thyroid hormones from the gland. The main result of this present work is to show the existence of a homoclinic orbit which forms the boundary for the asymptotically stable interior diseased steady state. This homoclinic orbit corresponds to the clinical condition of Hashitoxicosis.

The use of thyrotropin and free thyroid hormone assays to evaluate thyroid function is widespread, but in some situations the results are inconsistent with the patient's thyroid status.A 35-year-old woman with a known diagnosis of chronic autoimmune thyroiditis was referred to the authors' clinic at week 26 of her second pregnancy. The patient was clinically euthyroid. Consistent with this, her serum thyrotropin (TSH) was normal (0.79 mIU/L), but she had elevated free thyroid hormones-free triiodothyronine (fT3) and free thyroxine (fT4)-as determined by a one-step chemiluminescent assay. The patient was taking levothyroxine replacement therapy (125 μg/day), and the dose was confirmed. Previous blood tests showed concordance between TSH and free thyroid hormone values. The patient was followed up throughout gestation and at 12 months postpartum. During gestation, her free thyroid hormones remained high using one-step methods, while the total thyroid hormone concentration values were within the reference range, in agreement with the TSH values. Postpartum fT4 and fT3 values returned progressively to normality, in agreement with the TSH values. The presence of circulating thyroid hormone autoantibodies (THAb) was hypothesized, which are known to interfere, although to a variable extent, with thyroid hormone one-step assays. Using stored frozen sera, this hypothesis was confirmed indirectly by measuring normal levels of fT3 and fT4 with a two-step method, and directly by demonstrating THAb against the two hormones.Despite their relative rarity, circulating THAb may be suspected when laboratory data are not consistent and contrast with the clinical picture. To the authors' knowledge, no previous case of transient appearance of THAb in pregnancy has been described.

Papillary thyroid microcarcinoma (PTMC) is defined by the World Health Organization as papillary cancer measuring 10 mm or less in diameter. Generally, PTMC shows an indolent clinical behavior with a good prognosis, although a minority of PTMC is characterized by an aggressive course. However, efforts to identify this aggressive subset of PTMC after surgery remain inconclusive. : Several oncogenic pathways have been identified in thyroid cancer and have been applied translationally to improve prognosis and clinical management. In particular, the BRAFV600E mutation was found more frequently in large, aggressive, recurrent and advanced tumors. : We aimed at reviewing studies on BRAFV600E mutation as a prognostic factor in PTMC.

A phylogenetically conserved 5-residue thyroid hormone (TH)- binding motif was originally found in a few TH plasma carriers and, more recently, in all known plasma and cell-associated proteins interacting with TH as well as in proteins involved in iodide uptake. Minor variations of the motif were found, depending on the particular class of those proteins. Since thyroglobulin (Tg) is the protein matrix for TH synthesis starting from iodination of a selected number of tyrosines (to form first monoiodotyrosine (MIT) and diiodotyrosine (DIT) and then T3 and T4), we hypothesized that by searching the presence of perfect or imperfect versions of that motif in two Tg species (human and murine) in which the iodinated tyrosines and pattern of iodotyrosine/iodothyronine formation are known, we could have found relevant explanations. Explanations, which are not furnished by the simple possession of tyrosine-iodination motifs and sequence of the iodination motif, concern why only some (but not other) tyrosine residues in one species are iodinated and why they have a particular iodination pattern. In this bioinformatics study, we provide such explanations.

This prospective study evaluated the intraoperative ultrasound scan (IUSS) for nonpalpable breast lesions' detection. A total of 108 consecutive female patients underwent surgery using IUSS: Frozen sections demonstrated clear margins in 95.5% of neoplastic patients. Only four (4.5%) patients underwent local re-excision in the same operation. IUSS demonstrated to be quick, accurate, useful, effective, and safe for the intraoperative management of neoplastic nonpalpable breast lesions when performed by a surgeon who has undergone US training, particularly for people in whom alternative approaches can show some limitations due to contraindications or because of scheduling constraints, costs, and patient discomfort.

Cadmium (Cd) induces functional and morphological changes in kidney. Therefore, the effects of a natural nutraceutical antioxidant, myo-inositol (MI), were evaluated in mice kidneys after Cd challenge. Twenty-eight C57 BL/6 J mice were divided into these groups: 0.9% NaCl; MI (360 mg/kg/day); CdCl2 (2 mg/kg/day) plus vehicle; CdCl2 (2 mg/kg/day) plus MI (360 mg/kg/day). After 14 days, kidneys were processed for structural, biochemical and morphometric evaluation. Treatment with CdCl2 increased urea nitrogen and creatinine in serum and augmented tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression. Furthermore, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1) and myo-inositol oxygenase (MIOX) immunoreactivity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells number were significantly higher than control and MI groups. Glutathione (GSH) content and glutathione peroxidase (GPx) activity were reduced and structural changes were evident. The treatment with MI significantly lowered urea nitrogen and creatinine levels, TNF-α and iNOS expression, MCP-1, KIM-1 and MIOX immunoreactivity and TUNEL positive cells number, increased GSH content and GPx activity and preserved kidney morphology. A protection of MI against Cd-induced damages in mice kidney was demonstrated, suggesting a strong antioxidant role of this nutraceutical against environmental Cd harmful effects on kidney lesions.

Levothyroxine, a largely prescribed drug with a narrow therapeutic index, is often a lifelong treatment. The therapeutic efficacy of T4 may be marred by behavioral, pharmacologic, and pathologic issues acting as interfering factors. Despite a continuous search for an optimal T4 treatment, a significant number of patients fail to show a complete chemical and/or clinical response to this reference dose of T4. Gastrointestinal malabsorption of oral T4 represents an emerging cause of refractory hypothyroidism and may be more frequent than previously reputed. In this review, we examine the pharmacologic features of T4 preparations and their linkage with the intestinal absorption of the hormone. We have stressed the major biochemical and pharmacologic characteristics of T4 and its interaction with the putative transporter at the intestinal level. We have examined the interfering role of nutrients, foods, and drugs on T4 absorption at the gastric and intestinal levels. The impact of gastrointestinal disorders on T4 treatment efficacy has been also analyzed, in keeping with the site of action and the interfering mechanisms. Based on the evidence obtained from the literature, we also propose a schematic diagnostic workup for the most frequent and often hidden gastrointestinal diseases impairing T4 absorption.

Background: Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. Objective: As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Methods: Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. Results: CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. Conclusion: We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.

Graves' disease (GD) and autoimmune thyroiditis (AT) are the two main clinical presentations of AITD, and their clinical hallmarks are thyrotoxicosis and hypothyroidism, respectively. GD, and AT, can be associated with other organ specific, or systemic autoimmune diseases in the same patient. However discordant results have been reported in the literature about the possible associations. Here, we review the association of GD and other autoimmune syndromes. Furthermore, we report the results of our prospective study that investigated the prevalence of other autoimmune disorders in 3209 GD patients (984 with Graves' ophthalmopathy), with respect to 1069 healthy controls, or 1069 patients with AT, or 1069 with multinodular goiter (matched by age, gender, coming from the same area, with a similar iodine intake). On the whole, 16.7% of GD patients had another associated autoimmune disease; and the most frequently observed were: vitiligo (2.6%), chronic autoimmune gastritis (2.4%), rheumatoid arthritis (1.9%), polymyalgia rheumatica (1.3%), multiple sclerosis (0.3%), celiac disease (1.1%), diabetes (type 1) (0.9%), systemic lupus erythematosus and sarcoidosis (

Patients affected by autoimmune thyroiditis reached positive effects on indices of thyroid autoimmunity and/or thyroidal function, after following a treatment with selenomethionine (Se) alone, or Se in combination with Myo-inositol (Myo-Ins). Our purpose was to investigate if Myo-Ins alone, or a combination of Se + Myo-Ins, is effective in protecting thyroid cells from the effects given by cytokines, or hydrogen peroxide (H2O2). We assessed the interferon (IFN)-γ-inducible protein 10 (IP-10/CXCL10) secretion by stimulating primary thyrocytes (obtained from Hashimoto’s thyroiditis or from control patients) with cytokines in presence/absence of H2O2. Our results confirm: 1) the toxic effect of H2O2 in primary thyrocytes that leads to an increase of the apoptosis, to a decrease of the proliferation, and to a slight reduction of cytokines-induced CXCL10 secretion; 2) the secretion of CXCL10 chemokine induced by IFN-γ + tumor necrosis factor alpha (TNF)-α has been decreased by Myo + Ins, both in presence or absence of H2O2; 3) no effect has been shown by the treatment with Se. Therefore, a protective effect of Myo-Ins on thyroid cells has been suggested by our data, which exact mechanisms are at the basis of this effect need to be furtherly investigated.

In 236 pregnant women, we showed that selective or predominant consumption of swordfish (group A) was associated with high rates of positivity for serum thyroid autoantibodies (TPOAb and TgAb) throughout day 4 postpartum. In contrast, selective or predominant consumption of oily fish (group B) was associated with TPOAb and TgAb negativity. Rates were intermediate in group C (scanty consumption of swordfish) and group D (consumption of fish other than swordfish and oily fish). Gestational TPOAb positivity is a risk factor for postpartum thyroiditis (PPT), which evolves into permanent hypothyroidism (PH) in about 50% of cases. Purpose of this study was to verify that the different rates of thyroid autoantibodies in the four groups translated into different PPT rates. We expanded our previous cohort (n = 412) and duration of follow-up (month 12 postpartum), and measured frequency of PPT and PH. At first timester of gestation, we confirmed the different Ab positivity rates in group A vs. group B (TPOAb = 21.7% vs. 4.7%, P

About two third of the human microbial commensal community, namely the gut microbiota, is hosted by the gastrointestinal tract which represents the largest interface of the organism to the external environment. This microbial community co-evolved in a symbiotic relationship with the human beings. Growing evidence support the notion that the microbiota plays a significant role in maintaining nutritional, metabolic and immunologic homeostasis in the host. Microbiota, beside the expected role in maintaining gastrointestinal homeostasis also exerts metabolic functions in nutrients digestion and absorption, detoxification and vitamins’ synthesis. Intestinal microbiota is also key in the correct development of the lymphoid system, 70% of which resides at the intestinal level. Available studies, both in murine models and humans, have shown an altered ratio between the different phyla, which characterize a” normal” gut microbiota, in a number of different disorders including obesity, to which a significant part of the studies on intestinal microbiota has been addressed so far. These variations in gut microbiota composition, known as dysbiosis, has been also described in patients bearing intestinal autoimmune diseases as well as type 1 diabetes mellitus, systemic sclerosis and systemic lupus erythematosus. Being Hashimoto’s thyroiditis the most frequent autoimmune disorder worldwide, the analysis of the reciprocal influence with intestinal microbiota gained interest. The whole thyroid peripheral homeostasis may be sensitive to microbiota changes but there is also evidence that the genesis and progression of autoimmune thyroid disorders may be significantly affected from a changing intestinal microbial composition or even from overt dysbiosis. In this brief review, we focused on the main features which characterize the reciprocal influence between microbiota and thyroid autoimmunity described in the most recent literature.

Calcium carbonate was previously shown to interfere with l-thyroxine absorption. To estimate the magnitude of tablet l-thyroxine malabsorption caused by calcium carbonate, with resulting increase in serum thyrotropin (TSH), we performed a cohort study in a referral care center. Fifty postmenopausal hypothyroid l-thyroxine-treated women (age 71.7 ± 5.1 years) who added calcium supplementation (600–1000 mg/day) were considered. They were taking l-thyroxine 45–60 min before breakfast (setting 1). After 4.4 ± 2.0 years from initiation of l-thyroxine therapy, they took calcium supplemaentation within 2 h after l-thyroxine taking (setting 2) for 2.3 ± 1.1 years. Hence, we recommended postponing calcium intake 6–8 h after l-thyroxine (setting 3). We evaluated TSH levels, the prevalence of women with elevated TSH (>4.12 mU/L), total cholesterolemia, fasting glycemia, blood pressure, and the prevalence of hypercholesterolemia, hyperglycemia, and hypertension. TSH levels were 3.33 ± 1.93 mU/L versus 1.93 ± 0.51 or 2.16 ± 0.54 comparing setting 2 with setting 1 or 3 (P

Resistance to thyroid hormone (RTH) describes a rare syndrome in which serum levels of thyroid hormones are elevated but serum levels of thyroid stimulating hormone (TSH) are unsuppressed. The importance of thyroid hormones for the normal function of the adult brain is corroborated by the frequent association of thyroid dysfunctions with neurological and psychiatric symptoms. In this study we investigated whether adult thyroid hormone resistance affects cortical excitability and modulates inhibitory and excitatory intracortical circuitries by using transcranial magnetic stimulation. Cortical excitability was probed with transcranial magnetic stimulation in 4 patients with thyroid hormone resistance, 10 patients affected by overt hypothyroidism (OH) and 10 age-matched healthy controls. We tested motor thresholds, motor evoked potential recruitment curve, cortical silent period (CSP), short interval intracortical inhibition (SICI) and intracortical facilitation. In both OH and RTH patients, the inhibitory cortical circuits were affected compared with euthyroid controls, but in opposite ways. In OH patients, CSP was prolonged and SICI was decreased. On the contrary, in RTH patients CSP was shortened and SICI was increased. Thyroid hormones may influence cortical excitability and cortical inhibitory circuits.

Fish consumption or supplementation with omega-3 fatty acids was reported to cure and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for thyroid autoantibodies is a predictive marker of postpartum thyroiditis and postpartum depression. We hypothesized that stable consumption of the omega-3-rich oily fish was associated with a more favorable profile of serum thyroid antibodies throughout pregnancy and early postpartum compared with stable consumption of swordfish, a predator that concentrates pollutants. We prospectively measured serum thyroglobulin antibodies and thyroperoxidase antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236 thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We did not measure thyroid autoantibodies prior to pregnancy. Women were divided into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish + other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish and oily fish). Major endpoints were positivity rates and serum concentrations of the two autoantibodies. We resorted to previous studies for the estimated content of fatty acids and microelements in the consumed fish. Positivity rates and serum concentrations of both antibodies were the greatest in group A and the lowest in group B (P < 0.001 and P < 0.05 to < 0.001, respectively). Relationship between monthly fish consumption and serum concentrations of either antibody was direct in group A but inverse in group B. The estimated content of omega-3 fatty acids in fish consumed by group B was the greatest (P < 0.001 vs. any other group). These data reinforce recommendations that pregnant women should avoid consuming swordfish and indicate consumption of oily fish as a favorable alternative. Because thyroid autoantibodies are markers of autoimmune-related postpartum problems, our data suggest a dietary prophylaxis of such problems.

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed.A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force.These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided.In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

Autoimmune thyroid diseases (AITDs) can be associated with type 1 diabetes (DM1). The prevalence of serum antibodies against thyroid hormones (THAb) in subjects with autoimmune diseases other than DM1 is increasing. No data are available for DM1.The objectives were evaluate the rate of associated AITD; the rate of positiveness for serum THAb; the panel of THAb based on thyroid hormone interaction and on Ig class; and the association of AITD alone, THAb alone, or AITD plus THAb with diabetes-related complications.This was an observational, prospective study with 6-year (2005-2011) follow-up.The setting was an outpatient diabetes clinic.Fifty-two consecutive subjects (53.8% males; mean age, 37.4 ± 7.4 y; diabetes duration, 19.9 ± 8.2 y) with DM1. All participants completed the study.Main outcome measures were AITD rate; THAb positivity according to hormone interaction and Ig class; association of AITD and THAb with diabetes-related complications.AITD rate increased from baseline (34.6%) to follow-up (38.5%). Subjects with DM1 had a high prevalence of THAb (92.3%). The presence of AITD at baseline was associated with subsequent development of macroangiopathy (0 vs 33% at baseline and follow-up, respectively; P = .029). Some THAb patterns, the majority having T3 binding in common, were associated with the progression and development of diabetes-related complications.THAb synthesis in DM1 might be driven by increased glycosylation of thyroglobulin. Anti T3-THAb may cause a relative "tissue hypothyroidism" by sequestering thyroid hormone, this at least partially contributing to worsening diabetes-related vascular complications. In a clinical setting THAb positivity could identify subjects more likely to develop diabetes complications.

Purpose: Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy. Methods: A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed. Results: The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the "MMI embryopathy". Conclusions: While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy. © 2015 Italian Society of Endocrinology (SIE).

Great interest has recently been focused on a paper reporting characteristic deposits of amyloid-β protein associated with Alzheimer's disease in brains of adults who died of Creutzfeldt-Jakob disease. As they had contracted such disease after treatment with prion-contaminated human growth hormone extracted from cadaver-derived pituitaries, the authors have suggested that interhuman transmission of Alzheimer's disease had occurred. Our previous research led us to find that amyloid-forming peptides share amino acid sequence homology, summarized by a motif. Here, we probed the amino acid sequence of human growth hormone for such a motif, and found that 2 segments fit the motif and are potentially amyloid-forming. This finding was confirmed by Aggrescan, another well-known software for the prediction of amyloidogenic peptides. Our results, taken together with data from the literature that are missing in the aforementioned paper and associated commentaries, minimize the contagious nature of the iatrogenically-acquired coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease. In particular, the above mentioned paper misses literature data on intratumoral amyloidosis in growth hormone- and prolactin-secreting adenomas, tumors relatively frequent in adults, which are often silent. It cannot be excluded that some pituitaries used to extract growth hormone contained clinically silent microadenomas, a fraction of which containing amyloid deposits, and patients might had received a fraction of growth hormone (with or without prolactin) that already was an amyloid seed. The intrinsic amyloidogenicity of growth hormone, in the presence of contaminating prion protein (and perhaps prolactin as well) and amyloid-β contained in some cadavers' pituitaries, may have led to the observed co-occurring of Creutzfeldt-Jakob disease and Alzheimer's disease.

Central hypothyroidism is defined as low circulating free thyroxine (free T4) with inappropriately low circulating thyrotropin (TSH), in context of a hypothalamic pituitary pathology. Rare cases of idiopathic central hypothyroidism caused by a functional defect may occur, and the condition is often overlooked due to difficulty in achieving the correct diagnosis, sparse symptomatology of the condition and a high risk of misinterpretion of the biochemical changes in central hypothyroidism. Central hypothyroidism is mainly seen in patients with hypothalamic–pituitary pathology due to one of many possible aetiologies, where other hormone deficiencies often co-exist, and both the presence of other deficiencies and their replacement have a strong influence on the measurement of the thyroid-related hormones and thereby interpretation of the thyroid function variables in relation to the clinical impact of thyroid hormone substitution therapy. Conversely, lack of thyroid hormone has a similar strong influence on the interpretation of other pituitary hormone axes, as well as their replacement. Undertreating patients with central hypothyroidism may have serious metabolic consequences with a potentially increased risk of cardiovascular morbidity. The present review thus aims at describing central hypothyroidism, by an overview of interactions of hypothyroidism with other pituitary hormones, diagnosing/testing for central hypothyroidism, and focusing on consequences of undertreatment. Finally, it is mentioned how to deal with new diagnostic settings with lower a priori likelihood of hypopituitarism, particularly in view of the importance of stringent diagnostic testing in order to avoid overdiagnosing central hypothyroidism.

Vanadium is a grey metal, existing in different states of oxidation, whose most common form in commercial products is vanadium pentoxide (V2O5). All vanadium compounds have been considered toxic. A carcinogenic role of vanadium on the thyroid has recently been proposed. However no in vivo or in vitro studies have evaluated thyroid disruption in humans and/or animals after exposure to vanadium. In the present study we evaluate the effect of V2O5 on proliferation, and chemokine secretion in normal thyrocytes. Our study demonstrated that V2O5 has no effect on thyroid follicular cell viability or proliferation, but it is able to induce the secretion of T-helper (Th)1 chemokines into the thyroid, synergistically increasing the effect of important Th1 cytokines such as interferon (IFN)γ and tumor necrosis factor (TNF)α. Through this process, V2O5 promotes the induction and perpetuation of an inflammatory reaction in the thyroid. Further studies are necessary to evaluate thyroid function, and nodules, in subjects occupationally exposed, or living in polluted areas.