Purpose The prevalence of thyroid nodules (TN) in the general population has increased as screening procedures are implemented and an association with metabolic and cardiovascular disorders has been reported. The aim of this study was to investigate the reason leading to the diagnosis of TN and to compare the clinical characteristics of patients diagnosed incidentally with those of patients diagnosed for thyroid-related reasons. Methods We designed a retrospective cross-sectional study including consecutive patients with TN from two high-volume hospital-based centers for thyroid diseases (Pavia and Messina) in Italy. Data regarding reason leading to TN diagnosis, age, sex, BMI, presence of cardio-metabolic comorbidities were collected. Results Among the 623 enrolled subjects, the US diagnosis of TN was prompted by thyroid-related reasons in 421 (67.6%, TD group) and incidental in 202 (32.4%, ID group) with a similar distribution in the two centers ( p = 0.960). The ID group patients were more frequently males (38.6% vs 22.1%, p < 0.001) and significantly older (58.9 ± 13.7 vs 50.6 ± 15.5 years, p < 0.001) than the TD group ones, and had a higher rate of cardiovascular comorbidities (73.8% vs 47.5%, p < 0.001), despite having a similar BMI (27.9 ± 5.2 vs 27.8 ± 13.5, p = 0.893). Conclusions Stratification of patients with TN according to the diagnostic procedure leading to diagnosis allows a better epidemiological characterization of this inhomogeneous and large population.

Abstract Background Several authors implemented different biomarkers to evaluate and quantify the size of effective atrial fibrillation (AF) ablation lesions after pulmonary veins isolation (PVI) with thermal energy source. However, limited data have been reported on the effects of a new form of non-thermal energy such as electroporation obtained by means of a pulsed-field ablation (PFA, Farapulse) system. Purpose Our analysis aims to compare acute myocardial injury through different biomarkers variation after PVI performed with different technologies (PFA vs radiofrequency, RF). Methods All consecutive patients (pts) undergoing AF ablation with PFA at our center were included. A PFA protocol-directed PVI was applied using 2kV with 8 applications per vein. RF deliveries were deployed according to a wide antral lesion set around the PVs at 50W. Pre- and post-procedure samples of cardiac troponin I (hs-TnI, ng/l), creatinine kinase-MB (CK-MB, ng/dl), fibrinogen (FB, mg/dl), myoglobin (Myo, ng/ml), N-terminal (NT)-pro hormone B-type natriuretic peptide (NT-ProBNP, pg/ml) and C-reactive protein (CRP, mg/dl) values were collected before PVI and at 24h after ablation. Ablation endpoint was PVI. Results Fourty-nine pts were included (62±12 years, 63% male, 84% with paroxysmal AF). PFA cases were 35 (71.4%) whereas RF cases were 14 (28.6%). Evaluating the kinetic of each cardiac biomarker, no differences were found between baseline and 24h for both FB (363±93 at baseline vs 387±112 at 24h, p=0.4513) and NT-ProBNP (137[61-462] at baseline vs 227[157-423] at 24h, p=0.0544). On the contrary kinetics of remaining biomarkers differed and significantly increased from baseline to 24h: 61±22 to 112±101 for Myo level, p=0.0017; 0.38±0.2 to 1.45±2.2 for CRP values, p<0.0001; 1.5±0.7 to 19.4±14 for CK-MB level, p<0.0001 and 11.2±20 to 6177±5765 for hs-TnI level, p<0.0001. By looking at the effect of the ablation strategy on cardiac biomarkers, hs-TnI level, CRP level and CK-MB were significantly different between groups at 24h after PFA/RF (hs-TnI: 7556±6025 for PFA vs 2038±1257 for RF, p<0.0001; CRP: 1.6±2.3 for PFA vs 0.9±1.2 for RF, p=0.0297; CK-MB: 23.7±12 for PFA vs 6.3±9.6 for RF, p<0.0001). PVI was achieved in all patients (100%) using only RF or PFA. No major procedure-related adverse events were reported. Conclusion Our preliminary results showed that cardiac troponin I enzyme level, C-reactive protein and creatinine kinase-MB increased after PVI by means of both radiofrequency and pulsed-field ablation and were higher after cellular electroporation by PFA than RF.

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Azienda Ospedaliero-Univerisitaria delle Marche Background Pulmonary vein isolation (PVI) by radiofrequency (RF) ablation is a well-established and effective treatment for paroxysmal and persistent atrial fibrillation (AF). Compared to low-power-long-duration (LPLD) RF ablation, the high-power-short duration (HPSD) one produces shallower lesions reducing potential adverse effects, without affecting efficacy. The new TactiFlex Ablation Catheter, Sensor Enabled (TFSE), combining a flexible tip with fiber optic-based contact force sensing, can deliver HSPD RF, obtaining a faster PVI. Objective To test feasibility, safety, and effectiveness of RF AF ablation performed by TFSE, comparing it with LPLD RF AF ablation using TactiCath Contact Force Ablation catheter, Sensor Enabled (TCSE). Methods We conducted a prospective study including 50 consecutive patients admitted to our centre for paroxysmal or persistent AF catheter ablation. The patients were randomly divided into 2 groups according to ablation protocol: 25 patients were treated with HPSD performed by TFSE [63 (53-68) years, male 19]; 25 patients were treated with LPLD by TCSE [62 (51-69); male 12). In the HPSD group, the lesions were performed delivering 50W up to 10 seconds with a contact force (CF) index ranging from 5g to 20g. In the LPLD group, the lesions were performed delivering 40W in the anterior segments of veins (LSI 5-5.5) and 35W in the posterior segments (LSI 4-4.5). Results PVI was achieved in 100% of patients in both groups. No periprocedural complication was reported. No statistically significant differences were found in terms of clinical and echocardiographic characteristics. A significant decrease in PVI time was reported in TFSE group for every pulmonary vein (LSPV: 2.14±0.13 min vs 10.63±5.34, p<0.005; LIPV 2.10±0.12 min vs 10.50±5.56 min, p<0.005; RSPV: 2.20±0.14 min vs 10±6.35 min, p<0.005; RIPV 3.10±5.21 min vs 10.40±8.54 min, p<0.005). No difference was reported for the impendence drop (17 Ω, range 15.3-18 in TFSE vs 15 Ω, range 14.5-17.5 in TCSE, p=0.114). A shorter total procedural time (110 min, range 90-121 vs 155 min, range 128-190, p<0.005) and LA mapping time (8 min, range 6-10 vs 13 min, range 11-14, p<0.005) were reported in TFSE group, while no difference was reported in total fluoroscopy time (16 min, range 12-19.30 vs 19 min, range 14-27, p=0,062). The RF total time was superior in the TCSE group. Conclusions In our initial experience, TactiFlex catheter allows a safe, effective and faster PVI in patients affected by paroxysmal and persistent AF undergoing RF ablation. The shorter time for PVI is the main contributor for shortening total procedural times. However, our results have to be confirmed in larger studies.

The terms “vitamin A” and “retinoids” encompass a group of fat-soluble compounds essential for human nutrition. Some of them (retinol, retinal, 9-cis-retinoic acid, tretinoin, and 13-cis-retinoic acid) are fully natural, while others are synthetic compounds used mostly for therapeutic purposes. Some evidence indicates that the nutritional status of these retinoids (i.e., the presence or absence of deficiency) is able to modulate thyroid gland metabolism. Vitamin A deficiency is tightly correlated with structural and functional impairment of the thyroid gland and is often associated with iodine deficiency. Furthermore, retinoids are involved in different immune functions, as well as in the process of activation, proliferation, and differentiation of regulatory T cells (Treg). This is particularly significant given the high prevalence of thyroid autoimmune disorders, whose pathogenesis seems to be related to the altered homeostasis of regulatory T cells. Retinoids are also involved in the modulation of gene expression via their interaction with nuclear receptors, and they also act as cofactors in cell growth and differentiation. The ability of retinoic acid to increase iodine uptake and sodium-iodine symporter activity in human thyroid cancer cell lines suggests that some retinoids and their derivatives may be of use in the treatment of different thyroid tumors. This minireview summarizes the current knowledge on the link between nutritional intake of vitamin A and various thyroid disorders.

Vertebral fractures (VFs) were described in elderly patients with heart failure (HF) whereas their prevalence and determinants in younger HF patients are still unknown. This study aimed at assessing whether secondary hyperparathyroidism (SHPT) may influence the risk of VFs in middle-aged patients with HF. 84 patients (44 males, median age 48.5 years, range 43–65) with HF were prospectively evaluated at the baseline and after 36-month follow-up for bone mineral density (BMD) and VFs by quantitative morphometry on chest X-rays. Serum PTH, calcium, 25-hydroxyvitamin D and 24-h-urinary calcium were evaluated at the baseline and every 6–12 months during the study period. At baseline, SHPT, hypovitaminosis D and VFs were found in 43 patients (51.2%), 73 patients (86.9%) and 29 patients (34.5%), respectively. SHPT was associated with VFs at baseline [inverse probability-weighted (ipw) odds ratio (OR) 12.2, p < 0.001]. Patients were treated with vitamin D3 alone (56%), vitamin D3 plus calcium carbonate (21.4%), calcitriol alone (4.8%), bisphosphonates plus vitamin D3 (8.3%) or a combination of bisphosphonates, vitamin D3 and calcium carbonate (9.5%). At the end of follow-up, hypovitaminosis D was corrected in all patients, whereas 19/84 patients (22.6%) had persistent SHPT. During the follow-up, 16 patients developed incident VFs which resulted to be associated with baseline SHPT (ipw OR 55.7, p < 0.001), even after adjusting from BMD change from baseline to follow-up (ipw OR 46.4, p < 0.001). This study provides a first evidence that SHPT may be a risk factor for VFs in middle-aged patients with HF.

© 2018 American Chemical Society. Polysaccharides from feijoa fruit were extracted and analyzed; the composition of these polysaccharides conforms to those typically found in the primary cell walls of eudicotyledons. The two major polysaccharide extracts consisted of mainly pectic polysaccharides and hemicellulosic polysaccharides [xyloglucan (77%) and arabinoxylan (16%)]. A collection of commensal Bacteroides species was screened for growth in culture using these polysaccharide preparations and placed into five categories based on their preference for each substrate. Most of the species tested could utilize the pectic polysaccharides, but growth on the hemicellulose was more limited. Constituent sugar and glycosyl linkage analysis showed that species that grew on the hemicellulose fraction showed differences in their preference for the two polysaccharides in this preparation. Our data demonstrate that the members of the genus Bacteroides show differential hydrolysis of pectic polysaccharides, xyloglucan, and arabinoxylan, which might influence the structure and metabolic activities of the microbiota in the human gut.

Purpose Fine and balanced regulation of cell proliferation and apoptosis are key to achieve ovarian follicle development from the primordial to the preovulatory stage and therefore assure female reproductive function. While gonadotropins are the major and most recognized regulators of follicle cell growth and function, other factors, both systemic and local, play equally important roles. This work is aimed at evaluating the effects of thyroid hormones (THs) on human granulosa luteinized (hGL) viability. Methods Human GL cells derived from assisted reproduction treatments were exposed to T3 or T4. Cell viability was evaluated by MTT assay. Apoptosis was evaluated by the TUNEL assay and active caspase-3 staining. StAR, CYP19A1,Caspase-3, P53 and BAX mRNA were evaluated by real-time PCR. LC3-I/-II, AKT and pAKT were evaluated by western blot. Results T3 and T4 promoted cell viability in a dose-dependent modality and modulate StAR and CYP19A1 expression. T3 and to a lesser extent T4 mitigated cell death induced by serum starvation by inhibition of caspase-3 activity and expression of P53 and BAX; and attenuate cell death experimentally induced by C2-ceramide. Cell death derived from starvation appeared to be involved in autophagic processes, as the levels of autophagic markers (LC3-II/LC3-I ratio) decreased when starved cells were exposed to T3 and T4. This effect was associated with an increase in pAkt levels. Conclusion From the present study, THs emerge as potent anti-apoptotic agents in hGL cells. This effect is achieved by inhibiting the apoptosis signalling pathway of BAX and caspase-3, while maintaining active the PI3K/AKT pathway.

© 2019 American Chemical Society. Pectic polysaccharides from New Zealand (NZ) spinach (Tetragonia tetragonioides) and karaka berries (Corynocarpus laevigatus) were extracted and analyzed. NZ spinach polysaccharides comprised mostly homogalacturonan (64.4%) and rhamnogalacturonan I (5.8%), with side chains of arabinan (8.1%), galactan (2.2%), and type II arabinogalactan (7.1%); karaka berry polysaccharides comprised homogalacturonan (21.8%) and rhamnogalacturonan I (10.0%), with greater proportions of side chains (arabinan, 15.6%; galactan, 23.8%; and type II arabinogalactan, 19.3%). Screening of gut commensal Bacteroides showed that six were able to grow on the NZ spinach extract, while five were able to grow on the karaka berry extract. Analysis of the polysaccharides remaining after fermentation, by size-exclusion chromatography and constituent sugar analysis, showed that the Bacteroides species that grew on these two substrates showed preferences for the different pectic polysaccharide types. Our data suggest that, to completely degrade and utilize the complex pectin structures found in plants, members of Bacteroides and other bowel bacteria work as metabolic consortia.

PURPOSE:Autoimmune thyroid events (ATEs) are common side effects after alemtuzumab (ALZ) therapy in patients with multiple sclerosis (MS). Our purpose was to reach more robust evidence on prevalence and outcome of the spectrum of alemtuzumab-induced autoimmune thyroid events in patients with multiple sclerosis.METHODS:PubMed and Scopus were systematically searched through July 2019. Studies dealing with patients without personal history of thyroid dysfunctions and affected by MS treated with ALZ and reporting ATEs were selected. Data on prevalence and outcome of ATEs were extracted. A proportion of meta-analysis with random-effects model was performed.RESULTS:Considering the overall pooled number of 1362 MS patients treated with ALZ (seven included studies), a 33% prevalence of newly diagnosed ATEs was recorded. Among all ATEs, Graves' disease (GD) was the most represented [63% of cases, 95% confidence interval (CI) 52-74%], followed by Hashimoto thyroiditis (15%, 95% CI 10-22%). Interestingly, GD showed a fluctuating course in 15% of cases (95% CI 8-25%). Of all GD, 12% (95% CI 2-42%) likely had spontaneous remission, 56% (95% CI 34-76%) required only antithyroid drugs, 22% (95% CI 13-32%) needed additional RAI, and 11% (95% CI 0.9-29%) underwent definitive surgery.CONCLUSION:Among different categories of ATEs, Graves' hyperthyroidism was the most common thyroid dysfunction, occurring in more than half of cases. Antithyroid drugs should represent the first-line treatment for ALZ-induced GD patients. However, alemtuzumab-induced GD could not be considered as having a more favourable outcome than conventional GD, given the substantial chance to encounter a fluctuating and unpredictable course.

© 2018 American Society for Microbiology. Members of the bacterial genus Bifidobacterium generally dominate the fecal microbiota of infants. The species Bifidobacterium longum is prevalent, but the B. longum subsp. longum and B. longum subsp. infantis strains that are known to colonize the infant bowel are not usually differentiated in microbiota investigations. These subspecies differ in their capacities to metabolize human milk oligosaccharides (HMO) and may have different ecological and symbiotic roles in humans. Quantitative PCR provides a quick analytical method by which to accurately ascertain the abundances of target species in microbiotas and microcosms. However, amplification targets in DNA extracted from samples need to be dependably differential. We evaluated the tuf gene sequence as a molecular target for quantitative PCR measurements of the abundances of B. longum subsp. infantis and B. longum subsp. longum in fecal microbiotas. This approach resulted in the detection of a tuf gene variant (operational taxonomic unit 49 [OTU49]) in Chinese infants that has sequence similarities to both B. longum subsp. infantis and B. longum subsp. longum. We compared the genome sequence and growth and transcriptional characteristics of an OTU49 isolate cultured in HMO medium to those of other B. longum subsp. infantis cultures. We concluded from these studies that OTU49 belongs to B. longum subsp. infantis, that dependable quantitative PCR (qPCR) differentiation between the B. longum subspecies cannot be achieved by targeting tuf gene sequences, and that functional genes involved in carbohydrate metabolism might be better targets because they delineate ecological functions.

electrical cardioversion (ECV) of atrial fibrillation (AF) is a pivotal component of the rhythm control approach. Although ECV is safe and effective in the majority of patients, approximately one patient out of ten experiences an early or very early recurrence. In order to improve ECV’s success rate, oral or intravenous amiodarone pre-treatment is commonly prescribed and followed by a second ECV attempt. However, due to the long time needed to achieve therapeutic levels and the high risk of phlebitis, faster and safer strategies to facilitate ECV are highly needed.  to evaluate whether the administration of a flecainide or propafenone oral bolus followed by ECV would prove effective and safe in facilitating conversion to sinus rhythm in patients with persistent AF and a prior ECV failure. we conducted a prospective, open-label, single center observational study. The case group was formed by patients with persistent AF and a prior ECV failure receiving flecainide or propafenone oral bolus (at the same doses used for the "pill-in-the-pocket" approach) followed by a second ECV attempt 3 hours after drug ingestion. For comparison, we selected patients with a prior ECV failure that underwent amiodarone-facilitated ECV. Before ECV, amiodarone was either administered orally for at least 1 month or intravenously for 24 hours. The primary outcome was conversion to sinus rhythm, defined as sinus rhythm persisting for at least 12 hours after ECV. patient’s characteristics were well balanced in the 3 groups, apart from slightly lower left ventricular ejection fraction values in the amiodarone groups. The day after ECV failure, 29 patients received oral flecainide at a 200 mg (n = 15) or at a 300 mg (n = 14) dose and one patient received oral propafenone at a 600 mg dose before undergoing a second ECV attempt. In nine patients, amiodarone was given intravenously for 24 hours. Amiodarone was prescribed orally to 22 patients for a median of seven weeks at an average daily dose of 241.4 mg. In the flecainide/propafenone group, one patient converted to sinus rhythm one hour after drug ingestion; among the other 29 subjects, the second ECV was effective in 23 (cumulative effectiveness: 80.0%). In the intravenous amiodarone group, 2 patients converted to sinus rhythm during drug infusion; among the other 7, the second ECV proved effective in 4 (cumulative effectiveness: 66.7%). In the oral amiodarone group, ECV was successful in 17 patients (77.3%). When comparing the three groups, the primary outcome occurred in a similar proportion of patients (Chi-squared test: p = 0.34; Fisher’s exact test: p = 0.24). Serious adverse events were not reported. flecainide or propafenone oral bolus quickly facilitated conversion to sinus rhythm in the vast majority of patients with persistent AF and a prior ECV failure with a low inherent risk of adverse events. Flecainide effectiveness proved similar to intravenous or oral amiodarone.

© 2019 American Society for Microbiology. Infants fed breast milk harbor a gut microbiota in which bifidobacteria are generally predominant. The metabolic interactions of bifidobacterial species need investigation because they may offer insight into the colonization of the gut in early life. Bifidobacterium bifidum ATCC 15696 hydrolyzes 2=-O-fucosyllactose (2FL; a major fucosylated human milk oligosaccharide) but does not use fucose released into the culture medium. However, fucose is a growth substrate for Bifidobacterium breve 24b, and both strains utilize lactose for growth. The provision of fucose and lactose by B. bifidum (the donor) allowing the growth of B. breve (the beneficiary) conforms to the concept of syntrophy, but both strains will compete for lactose to multiply. To determine the metabolic impact of this syntrophic/competitive relationship on the donor, the transcriptomes of B. bifidum were determined and compared in steady-state monoculture and coculture using transcriptome sequencing (RNA-seq) and reverse transcription-quantitative PCR (RT-qPCR). B. bifidum genes upregulated in coculture included those encoding alpha-L-fucosidase and carbohydrate transporters and those involved in energy production and conversion. B. bifidum abundance was the same in coculture as in monoculture, but B. breve dominated the coculture numerically. Cocultures during steady-state growth in 2FL medium produced mostly acetate with little lactate (acetate:lactate molar ratio, 8:1) compared to that in monobatch cultures containing lactose (2:1), which reflected the maintenance of steady-state cells in log-phase growth. Darwinian competition is an implicit feature of bacterial communities, but syntrophy is a phenomenon putatively based on cooperation. Our results suggest that the regulation of syntrophy, in addition to competition, may shape bacterial communities.

Graves’ disease (GD) can present as an isolated disease (iGD) or in association with other autoimmune diseases (aGD). The aim of this study, performed in two Endocrine referral centers settled in different geographical areas of Italy, was to compare the anthropometric, clinical, and biochemical phenotype of iGD patients with that of the aGD ones. Clinical history, physical examination data, serum levels of TSH, FT4, FT3, thyroglobulin (TgAb), thyroid-peroxidase (TPOAb) and TSH-receptor (TRAb) antibody, presence of Graves’ orbitopathy (GO), and thyroid ultrasound examination at disease diagnosis were recorded. 68 aGD and 136 iGD patients were consecutively recruited. At diagnosis, aGD and iGD patients did not differ for F/M ratio, age at presentation, thyroid function parameters, serum levels of TRAb, TgAb, TPOAb, presence of GO, and thyroid volume. The serum levels of TRAb were strongly correlated with the circulating concentrations of both FT3 (ρ = 0.667; p < 0.0001) and FT4 (ρ = 0.628; p < 0.001) in iGD patient, but not in the aGD ones (FT3: ρ = 0.231; p = 0.058; FT4: ρ = 0.096; p = 0.435). Compared with iGD patients, the aGD ones displayed a higher rate of transition from the previous hypothyroidism to hyperthyroidism (χ2 = 6.375; p = 0.012). Despite similar anthropometric, clinical, and biochemical features at diagnosis, aGD patients display a higher rate of transition from a thyroid functional status to the other as compared with iGD patients.

PurposeThyroid disorders are clinically associated with impaired fertility in women, and these abnormalities can be improved by restoring the euthyroid state. The exact mechanisms of thyroid effect on female fertility are not well known; however, it is conceivable that thyroid hormones (THs) might act on ovarian physiology via receptors in granulosa cells. This work is aimed at evaluating the effects of THs on non-tumoral granulosa cells and follicles.MethodsFreshly isolated rat ovarian follicles and granulosa cells were exposed to T3 or T4 (THs). Cell growth and viability were evaluated by cell counting and the MTT assay, respectively, follicle growth was evaluated by volume measurements. Apoptosis was evaluated by the TUNEL assay and active Caspase 3 staining. rGROV cells were exposed to T3, and apoptosis was induced by serum deprivation. Bcl2, Bcl-2-associated X protein (BAX), Akt and pAkt expression were evaluated by western blot.ResultsT3 induced a 40% increase in follicle volume (after 7days). This increase was presumably due to the observed decrease (33%) in the apoptotic rate of the granulosa cell population. Both T3 and T4 caused a dose-dependent increase in rat granulosa cell number and viability. In addition, THs decreased the cell apoptotic rate in a dose-dependent manner. In both conditions, T3 appeared to be more efficient. In rGROV cells, 100nM T3 induced cell growth and, in the absence of growth factors, reduced cell apoptosis by 40%, downregulating Caspase 3 and BAX. This effect was associated with an increase in pAkt levels. The involvement of the PI3K pathway was confirmed by the ability of the PI3K specific inhibitor (LY-294,002) to abolish T3 pro-survival action.ConclusionsTHs influence cell survival of ovarian granulosa cells. This effect likely contributes to the TH-induced follicle volume increase.

The prevalence of sporadic duodenal polyps is estimated to be 0.3%-4.6% in patients referred for an upper endoscopy. Most of patients are asymptomatic (66-80%) at the time of diagnosis though bleeding, anemia and abdominal pain are the most commonly reported symptoms. These are related to the polyp's size, location and histological characteristics. We describe three cases of big, pedunculated nonampullary sporadic duodenal polyps (tubulovillous low-grade dysplasia adenomas) located in the second part of the duodenum and characterized by different clinical presentations, managed in our Endoscopic Unit within one year (between 2016 and 2017). Polypectomies were performed, either piece-meal or en-bloc using various endoscopic instruments. In one of our patients (case 1), a delayed bleeding (36 hours after the procedure) occurred eventually managed conservatively with two units of blood transfusion. In the same patient, in the following months after polypectomy, the pre-procedural state of anemia misclassified as Mediterranean anemia has improved with a significant rise of hemoglobin value (14.1g/dl). In a patient who previously underwent a renal transplant (case 2), endoscopy was indicated, based on the positive fecal occult blood test. In another patient (case 3), a big polyp induced pancreatitis since it exerted a strong traction on the duodenal wall during peristaltic movements. The removal of the polyp has led to the resolution of pancreatitis and associated symptoms.

Hyperhomocysteinemia is a known cardiovascular risk factor and a key player in the inflammatory activation of autoimmune diseases. Hashimoto’s thyroiditis (HT) is the leading cause of hypothyroidism which, in itself, has been associated with a significant raise of homocysteine (Hcy) levels and increased cardiovascular risk. Our aim was to assess the impact of HT on Hcy levels in patients with acute hypothyroidism.

There is a frequently encountered subset of hypothyroid patients who are refractory to standard thyroid hormone replacement treatment and require unexpectedly high doses of levothyroxine. In addition to clinical situations where hypothyroid patients are non-compliant, or where there is the possibility of excipient-induced disease exacerbation (gluten/celiac disease), therapeutic failure may be due to impaired absorption of the administered drug. The common approach to managing patients with unusual thyroxine needs is to escalate the dose of levothyroxine until targeted TSH levels are achieved. This approach can increase the risk for prolonged exposure to supratherapeutic doses of levothyroxine, which increase the chances of adverse outcomes. Repeated adjustments of levothyroxine can also escalate the costs of treatment, as frequent office visits and laboratory tests are required to determine and maintain the desired dose. Clinicians should take a systematic approach to managing patients whom they suspect of having treatment-refractory hypothyroidism. This may include searching for, and adjusting, occult medical conditions and/or other factors that may affect the absorption of levothyroxine, before up-titrating the dose of traditional levothyroxine therapy. Depending on the underlying pathology, another approach that may be considered is to try alternative formulations of levothyroxine that are less susceptible to intolerance issues related to excipients, or, in some cases, to malabsorption. The early discovery of these factors via a thoughtful patient work-up may avoid unnecessary thyroid medication adjustments and their consequences for both patients and clinicians.

Objective: Autonomously functioning thyroid areas may be associated with subclinical or overt hyperthyroidism, but may exist even in the presence of normal TSH. This study was aimed at comparing the rate of autonomously functioning areas and their cardiac sequelae in patients with nodular goitre studied with the usual and a novel approach.Design and methods: In total 490 adult outpatients with thyroid nodular goitre, living in a mild iodine-deficient area, were selected in our referral centre for thyroid diseases from 2009 to 2014 on the basis of a suspicion of thyroid functional autonomy. They were divided in three groups according to a non-conventional approach (excessive response to thyroxine treatment: group 1) or conventional approach (low/normal TSH with clinical suspicion or low TSH: groups 2 and 3). All patients of the study with the suspicion of thyroid functional autonomy underwent thyroid scan with radioactive iodine (I-131) uptake (RAIU).Results: The percentage of confirmed thyroid functional autonomy was 319/490, being significantly higher in group 3 than in groups 1 and 2 (81.5 vs 64.7 vs 52.6%; chi-square P < 0.0001). However, the diagnosis with non-conventional approach was made at a significant earlier age (P < 0.0001). Cardiac arrhythmias as well as atrial fibrillation were similarly detected by conventional and non-conventional approaches (chi-square test: P = 0.2537; P = 0.8425).Conclusions: The hyper-responsiveness to thyroxine treatment should induce the suspicion of thyroid functional autonomy at an early stage, allowing to detect autonomous functioning areas in apparently euthyroid patients.

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.