Search

Purpose Patients undergoing thyroidectomy for differentiated thyroid cancer (DTC) may require 131-radioactive iodine (RAI) administration for remnant ablation or disease treatment. After ingestion, RAI resides within the gastrointestinal tract potentially leading to mucosal damage and abnormalities in the absorption of levothyroxine (LT4). The aim of this study was to evaluate whether serum FT4 peak, induced by a LT4 challenge, changes according to the LT4 formulation (solid or liquid) in both RAI and non-RAI-treated DTC patients. Methods This was a monocentric controlled clinical trial, with a parallel two-groups (1:1) randomization of sequence of LT4 formulation. Patients received 200 mcg LT4 orally administered at 08:00 h, in both solid and liquid formulation, at one-week interval, at baseline and after 1, 3, and 6 months from RAI administration. At each time-point, circulating FT4 was evaluated both before LT4 assumption as well as after 1 and 3 h. FT4 increments were evaluated as area under the curve response (AUC). Analogous protocol with the same time-intervals was followed for non-RAI patients. Results The trial included 29 consecutive DTC patients, nineteen of whom were submitted to RAI. In RAI subjects, we observed an overall significant reduction in serum FT4 increments with the most relevant decrease at the 1-month time-point, (FT4 AUC: 4.46 ± 0.72 (M ± SD) vs 4.07 ± 0.63 in baseline vs 1-month, P = 0.001) without any difference between the two LT4 formulations. No difference in serum FT4 AUC was found in non-RAI subjects. Conclusion LT4-induced serum FT4 responses are reduced following RAI administration in thyroidectomized DTC patients.

ContextThe risk stratification of patients with differentiated thyroid cancer (DTC) is crucial in clinical decision making. The most widely accepted method to assess risk of recurrent/persistent disease is described in the 2015 American Thyroid Association (ATA) guidelines. However, recent research has focused on the inclusion of novel features or questioned the relevance of currently included features.ObjectiveTo develop a comprehensive data-driven model to predict persistent/recurrent disease that can capture all available features and determine the weight of predictors.MethodsIn a prospective cohort study, using the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339), we selected consecutive cases with DTC and at least early follow-up data (n = 4773; median follow-up 26 months; interquartile range, 12-46 months) at 40 Italian clinical centers. A decision tree was built to assign a risk index to each patient. The model allowed us to investigate the impact of different variables in risk prediction.ResultsBy ATA risk estimation, 2492 patients (52.2%) were classified as low, 1873 (39.2%) as intermediate, and 408 as high risk. The decision tree model outperformed the ATA risk stratification system: the sensitivity of high-risk classification for structural disease increased from 37% to 49%, and the negative predictive value for low-risk patients increased by 3%. Feature importance was estimated. Several variables not included in the ATA system significantly impacted the prediction of disease persistence/recurrence: age, body mass index, tumor size, sex, family history of thyroid cancer, surgical approach, presurgical cytology, and circumstances of the diagnosis.ConclusionCurrent risk stratification systems may be complemented by the inclusion of other variables in order to improve the prediction of treatment response. A complete dataset allows for more precise patient clustering.

Objectives There is evidence suggesting that in martial arts competitions athletes characterized by higher anxiety and harm avoidance may be more likely to lose a fight. This psychological profile has been hypothesized to explain in part the observation that cortisol is higher in losers before and in response to a competition. An important research target that needs further exploration is the identification of phenotypic traits that can be helpful in predicting athletes’ performance. Here we present a brief description of the theoretical bases that drives our research in the evolutionary psychobiology of sports and illustrate preliminary data on the relationship between the 5HTTLPR genotype, salivary cortisol, temperament and competition. Methods Sixty-five healthy male non-professional athletes provided saliva samples 10 min before and after a kumite session and filled out the Tridimensional Personality Questionnaire. Results Salivary cortisol levels 10 min before the competition were higher in losers and in athletes with the S allele. Temperament was associated with competition outcome and cortisol: losers were characterized by higher scores of harm avoidance and harm avoidance was positively correlated with cortisol levels. Conclusions The results confirm previous findings linking temperamental traits, pre-and post- competition physiological stress response with competition outcome in kumite fight. Moreover, they indicate an association between the 5HTTLPR polymorphism and pre-competition salivary cortisol, thus providing a preliminary but non-conclusive evidence on the role played by the 5HTTLPR genotype as a vulnerability factor in sport competition.

Most thyroid cancer are incidentally diagnosed. However, little is known on the different modalities of incidental diagnosis in adult versus older patients. We retrospectively analyzed data from 440 patients consecutively diagnosed with differentiated thyroid cancer (DTC) in a single institution. Modalities of diagnosis were categorized as follows: (A) clinically diagnosed, nonincidental cases; (B) incidental during carotid power-duplex (CPD); (C) incidental during neck imaging other than carotid power-duplex; (D) incidental during imaging workup of thyroid dysfunction or at histological examination after thyroidectomy for benign lesions. Demographics, histology and follow-up were compared between adult (

This individual participant data analysis assesses the cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia., Key Points Question Is thyroid dysfunction associated with cognitive decline? Findings In this individual participant data analysis of 23 cohorts including 74 565 participants with cognitive function and/or dementia measurements, subclinical thyroid dysfunction was not associated with global cognitive function at baseline (standardized mean difference, −0.02 for subclinical hyperthyroidism and 0.05 for subclinical hypothyroidism) or annual decline (standardized mean difference, −0.02 for subclinical hyperthyroidism and −0.00 for subclinical hypothyroidism). Meaning These findings do not support the need for screening for subclinical thyroid dysfunction for prevention of cognitive decline or dementia., Importance In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism—cross-sectionally (−0.06 standardized mean difference in score; 95% CI, –0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, –0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aim of this study was to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory (ITCO) database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p=0.65), tumor size >2 cm (OR 1.45, p=0.34), aggressive PTC histology (OR 0.55, p=0.15), and age at diagnosis (OR 0.90, p=0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27, 95% CI, p=0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and non-treated patients (p=0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease.

Background: One of the most widely used risk stratification systems for estimating individual patients' risk of persistent or recurrent differentiated thyroid cancer (DTC) is the American Thyroid Association (ATA) guidelines. The 2015 ATA version, which has increased the number of patients considered at low or intermediate risk, has been validated in several retrospective, single-center studies. The aims of this study were to evaluate the real-world performance of the 2015 ATA risk stratification system in predicting the response to treatment 12 months after the initial treatment and to determine the extent to which this performance is affected by the treatment center in which it is used. Methods: A prospective cohort of DTC patients collected by the Italian Thyroid Cancer Observatory web-based database was analyzed. We reviewed all records present in the database and selected consecutive cases that satisfied inclusion criteria: (i) histological diagnosis of DTC, with the exclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features; (ii) complete data of the initial treatment and pathological features; and (iii) results of 1-year follow-up visit (6-18 months after the initial treatment), including all data needed to classify the estimated response to treatment. Results: The final cohort was composed of 2071 patients from 40 centers. The ATA risk of persistent/recurrent disease was classified as low in 1109 patients (53.6%), intermediate in 796 (38.4%), and high in 166 (8.0%). Structural incomplete responses were documented in only 86 (4.2%) patients: 1.5% in the low-risk, 5.7% in the intermediate-risk, and 14.5% in the high-risk group. The baseline ATA risk class proved to be a significant predictor of structural persistent disease, both for intermediate-risk (odds ratio [OR] 4.67; 95% confidence interval [CI] 2.59-8.43) and high-risk groups (OR 16.48; CI 7.87-34.5). Individual center did not significantly influence the prediction of the 1-year disease status. Conclusions: The ATA risk stratification system is a reliable predictor of short-term outcomes in patients with DTC in real-world clinical settings characterized by center heterogeneity in terms of size, location, level of care, local management strategies, and resource availability.

Purpose Malignancy prediction in indeterminate thyroid nodules is still challenging. We prospectively evaluated whether the combination of ultrasound (US) risk stratification and molecular testing improves the assessment of malignancy risk in Bethesda Category IV thyroid nodules. Methods Ninety-one consecutively diagnosed Bethesda Category IV thyroid nodules were prospectively evaluated before surgery by both ACR- and EU-TIRADS US risk-stratification systems and by a further US-guided fine-needle aspiration cytology (FNAC) for the following molecular testing: BRAFV600E, N-RAS codons 12/13, N-RAS codon 61, H-RAS codons 12/13, H-RAS codon 61, K-RAS codons 12/13, and K-RAS codon 61 point-mutations, as well as PAX8/PPARγ, RET/PC1, and RET/PTC 3 rearrangements. Results At histology, 37% of nodules were malignant. No significant association was found between malignancy and either EU- or ACR-TIRADS. In total, 58 somatic mutations were identified, including 3 BRAFV600E (5%), 5 N-RAS 12/13 (9%), 13 N-RAS 61 (22%), 7 H-RAS 12/13 (12%), 11 H-RAS 61 (19%), 6 K-RAS 12/13 (10%), 8 K-RAS 61 (14%) mutations and 2 RET/PTC1 (4%), 0 RET/PTC 3 (0%), 3 PAX8/PPARγ (5%) rearrangements. At least one somatic mutation was found in 28% and 44% of benign and malignant nodules, respectively, although malignancy was not statistically associated with the outcome of the mutational test. However, the combination of ACR-, but not EU-, TIRADS with the presence of at least one somatic mutation, was significantly associated with malignant histology (P = 0.03). Conclusion US risk stratification and FNAC molecular testing may synergistically contribute to improve malignancy risk estimate of Bethesda category IV thyroid nodules.

Breast cancer (BC) is the most common tumor in women, 523.000 cases were estimated in Europe in 2018 and it remains the third cause of cancer related deaths after lung and colorectal cancer. The incidence of thyroid cancer (TC) in females is higher than in males.We have retrospectively collected all female patients undergone to surgery for breast or thyroid cancer in 2010The aim of the study was to value the incidence of BC in patients with a personal history of differentiated thyroid cancer (DTC) and conversely, the incidence of DTC in patients with previous BC within 5 years from the diagnosis of the first tumor in 2010.Among 76 BC patients, 11 were death and 22 didn't answer the phone call or refused to re-submit to thyroid ultrasound so they were excluded from the study and only 43 BC were further considered. Thyroid ultrasound was performed in 2010 and in 2016 and it described nodules in 13 (30%) patients in 2010 and in 21 (49%) patients in 2016. In 2010 no FNA was needed while in 2016 6 (14%) patients underwent to FNA with a benign response (Thyr 2). Among 61 DTC patients, 11 didn't answer the phone or the questions so 50 patients were included in the study. Breast cancer family history was reported in 14 (28%) patients and thyroid cancer family history in 8 (16%) patients. No relapse was reported during follow up.All patients underwent to mammography in 2015 or in 2016 within screening programs and no breast cancer were diagnosed.The female predominance of diseases of the thyroid and breast makes difficult the separation of an expected association with a casual linkageThe relationship between the co-occurrence of breast and thyroid cancer remains controversial and inconclusive.Breast cancer, Breast surgery, Hormone therapy, Thyroid cancer, Thyroidectomy.In considerazione del fatto che il tumore al seno (BC) è il tumore più comune nelle donne, 523.000 casi sono stati stimati in Europa nel 2018 e rimane la terza causa di morte per cancro dopo il cancro del polmone e del colon-retto., e che l’incidenza del carcinoma tiroideo (TC) nelle femmine è più alta che nei maschi, abbiamo raccolto in modo retrospettivo i dati di tutte le pazienti di sesso femminile sottoposte a chirurgia per carcinoma mammario o tiroideo nel 2010. L’obiettivo dello studio è di valutare l’incidenza di BC in pazienti con anamnesi positiva di carcinoma tiroideo differenziato (DTC) e, viceversa, l’incidenza di DTC nei pazienti con precedente BC entro 5 anni dalla diagnosi del primo tumore nel 2010. Tra le 76 pazienti con BC, 11 erano deceduti e 22 non rispondevano alla telefonata o rifiutavano di sottoporsi a ecografia tiroidea, quindi furono escluse dallo studio e solo 43 BC furono ulteriormente considerati. L’ecografia tiroidea è stata eseguita nel 2010 e nel 2016 e ha descritto i noduli in 13 (30%) pazienti nel 2010 e in 21 (49%) pazienti nel 2016. Nel 2010 non è stato necessario procedere a FNA mentre nel 2016 6 (14%) pazienti sono stati sottoposti a FNA con una risposta di benignità. (Thyr 2). Tra le 61 pazienti sottoposte a chirurgia per DTC, 11 non hanno risposto al telefono o alle domande, quindi sono state incluse nello studio 50 pazienti. Una storia familiare di cancro al seno è stata rintracciata in 14 (28%) pazienti e una storia familiare di cancro della tiroide in 8 (16%) pazienti. Durante il followup non è stata segnalata alcuna recidiva. Tutti le pazienti sono state sottoposte a mammografia nel 2015 o nel 2016 nell’ambito di un programmi di screening e non sono stati diagnosticati tumori al seno. In conclusione la predominanza femminile delle malattie della tiroide e della mammella rende difficile la separazione di un’associazione attesa con un legame casuale. La relazione tra la conoccorrenza del cancro della mammella e della tiroide rimane controversa e inconcludente anche nella nostra esperienza.

Thyroid hormone variation may be correlated with adverse health outcomes, even within the normal reference range in euthyroid individuals. To determine the association between plasma thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and physical performance score in middle age and older adults who had levels of all three hormones in the normal range. In this community-based, cross-sectional study, euthyroid participants of the Invecchiare in Chianti study, aged 23–102 years (N = 1060), were considered. Physical performance was evaluated by the Summary Physical Performance Battery (SPPB) score. Plasma TSH, FT3, and FT4 levels were predictors, and SPPB score was the outcome. At the univariate analyses, TSH, FT4, and FT3 were not significantly associated with SPPB score in young individuals, whereas, in older participants, SBBP score was positively (P

Background Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Methods Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. Results A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) −4.07 (−6.37 to −1.78) and −2.40 (−3.78 to −1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50–4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Conclusions Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

Stressful life events are a major factor in the etiology of several diseases, such as cardiovascular, inflammatory and psychiatric disorders (i.e., depression and anxiety), with the two sexes greatly differing in vulnerability. In humans and other animals, physiological and behavioral responses to stress are strongly dependent on gender, and conditions that are stressful for males are not necessarily stressful for females. Hence the need of an animal model of social chronic stress specifically designed for females. In the present study we aimed to compare the effects of two different chronic stress procedures in female mice, by investigating the impact of 4weeks of nonsocial unpredictable, physical stress by the Chronic Mild Stress paradigm (CMS; Exp.1) or of Social Instability Stress (SIS; Exp.2) on physiological, endocrine and behavioral parameters in adult female mice. CMS had a pronounced effect on females' response to novelty (i.e., either novel environment or novel social stimulus), body weight growth and hormonal profile. Conversely, 4weeks of social instability did not alter females' response to novelty nor hormonal levels but induced anhedonia. Our findings thus showed that female mice were more sensitive to nonsocial stress due to unpredictable physical environment than to social instability stressors. Neither of these stress paradigms, however, induced a consistent behavioral and physiological stress response in female mice comparable to that induced by chronic stress procedures in male mice, thus confirming the difficulties of developing a robust and validated model of chronic psychosocial stress in female mice.

Context Anemia and thyroid dysfunction often co-occur, and both increase with age. Human data on relationships between thyroid disease and anemia are scarce. Objective To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia. Design Individual participant data meta-analysis. Setting Sixteen cohorts participating in the Thyroid Studies Collaboration (n = 42,162). Main Outcome Measures Primary outcome measure was anemia (hemoglobin Results Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants [overt hypothyroidism, pooled OR 1.84 (95% CI 1.35 to 2.50), subclinical hypothyroidism 1.21 (1.02 to 1.43), subclinical hyperthyroidism 1.27 (1.03 to 1.57), and overt hyperthyroidism 1.69 (1.00 to 2.87)]. Hemoglobin levels were lower in all groups compared with participants with euthyroidism. In the longitudinal analyses (n = 25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 (95% CI 0.86 to 2.20) for overt hypothyroidism, 1.18 (1.00 to 1.38) for subclinical hypothyroidism, 1.15 (0.94 to 1.42) for subclinical hyperthyroidism, and 1.47 (0.91 to 2.38) for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups. Conclusion Higher odds of having anemia were observed in participants with both hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.

Background:Late-life depression is often associated with cognitive impairments and disability, which may persist even after adequate antidepressant drug treatment. Physical exercise is increasingly recognized as an effective antidepressant agent, and may exert positive effects on these features too. However, few studies examined this issue, especially by comparing different types of exercises.Methods:We performed secondary analyses on data from the Safety and Efficacy of Exercise for Depression in Seniors study, a trial comparing the antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non-progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by heart rate meters. Patients with late-life depression without severe cognitive impairment were recruited from primary care and assessed at baseline and 24 weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores) and Brief Disability Questionnaire. Analyses were based on Generalized Linear Models.Results:In total, 121 patients (mean age 75, 71% females) were randomized to the study interventions. Compared with the S group, patients in the S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and disability (p=0.02, effect size=−0.31). Participants in the S+NPE group did not display significant differences with the control group.Conclusions:Adding aerobic, progressive exercise to antidepressant drug treatment may offer significant advantages over standard treatment for cognitive abilities and disability. These findings suggest that even among older patients exercise may constitute a valid therapeutic measure to improve patients’ outcomes.

L’invecchiamento si accompagna a modificazioni endocrine con possibili ripercussioni sul sistema cardiovascolare. Importanti sono gli effetti della disfunzione tiroidea, incluse le forme subcliniche, e quelli legati alle modificazioni eta-correlate degli steroidi sessuali, degli ormoni surrenalici e della secrezione dell’ormone della crescita. In alcune di tali situazioni e gia attuabile un programma terapeutico; per altre, invece, gli approcci terapeutici sono ancora oggetto di studio.

Objectives Late-life major depression is associated with increased cardiovascular risk and impaired autonomic control of the heart, as evident from reduced heart rate variability (HRV). Moreover, antidepressant drug therapy also might be associated with further reductions of HRV. In the SEEDS study, we investigated whether sertraline associated with physical exercise protocols led to improvements of HRV, compared with antidepressant drug therapy alone. Design Single-blind randomized controlled trial. Setting Psychiatric consultation-liaison program for primary care. Participants Patients aged 65–85 years with major depression, recruited from primary care. Interventions Sertraline plus structured, tailored group physical exercise (S + EX) versus sertraline alone (S) for 24 weeks. Measurements HRV indices (RR, percentage of NN intervals greater than 50 msec [pNN50], square root of the mean squared differences of successive NN intervals [RMSSD], standard deviation of heart rate [SDHR], standard deviation of the NN interval [SDNN], high-frequency band [HF], low-frequency band [LF], and their ratio [LF/HF]) were measured at baseline, week 12, and week 24. Psychiatric and medical assessments. Results Participants displayed significant improvements of most HRV indices over time, irrespective of the group assignment (pNN50, RMSSD, SDHR, SDNN, HF, LF, and LF/HF). Moreover, patients in the S + EX group displayed greater increases of different HRV indices(RR, pNN50, RMSSD, SDHR, SDNN, HF, and LF) compared with those in the S group. Conclusions The combination of structured physical exercise and sertraline might exert positive effects on the autonomic control of the heart among older patients with major depression.

As for other tyrosine kinase inhibitors, a prolongation of ECG-recorded QTc intervals may be observed during lenvatinib treatment; a warning on this phenomenon has been stated. However, methods and frequency of ECG recordings have seldom been reported in this context. We present two cases of patients treated with lenvatinib for radioiodine-refractory differentiated thyroid cancer in whom the QTc interval was long monitored through a weekly 12-lead ECG registration. Overall, the maximum QTc increase above baseline was 3 and 31 ms in the first and second patient, respectively. QTc interval did not reach the toxicity value for drug withdrawal in either of the patients. These data may provide further information on cardiac safety profile of lenvatinib in a real-life practice.

Acute kidney injury (AKI) is frequent among hospitalized patients, especially in the intensive care unit (ICU) setting, with 2–5% of cases requiring renal replacement therapy (RRT). The average mortality risk associated with AKI remains very high (about 30% in the adult ICU population), though highly variable (16–49%) and depending on severity of illness, clinical setting, and presence of comorbidities. The implications of the syndrome stem from the key role of the kidneys in fluid and electrolyte/acid-base homeostasis, blood pressure control, and waste product excretion, but are not restricted to it. In fact, because the physiologic role of the kidneys extends to multiple endocrine functions, the occurrence of endocrine abnormalities in the course of AKI may be expected. Not only are several hormones synthesized or activated in the kidney (erythropoietin, angiotensins I and II, vitamin D, etc.), but the organ is also very important for their metabolism and excretion. In addition, the kidney is a target organ for several hormones involved in the regulation of its excretory and endocrine functions (thyroid hormones, antidiuretic hormone, etc.). The present chapter aims at focusing on some of the main renal-endocrine pathways involved in AKI with special regard to the ICU setting. To this end, glucose homeostasis derangements and insulin resistance, the hypothalamus-pituitary-thyroid axis, calcium-phosphorus metabolism and vitamin D, as well as erythropoietin will be reviewed.

To evaluate the causes of the first referral to an endocrine visit of patients with thyroid cancer in a mildly iodine-deficient area and to correlate them with prognostic features. We studied 298 consecutive patients (64 M and 234 F) with thyroid cancer. Of these, 281 had differentiated thyroid cancer. The causes of referral were categorized as follows: (Group A) clinical evidence of a neck lump; (Group B) incidental imaging in subjects without known thyroid diseases; (Group C) incidental imaging during a workup of thyroid disorders. Also, in differentiated thyroid cancer cases, clinical, histomorphologic, and prognostic parameters were compared among the three different groups of referral causes. In both total thyroid cancer and differentiated thyroid cancer cohorts, Group A, B, and C accounted for about 25, 35, and 40 % of causes, respectively. Considering the differentiated thyroid cancer, in Group B, ultrasound accounted for 94 % of cases, with 73 % resulting from screening or serendipitous study. Within a median follow-up of 5.6 [IQR: 2.7-9.5] years, disease-free survival was significantly lower in patients of Group A (Log-Rank test p = 0.030 vs. the other groups of causes). However, at the Cox multivariate analysis only male sex (p = 0.002) and stage (p = 0.005), but not referral cause, resulted independent predictors of events. In patients without known thyroid disease, unjustified thyroid ultrasound represents the main cause of referral of thyroid cancer patients to the first endocrine visit. The fact that this is not related to the disease-free survival strengthens the concept of the uselessness of thyroid cancer screening.

Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously.Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T-4, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L.Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95% CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes.Conclusion: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.

Background: Angiosarcoma (AS) of the thyroid is a rare and aggressive tumor. Its incidence is higher in iodine-deficient areas but cases unrelated to endemic goiter have been reported. Case Presentation: We describe a case of a 63-year-old Italian man living in a non-iodine-deficient area, with no previous diagnosis of thyroid disease with a history of radiation exposure. The patient-an interventional cardiologist who had worked for 15 years in an angiographic room- came to the clinical observation because of the rapid onset of dyspnea and dysphonia. Computed tomography (CT) showed a 13-cm inhomogeneous neck mass, originating from the left thyroid lobe which caused displacement and stenosis of the trachea. The patient underwent diagnostic fine-needle aspiration that was followed by total thyroidectomy and lymphadenectomy of central and left lateral cervical nodes. The final pathological diagnosis was epithelioid angiosarcoma (EAS), high grade. The preoperative staging by CT of the head, neck, abdomen, chest and pelvis was negative. At pathological staging, the tumor was angionvasive but it was limited to the thyroid; no lymphnode metastases were detected. Chemotherapy with Epirubicin and Ifosfamide was administered for 4 cycles and, then, it was discontinued due to significant bone marrow toxicity. Conclusion: One year after diagnosis, the CT of neck, abdomen, chest, and pelvis were negative. At 2 years after diagnosis, the FDG-PET was negative with no evidence of the disease at CT Due to the known association between the occurrence of angiosarcoma after radiation therapy it is tempting to speculate that in this patient the presence of thyroid EAS may be linked to radiation exposure.The patient is still alive at 62 months after diagnosis. He is on a follow-up program by a 6-month /1-year neck, chest, abdomen, and pelvis CT evaluation with no signs of metastases.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves’ disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets., Thyroid dysfunction is a common public health problem and associated with cardiovascular co-morbidities. Here, the authors carry out genome-wide meta-analysis for thyroid hormone (TH) levels, hyper- and hypothyroidism and identify SLC17A4 as a TH transporter and AADAT as a TH metabolizing enzyme.

Background: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. Methods: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Results: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26–1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. Conclusions: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16–18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as “metabolic disruptors”, in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

Idiopathic retroperitoneal fibrosis (IRF) is a rare disease often associated with autoimmune disorders. Whether IRF is associated with Hashimoto's thyroiditis (HT) is poorly understood and only addressed by case-reports. We evaluated the prevalence of HT in a large IRF cohort and in matched controls.We studied 73 consecutive patients with new-onset IRF and 71 controls. The association between HT and IRF was cross-sectionally evaluated in a referral center. Longitudinally, thyroid function tests were also performed. Serum concentrations of FT4, TSH, and anti-thyroperoxidase antibodies (AbTPO) were evaluated together with thyroid ultrasound (US). Lymphocytic infiltrates were characterized in thyroid nodule fine needle aspirates (FNAB). In patients undergoing thyroidectomy, thyroid histology was also reviewed.A higher prevalence of AbTPO positivity (P0.03) and US findings suggestive of autoimmune thyroiditis (US-AIT) (P0.0001) were found in IRF patients compared to controls. In the logistic regression analysis, the risk of AbTPO-diagnosed HT and that of US-AIT was significantly higher in IRF patients than in controls (ORs, 3.56, 95% CI 1.48-8.59, P=0.004 and 4.74, 95% C.I., 2.34-9.61, P0.0001 in AbTPO-diagnosed HT and US-AIT, respectively). Thyroid histology in IRF patients showed either classical or the fibrous variant of HT. At the end of the follow-up (median, 45 and 36 months in patients and controls, respectively), 25% of IRF patients and 3% of controls were receiving l-thyroxine.IRF patients have a higher risk of HT compared to controls. Thyroid function should be monitored in patients with IRF.

Objective: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T-4 levels. Data Extraction and Synthesis: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 personyears). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or >= 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Conclusions: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH

Context Hyperthyroidism is associated with increased fracture risk, but it is not clear if lower thyroid-stimulating hormone (TSH) and higher free thyroxine (FT4) in euthyroid individuals are associated with fracture risk. Objective To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals. Design Individual participant data analysis. Setting Thirteen prospective cohort studies with baseline examinations between 1981 and 2002. Participants Adults with baseline TSH 0.45 to 4.49 mIU/L. Main Outcome Measures Primary outcome was incident hip fracture. Secondary outcomes were any, nonvertebral, and vertebral fractures. Results were presented as hazard ratios (HRs) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45 to 0.99 mIU/L; 1.00 to 1.49 mIU/L; 1.50 to 2.49 mIU/L; 2.50 to 3.49 mIU/L; and 3.50 to 4.49 mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results During 659,059 person-years, 2,565 out of 56,835 participants had hip fracture (4.5%; 12 studies with data on hip fracture). The pooled adjusted HR (95% CI) for hip fracture was 1.25 (1.05 to 1.49) for TSH 0.45 to 0.99 mIU/L, 1.19 (1.01 to 1.41) for TSH 1.00 to 1.49 mIU/L, 1.09 (0.93 to 1.28) for TSH 1.50 to 2.49 mIU/L, and 1.12 (0.94 to 1.33) for TSH 2.50 to 3.49 mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 [HR (95% CI) 1.22 (1.11 to 1.35) per one standard deviation increase in FT4]. FT4 only was associated with any and nonvertebral fractures. Results remained similar in sensitivity analyses. Conclusions Among euthyroid adults, lower TSH and higher FT4 are associated with an increased risk of hip fracture. These findings may help refine the definition of optimal ranges of thyroid function tests.

The goal of evidence-based practice guidelines is to optimize the management of emerging diseases, such as differentiated thyroid cancer (DTC). The aim of this study was to assess therapeutic approaches for DTC in Italy and to see how closely these practices conformed to those recommended in the 2009 American Thyroid Association (ATA) guidelines.The Italian Thyroid Cancer Observatory was established to collect data prospectively on thyroid cancers consecutively diagnosed in participating centers (uniformly distributed across the nation). Data on the initial treatment of all pathologically confirmed DTC cases present in the database from January 1, 2013 (database creation) to January 31, 2016, were analyzed.A total of 1748 patients (77.2% females; median age 48.1 years [range 10-85 years]) were enrolled in the study. Most (n = 1640; 93.8%) were papillary carcinomas (including 84 poorly differentiated/aggressive variants); 6.2% (n = 108) were follicular and Hürthle cell carcinomas. The median tumor diameter was 11 mm (range 1-93 mm). Tumors were multifocal in 613 (35%) and presented extrathyroidal extension in 492 (28%) cases. Initial treatments included total thyroidectomy (involving one or two procedures; n = 726; 98.8%) and lobectomy (n = 22; 1.2%). A quarter of the patients who underwent total thyroidectomy had unifocal, intrathyroidal tumors ≤1 cm (n = 408; 23.6%). Neck dissection was performed in 40.4% of the patients (29.5% had central compartment dissection). Radioiodine remnant ablation (RRA) was performed in 1057 (61.2%) of the 1726 patients who underwent total thyroidectomy: 460 (41.2%) of the 983 classified by 2009 ATA guideline criteria as low-risk, 570 (87.1%) of the 655 as intermediate-risk, and 82 (93.1%) of the 88 as high-risk patients (p 0.001). RRA was performed in 44% of the cases involving multifocal DTCs measuring ≤1 cm.The treatment approaches for DTCs used in Italy display areas of inconsistency with those recommended by the 2009 ATA guidelines. Italian practices were characterized by underuse of thyroid lobectomy in intrathyroidal, unifocal DTCs ≤1 cm. The use of RRA was generally consistent with risk-stratified recommendations. However, its frequent use in small DTCs (≤1 cm) that are multifocal persists, despite the lack of evidence of benefit. These data provide a baseline for future assessments of the impact of international guidelines on DTC management in Italy. These findings also illustrate that the dissemination and implementation of guideline recommendations, and the change in practice patterns, require ongoing education and time.

Hashimoto’s thyroiditis (HT) has been considered for many years a well-defined clinicopathological condition. However, the recent observation, in some HT cases, of marked fibrosis and thyroid inflammation rich in immunoglobulin G4 (IgG4)-positive plasma cells, has led to the notion that subtypes of HT may exist. The increased IgG4-positive plasma cell infiltration suggests that this type of HT may have a close relationship with IgG4-related disease (IgG4-RD). This subgroup of HT, now called IgG4-thyroiditis, can be differentiated from non-IgG4 thyroiditis on the basis of clinical, sonographical, and serological findings. In addition, not only some cases of classical HT but also the well-known fibrous variant of HT has been included in the IgG4-thyroiditis spectrum. It is still under investigation whether Riedel’s thyroiditis (RT) as well may be considered as an IgG4-thyroiditis. As a matter of fact, RT is characterized by thyroid inflammatory lesions which involve the surrounding tissues, a finding not reported in IgG4-thyroiditis. However, according to some reports, RT with increased IgG4-positive plasma cells may represent the first clinical manifestation of an underlying IgG4-RD.

The incidence of palpables thyroid nodules in general population is 5% and the prevalence of non -palpable nodules is higher (35-60%) in the endemic goiter area. In the last years the new guidelines and new classification related to thyroid nodule have changed the indication to treat it.We analyzed the patients treated from January 2013 to June 2016 for Thyr 3 and Thyr 4 thyroid nodule sec. Bethesda system. We have divided in I and II period related to the 2.2014 and 2015 ATA guidelines and we have evaluated the indication to treat, the type of surgical procedure, the incidence of thyroid carcinoma and the adverse events.We selected from 909 cases, 252 cases surgically treated with preoperative diagnosis of Thyr 3(80 cases) and Thyr 4(172 cases); carcinoma was found in 21/80 (26.2%) and in 62/172 (26.05%). The period was divided from January 2013 to December 2014 and from January 2015 to june 2016 (first and second period). In II period we found carcinoma in 8/40 Thyr3 and in 26/88 Thyr 4. The incidence of lobectomy in II period was higher than I period (p 0.0001) sec.guidelines indications. No difference in adverse events. The number of cancer is lower in patients treated with lobectomy than those who underwent total thyroidectomy (12,5%vs 21,8% in Thyr 3; 15,3% vs 32% in Thyr 4).The indications to treat related to Thyr 3 and Thyr4 are changed in the two periods. The number of cancer is lower in patients treated with lobectomy. The new guidelines have changed the surgical approach to thyroid nodule.

Cognition can be deteriorated in older persons because of several potential mechanisms including the hormonal changes occurring with age. Stress events cause modification in hormonal balance with acute and chronic changes such as increase in cortisol and thyroid hormones, and simultaneous alterations in dehydroepiandrosterone sulphate, testosterone and insulin like growth factor-1 levels. The ability to cope with stress and regain previous healthy status, also called resiliency, is particularly impaired in older persons Thus, stressful conditions and hormonal dysregulation might concur to the onset of cognitive impairment in this population. In this review we address the relationship between stress hormones and cognitive function in older persons focusing on the role of one of the main stress factors, such as sleep deprivation (SD). We extracted and cross-checked data from 2000 to 2013 March and selected 112 full-text articles assessed for eligibility. In particular we considered 68 studies regarding the contribution of hormonal pathway to cognition in older adults, and 44 regarding hormones and SD both in rats and humans. We investigated how the activation of a stress-pattern response, like the one evoked from SD, can influence cognitive development and worsen cognitive status in the elderly. We will show the limited number of studies targeting the effects of SD and the consequent changes in stress hormones on cognitive function in this age group. We conclude that the current literature is not strong enough to give definitive answers on the role of stress hormonal pathway to the development of cognitive impairment in older individuals.

OBJECTIVES: The effects of vitamin D on the heart have been studied in patients with cardiac disease, but not in healthy persons. We investigated the relation between vitamin D status and left ventricular (LV) structure and function in community-dwelling subjects without heart disease. DESIGN: The relationship between concentrations of 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D reserve, and LV transthoracic echocardiography measures was analysed in 711 participants in the Baltimore Longitudinal Study of Aging who were without cardiac disease. RESULTS: Mean 25(OH)D in the study population was 32.3 ± 11.4 ng mL(-1) ; only 15.5% of subjects had moderate or severe vitamin D deficiency [25(OH)D < 20 ng mL(-1) ]. Adjusting for age, body mass index, cardiovascular disease risk factors, physical activity, calcium and parathyroid hormone, 25(OH)D was positively correlated with LV thickness (β 0.095, SE 0.039, P < 0.05) and LV mass index (β 7.5, SE 2.6, P < 0.01). A significant nonlinear relation between 25(OH)D and LV concentric remodelling was observed. LV remodelling was more likely in participants with 25(OH)D levels

Liquid levothyroxine (LT4) given at breakfast normalizes TSH in hypothyroid patients. However, a few studies are available on circulating free thyroxine (FT4) concentrations after liquid vs solid LT4 preparations.During an "ad interim" analysis on serum FT4 after 200 mcg liquid LT4 consumption while fasting in thyroidectomized thyroid cancer patients, we found that seven subjects fortuitously took liquid LT4 at breakfast. As established in the original protocol, serum FT4 was measured both at baseline as well as at 3 and 4 hours after solid or liquid LT4 consumption. We compared serum profile of FT4 in these subjects with those obtained in other subjects participating in the same study who took liquid LT4 (n. 7 subjects) or solid LT4 (n. 7 subjects) while fasting. The percentage increase of circulating FT4 was calculated at the above reported peak-times over the baseline values.Circulating FT4 increased of about 40% in each group of subjects at both the 3rd and the 4th hour with no difference between these two time points in either group. The maximum FT4 % increase, irrespective of the time point, was 44.62 ± 3.05 (Mean ± SE), 44.84 ± 5.43, and 43.83 ± 1.30 after fasting solid, fasting liquid, and breakfast liquid LT4 consumption, respectively, with no differences among the three groups.Circulating FT4 obtained after 3 and 4 hours from the ingestion of 200 mcg liquid LT4 is not influenced by meal and is comparable with that observed after solid LT4 preparations ingested while fasting.

Background Data relating the size of thyroid cancer with histological types and variants are scarce. Methods All incident thyroid cancer diagnosed between 2003 and 2012 in a mildly iodine-deficient area were derived from a population-based tumor registry. Undifferentiated/anaplastic thyroid cancer and incidental cases were excluded. Major diameter of thyroid cancer, as assessed by pathological examination, was stratified in classes: ≤10 mm; 11-20 mm; 21-40 mm; and >40 mm. For each class, absolute and relative frequencies of histological types were calculated. Results Tumors >20 mm were more frequent among follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma than in other histotypes, with median size of 22.50 mm (95% confidence interval [CI] 16.71-28.29) and 25.00 mm (95% CI 17.04-32.96) in FTC and Hurthle cell carcinoma, respectively. Odds ratio for tumors >20 mm was significant for FTC and Hurthle cell carcinoma only (P < .0001). Conclusion Among the histotypes and variants of differentiated thyroid cancer, FTC and Hurthle cell carcinoma are characterized by the largest size.

Objective To explore the use of ultrasonography as a diagnostic alternative to the traditional “gold standard” imaging study of nuclear scintigraphy in the evaluation of thyrotoxicosis. Methods We review the relevant literature and share our own experience to highlight the promising role of ultrasonography in thyrotoxicosis. In addition, we present a diagnostic algorithm suggesting liberal use of ultrasonography in the evaluation of thyrotoxicosis. Results Ultrasonography has proved effective not only in the differentiation of Graves disease from other types and causes of thyrotoxicosis but also in the detection of subtle thyroid nodules. The latter role is emphasized in light of the recent observation of an increased risk of occurrence of papillary thyroid carcinoma in patients with Graves disease. Conclusion Ultrasonography is a cost-effective, noninvasive, portable, and safe imaging modality in the evaluation of thyrotoxicosis, both for physiologic assessment and for detection of nonpalpable thyroid cancers that may elude identification on physical examination and nuclear imaging studies. Although thyroid scintigraphy remains a standard radiologic study, thyroid ultrasonography can be a practical alternative in many cases and the primary imaging modality in some situations such as during pregnancy and lactation and for evaluation and management of amiodarone-induced thyrotoxicosis. (Endocr Pract. 2012;18: 567-578)

In the adult, subclinical hyperthyroidism (Shyper) may alter skeletal muscle mass and strength. However, whether these effects are present in elderly subjects is not known. We explored the relationship between mild hyperthyroidism and physical function in a population-based sample of older persons.In a cross-sectional analysis, calf muscle cross-sectional area (CMA), handgrip strength, nerve conduction velocity (NCV), and Short Physical Performance Battery (SPPB) scores were compared between 364 euthyroid (Eut) and 28 Shyper men as well as between 502 Eut and 39 Shyper women. In a longitudinal analysis, we evaluated the relationship between baseline plasma TSH, FT3 and FT4 and the 3-year change in SPPB score in 304 men and 409 women who were euthyroid at enrolment.At the cross-sectional analysis, Shyper men, but not women, had a significantly (p = 0.02) lower SPPB score than Eut controls, although with comparable CMA, grip strength and NCV, and were more likely to have poor physical performance (odds ratio = 2.97, p0.05). Longitudinal analysis showed that in Eut men higher baseline FT4 was significantly (p = 0.02) predictive of a lower SPPB score at the 3-year follow-up.Even a modest thyroid hormone excess is associated with a reduced physical function in elderly men.

Context: In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. Objective: The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. Design and Patients: We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. Results: In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. Conclusion: In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state.

Background: Pre-operative cytology in thyroid disease remains the most appropriate diagnostic test for defining the nature of a thyroid nodule before surgical excision. Materials and methods: We selected the most recent 825 surgical thyroid procedures performed in our institution from January 2004 to June 2007; 776 were total thyroidectomies, 23 were lobe-isthmectomies, and 26 were radical neck dissections. We distributed the data based on pre-operative cytology. Each cytological diagnosis was compared to results obtained by definitive histology. Tumors were called incidentalomas if they consisted of a neoplastic focus with a low grade of aggressiveness, as demonstrated by dimension