Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry.

BACKGROUND: Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance-IR or diabetes mellitus-T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. METHODS: Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. RESULTS: Compared with EU and IR, T2D was associated with increased filling pressures (E/e'ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, - 21% decline in TAPSE/PAPS ratio and - 20% decrease in peak VO2). CONCLUSION: The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017.

Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

[Principles of acute pain therapy-An overview taking special features in the patient collective of ophthalmology into consideration]. / Grundlagen zur Akutschmerztherapie ­ Eine Übersicht unter Berücksichtigung von Besonderheiten im Patientenkollektiv der Augenheilkunde.

For many years the quality of perioperative pain management in general has been repeatedly reported as inadequate and there is significant evidence to indicate that this is also true after surgical procedures in ophthalmology. The patient population in ophthalmology is quite challenging due to numerous comorbidities and a high average age resulting in numerous contraindications and organ dysfunctions and requiring special knowledge to ensure high quality acute pain management. The following overview covers basic knowledge of acute pain management, with a particular focus on analgesic approaches and the specifics of the patient population and the associated limitations in terms of analgesic and co-analgesic pharmacological options.

[Resolution of the Federal Joint Committee on the mandatory introduction and implementation of acute pain management concepts-Importance and consequences for ophthalmology]. / Beschluss des Gemeinsamen Bundesausschuss (G-BA) zur verpflichtenden Einführung und Umsetzung von Akutschmerzmanagementkonzepten ­ Bedeutung und Konsequenzen für die Ophthalmologie.

Patient-centered and adequate postoperative pain management is an important part of a modern treatment concept and should also be standard in ophthalmology. Due to the "Regulation on the mandatory introduction and implementation of acute pain management concepts for adequate postoperative pain therapy" prescribed by the Federal Joint Committee of the German statutory healthcare system (G-BA), hospitals and outpatient facilities have been required to have regulations on pain management in place since 9 December 2020. It is very likely that the need of pain management in ophthalmic surgery has been systematically underestimated so far and studies on postoperative pain hardly exist. In the opinion of the authors, the decision represents an opportunity to pay more attention to the topic and to develop standards for ophthalmology as well. This article explains the G­BA decision and the resulting consequences for ophthalmic surgical institutions.

A Data-Driven Approach to Refine Predictions of Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study.

CONTEXT: The 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. OBJECTIVE: To develop a comprehensive data-driven model to predict persistent/recurrent disease that can capture all available features and determine the weight of predictors. METHODS: In 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. RESULTS: By 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. CONCLUSION: Current 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.

Testosterone deficiency independently predicts mortality in women with HFrEF: insights from the T.O.S.CA. registry.

AIMS: Testosterone deficiency (TD) is associated with increased morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). However, data in women are scanty. The aim of this study was to investigate the prognostic impact of TD on women with HFrEF. METHODS: Among 480 patients prospectively enrolled in the T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, a prospective, multicentre, nationwide, observational study, 94 women were included in the current analysis. The TD was defined as serum testosterone levels lower than 25 ng/dl. Data regarding clinical status, echocardiography, exercise performance, cardiovascular hospitalization, and survival after an average follow-up of 36 months were analysed. RESULTS: Thirty patients (31.9%) displayed TD. TD was associated with lower tricuspid annular plane excursion (TAPSE) to pulmonary arterial systolic pressure PASP ratio (TAPSE/PASP) (P = 0.008), peak oxygen consumption (VO2 peak) (P = 0.03) and estimated glomerular filtration rate (P < 0.001). TD was an independent predictor of the combined endpoint of all-cause mortality/cardiovascular hospitalization (HR: 10.45; 95% CI: 3.54-17.01; P = 0.001), all-cause mortality (HR: 8.33; 95%: 5.36-15.11; P = 0.039), and cardiovascular hospitalization (HR: 2.41; 95% CI: 1.13-4.50; P = 0.02). CONCLUSIONS: One-third of women with HFrEF displays TD that impacts remarkably on their morbidity and mortality. TD is associated with a worse clinical profile including exercise capacity, right ventricular-pulmonary arterial coupling, and renal function. These findings lend support to an accurate profiling of women with HF, a problem often overlooked in clinical trials.

Serum thyroglobulin reference values according to NACB criteria in healthy subjects with normal thyroid ultrasound.

BACKGROUND: The present study was undertaken to establish serum thyroglobulin (Tg) normal reference values in a large group of healthy subjects. METHODS: Four hundred and thirty-eight non-smoking healthy subjects were selected to assess the Tg reference values (209 males, 229 non-pregnant females, age 34.7±13.1 years). Inclusion criteria were: no personal or familial history of thyroid disease, thyrotropin levels from 0.5 to 2.00 mUI/L, negative thyroperoxidase and thyroglobulin antibodies. In addition, the patients had a normal size thyroid (females ≤18 mL, males ≤25 mL) without nodules on the thyroid ultrasound (TUS). According to National Academy of Clinical Biochemistry (NACB) criteria the Tg results were transformed to a logarithmic scale and reference ranges were calculated as mean±2 SD. RESULTS: Serum Tg was measured on the Beckman Coulter UniCel DxI 800 automated platform by the simultaneous 1-step immunoenzymatic Access Thyroglobulin assay (Beckmann-Coulter SA, Nyon, Switzerland). Serum Tg levels were higher in females than in males (p=0.0022). Accordingly, gender-specific reference values were calculated (i.e., males: 1.40-29.2 ng/mL; females: 1.50-38.5 ng/mL). CONCLUSIONS: To the best of the authors' knowledge, the first reference interval study for Tg that integrates NACB criteria and TUS assessment for the selection of the reference population is provided here.

Thyroid volume influences serum calcitonin levels in a thyroid-healthy population: results of a 3-assay, 519 subjects study.

BACKGROUND: We aimed to assess determinants for serum calcitonin (CT) levels and to define reference ranges for different CT immunoassays integrating thyroid ultrasonography (TUS) and conventional clinical and biochemical criteria to select the reference population. METHODS: Five hundred and nineteen thyroid-healthy subjects were included in this prospective cross-sectional population study. Thyroid volume was measured by TUS, while serum CT levels were measured by three different immunoassays. RESULTS: Significant interassay differences were found and the agreement between assays was poor. CT levels were higher in males than in females in all immunoassays. Using the first two assays, both gender and thyroid volume were independent determinants for CT levels. While using the third assay, one thyroid volume was the only determinant for CT levels. CONCLUSIONS: Thyroid volume is a relevant determinant for CT levels. In the clinical practice, the difference of the thyroid sizes in males and females warrants gender-specific reference ranges.

The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.

In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30-1.70; P = 5.9x10(-9)). Functional assays of rs1867277 (NM_004473.3:c.-283G>A) within the FOXE1 5' UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/alphaCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era.

Impact of the COVID-19 pandemic on the energy performance of residential neighborhoods and their occupancy behavior.

Several contrasting effects are reported in the existing literature concerning the impact assessment of the COVID-19 outbreak on the use of energy in buildings. Following an in-depth literature review, we here propose a GIS-based approach, based on pre-pandemic, partial, and full lockdown scenarios, using a bottom-up engineering model to quantify these impacts. The model has been verified against measured energy data from a total number of 451 buildings in three urban neighborhoods in the Canton of Geneva, Switzerland. The accuracy of the engineering model in predicting the energy demand has been improved by 10%, in terms of the mean absolute percentage error, as a result of adopting a data-driven correction with a random forest algorithm. The obtained results show that the energy demand for space heating and cooling tended to increase by 8% and 17%, respectively, during the partial lockdown, while these numbers rose to 13% and 28% in the case of the full lockdown. The study also reveals that the introduced detailed occupancy scenarios are the key to improving the accuracy of urban building energy models (UBEMs). Finally, it is shown that the proposed GIS-based approach can be used to mitigate the expected impacts of any possible future pandemic in urban neighborhoods.

Insulin-like growth factor-1 (IGF-1) as predictor of cardiovascular mortality in heart failure patients: data from the T.O.S.CA. registry.

INTRODUCTION: Data from the "Trattamento Ormonale nello Scompenso CArdiaco" (T.O.S.CA) registry showed that heart failure (HF) represents a complex clinical syndrome with different hormonal alterations. Renal failure represents a frequent complication in HF. We evaluated the relationship between renal function and insuline-like growth factor-1 (IGF-1) deficiency and its impact on cardiovascular mortality (CVM) in patients enrolled in the T.O.S.CA. registry. METHODS: At the enrolment, all subjects underwent chemistry examinations, including circulating hormones and cardiovascular functional tests. COX regression analysis was used to evaluate factors related to CVM during the follow-up period in all populations, in high-risk patients and in the young-adult population. Also, we evaluate the effects of renal function on the CVM. RESULTS: 337 patients (41 deceased) were analyzed. CVM was related to severe renal dysfunction (HR stages IV-V = 4.86), high-risk conditions (HR 2.25), serum IGF-1 (HR 0.42), and HF etiology (HR 5.85 and HR 1.63 for valvular and ischemic etiology, respectively). In high-risk patients, CVM was related to IGF-1 levels, severe renal dysfunction and valvular etiology, whereas in young patients CMV was related to the high-risk pattern and serum IGF-1 levels. CONCLUSIONS: Our study showed the clinical and prognostic utility of the IGF-1 assay in patients with HF.

Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. Registry.

AIMS: Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. METHODS AND RESULTS: The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37-2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28-3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01). CONCLUSION: MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT023358017.

Real-World Performance of the American Thyroid Association Risk Estimates in Predicting 1-Year Differentiated Thyroid Cancer Outcomes: A Prospective Multicenter Study of 2000 Patients.

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.

Adherence to Levothyroxine Treatment Among Patients With Hypothyroidism: A Northeastern Italian Survey.

Background: A significant number of patients show sub-optimal adherence to levothyroxine (LT4) therapy, mainly because they have to postpone their breakfast by at least 30 min. The aim of this observational cross-sectional study was to assess the therapeutic compliance of patients on LT4 treatment and to verify the preference of a lifetime treatment in tablet or liquid form. Patients and Methods: Ambulatory care patients aged 18 years or older, affected by hypothyroidism and on LT4 treatment (in tablet or liquid form) were administered the eight-item Morisky Medication Adherence Scale (MMAS-8). The MMAS-8 questionnaire was supplemented with 3 further items to specifically evaluate preference between tablet and liquid forms of LT4 for lifetime treatment. Results: A total of 320 patients (272 female), median age 47.9 ± 15.6 years (range, 20-78 years), completed the MMAS-8 questionnaire. Eighty-seven percent of the participants were adhering to their treatment for both tablet and liquid LT4 formulations, although significant differences emerged. Patients on LT4 tablets forgot to take their medication more frequently (p < 0.001), felt hassled about sticking to their treatment plan (p < 0.001), and had difficulty remembering to take all their medication(s) (p < 0.001) than those on liquid LT4 treatment. Conclusions: Adherence to LT4 treatment was high for both tablet and liquid formulations. Taking LT4 at breakfast was the most convenient option for most patients.

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults.

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Treatment of polycystic ovary syndrome with spironolactone plus licorice.

OBJECTIVE: The aim of the study was to compare the effect of spironolactone (antagonist of mineralocorticoid and androgen receptors) versus spironolactone plus licorice (agonist of mineralocorticoid receptors and mild inhibitor of androgen synthesis) on plasma renin activity, aldosterone and androgen levels in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Thirty-two women with PCOS were divided into two groups: 16 received 100 mg spironolactone and 16 spironolactone plus 3.5 g of licorice a day. Blood pressure, body mass index, serum electrolytes, plasma renin activity, plasma aldosterone and cortisol, serum testosterone, and urinary tetrahydrocortisol/tetrahydrocortisone ratio were measured before and during treatment. RESULTS: Mean blood pressure was significantly reduced during spironolactone treatment, while it was unchanged in women receiving spironolactone plus licorice. Twenty percent of women treated with spironolactone and none treated with the addition of licorice complained of symptoms related to volume depletion. Consistently, the activation of the renin-aldosterone system was significantly lower during spironolactone plus licorice than with spironolactone alone. The prevalence of metrorrhagia was lower in the combined therapy. CONCLUSIONS: In patients with PCOS the mineralocorticoid properties of licorice can reduce the prevalence of side effects related to the diuretic activity of spironolactone.

Clustering of cardiovascular risk factors associated with the insulin resistance syndrome: assessment by principal component analysis in young hyperandrogenic women.

OBJECTIVE: Hyperinsulinemia is often associated with several metabolic abnormalities and increased blood pressure, which are risk factors for cardiovascular disease. It has been hypothesized that insulin resistance may underlie all these features. However, recent data suggest that some links between insulin resistance and these alterations may be indirect. The aim of our study was to further investigate this issue in a sample of young hyperandrogenic women, who often show insulin resistance and other metabolic abnormalities typical of the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: We tested the hypothesis of a single factor underlying these features by principal component analysis, which should recognize one component if a single mechanism explains this association. The analysis was carried out in a sample of 255 young nondiabetic hyperandrogenic women. Variables selected for this analysis included the basic features of the insulin resistance syndrome and some endocrine parameters related to hyperandrogenism. RESULTS: Principal component analysis identified four separate factors, explaining 64.5% of the total variance in the data: the first included fasting and postchallenge insulin levels, BMI, triglycerides, HDL cholesterol, and uric acid; the second, BMI, blood pressure, and serum free testosterone; the third, fasting plasma glucose, postchallenge glucose and insulin levels, serum triglycerides, and free testosterone; and the fourth, postchallenge plasma insulin, serum free testosterone, and gonadotropin-releasing hormone agonist-stimulated 17-hydroxyprogesterone. CONCLUSIONS: These results support the hypothesis of multiple determinants in the clustering of abnormalities in the so-called insulin resistance syndrome.

High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized, Multicenter Study.

Context: Increase in drug frequency or dose is recommended for acromegaly patients with partial response to long-acting somatostatin receptor ligands (SRLs). However, the efficacy and safety data with lanreotide (LAN) Autogel (LAN-ATG) at high dose (HD) or high frequency (HF) are still scanty. Objective: To evaluate the biochemical efficacy and safety of HF and HD LAN-ATG in patients with active acromegaly. Design: Twenty-four-week prospective, multicenter, randomized, open-label trial. Patients and Interventions: Thirty patients with active acromegaly, partial responders to SRLs, were randomized to HF (120 mg/21 days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. Outcomes: Normalization of serum insulin-like growth factor-I (IGF-I) and reduction in random growth hormone (GH) values < 1.0 µg/L, reduction in serum IGF-I and GH from baseline, differences in biochemical response between HF and HD LAN-ATG, adverse events. Results: IGF-I decreased significantly (P = 0.007) during the 24-week treatment, with greater decrease in HD (P = 0.03) vs HF group (P = 0.08). Normalization in IGF-I values occurred in 27.6% of patients (P = 0.016 vs baseline), without a significant difference between HF and HD groups (P = 0.59). The decrease in serum IGF-I significantly correlated with serum LAN values (P = 0.04), and normalization of IGF-I was predicted by baseline IGF-I values (P = 0.02). Serum GH values did not change significantly (P = 0.22). Overall, 19 patients (63.3%) experienced adverse events, all being mild to moderate and transient, without differences between the two therapeutic arms. Conclusion: HF and HD LAN-ATG regimens are effective in normalizing IGF-I values in about one-third of patients with active acromegaly inadequately controlled by long-term conventional SRLs therapy.

The upper reference limit for thyroid peroxidase autoantibodies is method-dependent: A collaborative study with biomedical industries.

BACKGROUND: The determination of the upper reference limit (URL) for thyroid peroxidase autoantibodies (TPOAbs) is a contentious issue, because of the difficulty in defining the reference population. The aim of this study was to establish the URL (eURL) for TPOAbs, according to the National Academy of Clinical Biochemistry (NACB) guidelines and to compare them with those obtained in a female counterpart, by the use of six commercial automated platforms. METHODS: 120 healthy males and 120 healthy females with NACB-required characteristics (<30years, TSH between 0.5 and 2.0mIU/L, normal thyroid ultrasound, without personal/family history of thyroid and non-thyroid autoimmune diseases) were studied. Sera were analyzed for TPOAbs concentration using six immunoassay methods applied in automated analyzers: Advia Centaur XP (CEN), Siemens Healthcare Diagnostics; Maglumi 2000 Plus, Shenzen New Industries Biomedical Engineering; Architect ci4100, Abbott; Cobas e411 (COB) Roche Diagnostics; Unicel DxI (UNI) and Lumipulse G1200, Fujirebio. RESULTS: Within each method, TPOAbs values had a high degree of dispersion and the eURLs were lower than those stated by the manufacturer. A statistically significant difference (p<0.05) between medians of males and females was observed only for COB and for UNI. However, the comparison of the male and female proportions positive for TPOAbs using the eURL of the counterpart, showed the lack of clinical significance of the above differences (Chi-square test, p>0.05). CONCLUSIONS: Despite the analytical harmonization, the wide dispersion of the results and the differences of the eURLs between methods suggest the need of further studies focusing on TPO antigen preparations as the possible source of variability between different assays. In addition, the lack of clinical significant difference between males and females, in terms of TPOAb eURLs, confirms the suitability of the NACB recommendations.