Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendati...

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Revised American thyroid association guidelines for the management of medullary thyroid carcinoma

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

Mechanisms of diabetes mellitus-induced bone fragility

Background: Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. Objectives: To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. Search methods: We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. Selection criteria: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake. Data collection and analysis: Two review authors independently assessed studies for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. Main results: We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses - LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear. Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression. There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence). Authors' conclusions: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event risk, CHD mortality and arrhythmia.

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Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.

Bone health and maintenance of bone integrity are important components of comprehensive cancer care in both early and late stages of disease. Risk factors for osteoporosis are increased in patients with cancer, including women with chemotherapy-induced ovarian failure, those treated with aromatase inhibitors for breast cancer, men receiving androgen-deprivation therapy for prostate cancer, and patients undergoing glucocorticoid therapy. The skeleton is a common site of metastatic cancer recurrence, and skeletal-related events are the cause of significant morbidity. The National Comprehensive Cancer Network (NCCN) convened a multidisciplinary task force on Bone Health in Cancer Care to discuss the progress made in identifying effective screening and therapeutic options for management of treatment-related bone loss; understanding the factors that result in bone metastases; managing skeletal metastases; and evolving strategies to reduce bone recurrences. This report summarizes presentations made at the meeting.

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NCCN Task Force Report: Bone Health in Cancer Care

The primary goal of this study was to assess peripheral bone microarchitecture and strength in postmenopausal women with type 2 diabetes with fragility fractures (DMFx) and to compare them with postmenopausal women with type 2 diabetics without fractures (DM). Secondary goals were to assess differences in nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic postmenopausal women without fragility fractures (Co), and in DM and Co women. Eighty women (mean age 61.3 ± 5.7 years) were recruited into these four groups (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density and cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro–finite element analysis (µFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009; +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the distal radius DMFx had 4.7-fold greater relative porosity (p < 0.0001) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p = 0.031; −6.8%, p = 0.011) than DM. DMFx exhibited significantly higher pore-related deficits in stiffness, failure load, and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing nondiabetic Fx and Co, we only found a nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women. © 2013 American Society for Bone and Mineral Research

Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures

Context: Diabetes mellitus is a risk factor for osteoporotic fractures. Sclerostin is an inhibitor of bone formation. However, there are no data about sclerostin levels in type 2 diabetes mellitus (T2DM). Objectives: The aims were to evaluate serum sclerostin in T2DM patients and to analyze its relationship with bone metabolism. Design, Setting, and Patients: This was a cross-sectional study. We compared serum sclerostin in the T2DM group (n = 74) and control group (n = 50), and we analyzed its relationship with calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures. Results: Sclerostin levels were significantly higher in T2DM patients than control subjects (P < 0.001) and in T2DM males than in T2DM females (P < 0.001). Serum sclerostin was positively correlated with age in males T2DM (P = 0.031). In linear regression analysis, gender, study group, and age were predictive of sclerostin levels (P < 0.05). Sclerostin concentrations were positively asso...

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Circulating Levels of Sclerostin Are Increased in Patients with Type 2 Diabetes Mellitus

OBJECTIVE Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years). RESULTS Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group ( P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD ( P = 0.04), abnormal intima-media thickness (IMT) ( P = 0.004), carotid plaques ( P P P = 0.03) and aortic calcifications ( P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561–2.586], P = 0.003) and IMT (β = 0.330 [14.237–67.693], P = 0.003) were positive correlated with sclerostin. CONCLUSIONS Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients.

https://care.diabetesjournals.org/content/diacare/36/6/1667.full.pdf

Atherosclerotic Disease in Type 2 Diabetes Is Associated With an Increase in Sclerostin Levels

Previous studies of bone turnover markers in diabetes are limited, and the results are conflicting. Our aim was to evaluate differences in bone turnover markers and i-PTH between T2DM and non-diabetes subjects. Cross-sectional study including 133 subjects (78 T2DM, 55 without diabetes). BMD were measured by dual X-ray absorptiometry. Bone turnover markers were determined in serum. Serum levels of bone resorption markers (CTX and TRAP5b) were lower in T2DM compared with non-diabetes subjects. There were no differences in bone formation markers. i-PTH serum levels were lower in T2DM: 38.35 ± 18.20 pg/ml versus 50.22 ± 18.99 pg/ml, P < 0.05. TRAP5b and CTX were positively correlated with i-PTH (CTX: r = 0.443, P < 0.001; TRAP5b: r = 0.180, P = 0.047). There was an inverse relationship between TRAP5b levels and diabetes duration (r = −0.269, P = 0.021). T2DM patients have lower levels of bone resorption markers, and i-PTH compared with subjects without diabetes. Lower levels of PTH may induce a low turnover state as reflected by lower levels of bone resorption markers, and this situation may influence the higher risk of fracture of T2DM.

Serum levels of bone resorption markers are decreased in patients with type 2 diabetes.

Routine measurement of parathormone (PTH) has lead to the identification of high PTH levels without hypercalcemia. This situation, which is known as normocalcemic hyperparathyroidism [1], was defined by Wills in 1962 and is established after ruling out the main causes of secondary hyperparathyroidism. There are conflicting data about its bone effects and clinical course. The aims of our study was to evaluate the frequency of normocalcemic hyperparathyroidism in postmenopausal, to analyse parameters related to bone metabolism, and to assess changes after one-year follow-up. We conducted a prospective study conducted in a cohort of 100 healthy postmenopausal women. Clinical and biochemical data and bone mass by quantitative ultrasound (QUS) were determined at baseline and after 1 year. The study protocol was approved by the ethical review board of our hospital and was done conformed to the ethics guidelines for research in humans. All the participants in the study provided written informed consent. Baseline characteristics of the study groups are shown in Table 1. 16 patients had high PTH levels, one woman with criteria of primary hyperparathyroidism (PTH 109 pg/ml and calcium 11.2 mg/dl) who was excluded from the study and 15 of them with normal calcium serum levels (PTH 78 ± 13 pg/ml and serum calcium 9.3 ± 0.3 mg/dl). In this group, six patients had high PTH with 25-OH vitamin D [30 ng/ml and were classified as normocalcemic primary hyperparathyroidism. There were no differences in biochemical and clinical variables between women with secondary hyperparathyroidism and normocalcemic hyperparathyroidism except for 25-OH vitamin D: 17.4 ± 10 versus 33.2 ± 2.6 ng/ml, p \ 0.001 (Table 1). There was a high percentage of women in both groups with low 25-OH vitamin levels: 72.6 % (61/84) in normal PTH group versus 57.2 % in women with secondary hyperparathyroidism (9/15) (p = 0.32). Women with secondary hyperparathyroidism and normocalcemic hyperparathyroidism have normal values of renal function, bone turnover markers and bone mass measured by QUS. In the group consisting of secondary and normocalcemic hyperparathyroidism, PTH showed a negative correlation with QUS parameters: QUI: r = -0.621, p = 0.013; BMD r = -0.554, p = 0.032; Tscore r = -0.571, p = 0.026. No correlation was observed between PTH and bone mass in the group with normal PTH levels. After one-year of follow-up, PTH remained high in 86.7 % (13/15) of women and in 13.3 % (2/15) PTH has dropped to normal values. In women with secondary hyperparathyroidism there were no significant changes in biochemical and clinical variables (Table 1). The six women with baseline criteria of normocalcemic hyperparathyroidism remained in this category after 1 year. No episodes of hypercalcemia or other relevant clinical events were observed in this group. To our knowledge, no previous studies have evaluated the frequency of normocalcemic hyperparathyroidism in postmenopausal Spanish women. In the Canadian Multicentre Osteoporosis normocalcemic hyperparathyroidism was diagnosed in 16.7 % of subjects, but they considered 25-OH vitamin D \20 ng/ml as vitamin D deficiency which may have contributed to the higher prevalence observed. The evaluation of well known causes of secondary hyperparathyroidism in our sample (low vitamin D, renal disease, malnutrition) allowed us to exclude women A. Garcia-Martin (&) R. Reyes-Garcia M. Munoz-Torres Bone Metabolic Unit, Endocrinology Division, University Hospital San Cecilio, Avenida Doctor Oloriz 16, 18012 Granada, Spain e-mail: garciamartin_t@hotmail.com

Normocalcemic primary hyperparathyroidism: one-year follow-up in one hundred postmenopausal women.

In vitro and animals models have shown follicle-stimulating hormone (FSH) effects on osteoclastic function, and FSH levels seem to influence bone loss independently of estrogen concentrations in humans. Our aim was to evaluate the role of serum FSH measurement in the assessment of bone resorption in postmenopausal women. We conducted a cross-sectional study including 92 postmenopausal healthy women aged 56.2 (3.6) and 7.2 (4) years since menopause. Serum FSH, luteinizing hormone (LH), estradiol (E2) and bone turnover markers as osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) were measured. We analyzed the relationship between serum levels of gonadotropins, E2, and bone turnover markers. Serum levels of OC and CTX were positively related to FSH (r = 0.234, P = 0.047 and r = 0.384, P = 0.003) and LH (r = 0.319, P = 0.012 and r = 0.273, P = 0.038). There was no relationship with E2 levels. When gonadotropins levels were divided into quartiles, we found significant differences in bone turnover markers between the first and the fourth quartile. OC levels were higher in the highest quartile of FSH (P = 0.024) and LH (P = 0.001). Serum CTX was also higher in the highest quartile of FSH (P = 0.004) and LH (P = 0.039). FSH levels could explain approximately 14.7% of the chances in CTX. In summary, gonadotropins were related to bone turnover in postmenopausal healthy women. Moreover, the rise in FSH appears to contribute to higher bone resorption. Our results suggest that the measurement of FSH could be usefulness to perform a more comprehensive assessment of bone loss in these women.

Antonia García-Martín

Papers

Circulating Levels of Sclerostin Are Increased in Patients with Type 2 Diabetes Mellitus

Atherosclerotic Disease in Type 2 Diabetes Is Associated With an Increase in Sclerostin Levels

Serum levels of bone resorption markers are decreased in patients with type 2 diabetes.

Normocalcemic primary hyperparathyroidism: one-year follow-up in one hundred postmenopausal women.

Role of serum FSH measurement on bone resorption in postmenopausal women