Purpose: Unwanted weight loss is one of the established criteria for the diagnosis of frailty. However, the relevance of this criterion to detect frailty in obese older adults has not been assessed. In particular, with the exception of malignancy, unwanted weight loss is not commonly seen in older obese subjects. Therefore, we tested the possibility that some obesity phenotypes and/or diabetes might be more useful in the detection of frailty in this setting. Patients and methods: A preliminary cross-sectional study of 50 consecutive subjects was conducted at The Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center. Inclusion criteria were: young elderly (aged 65–75 years), with general and/or abdominal obesity, without cancer. Frailty was assessed directly using the Fried model, the five-item fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale. Eventually, in the assessment of frailty, the weight loss criterion was replaced by one or several of obesity/diabetes-related variables each time: severity of obesity by body mass index, waist circumference (and their interaction), body fat, and diabetes. The receiver operating characteristic curves for functional impairment indices were plotted to compare the usefulness of the frailty accepted and adjusted models. Results: The prevalence of frailty and pre-frailty in this cohort were 7/50 (14%) and 27/50 (54%), respectively, but unwanted weight loss was seen in three subjects (6%) only. The level of abdominal obesity had the strongest correlation with functional score (r=0.292, P<0.05). Frailty models which included either severe abdominal obesity or diabetes in lieu of unwanted weight loss had good sensitivity rates per each frailty score as compared with the original Fried model. Conclusion: For detecting and/or screening for the frailty syndrome in obese young elderly, the level of abdominal obesity or diabetes may provide a useful marker.

Subclinical hypothyroidism (SCH) is defined as an elevated serum thyroid-stimulating hormone (TSH) level with a normal serum-free thyroxine (FT4) level. SCH has been associated with an increased risk of adverse cardiovascular outcomes. We investigated possible associations of unknown SCH with in-hospital outcomes and short- and long-term all-cause mortality in a large cohort of patients with ST segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). This retrospective, single-center observational study evaluated the TSH and FT4 levels of 1593 STEMI patients with no known history of hypothyroidism or thyroid replacement treatment who were admitted to the coronary care unit and underwent PCI between 1/2008 and 8/2017. SCH was defined as TSH levels ≥ 5 mU/mL in the presence of normal FT4 levels. Unknown SCH was detected in 68/1593 (4.2%) STEMI patients. These patients had significantly worse in-hospital outcomes compared to patients without SCH, including higher rates of acute kidney injury (p = 0.003) and left ventricular ejection fraction ≤ 40% (p = 0.03). Moreover, 30-day mortality (p = 0.02) and long-term (mean 4.2 ± 2.3 years) mortality (p = 0.007) were also significantly higher in patients with SCH. The thyroid function of STEMI patients should be routinely tested before they undergo a planned PCI procedure.

Background: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the long-term all-cause mortality in TC survivors compared to the general population, and its association with cardiovascular risk factors. Methods: Individuals diagnosed with TC during 2001–2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status. Results: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5677 (10.2%) TC patients and 1235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR = 1.89, 95%CI 1.71–2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR = 1.49, 95%CI 1.33–1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P < 0.001), and more cardiovascular disease (33.6% vs. 22.3%, P = 0.05) compared to those who died in the non-TC group. Conclusions: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.

Background: Thyroid hormones heavily impact energy expenditure, body mass, and body composition. Their role in the state of exogenous subclinical hyperthyroidism in differentiated thyroid carcinoma (DTC) patients, however, is less well defined. The first aim of this study was to assess changes in body weight, body composition, resting energy expenditure (REE), respiratory quotient (RQ), and metabolic parameters in female DTC patients, starting from the phase of a euthyroid state before total thyroidectomy through the subsequent year after thyrotropin (TSH) suppression. The second aim was to assess the relationship between these variables and thyroid function parameters. Methods: This observational case series analyzed changes in body composition, calorimetric, and metabolic parameters of 15 DTC female patients at 5 time points: (1) at initial DTC diagnosis (euthyroid state), (2) at 2–3 weeks after thyroidectomy (hypothyroid state), (3) at 2–3 months of levothyroxine (LT4) treatment (exogenous euthyroid state), (4) after 6–9 months, and (5) after 1 year of TSH suppressive LT4 therapy (exogenous subclinical hyperthyroid state). A generalized estimating equation (GEE) analysis was performed to estimate the longitudinal correlations of the total triiodothyronine (TT3)/free thyroxine (fT4) ratio (as an independent variable) with body composition, metabolic, and calorimetric parameter changes (as dependent variables). Results: REE, REE per kilogram of lean body mass (REE/LBM), pulse, and systolic and diastolic blood pressure were significantly higher after TSH suppressive LT4 therapy. The GEE analysis revealed longitudinal negative correlations between the TT3/fT4 ratio and systolic blood pressure, fasting blood glucose, body mass index, android (abdominal wall and visceral mesentery) fat distribution, trunk, and arm fat distribution, REE, and REE/LBM. There was a positive correlation with RQ. Conclusions: REE, REE/LBM, pulse, and systolic and diastolic blood pressure were significantly higher after thyroidectomy, radioiodine and TSH suppressive therapy in female DTC patients, while no changes were observed in body weight or body composition. A lower TT3/fT4 ratio longitudinally correlated with increases in REE, REE/LBM, abdominal fat distribution, systolic blood pressure, and fasting blood glucose, as well as with decreased RQ. These findings highlight the importance of judicial balancing of the benefits and detriments of TSH suppression with subsequent decreased TT3/fT4 ratios for female DTC patients.

Background: Estrogens may enhance thyroid cancer cell growth. We have recently reported that a novel isoflavone-derived anti-estrogenic compound developed in our laboratory, the N-t-boc-hexylenediamine derivative of 7-(O)-carboxymethyl daidzein (cD-tboc), can induce apoptosis and retard growth in human thyroid carcinoma cell lines through inhibitory interaction on estrogen receptor β. Here we tested the hypothesis that cD-tboc can likewise retard cell growth in cultured human thyroid papillary carcinoma cells, normal thyroid cells, and goiter cells removed during thyroidectomy. Methods: In vitro experiments in cultured human thyroid normal, goiter, and papillary thyroid carcinoma (PTC) cells were performed. Estrogen receptors α and β (ERα and ERβ), DNA synthesis and creatine kinase (a marker of estrogenic genomic response), and the effects of cD-tboc on DNA synthesis in cultured human PTC cells were assessed. Results: First, all cell types thus harvested and grown in culture expressed both ERα and ERβ, with a variably higher abundance of ERβ over ERα seen in the goiter and PTC cells, but not in the normal thyroid cells. Second, DNA synthesis and creatine kinase were increased in response to estradiol-17β (E2), the ERα agonist propyl-pyrazole-trisphenol as well as the ERβ agonist diarylpropionitrile. Third, cD-tboc dose-dependently inhibited DNA synthesis in cultured human PTC cells (−65%) and to a lesser extent in goiter cells (∼−30%). Conclusion: This study provides the first evidence that cD-tboc can act to inhibit growth in primary cultures of human PTC cells and goiter cells removed during thyroidectomy. Whether this can be utilized for the treatment of human thyroid cancer and/or goiter remains to be explored.

Background: The prevalences of diabetes mellitus and hypertension, both of which are components of metabolic syndrome, are known to be increased among patients with multiple myeloma (MM), but remain undetermined among patients with smoldering MM (SMM). Methods: Changes in various components of metabolic syndrome were investigated during the follow-up of patients with either MM or SMM compared to healthy controls. The data of 153 patients (105 with MM and 48 with SMM) and 138 controls were accessed from our medical center’s records between 2008 and 2015. We analyzed the patients’ data at diagnosis (baseline) and after 1, 3, and 5 years of follow-up. Results: Patients with SMM had a significantly higher prevalence of diabetes, hypertension, and dyslipidemia at baseline compared to controls. A multivariate Cox regression analysis revealed a higher risk to develop dyslipidemia after 1, 3, and 5 years of follow-up among the SMM patients. The MM patients had a higher risk to develop diabetes after 1 year, hypertension after 5 years, and dyslipidemia after 1, 3, and 5 years of follow-up. Conclusions: These data demonstrate that patients with SMM and those with MM are more prone to develop various components of metabolic syndrome, and they stress the importance of following-up metabolic syndrome components in both groups of patients.