The Association Between Hypothyroidism Treatment and Mortality in Patients Hospitalized in Surgical Wards.

Limited data are available regarding the association between pre-admission thyroid-stimulating hormone (TSH) levels and prognosis in hospitalized surgical patients treated for hypothyroidism. We retrospectively evaluated a cohort of 1,451 levothyroxine-treated patients, hospitalized to general surgery wards. The 30-day mortality risk was 2-fold higher for patients with TSH of 5.0-10.0 mIU/L (adjusted OR, 2.3; 95% CI 1.1-5.1), and 3-fold higher for those with TSH > 10.0 mIU/L (3.4; 95% CI 1.3-8.7). Long-term mortality risk was higher in patients with TSH of 5.0-10.0 and above 10.0 mIU/L (adjusted HR, 1.2; 95% CI, 1.0-1.6, and 1.7; 95% CI 1.2-2.4, respectively). We found that in levothyroxine-treated adults hospitalized to surgical wards, increased pre-admission TSH levels are associated with increased short- and long-term mortality.

DISEASE PRESENTATION AND REMISSION RATE IN GRAVES DISEASE TREATED WITH ANTITHYROID DRUGS: IS GENDER REALLY A FACTOR?

OBJECTIVE: Male gender is considered an adverse prognostic factor for remission of Graves disease treatment with antithyroid drugs (ATDs), although published data are conflicting. This often results in early consideration of radioiodine treatment and surgery for men. Our objective was to compare disease presentation and outcome in men versus women treated with ATDs. METHODS: Retrospective study of 235 patients (64 men, 171 women) with Graves disease who were evaluated for features at presentation and outcome at the end of follow-up between 2010 and 2015. RESULTS: Disease presentation was similar in men and women for age at diagnosis (41.4 ± 14 years vs. 40 ± 15 years), duration of follow-up (6.6 ± 7 years vs. 7.7 ± 6 years), rates of comorbid autoimmune diseases, and rate of Graves ophthalmopathy. Smoking was more prevalent in males (31% vs. 15%; P = .009). Free thyroxine and triiodothyronine levels were comparable. ATDs were first-line treatment in all males and in 168 of 171 females, for a median duration of 24 and 20 months, respectively ( P = .55). Remission rates were 47% in men and 58% in women ( P = .14). Males had fewer adverse events (9% vs. 18%) and treatment discontinuation (5% vs. 16%). Disease recurrence was comparable (14% vs. 20%; P = .32), as was requirement for second-line treatment, either radioiodine therapy or thyroidectomy. CONCLUSION: Graves disease presentation is similar in men and women. Men treated with ATDs have high remission rates and similar recurrence rates compared to women, with fewer adverse events and less discontinuation of treatment. ATDs are an attractive first-line treatment for both genders. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; GO = Graves ophthalmopathy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Body mass index and mortality in patients with and without diabetes mellitus.

OBJECTIVE: Investigate the association between body mass index (BMI), length of stay (LOS), and mortality in hospitalized patients with and without diabetes mellitus (DM). METHODS: Historical prospectively collected data of adult patients hospitalized between 2011 and 2013. Body mass index was calculated according to measurement or self-report on admission and classified as follows: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), obese (30-34.9), and severely obese (≥35). The main outcomes were LOS, in-hospital, and end-of-follow-up mortality. RESULTS: Cohort included 24 233 patients (53% male; mean age ± SD, 65 ± 18), including 7397 patients with DM (31%). Among patients with normal BMI, LOS was shorter compared with underweight patients, but it was longer compared with overweight and obese patients. Following multivariate adjustment, this difference remained significant only for patients with DM. There was a significant interaction between DM status and BMI group, in the models for in-hospital and end-of-follow-up mortality. Compared with normal BMI, in-hospital mortality risk was increased by 80% and 100% for the underweight with and without DM, respectively. For patients with and without DM, in-hospital mortality risk was 30% to 40% lower among overweight and obese patients, and there was no difference between severely obese and normal weight patients. At the end-of-follow-up, mortality risk was 1.6-fold and 1.7-fold higher among underweight patients with and without DM, respectively. For overweight, obese, and severely obese patients, mortality risk was decreased by 30% to 40% in those with DM and by 20% to 30% in those without DM. CONCLUSIONS: In hospitalized patients with and without DM, there was an inverse association between BMI and mortality.

Outcomes of hyperglycemia in patients with and without diabetes hospitalized for infectious diseases.

OBJECTIVE: To examine the prognostic implications of diabetes mellitus (DM) and the importance of glycemic control during hospitalization for infectious diseases. METHODS: Historical prospectively collected data of patients hospitalized between 2011 and 2013. Infection-related hospitalizations were classified according to site of infection. Median follow-up was 4.5 years. Outcome measures included in-hospital and end-of-follow-up mortality. RESULTS: The cohort included 8051 patients (50% female, mean age ± SD, 68 ± 20 years) with a primary diagnosis of an infectious disease. Of these, 2363 patients (29%) had type 2 DM. The most common infectious sites included respiratory tract (n = 3285), genitourinary tract (n = 1804), skin and soft tissue (n = 934) and gastrointestinal tract (n = 571). There was no difference in admission rates of patients with and without DM according to the site of infection, except for skin and soft tissue infection which were more common among patients with DM (16% vs 10%). In-hospital mortality risk was greater in patients with DM (aOR = 1.3, 95% CI = 1.1-1.7). In the entire cohort, adjusted mortality risk (aHR, 95% CI) at the end-of-follow-up was greater among patients with DM (1.2, 1.1-1.4), with increased mortality risk following hospitalization for respiratory (1.1, 1.0-1.4) and skin and soft tissue infections (1.7, 1.3-2.3). In-hospital and end-of-follow-up mortality risk were highest among patients with and without DM with median glucose >180 mg/dL during hospitalization. CONCLUSIONS: In patients hospitalized for infectious diseases, DM is associated with increased long-term mortality risk, specifically following hospitalization for respiratory and skin and soft tissue infections. Poor glycemic control during hospitalization is associated with increased long-term mortality.

Medication-induced SIADH: distribution and characterization according to medication class.

AIMS: The aims of the current study were to determine the distribution of aetiologies for the drug-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients, and to characterize them according to the different drug groups. METHODS: A single-centre retrospective study was carried out, including all patients diagnosed with SIADH in a large community hospital and tertiary centre between 1 January 2007 and 1 January 2013 who were treated with drugs known to be associated with SIADH. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. RESULTS: The study cohort included 198 patients who had SIADH and received drugs associated with SIADH. Most patients [146 (73.7%)] were diagnosed with drug-associated SIADH, while 52 (26.3%) were diagnosed with SIADH due to other aetiologies. The Naranjo algorithm differentiated well between the two groups (P < 0.001). Five drug classes (antidepressants, anticonvulsants, antipsychotic agents, cytotoxic agents and pain medications) were implicated in 82.3% of patients diagnosed with drug-associated SIADH. Specific serotonin reuptake inhibitors and carbamazepine were commonly implicated. There were no clinically significant differences in the characteristics or severity of SIADH according to drug class. CONCLUSIONS: The clinical characteristics of SIADH caused by different drugs are comparable. Patients with SIADH treated with drugs from five common medication classes will probably be diagnosed with drug-induced SIADH. Physicians should be aware of the significance of these medication classes as SIADH aetiologies.

Glycemic Management Among Adults With Type 1 Diabetes During Passover: A Pre-Post Single-center Study.

OBJECTIVES: No data are available regarding glycemic management of individuals with type 1 diabetes (T1D) during Passover. Our aim in this study was to assess the effect of Passover on diabetes management and glycemic management in adults with T1D with nutritional changes during Passover (observant) compared with those who did not change their dietary habits during Passover (nonobservant). METHODS: We conducted an observational pre-post study of adults with T1D, followed in a diabetes clinic in Israel. Data were downloaded from insulin pumps and continuous glucose monitoring for 37 days: 2 weeks before Passover, 9 days of Passover, and 2 weeks thereafter. Differences in percentage of time spent above target (>10.0 to >13.9 mmol/L), at target (3.9 to 10.0 mmol/L), and below target (<3.9 to <3.0 mmol/L) were compared using paired t tests or paired signed rank tests. RESULTS: The study cohort included 43 individuals with T1D (23 observant, 20 nonobservant). The average blood glucose was significantly higher during Passover compared with the period before Passover---in nonobservant patients 8.2±1.5 mmol/L and 7.9±1.3 mmol/L (p=0.043), respectively, and in observant patients 8.7±1.6 mmol/L and 8.4±1.6 mmol/L (p=0.048), respectively. Time above range 10 to 13.9 mmol/L was increased in observant individuals during Passover, as compared with the period before Passover, at 24.9±16.2% and 20.6±12.4% (p=0.04), respectively. The dose of bolus insulin had increased significantly in observant individuals: 27.4±13.9 units during Passover, as compared with 24.2±11.2 units before Passover (p=0.02). CONCLUSIONS: Passover alters glycemic management and insulin needs in Jewish adults with T1D. It is advisable to make specific adjustments to maintain the recommended glycemic management.

Glucagon-like Peptide 1 Receptor Agonists and Cardiovascular Outcomes in Solid Organ Transplant Recipients With Diabetes Mellitus.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in type 2 diabetes. Limited data are available on diabetes treatment after solid organ transplantation. We aimed to explore the effect of GLP1-RAs on cardiovascular outcomes in transplanted recipients with diabetes. METHODS: We extracted data on adult transplant recipients (kidney, lungs, liver, heart) insured in a large health maintenance organization. Death-censored patients with diabetes treated with GLP1-RAs were matched with nonusers. The primary outcome was a composite of major cardiovascular events (MACEs): a nonfatal cardiac event (myocardial infarction, stable/unstable angina, coronary bypass, and coronary angiography), ischemic stroke and all-cause mortality. Secondary outcomes were MACE or peripheral vascular disease (MACE-PVD), and all-cause mortality. Safety outcomes included biliopancreatic adverse events. RESULTS: We included 318 patients (69% males, average age 58.3 ±â€…11.0 y) with a 3.1-y median follow-up. The incidence of MACE was 101 of 1000 patient-years in GLP1-RAs users compared with 134 of 1000 in controls (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.27-0.78). GLP1-RAs similarly reduced the risk of MACE-PVD (HR 0.53; 95% CI, 0.33-0.88) and the risk of all-cause mortality (HR 0.39; 95% CI, 0.18-0.84). Biliopancreatic adverse events occurred less in GLP1-RA users. CONCLUSIONS: Transplant recipients with diabetes who used GLP1-RAs had lower risks for MACE and all-cause mortality. These results may profoundly implicate the daily management of posttransplant recipients with diabetes, a population with a high prevalence of cardiometabolic risk factors and cardiovascular death. Transplant patients are usually excluded from randomized controlled trials and, hence might be undertreated with disease-modifying drugs. Larger prospective studies are needed in this unique population.

Denosumab-associated hypocalcemia: Does gender play a role?

OBJECTIVE: It is well recognized that the presentation, treatment, and outcomes of various diseases may differ between men and women. We recently reported a 7.4% rate of denosumab-associated hypocalcemia in community-dwelling osteoporotic patients. This study sought to investigate the role of gender in this complication. STUDY DESIGN: Retrospective community-dwelling cohort. METHOD: The databases of a large health maintenance organization were searched for adult patients treated with denosumab for osteoporosis in 2010-2018. Rates and predictors of denosumab-associated hypocalcemia (serum calcium ≤8.5 mg/mL) were analyzed by gender. RESULTS: The cohort included 1871 women and 134 men. Compared with the women, the men were characterized by older median age (81 vs. 77 years, p = 0.005), higher likelihood to receive denosumab as a first-line treatment (22% vs. 6%, p < 0.001), less treatment with calcium supplements (42% vs. 53%, p = 0.012), and lower median eGFR level (66.1 vs. 79.8 mL/min/1.73m2, p < 0.001). Denosumab-associated hypocalcemia developed in 133 women (7.1%) and 16 men (11.9%) (p = 0.04); the drug was discontinued in 75% and 61%, respectively. The strongest predictors of hypocalcemia in women were levels of pretreatment albumin-adjusted serum calcium (OR 0.08, 95% CI (0.04, 0.14)) and creatinine (OR 2.43, 95% CI (1.45, 4.05)). There were no predictors in men. On propensity matching of 126 men and 126 women, gender was not a predictor of hypocalcemia. CONCLUSION: Denosumab-treated men were significantly older than treated women and had a lower eGFR and more advanced osteoporosis. These findings suggest that selection bias rather than male genderper se underlies the higher rate of denosumab-associated hypocalcemia in men.

Risk for Infections During Treatment With Denosumab for Osteoporosis: A Systematic Review and Meta-analysis.

CONTEXT: Denosumab inhibits the receptor activator of nuclear factor κ-Β ligand, an immune system modulator. Safety endpoints including risk for infections were assessed as secondary outcomes in randomized controlled trials (RCTs) of the drug. OBJECTIVE: To assess the risk of serious adverse events of infections (SAEI) in denosumab-treated patients. DATA SOURCES: PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019. STUDY SELECTION: All RCTs of denosumab (60 mg every 6 months) versus any comparator were included. We excluded trials in cancer patients for prevention of skeletal-related events. DATA EXTRACTION: Two reviewers independently applied selection criteria and extracted the data. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a fixed effect model. Sensitivity analysis was based on risk of bias. DATA SYNTHESIS: Thirty-three studies (22 253 patients) were included. There was a higher incidence of SAEI during denosumab treatment versus any comparator (RR, 1.21; 95% CI, 1.04-1.40; I2 = 0%), mainly of ear, nose, and throat (RR, 2.66; 95% CI, 1.20-5.91) and gastrointestinal origin (RR, 1.43; 95% CI, 1.02-2.01). RR was similar in a sensitivity analysis based on adequate allocation concealment. The RR of any infection (RR, 1.03; 95% CI, 0.99-1.06) and infection-related mortality (RR, 0.50; 95% CI, 0.20-1.23) was comparable between groups. CONCLUSIONS: A higher incidence of SAEI is demonstrated during treatment with denosumab in an osteoporosis dose. Nevertheless, the overall risk for any infection or related mortality is similar to comparator groups. These findings merit consideration before therapy initiation.

Detecting Recurrence Following Lobectomy for Thyroid Cancer: Role of Thyroglobulin and Thyroglobulin Antibodies.

BACKGROUND: The use of thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) for detecting disease recurrence is well validated following total thyroidectomy and radioiodine ablation. However, limited data are available for patients treated with thyroid lobectomy. METHODS: Patients who had lobectomy for papillary thyroid cancer followed for >1 year, with sufficient data on Tg and TgAb, including subgroup analysis for Hashimoto's thyroiditis and contralateral nodules. RESULTS: One-hundred sixty-seven patients met the inclusion criteria. Average tumor size was 9.5 ±â€…6 mm. Following lobectomy, Tg was 12.1 ±â€…14.8 ng/mL. Of 52 patients with Hashimoto's thyroiditis, 38% had positive TgAb with titers of 438 ±â€…528 IU/mL, and in patients without TgAb the mean Tg level was 14.7 ±â€…19.0 ng/mL. In 34 patients with contralateral nodules ≥1 cm, Tg was 15.3 ±â€…17 ng/mL. During the first 2 years of follow-up, Tg declined ≥1 ng/mL in 42% of patients (by 5.1 ±â€…3.7 ng/mL), remained stable in 22%, and increased in 36% (by 4.9 ±â€…5.7 ng/mL). During a mean follow-up of 6.5 years (78 ±â€…43.5 months), 18 patients had completion thyroidectomy and 12 were diagnosed with contralateral cancer (n = 8) or lymph node metastases (n = 4). In patients with recurrence followed for >2 years, there was a rise in Tg in 3 cases, Tg was stable in 2 cases, and in 1 TgAb decreased from 1534 to 276 IU/mL despite metastatic lymph nodes. Basal Tg and Tg dynamics did not predict disease recurrence. CONCLUSIONS: Serum thyroglobulin used independently is of limited value for predicting or detecting disease recurrence following thyroid lobectomy. Other potential roles of Tg, such as detecting distant metastases following lobectomy, should be further studied.

Hyperparathyroidism in patients over 75: Clinical characteristics and outcome. Is conservative treatment a safe alternative?

OBJECTIVE: With the current aging of the world's population, primary hyperparathyroidism (PHPT) is increasingly detected in the elderly. Yet data on the presentation and outcome of PHPT in this group are scarce. The objective was to describe a cohort of patients aged 75 years or more with PHPT observed in our endocrine clinic. STUDY DESIGN: A retrospective analysis of medical records in an endocrine clinic at a tertiary hospital. We evaluated 182 patients with PHPT, aged 75 years or more at their last follow-up, all diagnosed at age 65 or more. Laboratory data were compared at diagnosis and last follow-up. RESULTS: Mean age at diagnosis was 73 ± 4 years, last follow-up was at 83 ± 4 years, and mean follow-up was 11.3 ± 5.5 years. Osteoporosis, fractures, and nephrolithiasis were diagnosed in 114(63 %), 84(46 %), and 43(24 %) patients, respectively. Overall, 150 patients had an indication for surgery; of them, the 29 who underwent parathyroidectomy were younger than the non-operated patients and had higher rates of hypercalciuria. During the follow-up of the 141 patients who did not undergo operation, serum and urinary calcium levels significantly had decreased, and vitamin D level had increased at last visit (10.4 ± 0.5 mg/dl, 161 ± 70 mg/24 h, 69 ± 17 nmol/l, p < 0.01 respectively) compared with levels at diagnosis (10.6 ± 0.2 mg/dl, 223 ± 95 mg/24 h, 53 ± 15 nmol/l, respectively, p = 0.001). Overall, 38 of the 182 patients (20 %) died during follow-up; these patients were significantly older at diagnosis (76 ± 5 vs. 72 ± 4 years) but there were no differences in laboratory variables. CONCLUSIONS: While most patients had a formal indication for surgery, few underwent parathyroidectomy. Serum and urinary calcium significantly decreased during follow-up in patients who did not undergo surgery. Our data are reassuring and support at least the consideration of conservative treatment for these patients.

Glycemic variability and mortality in patients hospitalized in general surgery wards.

BACKGROUND: Glucose variability is common among hospitalized patients, but the prognostic implications among patients hospitalized in surgical wards are unknown. The objective of this study was to investigate the association between glucose variability, length of stay, and mortality. METHODS: Historical prospectively collected data of patients ≥18 years of age, hospitalized in general surgery wards between January 2011 and December 2017. Glucose variability was assessed by coefficient of variance and standard deviation of glucose values during hospitalization. The main outcomes were length of stay and 30-day and end-of-follow-up mortality. RESULTS: The cohort included 8,894 patients (mean age 63 ± 19 years, 48% male, mean follow-up 3.0 ± 1.8 years). A total of 2,012 (23%) patients had diabetes mellitus. The mean length of stay was longer with a higher coefficient of variance or standard deviation in patients without and with diabetes mellitus. The 30-day mortality was 6%, associated with a higher versus a lower coefficient of variance (9% vs 3%) and standard deviation (9% vs 3%) in patients without diabetes mellitus and with diabetes mellitus (9% vs 5%; 8% vs 5%, respectively). Mortality at the end of follow-up was increased in patients without diabetes mellitus with a higher coefficient of variance (27% vs 18%) and standard deviation (29% vs 17%) and in patients with diabetes mellitus (33% vs 24% and 32% vs 21%, respectively). Multivariate analysis indicated an increased risk for 30-day and end-of-follow-up mortality, in both groups. Adjustment for glucocorticoid treatment or hypoglycemia did not affect the results. In patients with a high or low coefficient of variance, mortality was higher with median glucose levels during hospitalization ≥180 mg/dl, compared with <180 mg/dl. CONCLUSION: In patients with and without diabetes mellitus hospitalized in general surgery wards, increased glucose variability is associated with longer hospitalization and increased short-term and long-term mortality.

Bone-Marrow Suppression in Elderly Patients Following Empiric Radioiodine Therapy: Real-Life Data.

Background: Elderly patients with differentiated thyroid cancer (DTC) tend to have more advanced disease at presentation, for which high activities of radioiodine (RAI) are often recommended. However, the 2015 American Thyroid Association guidelines recommend that empirically administered activities of RAI >150 mCi should be avoided in patients >70 years of age, based on calculated bone-marrow exposure according to two dosimetry-based studies. This study aimed to evaluate the effect of RAI treatment on bone-marrow function in elderly DTC patients. Methods: DTC patients ≥70 years of age who received RAI treatment and on whom a complete blood count was performed before and after treatment were included. Blood counts within one year before RAI and one year following treatment were compared in order to assess for marrow suppression. The impact of demographic, clinical, and laboratory variables on complete blood count were assessed. Results: One hundred fifty-three treatments in 122 patients met inclusion criteria, with a mean patient age of 76 ± 4.3 years, and 75% were women. High-risk features at presentation included T4 disease in 17%, lymph node metastases in 34%, and distant metastases in 14%. Mean RAI activity was 136.8 ± 48 mCi (82% ≥ 100 mCi, 66% ≥ 150 mCi). Of 153 RAI treatments analyzed, 114 (74%) were first treatments, 28 (18%) second treatments, seven (5%) third treatments, and four (3%) fourth treatments. At 0-3 months after RAI treatment, there was a statistically significant decrease in platelets (238 ± 66 vs. 216 ± 69 × 109/L, 10% decrease; p < 0.001), white blood cells (WBC; 6.9 ± 2 vs. 6.1 ± 1.9 × 109/L, 13% decrease; p < 0.001), and hemoglobin (Hb) in women (12.8 ± 1.1 vs. 12.4 ± 1.1 g/dL, 3% decrease; p = 0.01). Mean platelets, WBC, Hb in women, and lymphocytes remained decreased (but within the reference range) one year after treatment. Subgroup analysis demonstrated platelet suppression only with activities ≥100 mCi, and WBC and Hb suppression only with activities ≥150 mCi, with mean values within the reference ranges. There were no clinically significant cytopenia events during follow-up. Conclusions: Empiric RAI treatment in elderly patients causes mild bone-marrow suppression, with little clinical significance. Activities of 150-200 mCi can be safely used when indicated.

Predictors of hypoglycemia in hospitalized patients with diabetes mellitus.

Hypoglycemia is common among hospitalized patients with diabetes mellitus (DM), and is associated with increased morbidity and mortality. Identify pre-admission risk factors associated with in-hospital hypoglycemia. Historical prospectively collected data of adult DM patients hospitalized to medical wards between 2011 and 2013. Hypoglycemia and serious hypoglycemia were defined as at least one blood glucose measurement ≤ 70 and < 54 mg/dl, respectively, during hospitalization. The primary outcome was in-hospital hypoglycemia. The cohort included 5301 patients (mean age 73 ± 13 years, 51% male), including 792 patients (15%) with hypoglycemia, among them 392 patients (7%) with serious hypoglycemia. Patients with hypoglycemia or serious hypoglycemia during hospitalization were older, compared to patients without hypoglycemia and more likely to have chronic renal failure and cerebrovascular disease. Malignancy and female gender were risk factors for hypoglycemia, but not for serious hypoglycemia, while congestive heart failure was associated with increased risk only for serious hypoglycemia. Diabetes mellitus' duration over 10 years was associated with an almost threefold increased risk for hypoglycemia, compared to DM duration less than a year. Insulin treatment and glycated hemoglobin > 9% were also more common in patients with hypoglycemia. Insulin treatment was associated with a fourfold increase in the risk for hypoglycemia among all glycated hemoglobin categories. Our results identified several risk factors for in-hospital hypoglycemia in patients with DM. These findings may lead to appropriate monitoring and early intervention to prevent hypoglycemia and to reduce morbidity and mortality associated with in-hospital hypoglycemia.

Impact of Minimal Extra-Thyroid Extension in Differentiated Thyroid Cancer: Systematic Review and Meta-analysis.

BACKGROUND: Minimal extra-thyroid extension (mETE) in differentiated thyroid cancer (DTC) patients was defined as an intermediate risk feature in the 2015 American Thyroid Association guidelines. However, controversy persists as several studies suggested mETE has little effect on disease outcome. OBJECTIVE: To assess the impact of mETE on DTC patients' outcome. METHODS: Meta-analysis of controlled trials comparing DTC patients with and without mETE. DATA EXTRACTION AND SYNTHESIS: Thirteen retrospective studies including 23,816 patients were included, with a median follow-up of 86 months. mETE in patients without lymph node involvement (N0 disease) was associated with increased risk of recurrence (7 studies, OR 1.73, 95%CI 1.03-2.92). The absolute risk of recurrence was 2.2% in patients without extension and 3.5% in patients with mETE (p=0.04). In studies including patients with and without lymph-node involvement (N1/N0 disease), mETE resulted in a significantly higher risk of recurrence (8 studies, OR 1.82, 95%CI 1.14-2.91). The absolute risk of recurrence was 6.2% in patients without extension and 7% in patients with mETE (p=0.01). In patients with micro-papillary carcinoma (<1cm) the impact of mETE was non-significant (OR 2.40, 95%CI 0.95-6.03). Minimal ETE had no impact on disease-related mortality (8 studies, OR 0.5, 95%CI 0.11-2.21). CONCLUSION: mETE increases risk of recurrence in DTC patients. However, the absolute increase in risk is small, and in patients with N0 disease the risk is within the low-risk of recurrence category at 3.5%. Minimal ETE has no impact on disease-related mortality, and should not change tumor stage.

Endocrinopathy-induced euvolemic hyponatremia.

Euvolemic hyponatremia results from either the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, or adrenal insufficiency. Furthermore, the criteria for diagnosis of SIADH entail the exclusion of hypothyroidism and hypoadrenalism. We aim to assess the yield of euvolemic hyponatremia workup focusing on underlying endocrinopathies in a real-world setting. A single-center retrospective study includes all patients diagnosed with euvolemic hyponatremia in a tertiary hospital between 1.1.2007 and 1.1.2013. Demographic, clinical, and laboratory data were collected from medical charts. Euvolemic hyponatremia was detected in 564 patients. Thyroid function was tested in 69% (391/564) and adrenal function was assessed in 29% (164/564) of cases. Endocrinopathy-induced euvolemic hyponatremia was diagnosed in nine (1.6%) patients: three patients were diagnosed with hypothyroidism-induced hyponatremia, three with adrenal insufficiency as an underlying cause, and three with central hypothyroidism and central hypoadrenalism. All nine had medical history and symptoms suggestive of endocrine deficiencies other than the hyponatremia, which resolved within 1-3 days after administration of hormone replacement therapy. Yield of performed workup for hypothyroidism and hypoadrenalism in euvolemic hyponatremia was low. However, in this real-world study, only a limited number of patients underwent a full ascertainment of hypoadrenalism and hypothyroidism, which was diagnosed only in patients with additional findings supportive of these endocrinopathies; a higher rate of undiagnosed endocrinopathies cannot be ruled out. As both hypoadrenalism and hypothyroidism are easily treatable, potentially life-threatening conditions, there are insufficient data to change current recommendation for their universal evaluation in patients with euvolemic hyponatremia.

Natural History of Contralateral Nodules After Lobectomy in Patients With Papillary Thyroid Carcinoma.

Background: Bilateral thyroid nodularity is considered an indication for total thyroidectomy in papillary thyroid carcinoma (PTC). However, the natural history and outcome of contralateral nodules have never been studied. Objective: To investigate the natural history of nonsuspicious contralateral nodules after lobectomy for PTC. Methods: We included patients who had one or more solid nodules (≥3 mm) in the contralateral lobe with benign cytology before surgery or small nonsuspicious nodules per ultrasonography. Results: One hundred and twelve patients were included. Median age was 57 years, and median size of the PTC (initial lobectomy) was 8 mm (range, 0.5 to 28 mm). On the contralateral side, the median size of nodules was 7 mm (range, 3 to 30 mm). Thirty-three nodules (29%) had fine-needle aspiration (FNA) before surgery, and all were benign. After a median follow-up of 6 years, median growth was zero (range, -20 to 19 mm). Twenty-six nodules (23%) increased ≥3 mm in size (median, 6 mm; range, 4 to 19 mm). Twenty patients (18%) developed new nodules. Twelve patients (11%) underwent completion thyroidectomy for growth (three), suspicious FNA (seven; Bethesda III to V), malignancy (one), or unknown reason (one). Overall, according to the completion thyroidectomy specimen, six patients (5%) were diagnosed with contralateral PTC (five micro-PTCs, one 20 mm), and all were without evidence of disease at the end of follow-up. There were no surgical difficulties or local complications during completion surgery. Conclusions: Lobectomy for low-risk patients with a small PTC and nonsuspicious contralateral thyroid nodule(s) is a reliable and safe initial treatment option. In the few patients who required completion thyroidectomy, treatment with surgery and radioiodine was effective.

Sodium levels on admission are associated with mortality risk in hospitalized patients.

AIMS: Abnormal sodium values are common among hospitalized patients. We aimed to investigate the association of admission sodium values and mortality. METHODS: Historical prospectively data of adult patients hospitalized to medical wards between January 2011 and December 2013. Admission sodium values were classified to five categories: severe hyponatremia (<125mEq/L), mild hyponatremia (125-135mEq/L), normal sodium values (135-145mEq/L), mild hypernatremia (145-150mEq/L) and severe hypernatremia (>150mEq/L). Main outcomes were length of hospitalization, in-hospital mortality and mortality at the end-of-follow-up. RESULTS: The cohort included 27,889 patients (mean age 67±18years, 52% males). The total follow-up was 1065days. Most patients had normal sodium values (76%), 22% had hyponatremia, 3% had hypernatremia. Mean age increased with increase in severity of hyponatremia or hypernatremia. Median length of hospitalization was longer with mild and severe hypernatremia (7 and 5days, respectively) or with mild and severe hyponatremia (4 and 4days, respectively), compared to normal sodium levels (3days). Compared to in-hospital mortality with normal sodium levels (5%), mortality was higher with mild and severe hyponatremia (9% and 14%, respectively) and was highest with mild (28%), and severe hypernatremia (52%). Mortality rate at the end of follow-up was 28% with normal sodium levels, 44% and 48% with mild and severe hyponatremia, 66% and 90% with mild and severe hypernatremia, respectively. CONCLUSIONS: Abnormal sodium values on admission were associated with longer hospitalization and increased short- and long-term mortality. Mortality risk was higher with hypernatremia, compared to hyponatremia.

High Glucose Variability Increases Mortality Risk in Hospitalized Patients.

Context: Glucose variability (GV) is common among hospitalized patients, but the prognostic implications are not understood. Objective: Investigate the association between GV, hospital length of stay (LOS), and mortality. Methods: GV was assessed by coefficient of variance (CV) and standard deviation (SD) of glucose values during hospitalization. Setting: Historical prospectively collected data of patients hospitalized between January 2011 and December 2013. Patients: Patients ≥18 years old. Main outcome: LOS, and in-hospital and mortality at end of follow-up. Results: The cohort included 20,303 patients (mean age ± SD, 70 ± 17 years; 51% men; median follow-up, 1022 days), of whom 8565 patients (42%) had diabetes mellitus (DM). Mean LOS was longer with higher CV or SD tertiles in patients without and with DM. In-hospital mortality was 8.2%, associated with higher tertiles of CV (4%, 10%, 19%) and SD (4%, 11%, 21%) in patients without DM and with DM (3%, 5%, 10%; and 2%, 4%, 9%, respectively). Mortality at the end of follow-up was increased in patients without DM with higher CV (28%, 42%, 55%) and SD (28%, 44%, 57%) tertiles and in patients with DM (26%, 35%, 45%; and 25%, 34%, 44%, respectively). Multivariate analysis indicated increased risk for in-hospital and end of follow-up mortality, in both groups. Adjustment for glucocorticoid treatment or hypoglycemia did not affect the results. Glucose levels during hospitalization and GV were two independent factors affecting LOS and in-hospital mortality. In each CV tertile, mortality was higher with median glucose ≥180 mg/dL, compared with <180 mg/dL. Conclusions: In hospitalized patients with and without DM, increased GV is associated with longer hospitalization and increased short- and long-term mortality.