The effect of over- and undertreatment of hypothyroidism on hospitalization outcomes of patients with decompensated heart failure.

The effect of over- and undertreatment of hypothyroidism on hospitalization outcomes of patients with acute decompensated heart failure (HF) has not been evaluated yet. We conducted retrospective cohort analyses of outcomes among 231 consecutive patients with treated hypothyroidism who were admitted to internal medicine departments of Shamir Medical Center with HF (2011-2019). Patients were divided into three groups according to their thyroid-stimulating hormone (TSH) levels: well treated (TSH: 0.4-4 mIU/L), overtreated (TSH: <0.4 mIU/L), and undertreated (TSH: >4 mIU/L). The main outcomes were mortality and recurrent hospitalization within 3 months. Among 231 patients, 106 were euthyroid, 14 were overtreated, and 111 undertreated. Patients' mean age was 79.8 ± 9.4 years. In-hospital mortality occurred in 4.7% in euthyroid patients, 14.3% in the overtreated group, and 10.7% in the undertreated group (p = 0.183). Differences in 30-day (p = 0.287) and 90-day (p = 0.2) mortality or recurrent hospitalization (p = 0.438) were not significantly different as well. However, in patients who were markedly undertreated and overtreated (TSH: >10 mIU/L or below 0.4 mIU/L) compared with 0.4-10 mIU/L, a significant increase in 90-day mortality was observed (33.3% vs 15.1% p = 0.016). Treatment status was independently associated with 90-day mortality after controlling for confounders with an adjusted odds ratio of 3.55 (95% confidence interval: 1.39-9.06). Although mild under- or overtreatment of hypothyroidism does not have a significant detrimental effect on hospitalization outcomes of patients with acute decompensated HF, markedly under- and overtreatment are independently associated with rehospitalizations and 90-day mortality. Larger cohorts are needed to establish the relationship between treatment targets and hospitalization outcomes of patients at risk for HF hospitalization.

The Gut Microbiome of Adults With Type 1 Diabetes and Its Association With the Host Glycemic Control.

OBJECTIVE: Previous studies have demonstrated an association between gut microbiota composition and type 1 diabetes (T1D) pathogenesis. However, little is known about the composition and function of the gut microbiome in adults with longstanding T1D or its association with host glycemic control. RESEARCH DESIGN AND METHODS: We performed a metagenomic analysis of the gut microbiome obtained from fecal samples of 74 adults with T1D, 14.6 ± 9.6 years following diagnosis, and compared their microbial composition and function to 296 age-matched healthy control subjects (1:4 ratio). We further analyzed the association between microbial taxa and indices of glycemic control derived from continuous glucose monitoring measurements and blood tests and constructed a prediction model that solely takes microbiome features as input to evaluate the discriminative power of microbial composition for distinguishing individuals with T1D from control subjects. RESULTS: Adults with T1D had a distinct microbial signature that separated them from control subjects when using prediction algorithms on held-out subjects (area under the receiver operating characteristic curve = 0.89 ± 0.03). Linear discriminant analysis showed several bacterial species with significantly higher scores in T1D, including Prevotella copri and Eubacterium siraeum, and species with higher scores in control subjects, including Firmicutes bacterium and Faecalibacterium prausnitzii (P < 0.05, false discovery rate corrected for all). On the functional level, several metabolic pathways were significantly lower in adults with T1D. Several bacterial taxa and metabolic pathways were associated with the host's glycemic control. CONCLUSIONS: We identified a distinct gut microbial signature in adults with longstanding T1D and associations between microbial taxa, metabolic pathways, and glycemic control indices. Additional mechanistic studies are needed to identify the role of these bacteria for potential therapeutic strategies.

Insulin treatment of patients with gestational diabetes: does dosage play a role?

BACKGROUND AND OBJECTIVE: In nonpregnant patients high insulin requirements are associated with hypoglycemia and weight gain but not with improvement in glucose control. The effect of insulin requirement on maternal and neonatal outcomes in gestational diabetes mellitus (GDM) is yet unknown. METHODS: We conducted a retrospective cohort study of maternal and neonatal outcomes of pregnancy according to insulin requirements in women with GDM who were followed and delivered at the Yitzhak Shamir Medical Center between 2006 and 2016. The daily insulin dose in units per body weight was divided into quartiles and analyses were performed to compare the lowest, highest, and two middle quartiles. The primary outcome was a composite of any of the following: cesarean-section (CS), preeclampsia, macrosomia and large for gestational age (LGA) birth weight, neonatal intensive care unit admission, need for phototherapy, and neonatal hypoglycemia. RESULTS: Women were divided according to their insulin requirements as follows: 79 (24.8%) women who needed <0.13 IU/kg/day of insulin (insulin-sensitive group), 160 (50%) women who needed 0.14-0.42 IU/kg/day of insulin (comparison-group), and the rest who needed >0.43 IU/kg/day of insulin (insulin resistant group). There were no differences in the composite outcome between the groups (64.6, 61.3, and 69.6% for the insulin sensitive-, comparison- and resistant- groups, respectively, p = .44). Women in the insulin-resistant group had higher fasting glucose levels in the first trimester (91, 98 and 102 mg/dL for women in the insulin sensitive-, comparison- and insulin-resistant groups, respectively; p = .01). Women in the insulin-sensitive group had significantly better glycemic control (fasting glucose levels ≤90 mg/dL and 1-hour and 2-hour postprandial glucose levels ≤140 mg/dL and ≤120 mg/dL for more than 80% of measurements) than those in the insulin-resistant group (70.3 versus 29.9%; p < .001). The rate of CS was significantly higher in the insulin-resistant group (42.3 versus 24.1%; p = .03), but the rate of LGA birth weight was surprisingly higher in the insulin-sensitive group (29.5 versus 16.7%, p = .04). After controlling for confounders, women in the insulin-sensitive group had a decreased risk for CS in relation to the comparison group (OR = 0.46, 95%CI 0.23-0.9, p = .025). CONCLUSION: We found no association between insulin requirements and adverse composite outcome in women with GDM. However, those with higher insulin requirements have poorer glucose control and higher rates of CS than those with lower insulin requirements. Larger studies are needed to inquire short- and long-term outcomes of insulin requirements on fetal and maternal outcomes.

Prediction of Personal Glycemic Responses to Food for Individuals With Type 1 Diabetes Through Integration of Clinical and Microbial Data.

OBJECTIVE: Despite technological advances, results from various clinical trials have repeatedly shown that many individuals with type 1 diabetes (T1D) do not achieve their glycemic goals. One of the major challenges in disease management is the administration of an accurate amount of insulin for each meal that will match the expected postprandial glycemic response (PPGR). The objective of this study was to develop a prediction model for PPGR in individuals with T1D. RESEARCH DESIGN AND METHODS: We recruited individuals with T1D who were using continuous glucose monitoring and continuous subcutaneous insulin infusion devices simultaneously to a prospective cohort and profiled them for 2 weeks. Participants were asked to report real-time dietary intake using a designated mobile app. We measured their PPGRs and devised machine learning algorithms for PPGR prediction, which integrate glucose measurements, insulin dosages, dietary habits, blood parameters, anthropometrics, exercise, and gut microbiota. Data of the PPGR of 900 healthy individuals to 41,371 meals were also integrated into the model. The performance of the models was evaluated with 10-fold cross validation. RESULTS: A total of 121 individuals with T1D, 75 adults and 46 children, were included in the study. PPGR to 6,377 meals was measured. Our PPGR prediction model substantially outperforms a baseline model with emulation of standard of care (correlation of R = 0.59 compared with R = 0.40 for predicted and observed PPGR respectively; P < 10-10). The model was robust across different subpopulations. Feature attribution analysis revealed that glucose levels at meal initiation, glucose trend 30 min prior to meal, meal carbohydrate content, and meal's carbohydrate-to-fat ratio were the most influential features for the model. CONCLUSIONS: Our model enables a more accurate prediction of PPGR and therefore may allow a better adjustment of the required insulin dosage for meals. It can be further implemented in closed loop systems and may lead to rationally designed nutritional interventions personally tailored for individuals with T1D on the basis of meals with expected low glycemic response.

The risk of small and large for gestational age newborns in women with gestational diabetes according to pre-gestational body mass index and weight gain.

AIM: To explore the effects of pregestational body mass index (BMI) and gestational weight gain (GWG) on maternal and neonatal outcomes of women with gestational diabetes mellitus (GDM). METHODS: We conducted retrospective cohort analyses of outcomes among women with GDM who delivered at Shamir Medical Center, Israel (2017-2018). RESULTS: We included 673 women with GDM in our analysis, 217 (32.24%) with appropriate GWG (aGWG), 247 (36.7%) with excessive GWG (eGWG), and 209 (31%) with insufficient GWG (iGWG). Cesarean section (CS) was less prevalent among women with iGWG (19.6%), compared with women with eGWG (31.2%) and aGWG (31.1%) (p = .008). Small for gestational weight (SGA) newborns were more prevalent in women with iGWG 9.1%, compared with 2% and 0.9% for women with eGWG and aGWG, respectively (p<.001). Large for gestational age (LGA) newborns were significantly more prevalent in women with eGWG 17.4% compared with 4.8% and 9.7% in patients with iGWG and aGWG women, respectively (p<.001). SGA and LGA newborns were more prevalent in women with iGWG and e-GWG across all pre-gestational BMI groups >18.5 kg/m2. CONCLUSIONS: A complex interplay exists between pregestational weight, GWG, and GDM and pregnancy outcomes, specifically SGA and LGA newborns. A strict follow-up considering the pregestational BMI, GWG, blood glucose levels, treatment modality, and fetal abdominal circumference could assist in managing the complex interplay of patients with GDM for better neonatal outcomes.

Ovarian adrenal rest tumor in congenital adrenal hyperplasia: Is medical treatment the first line option?

SUMMARY Ovarian adrenal rest tumors (OARTs) are very rare. We describe a case of a young woman with uncontrolled classical congenital adrenal hyperplasia (CCAH), presenting with bilateral OARTs, successfully treated with steroid replacement. A 20-year-old woman, known to have 21OH-CCAH, presented with severe abdominal pain, vomiting, diarrhea, and fever. As a result of poor compliance, 6 months before her admission hirsutism worsened and amenorrhea, hyperpigmentation, and weakness developed. ACTH levels were 278 < pmol/L and 17OHP 91.3 nmol/L. She was admitted for parenteral antibiotics and high-dose hydrocortisone treatment. CT revealed bilateral juxta-ovarian masses (6.2 x 3.6 x 7.4 cm left and 5 x 2.2 x 3.2 cm right) that on MRI were iso-intense in T1 and hypointense in T2, with early enhancement and rapid washout. One week of high-dose hydrocortisone resulted in significant clinical and laboratory improvement and the patient was discharged with 2 mg dexamethasone/day. One month later US revealed shrinkage of the masses and dexamethasone dose was decreased. At three months from discharge, she has resumed regular menses, and a repeated MRI revealed the para-ovarian masses have shrunk. One year after the diagnosis, the para-ovarian masses have shrunk more to 2.8 x 1.9 x 4.3 on the left and 2.1 x 0.9 x 1.2 on the right with less contrast enhancement in comparison to previous test possibly due to fibrotic changes of the tissue. OARTs are rare tumors with a poorly known natural history, and surgery has been the first option in the few reported cases. We demonstrate that medical treatment is a good alternative, leading to significant tumor shrinkage over a short period.

Ovarian adrenal rest tumor in congenital adrenal hyperplasia: Is medical treatment the first line option?

Ovarian adrenal rest tumors (OARTs) are very rare. We describe a case of a young woman with uncontrolled classical congenital adrenal hyperplasia (CCAH), presenting with bilateral OARTs, successfully treated with steroid replacement. A 20-year-old woman, known to have 21OH-CCAH, presented with severe abdominal pain, vomiting, diarrhea, and fever. As a result of poor compliance, 6 months before her admission hirsutism worsened and amenorrhea, hyperpigmentation, and weakness developed. ACTH levels were 278 < pmol/L and 17OHP 91.3 nmol/L. She was admitted for parenteral antibiotics and high-dose hydrocortisone treatment. CT revealed bilateral juxta-ovarian masses (6.2 × 3.6 × 7.4 cm left and 5 × 2.2 × 3.2 cm right) that on MRI were iso-intense in T1 and hypointense in T2, with early enhancement and rapid washout. One week of high-dose hydrocortisone resulted in significant clinical and laboratory improvement and the patient was discharged with 2 mg dexamethasone/day. One month later US revealed shrinkage of the masses and dexamethasone dose was decreased. At three months from discharge, she has resumed regular menses, and a repeated MRI revealed the para-ovarian masses have shrunk. One year after the diagnosis, the para-ovarian masses have shrunk more to 2.8 × 1.9 × 4.3 on the left and 2.1 × 0.9 × 1.2 on the right with less contrast enhancement in comparison to previous test possibly due to fibrotic changes of the tissue. OARTs are rare tumors with a poorly known natural history, and surgery has been the first option in the few reported cases. We demonstrate that medical treatment is a good alternative, leading to significant tumor shrinkage over a short period.

Differentiated Thyroid Cancer with Biochemical Incomplete Response: Clinico-Pathological Characteristics and Long Term Disease Outcomes.

Although most patients with differentiated thyroid cancer (DTC) and biochemical incomplete response (BIR) follow a good clinical outcome, progression to structural disease may occur in 8-17% of patients. We aimed to identify factors that could predict the long-term outcomes of BIR patients. To this end, we conducted a retrospective review study of 1049 charts from our Differential Thyroid Cancer registry of patients who were initially treated with total thyroidectomy between 1962 and 2019. BIR was defined as suppressed thyroglobulin (Tg) > 1 ng/mL, stimulated Tg > 10 ng/mL or rising anti-Tg antibodies, who did not have structural evidence of disease, and who were assessed 12-24 months after initial treatment. We found 83 patients (7.9%) matching the definition of BIR. During a mean follow-up of 12 ± 6.6 years, 49 (59%) patients remained in a state of BIR or reverted to no evidence of disease, while 34 (41%) progressed to structural disease. At the last follow-up, three cases (3.6%) were recorded as disease-related death. The American Thyroid Association (ATA) Initial Risk Stratification system and/or AJCC/TNM (8th ed.) staging system at diagnosis predicted the shift from BIR to structural disease, irrespective of their postoperative Tg levels. We conclude that albeit 41% of BIR patients may shift to structural disease, and most have a rather indolent disease. Specific new individual data enable the Response to Therapy reclassification to become a dynamic system to allow for the better management of BIR patients in the long term.

The Prevalence of Hypomagnesemia in Hospitalized Type 2 Diabetic Patients Treated with Diuretics and/or Proton Pump Inhibitors.

BACKGROUND: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM. OBJECTIVES: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics. METHODS: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission. RESULTS: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels. CONCLUSIONS: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia.

Is Familial Nonmedullary Thyroid Cancer A More Aggressive Type of Thyroid Cancer?

OBJECTIVES: Familial non-medullary thyroid cancer (FNMTC) is a distinct entity, increasingly diagnosed. By lacking an accurate genetic diagnostic test, its diagnosis is currently clinically based, with an ongoing debate over whether it has a more aggressive clinical behavior than sporadic non-medullary thyroid cancer (SNMTC). We seek to compare in this study, the clinicopathological variables, and the outcome of FNMTC versus SNMTC patients. METHODS: We retrospectively searched a database of 465 patients that underwent thyroidectomy at Assaf Harofeh Medical Center (91.4% between 1990 and 2019) for demographics, risk factors, medical history, diagnostic workup, primary treatment, follow-up, and disease outcome data. We compared 47 FNMTC versus 321 SNMTC patients, and FNMTC patients with ≥2 (n = 34) versus ≥3 (n = 13) first-relative affected members. RESULTS: There were no significant differences in demographics, histopathology, TNM stage, treatment, and disease outcome between the FNMTC and SNMTC groups. The T2 and T4 tumor stage in the ≥3-member group were 25% and 8.3% compared to 0% and 0% in the two-member group (P = .02 and P = ns, respectively). Also, LN involvement was significantly higher in the ≥3-member group (61.6% vs. 24.2%, respectively; P = .036). CONCLUSION: FNMTC is not a more aggressive disease than SNMTC, but this may not apply for the ≥3-affected-relatives group. A large multicenter study including only families with three or more affected relatives is needed. Until then, a family history of NMTC should not be overlooked. LEVEL OF EVIDENCE: 3/5 Laryngoscope, 131:E677-E681, 2021.

The association of diabetes and hyperglycemia with sepsis outcomes: a population-based cohort analysis.

The independent association of diabetes and hyperglycemia on the outcomes of sepsis remains unclear. We conducted retrospective cohort analyses of outcomes among patients with community-onset sepsis admitted to Shamir Medical Center, Israel (08-12/2016). Statistical associations were queried by Cox and logistic regressions, controlled for by matched propensity score analyses. Among 1527 patients with community-onset sepsis, 469 (30.7%) were diabetic. Diabetic patients were significantly older, with advanced complexity of comorbidities, and were more often exposed to healthcare environments. Despite statistically significant univariable associations with in-hospital and 90-day mortality, the adjusted Hazard Ratios (aHR) were 1.21 95% CI 0.8-1.71, p = 0.29 and 1.13 95% CI 0.86-1.49, p = 0.37, respectively. However, hyperglycemia at admission (i.e., above 200 mg/dl (was independently associated with: increased in-hospital mortality, aHR 1.48 95% CI 1.02-2.16, p = 0.037, 30-day mortality, aHR 1.8 95% CI 1.12-2.58, p = 0.001), and 90-day mortality, aHR 1.68 95% CI 1.24-2.27, p = 0.001. This association was more robust among diabetic patients than those without diabetes. In this study, diabetes was not associated with worse clinical outcomes in community-onset sepsis. However, high glucose levels at sepsis onset are independently associated with a worse prognosis, particularly among diabetic patients. Future trials should explore whether glycemic control could impact the outcomes and should be part of the management of sepsis, among the general adult septic population.

Effect of Mini-invasive Floating Metatarsal Osteotomy on Plantar Pressure in Patients With Diabetic Plantar Metatarsal Head Ulcers.

BACKGROUND: Distal metatarsal osteotomy has been used to alleviate plantar pressure caused by anatomic deformities. This study's purpose was to examine the effect of minimally invasive floating metatarsal osteotomy on plantar pressure in patients with diabetic metatarsal head ulcers. METHODS: We performed a retrospective case series of prospectively collected data on 32 patients with diabetes complicated by plantar metatarsal head ulcers without ischemia. Peak plantar pressure and pressure time integrals were examined using the Tekscan MatScan prior to surgery and 6 months following minimally invasive floating metatarsal osteotomy. Patients were followed for complications for at least 1 year. RESULTS: Peak plantar pressure at the level of the osteotomized metatarsal head decreased from 338.1 to 225.4 kPa (P < .0001). The pressure time integral decreased from 82.4 to 65.0 kPa·s (P < .0001). All ulcers healed within a mean of 3.7 ± 4.2 weeks. There was 1 recurrence (under a hypertrophic callus of the osteotomy) during a median follow-up of 18.3 months (range, 12.2-27). Following surgery, adjacent sites showed increased plantar pressure and 4 patients developed transfer lesions (under an adjacent metatarsal head); all were managed successfully. There was 1 serious adverse event related to surgery (operative site infection) that resolved with antibiotics. CONCLUSION: This study showed that the minimally invasive floating metatarsal osteotomy successfully reduced local plantar pressure and that the method was safe and effective, both in treatment and prevention of recurrence. LEVEL OF EVIDENCE: Level III, retrospective case series of prospectively collected data.

Obestatin levels in response to a meal and association with subsequent appetite sensations in maintenance hemodialysis patients.

BACKGROUND: Obestatin, a physiological opponent of acylated ghrelin, is linked to appetite suppression regulation in mice but its anorexigenic properties in humans are controversial. We aimed to investigate obestatin's potential role in dietary intake regulation by examining response to a meal in maintenance hemodialysis (MHD) patients. METHODS: In this prospective observational case series study, we investigated the response of obestatin to a fixed calorie meal (500 kcal) in 21 MHD patients (age 69.2 ± 13.1 years, 10 women, with a body mass index 27.2 ± 5.5 kg/m2). Parallel changes in serum obestatin and insulin levels and subjective scores of appetite (visual analogue scales for hunger, satiety, fullness and prospective food consumption) were recorded on fasting and 30, 60 and 120 min after the meal. RESULTS: In a linear mixed effects model controlling for baseline demographics and clinical parameters including serum insulin concentrations, postprandial levels of obestatin did not change significantly from baseline in response to the meal. The response was the same in MHD patients treated with high- or low-flux dialyzers. However, postprandial obestatin levels were associated with the rate of change in sensation of fullness (linear estimate: 11.60 (95% confidence interval 0.17 to 23.04, P < 0.05)). The remaining sensations of appetite did not correlate with postprandial obestatin levels in time. CONCLUSIONS: Obestatin levels do not change acutely with food administration in MHD patients, but associate with the changes in sensation of fullness. This supports the possible role of obestatin in the long-term regulation of appetite in MHD patients.

Effect of pre-gestational weight and gestational weight gain in women with gestational diabetes controlled with medication on pregnancy outcomes - is recommended weight gain too liberal?

This is a retrospective cohort study of women with GDM treated with glucose-lowering agents that were followed and gave birth between 2005 and 2015 in the Assaf Harofeh medical center, Israel. Classification and regression tree method identified four groups according to adverse outcomes, consisted of 74 women with pre-gestational BMI below 25, 98 women with BMI 25-31, 90 women 31-39 and 18 women above 39. Respectively, median GWG was 12 kg (8-16), 11 kg (8-15), 7.5 kg (3.75-11) and 5 kg (-1.5 to 11.5) (p < .001). The risk for composite adverse outcomes was higher in the groups of BMI 25-31 (73.5%) and 31-39 (83.3%) in comparison to BMI <25 (51.4%) and 39 < (55.6%), p < .001. In women with pre-gestational BMI of <25, GWG of more than the median resulted in odds ratio of 2.75 (1.07-7.08, p = .036) for adverse pregnancy outcomes compared with participants who gained less than the median. Maternal obesity is related to adverse pregnancy outcomes. Women with GDM with normal pre-gestational BMI who gained weight according to IOM recommendations still experienced adverse outcomes.

A 2017 SURVEY OF THE CLINICAL PRACTICE PATTERNS IN THE MANAGEMENT OF RELAPSING GRAVES DISEASE.

OBJECTIVE: Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists. METHODS: Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse. RESULTS: The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI ( P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment. CONCLUSION: Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naïve patients and a less than optimal adherence to recently published clinical guidelines. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin.

Long-Term Outcome after Hemithyroidectomy for Papillary Thyroid Cancer: A Comparative Study and Review of the Literature.

Background: The extent of surgery for differentiated thyroid cancer (DTC) remains a controversial issue. Since a less aggressive approach is becoming more predominant, we aim here to study the short- and long-term outcomes of DTC patients after hemithyroidectomy. Methods: From a total of 1252 consecutive papillary thyroid cancer (PTC) patients, 109 treated with hemithyroidectomy and 50 with total thyroidectomy but no I131 were included. Persistent or recurrent disease was defined based on histopathology, imaging studies, and thyroglobulin levels. Results: Our hemithyroidectomy cohort included females (84.4%), microcarcinomas (81.9%), TNM stage I (95.4%), and a low American Thyroid Association (ATA) recurrence risk (94.5%). At one-year post-treatment, 3.7% had persistent disease (all female, median age 55 years, tumor size 7.5 mm). Recurrent disease was detected in 7.5% of those with excellent response at 1-year. With a follow-up of 8.6 years (1⁻48), all 109 patients were disease free at last visit, including the 11 patients (10.1%) who received additional treatment. Also, when comparing the hemi- and total thyroidectomy groups no significant differences were found in the rate of persistent and recurrent disease, overall mortality, and disease status at last visit. Conclusions: For properly selected low-risk PTC patients, hemithyroidectomy is a safe treatment option with a favorable long-term outcome.

Short-term Adherence with Discharge Recommendation for Insulin Treatment among Patients with Type 2 Diabetes.

BACKGROUND: Basal-bolus (BB) insulin treatment is increasingly used in poorly controlled diabetes patients during hospitalization and is commonly recommended at discharge; however, the extent of adherence with this recommendation is unknown. OBJECTIVES: To determine short-term adherence of type 2 diabetes mellitus (T2DM) patients discharged from internal medicine wards with recommendation for BB insulin treatment. METHODS: Prescription (primary physician adherence) and purchase (patient adherence) of long-acting and short-acting insulins during the first month following discharge from internal medicine wards was determined in 153 T2DM patients. Adherence was defined as full if prescription/purchase of both basal (long-acting) and bolus (short-acting) insulin was completed, and as partial if only one kind of insulin (basal or bolus) was prescribed/purchased. Association between demographic and clinical parameters and adherence was determined. RESULTS: Full adherence with discharge instructions was higher for primary physicians than for patients )79.1% vs. 69.3%, respectively, P = 0.0182). Pre-hospitalization hemoglobin A1C was significantly associated with adherence by both patients and primary physicians (full-adherence group 9.04% ± 2.04%; no-adherence group 7.51% ± 1.35%, P = 0.002). Age was negatively associated with adherence of both primary physicians and patients; however, this association did not reach statistical significance. Patients with certain background diseases such as atrial fibrillation, coronary heart disease, and chronic heart failure had significantly worse adherence (P < 0.05). When the sole cause of admission was diabetes, full adherence (100%) of both primary physicians and patients was found. CONCLUSIONS: Short-term adherence with discharge recommendation for BB insulin treatment is associated with pre-hospitalization patient characteristics.

Adherence to ATA 2015 guidelines in the management of unifocal non-invasive papillary thyroid cancer: a clinical survey among endocrinologists and surgeons.

BACKGROUND: Despite updated guidelines, management of thyroid nodules remains controversial. We aim to check implementation of new guidelines by ear-nose-throat (ENT) surgeons and endocrinologists. METHODS: A questionnaire was e-mailed including demographic data and an index case: a healthy 26-year-old women with a 3-cm Bethesda III (B3) atypia of undetermined significance solitary nodule and eventually papillary thyroid cancer (PTC). RESULTS: Respondent rate was 50.5%, 93 endocrinologists, 55 surgeons. For this case, 77.4% would repeat fine-needle aspiration (FNA), 25.3% order molecular analysis and 22.6% do surgery. If repeated FNA remained B3, 51% would choose surgery, 17.3% molecular analysis and 31.6% follow-up only. If repeated FNA was B6, 58.5% would recommend total (TTx) and 41.5% hemithyroidectomy (HTx). In pathologically confirmed PTC after HTx, 42.4% would recommend completion, 26.8% radioactive iodine (RAI) treatment. For a > = 4-cm tumor, 49.2% would recommend TTx. For a tumor 2-4 cm, 41% would recommend TTx. Variables favoring TTx were family history and radiation exposure. Only 17.4% would prefer TTx when small benign contralateral tumor is present. Reassessment at 1 year with undetectable thyroglobulin (Tg) included stimulated Tg (stTg) (72.5%), neck US only (27.5%) and combined US-stTg (59.4%); only 10.3% would order a diagnostic scan. For recurrence in two (13-9 mm) lymph nodes, 59.3% recommend reoperation, 16.3% RAI and 24.4% active surveillance. There were no major differences between endocrinologists and ENT surgeons. CONCLUSIONS: We report a considerable lack of adherence to new guidelines, with only 50% recommending HTx for a 4-cm unifocal low-risk PTC tumor.

[NEW TREATMENTS IN DIABETES MELLITUS - AN UPDATE].

INTRODUCTION: Diabetes is one of the most common chronic diseases. Most patients with type 2 diabetes are obese, and the global epidemic of obesity largely explains the dramatic increase in the incidence and prevalence of type 2 diabetes over the past 20 years. In the last decade intensive research has brought about an enormous change in the clinical approach to diabetes treatment. In this review we briefly discuss the main changes in diabetes treatment, such as new medications, bariatric surgeries and technology innovations. We hope that this short review would urge the reader to expand his knowledge on the subject.

Humoral hypercalcemia of pregnancy treated with bisphosphonates.

Hypercalcemia can be hazardous during pregnancy, most cases being due to primary hyperparathyroidism. We report a case of hypercalcemia with suppressed PTH levels necessitating treatment with bisphosphonates during pregnancy. A 38-year-old woman at the 26th week gestation was admitted because of symptomatic hypercalcemia. She did not take any medication that could influence her calcium levels. Physical examination was unremarkable. Laboratory tests on admission were: calcium 12.7 mg/dL (8.5-10.5 mg/dL), phosphorus 1.8 mg/dL (2.5-4.5 mg/dL) and PTH on 3 consecutive tests 1.2, 1.3 and 1.2 pg/mL (15-65 pg/mL). Her 24h urine calcium was 900 mg, 25-OH-D 40 ng/mL (30-58 ng/mL) and 1,25-OH-D 99 pg/mL (80-146 for women in the third trimester). Abdominal ultrasound revealed multiple hypervascular liver lesions consistent with hemangiomas by MRI. Breast and neck ultrasound were normal, and chest CT revealed few non-significant 0.3-0.7 cm pulmonary nodules with no change after an interval of 3 months. She was treated with isotonic saline, loop diuretics and calcitonin. Despite this treatment, calcium levels remained high (14.1 mg/dL), and pamidronate was initiated. On 35th week gestation, she underwent a cesarean section complicated by hypocalcemia of the newborn. Eight weeks after delivery, her calcium levels are 9.4 mg/dL and PTH 18 mg/dL. According to the extensive workup and the post-partum normalization of PTH and calcium levels, we conclude that excessive secretion of placental PTHrP was the cause of hypercalcemia in this patient. No significant adverse effect of bisphosphonate on the mother or baby were seen at the short term follow up.