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CONTEXT:Hypoglycemia is common among hospitalized patients with and without diabetes mellitus. OBJECTIVE:Investigate the association between spontaneous or insulin-related hypoglycemia and mortality in hospitalized patients. DESIGN:Hypoglycemia was defined as blood glucose <70 mg/dl (3.9 mmol/l), including moderate (40 to 70 mg/dl, 2.2 to 3.9 mmol/l) and severe hypoglycemia (<40 mg/dl, 2.2 mmol/l). Use of insulin during hospitalization defined insulin-related hypoglycemia, thus patients were classified into 6 groupsnon-insulin treated (NITC) and insulin-treated controls (ITC), insulin-related hypoglycemia (IH) or severe hypoglycemia (ISH), and non insulin-related hypoglycemia (NIH) and severe hypoglycemia (NISH). SETTING AND PATIENTS:Historical prospectively data of patients ≥ 18 years of age, hospitalized in medical wards for any cause between January 2011 and December 2013. MAIN OUTCOME MEASURE:All-cause mortality at the end of follow-up. RESULTS:The cohort included 33,675 patients, including 2605 with moderate hypoglycemia (IH, 1011; NIH, 1594) and 342 with severe hypoglycemia (ISH, 201; NISH,141). Overall end-of-follow-up mortality was 31.9% (NITC, 28.0%; ITC, 42.9%; NIH, 50.7%; IH, 55.3%; NISH, 70.9%; ISH, 69.1%). Compared with NITC, unadjusted hazard ratios (95% confidence intervals) for mortality were as followsITC, 1.7 (1.6 to 1.8), NIH, 2.2 (2.0 to 2.4), IH, 2.5 (2.2 to 2.7), NISH, 4.2 (3.5 to 5.2), and ISH, 3.8 (3.2 to 4.5); with P < 0.001. Following multivariate analysis, respective hazard ratios were 1.8, 2.1, 2.4, 3.2, and 3.6 (P < 0.001). Cause of admission did not affect the association. CONCLUSIONS:In hospitalized patients, hypoglycemia, either with insulin use or spontaneous, is associated with increased short- and long-term mortality.

ContextProlactinomas in men are usually large and invasive, presenting with signs and symptoms of hypogonadism and mass effects, including visual damage. Prolactin levels are high, associated with low testosterone, anemia, metabolic syndrome and if long-standing also osteoporosis.ResultsMedical treatment with the dopamine agonist, cabergoline, became the preferred first-line treatment for male prolactinomas as well as for giant tumors, leading to prolactin normalization in ~ 80% of treated men, and tumor shrinkage, improved visual fields and recovery of hypogonadism in most patients. Multi-modal approach including surgery and occasionally radiotherapy together with a high-dose cabergoline is saved for resistant and invasive adenomas. Experimental treatments including temozolomide or pasireotide may improve clinical response in men harboring resistant prolactinomas.ConclusionsCompared to other pituitary adenomas, secreting and non-secreting, where pituitary surgery is the recommended first-line treatment, men with prolactinomas will usually respond to medical treatment with no need for any additional treatment.

This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy. Management of prolactinoma in special situations is discussed, including cystic lesions, mixed growth hormone-secreting and prolactin-secreting adenomas and giant and aggressive prolactinomas. Furthermore, considerations for pregnancy and fertility are outlined, as well as management of prolactinomas in children and adolescents, patients with an underlying psychiatric disorder, postmenopausal women, transgender individuals and patients with chronic kidney disease. The workshop concluded that, although treatment resistance is rare, there is a need for additional therapeutic options to address clinical challenges in treating these patients and a need to facilitate international registries to enable risk stratification and optimization of therapeutic strategies.This Consensus Statement, which is endorsed by the Pituitary Society, offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas.

Abstract 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 ± 6 mm. Following lobectomy, Tg was 12.1 ± 14.8 ng/mL. Of 52 patients with Hashimoto’s thyroiditis, 38% had positive TgAb with titers of 438 ± 528 IU/mL, and in patients without TgAb the mean Tg level was 14.7 ± 19.0 ng/mL. In 34 patients with contralateral nodules ≥1 cm, Tg was 15.3 ± 17 ng/mL. During the first 2 years of follow-up, Tg declined ≥1 ng/mL in 42% of patients (by 5.1 ± 3.7 ng/mL), remained stable in 22%, and increased in 36% (by 4.9 ± 5.7 ng/mL). During a mean follow-up of 6.5 years (78 ± 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.

Abstract Objective The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013. Participants The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration. Evidence This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities. Consensus Process Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system. Conclusions Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.

Purpose The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy. Methods Fifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes. Results In a patient with typical acromegaly features, insulin-like growth factor (IGF)-I > 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches. Conclusion Consensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.

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.Increased glucose variability in hospitalized patients with and without DM is associated with longer hospitalization and increased short- and long-term mortality.

Background While obesity is commonly associated with increased morbidity and mortality, in patients with chronic diseases, it has have been associated with a better prognosis, a phenomenon known as the 'obesity paradox'. Objective We investigated the relationship between mortality, length of hospital stay (LOHS), and body mass index (BMI) in patients hospitalized to general surgical wards. Methods We extracted data of patients admitted to the hospital between January 2011 and December 2017. BMI was classified according to the following categories: underweight (< 18.5), normal weight (18.5–24.9), overweight (25–29.9), obesity (30–34.9) and severe obesity (≥ 35). Main outcomes were mortality at 30-day mortality and at the end-of-follow-up mortality), as well as LOHS. Results A total of 27,639 patients (mean age 55 ± 20 years; 48% males; 19% had diabetes) were included in the study. Median LOHS was longer in patients with diabetes vs. those without diabetes (4.0 vs 3.0 days, respectively), with longest LOHS among underweight patients. A 30-day mortality was 2% of those without (371/22,297) and 3% of those with diabetes (173/5,342). In patients with diabetes, 30-day mortality risk showed a step-wise decrease with increased BMI: 10% for underweight, 6% for normal weight, 3% for overweight, 2% for obese and only 1% for severely obese patients. In patients without diabetes, 30-day mortality was found to be 6% for underweight, 3% for normal weight and 1% across the overweight and obese categories. Mortality rate at the end-of-follow-up was 9% of patients without diabetes and 18% of those with diabetes (adjusted OR = 1.3, 95% CI, 1.2–1.5). In patients with diabetes, mortality risk showed an inverse association with respect to BMI: 52% for underweight, 29% for normal weight, 17% for overweight, 14% for obesity and 7% for severely obese patients, with similar trend in patients without diabetes. Conclusions The results support the ‘obesity paradox’ in the general surgical patients as those with and without diabetes admitted to surgical wards, BMI had an inverse association with short- and long-term mortality.

Abstract Background Minimal extrathyroid extension (mETE) in patients with differentiated thyroid cancer (DTC) 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 patients with DTC 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 [seven studies: odds ratio (OR), 1.73; 95% confidence interval (CI), 1.03 to 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 (eight studies: OR, 1.82; 95% CI, 1.14 to 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 micropapillary carcinoma (<1 cm), the impact of mETE was nonsignificant (OR, 2.40; 95% CI, 0.95 to 6.03). mETE had no impact on disease-related mortality (eight studies: OR, 0.5; 95% CI, 0.11 to 2.21). Conclusion mETE increases risk of recurrence in patients with DTC; 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%. mETE has no impact on disease-related mortality and should not change tumor stage. In a meta-analysis of 23,816 patients, minimal extrathyroidal extension increases risk of recurrence, but the absolute risk is small, and in N0 disease the risk is within the low-risk category.