Day 4 Coverage of ENDO 2015






LB-OR02-Glucose Metabolism: From Bedside to Bench

A meta-analysis of the safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in Type 2 diabetes
CH Wysham, J Lin, L Kuritzky

Hypoglycemia in patients newly-initiated on basal insulin: Impact on treatment discontinuation
M Dalal, M Kazemi, F Ye

OR36-Metabolism and Gestational Diabetes

Impact of gestational diabetes on long-term vascular function
O Ajala, L Jensen, EA Ryan, CL Chik

OR40-Obesity: Human Studies in Body Weight Regulation

Increased protein intake during overfeeding increases energy expenditure, satiety, and urinary cortisol
A Graham, MC Schlogl, J Krakoff, MS Thearle

OR40-Obesity: Human Studies in Body Weight Regulation–Winner: Outstanding Abstract Award

Acute weight loss stimulates lipolysis and macrophage infiltration in the subcutaneous adipose tissue of obese women
JO Alemán, NM Iyengar, J Walker, J Gonzalez, GL Milne, DD Giri, CA Hudis, JL Breslow, PR Holt, AJ Dannenberg

OR44-Thyroid Cancer

Salvage therapy: When a tyrosine kinase inhibitor (TKI) fails in advanced medullary thyroid cancer (MTC)
SP Weitzman, KT Peicher, R Dadu, MI-N Hu, C Jimenez, C Gardner, A Qayyum, M Hernandez, ME Cabanillas

OR44-Thyroid Cancer – Winner: Outstanding Abstract Award

Phase II clinical trial of sunitinib as adjunctive treatment in patients with advanced differentiated thyroid cancer
A Bikas, P Kundra, JA Wexler, M Mete, S Desale, L Wray, C Barett, B Clark, L Wartofsky, K Burman

OR45-What Is New in Vitamin D?

Bioavailable fractions are better markers than 25 hydroxy vitamin D for monitoring vitamin D status during pregnancy
MR Pandian, J Pandian, Z Seres, AN Elias

High dose vitamin D2 supplementation for a year does not cause serious adverse events including emergency room visits and hospitalizations in African American men with high burden of chronic disease
C Onochie, I Ciubotaru, A Domenico, Y Eisenberg, SC Kukreja, A Kouser, E Barengolts

OR45-What Is New in Vitamin D? – Winner: Outstanding Abstract Award

Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older and younger women: A comparison between Caucasians and African Americans in two randomized trials
SH Tella, JC Gallagher, S Yousefian, V Yalamanchili

Does a normal urine free cortisol result rule out Cushing’s syndrome?



March 07, 2015

SAT 379-412-Cushing’s Syndrome

Does a normal urine free cortisol result rule out Cushing’s syndrome?

ST Sharma, LK Nieman

Summary: Researchers conducted this study to assess the diagnostic accuarcy of urine free cortisol (UFC) and 24-hour urine 17-hydroxycorticosteroids (170HCS) in patients with Cushing’s syndrome, concluding that in patients with mild CS, UFC can be falsely normal or only minimally elevated. Further, they found that to help in making a diagnosis and prevent treatment delays, clinicians may consider incorporating multiple collections and use of complimentary screening tests including 24-hour urine 17OHCS and late night salivary cortisol (LNSC) testing.


  • For this retrospective study, researchers included all CS patients evaluated at the National Institutes of Health (NIH) from 2009 to 2014.
  • The screening tests used for CS included UFC, 17OHCS, midnight serum cortisol and low dose (1 mg overnight or 2-day 2 mg/day) dexamethasone suppression test (DST).
  • They defined abnormal as values above reference range for UFC, 17OHCS and LNSC, a midnight serum cortisol ≥7.5 mcg/dL, and post-dexamethasone cortisol values ≥1.8 mcg/dL.
  • Hourly 24-hour sampling for cortisol was performed in a few cases with a mild clinical phenotype and equivocal test results.
  • Researchers measured UFC using liquid chromatography/tandem mass spectrometry (LC-MS/MS), and 17OHCS was measured using colorimetric methodology with Porter-Silber reaction (reported as mg/g of creatinine).
  • For this study, they used the mean of the first two UFC and 17OHCS values (appropriate collection by urine volume and creatinine) obtained within 30 days of initial NIH presentation.


  • In all, 72 patients were diagnosed with CS (aged 18-77 years, 51 females), 51 of whom had CD, 10 had ectopic CS, and 2 had an adrenal source of Cushing’s based on pathology.
  • Biochemical tests such as inferior petrosal sinus sampling (IPSS) suggested ectopic CS, but no tumor was found (occult) in 6 patients.
  • In 2 patients with failed transsphenoidal surgery, IPSS was indicative of a pituitary source, and one patient did not complete evaluation for ACTH-dependent CS.
  • UFC results were available in all patients, 17OHCS in 70, LNSC in 21, midnight serum cortisol in 68, and DST results in 37 patients.
  • UFC was falsely normal in 6 patients and only minimally elevated (<2 x ULN) in 13 patients (normal renal function, no history of cyclicity, all had CD); of these 19 patients, 24-hour 17OHCS was abnormal in all, LNSC was abnormal in 12, midnight serum cortisol was abnormal in 18, and DST was abnormal in 12 patients.
  • Hourly 24-hour sampling for cortisol performed in 3 of these patients revealed abnormal nadir (>7.5 mcg/dL) and mean daily serum cortisol (>9 mcg/dL) levels.


Day 3 Coverage of ENDO 2015



OR24-Adrenal Tumors: Clinical Implications of the Recent Molecular and Genetic Findings

Long term follow-up of a pivotal phase 2 study of Ultratrace® Iobenguane I-131 (AZEDRA) in patients with malignant relapsed/refractory pheochromocytoma/paraganglioma
C Jimenez, DA Pryma, DC Sullivan, JK Schwarz, RB Noto, N Stambler, T Armor, JD Jensen, RJ Israel

OR27-Hyperandrogenic Ovarian Dysfunction — Winner: Outstanding Abstract Award

The neurokinin B receptor antagonist AZD4901 decreases LH and testosterone secretion in women with PCOS: A randomized, double-blind, placebo-controlled clinical trial
JT George, R Kakkar, J Marshall, ML Scott, R Finkelman, T Ho, S McIntosh, JD Veldhuis, RA Anderson, L Webber

OR28-Lipids – Liver, Muscle, and Patient Bench to Bedside

Diagnosing familial hypercholesterolemia (FH) in the United States: Results from the CASCADE FH patient registry
Z Ahmad, C Newman, E O’Brien, P Shrader, EM deGoma, CD Ahmed, PM Moriarty, MRF Linton, MD Shapiro, PB Due, CM Ballantyne, WA Neal, D Duffy, L Hudgins, LC Hemphill, JA Underberg, KE Watson, SS Gidding, S Baum, K Wilemon, D Pickhardt, I Kindt, DJ Rader, M Roe, JW Knowles


Assessment of primary cancers in growth hormone-treated pediatric patients compared to population databases: An epidemiological analysis of a large, multinational, prospective observational study
CJ Child, AG Zimmermann, N Jia, LL Robison, JH Bramswig, WF Blum

Hypophysitis in the age of cancer immunotherapy: Experience in a large cancer center
MJoelle Pitteloud, R Dadu, ME Cabanillas, K Shah, MI-N Hu, MA Habra, SG Waguespack

OR34-Testosterone Replacement Therapy: Risks and Benefits

The association between testosterone use and major adverse cardiovascular events (MACE): An exploratory retrospective cohort analysis of two large, contemporary, coronary heart disease clinical trials
S Janmohamed, G Cicconetti, CE Koro, RV Clark, E Tarka

Oral Presentations in Reproductive Science–Winner: Oral Abstract Award in Reproductive Science

Effects of androgens and estrogens on cardiometabolic parameters in young adult men
EW Yu, H Lee, S-AM Burnett-Bowie, SC Hirsch, G Abrishamian-Garcia, LF Borges, DW Goldstein, AP Taylor, KE Wulczyn, AF Moore, JS Finkelstein

PP27-Hyperandrogenic Ovarian Dysfunction

Role of insulin resistance and hyperandrogenemia in early vascular dysfunction in adolescents with PCOS
SK Bartz, MC Caldas, R Krishnamurthy, R Krishnamurthy, FF Bacha

SAT 379-412-Cushing’s Syndrome

Does a normal urine free cortisol result rule out Cushing’s syndrome?
ST Sharma, LK Nieman

SAT 418-443-Biochemical, Genetic and Pharmacological Studies of the Pituitary and Hypothalamus

Clinical and molecular differences between invasive and non-invasive pituitary adenomas
DA Cano, M Mendez-Muros, E Venegas, N Gros, E Dios, N Garcia-Hernandez, A Madrazo-Atutxa, I Martin-Scheffer, E Cardenas, A Kaen, F Roldan, A Soto-Moreno

Reduced mortality in patients with GH replacement therapy – a Swedish study based on more than 4,000 patient-years



March 06, 2015

OR20-Pituitary Tumors-New Clinical Considerations

Reduced mortality in patients with GH replacement therapy – a Swedish study based on more than 4,000 patient-years

DS Olsson, AG Nilsson, P Trimpou, B-A Bengtsson, E Andersson, G Johannsson

Summary: In this study, researchers assessed mortality in patients with hypopituitarism with and without long-term growth hormone (GH) replacement therapy (GHRT). Theirs is the first study to report a reduced mortality in non-functioning pituitary adenoma (NFPA) patients with long-term GHRT compared with both the general population and NFPA patients who have not received GHRT, despite a more severe hypopituitarism. Further, researchers found that mortality due to circulatory diseases was not increased in NFPA patients regardless of GHRT. Finally, they found that death due to malignant tumors was decreased in the GHRT-group.


  • To eliminate the influence of the etiology of hypopituitarism on mortality, researchers included only  patients with NFPA were studied.
  • Using the Swedish National Patient Registry, researchers identified NFPA patients within the Sahlgrenska University Hospital’s catchment-area (1.5 million inhabitants), and retrospectively reviewed records of all identified NFPA patients from 1987 to 2011.
  • Standardized mortality ratios (SMRs) with 95% confidence intervals (reference: Swedish population) were calculated and cox-regression analyses were used to identify predictors for mortality.


  • Researchers identified 437 patients with NFPA, of whom 435 (99%) had complete records and were included in the study.
  • They observed that GHRT had been used for at least 1 year by 188 patients (132 men, 56 women), while 247 patients had not been treated with GHRT (148 men, 99 women).
  • Mean (±SD) age at diagnosis was lower (P<0.001) in the GHRT-group (54.2±11.7) compared to the non-GHRT-group (63.8±15.6).
  • Mean duration of GHRT was 10.9 (6.7) years, and mean follow-up time in the non-GHRT-group was 7.0 (5.4) years.
  • In the GHRT-group, ACTH deficiency, gonadotropic deficiency and thyrotrophic deficiency were more frequent (71%, 74% and 93%, respectively) compared with the non-GHRT-group (38%, 34% and 50%).
  • The total number of events/deaths in the study was 83.
  • In the GHRT group, SMR was 0.49 (0.27-0.80, P=0.002) compared with 0.98 (0.76-1.24;P=0.94) in the non-GHRT-group; SMR was lower in the GHRT-group compared to the non-GHRT-group (P=0.02).
  • Researchers found that Cox-regression analyses identified GHRT (P=0.01) and younger age at diagnosis (P<0.0001) as predictors of decreased mortality.
  • They also found that cause-specific mortality due to circulatory diseases was not increased (GHRT-group, SMR 0.62; 0.25-1.28; Non-GHRT-group, SMR 0.96; 0.65-1.36).
  • SMR for malignant tumors was reduced in the GHRT-group (SMR 0.19; 0.02-0.68; P=0.003), and as expected in the non-GHRT-group (SMR 0.74; 0.37-1.31; P=0.37).


OR17-Novel Aspects of Adrenal Tumors and the HPA Axis



March 06, 2015

OR17-Novel Aspects of Adrenal Tumors and the HPA Axis

Epigenetic modulation of DNA Is associated with fatigue, depression and anxiety in patients with Cushing’s syndrome in remission: A genome-wide methylation study

CAM Glad, JC Andersson-Assarsson, P Berglund, R Bergthorsdottir, O Ragnarsson, G Johannsson

Summary: Researchers conducted this study to determine whether patients with Cushing’s syndrome (CS) that is in remission have specific epigenetic alterations that are associated with persistent cognitive impairments, anxiety, fatigue, and depression. Patients with CS in remission were shows to have specific DNA methylation that differed from that of healthy controls and was strongly correlated with clinical traits of anxiety, depression and fatigue, they concluded, adding that their results may suggest that an interaction between the glucocorticoid and the retinoic acid receptor is implicated in the long-term outcome of patients with CS in remission. The persistent cognitive impairment observed in patients with CS in remission, therefore, may be due to epigenetic modulation of DNA, they concluded.


  • For this cross-sectional, case-controlled, single center study, researchers included 48 women with CS in remission (mean age±SD: 52.9±14 years) and 16 controls (mean age±SD: 53.6±16 years) matched for age, gender and educational level.
  • The mean age at diagnosis of CS was 37±14 years and the median (interquartile range) duration of remission was 13 (5-19) years.
  • In all, 37 patients had Cushing’s disease (CD) and 11 had a cortisol producing adrenal adenoma.
  • Researchers used the fatigue impact scale (FIS) to evaluate fatigue, and the comprehensive psychopathological rating scale to evaluate depression and anxiety; they assessed cognitive function by standardized neuropsychological tests.
  • DNA was isolated from whole blood, and DNA methylation was analyzed on the Illumina Infinium HumanMethylation450K BeadChip, which simultaneously interrogates >465,000 methylation sites per sample.
  • Researchers performed data quality control and analysis using the ChAMP methylation analysis package in R, and used Spearmen’s rho to perform correlation analyses.


  • Researchers found that patients had higher median score for FIS, depression and anxiety.
  • Methylation analysis identified 3,903 probes (in 340 genes) in regions that were differently methylated between CS patients and controls, and they found that 28% of these were significantly correlated to at least one of the clinical traits.
  • Fatigue, depression and anxiety were the most commonly correlated traits, and two of the most highly correlated genes were RXRB and COL11A2.
  • Gene ontology analysis revealed that these belong to the same GO-terms and are involved in retinoic acid receptor activity.
  • Finally, researchers found that both genes were specifically hypomethylated in cases as compared to controls.


This project has received financial support from the Swedish federal government under the LUA/ALF agreement, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, The Swedish Society of Medicine and The Swedish Society of Endocrinology.


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