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

ENDO_2015

 

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.

Methods:

  • 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.

Results:

  • 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).

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ5BA369FDE9DE4CED82CB6A7CD5BFD1BE/42341/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2015&nonus=0

OR17-Novel Aspects of Adrenal Tumors and the HPA Axis

ENDO_2015

 

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.

Methods:

  • 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.

Results:

  • 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.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ5BA369FDE9DE4CED82CB6A7CD5BFD1BE/42321/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2015&nonus=0

Day 2 Coverage of ENDO 2015

ENDO_2015

 

OR22-Osteoporosis–Winner: Outstanding Abstract Award

Effects of teriparatide on bone microarchitecture in postmenopausal women with osteoporosis
S Orlov, R Ridout, L Tile, M Kapral, S Cardew, MR Werb, SD Sandler, J Chang, H Hu, E Szabo, C Derzko, A Cheung


FRI 224-247-Metabolic and Genetic Bone Disorders

The effect of vitamin D supplementation on falls and physical performance in elderly women. A randomized clinical trial
S Yousefian, JC Gallagher, SH Tella


The etiology and risk factors analysis in hypercalcemic crisis
H Liao, DL Lorber, E Cohen


LBF 001-014-Late-breaking Thyroid/HPT Axis II

Diagnostic lobectomy for thyroid nodules >4 cm with benign cytology after fine-needle aspiration is associated with improved outcomes at an acceptable cost compared to observation: …
L Lee, E Theodosopoulos, EJ Mitmaker, JA Lee, J Chabot, JH Kuo


LBF 015-023-Late-breaking Reproductive Endocrinology II

Effect of testosterone treatment on cardiac biomarkers in a randomized controlled trial of men with type 2 diabetes
EJ Gianatti, R Hoermann, Q Lam, P Dupuis, JD Zajac, M Grossmann


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


Pharmacogenetic analysis of glucocorticoid gene polymorphisms and prediction of daily dexamethasone doses in adults with congenital adrenal hyperplasia
JS Frassei, LG Gomes, RP Moreira, G Madureira, BB Mendonca, TA Bachega


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


OR22-Osteoporosis

Denosumab restores cortical bone loss at the 1/3 radius associated with aging and reduces wrist fracture risk: Analyses from the Freedom extension cross-over group
JP Bilezikian, CL Benhamou, CJF Lin, JP Brown, NS Daizadeh, PR Ebeling, A Fahrleitner-Pammer, E Franek, N Gilchrist, PD Miller, JA Simon1, I Valter, AF Zerbini, C Libanati


OR22-Osteoporosis–Winner Clinical Fellows Abstract Award Travel Grants in Womens Health

Estrone may be more important than testosterone and estradiol for bone health and prevention of fractures in post-menopausal women
G Toraldo, TG Travison, X Zhang, KE Broe, S Bhasin, DP Kiel, AD Coviello

Cortisol Dysregulation and Alcoholism: Consequence, Correlation or Causality?

What

The National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, announces that Gary S. Wand, M.D., will deliver the 7th Annual Jack Mendelson Honorary Lecture. Dr. Wand is an internationally recognized neuroendocrinologist and the inaugural Rivière Professor in Endocrinology and Metabolism at The Johns Hopkins University School of Medicine. The title of his presentation is “Cortisol Dysregulation and Alcoholism: Consequence, Correlation or Causality?”

Who

Dr. Wand’s research has advanced our understanding of the genetic and environmental determinants of the stress response and has elucidated how excessive stress hormone production may contribute to neurobiological conditions such as alcohol or drug disorders.

Some of Dr. Wand’s seminal discoveries include identifying unique pharmacological responses to naloxone in individuals at increased risk for alcohol use disorders, identifying specific hormonal responses in subjects with alcohol use disorders, and characterizing human brain neurochemical changes using imaging in subjects with substance use disorders.

Dr. Wand is studying the epigenetic modulation of stress and cortisol exposure in rodent and human models, based on the hypothesis that specific epigenetic events affect how much cortisol an individual produces, which in turn influences dopamine transmission.

Dr. Wand received his medical degree and subsequent training in internal medicine from the George Washington University. Following post-doctoral training in Endocrinology and Metabolism at The Johns Hopkins University School of Medicine, he was a fellow in the peptide laboratories of Richard Mains, Ph.D. and Betty Eipper, Ph.D. in JHU’s Department of Neuroscience. Dr. Wand then joined the faculty of the Johns Hopkins University School of Medicine.

In 2000, NIAAA and the NIH honored Dr. Wand with a 10-year Merit Award to continue his research on the role of the HPA axis in alcoholism. He has also received numerous local and national “Best Doctor” awards. Dr. Wand is the author of more than 175 articles and chapters and is on the editorial board of several journals.

When

Thursday, March 19th at 1:30 p.m. EDT

Where

Masur Auditorium, NIH Building 10, Bethesda, Maryland

Background

NIAAA established the Jack Mendelson Honorary Lecture Series as a tribute to Dr. Jack Mendelson, who made remarkable scientific contributions to the field of clinical alcohol research. The purpose of this honorary lecture series is to highlight clinical/human research in the alcohol field by an outstanding investigator who has made significant and long-term contributions to our understanding of alcoholism susceptibility, alcohol’s effects on the brain and other organs, and the prevention and treatment of alcohol use disorders. NIAAA is pleased to present this series of scientific lectures to acknowledge the advances researchers are making in a wide range of alcohol-related areas of clinical research, and to honor the memory of an individual whose exciting and pioneering research with human alcoholics remains relevant today.

For additional information about the lecture see: http://www.niaaa.nih.gov/about-niaaa/our-work/research-portfolio/projects-initiatives/keller-and-mendelson-honorary-lecture

The Mendelson Honorary Lecture is free and open to the public. Sign language interpreters will be provided. For other reasonable accommodations or further information call Joanna Mayo, 301-443-3860, or visit www.niaaa.nih.gov. For TTY callers, please call the above number through the Federal Relay Service at 1-800-877-8339.

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at http://www.niaaa.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Corcept Therapeutics Announces Nine Poster Presentations on Mifepristone for the Treatment of Cushing’s Syndrome at the 97th Annual Endocrine Society Meeting – MarketWatch

ENDO_2015

 

Corcept Therapeutics Incorporated CORT,  a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic, oncologic and psychiatric disorders, today announced that a variety of posters about Korlym(R) (mifepristone) will be presented at the 97th annual Endocrine Society Meeting (ENDO 2015) being held at the San Diego Convention Center from March 5 – 7, 2015.

“We are pleased to see the breadth of new data being presented at ENDO 2015 about Korlym (mifepristone), which adds to the already substantial literature describing the use of mifepristone to treat Cushing’s Syndrome,” said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer. “We are committed to bringing innovative therapies to patients in need, and we look forward to continuing our pivotal role in advancing the scientific understanding of Cushing’s syndrome and other rare and debilitating diseases.”

Multiple endocrinologists, researchers and centers of excellence are presenting a total of nine abstracts.

Read the entire article at Corcept Therapeutics Announces Nine Poster Presentations on Mifepristone for the Treatment of Cushing’s Syndrome at the 97th Annual Endocrine Society Meeting – MarketWatch.

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