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

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.

Day 1 Coverage of ENDO 2015

ENDO_2015

 

Late-breaking Neuroendocrinology and Pituitary I

6-month interim safety and efficacy of different dose levels of TransCon HGH administered once weekly versus standard daily human growth hormone replacement therapy in pre-pubertal children with GHD
P Chatelain, O Malievsky, K Radziuk, HH Elsedfy, E Mikhailova, M Beckert


OR01-Clinical Issues in Type 1 and Type 2 Diabetes

Metformin as an adjunct therapy does not improve glycemic control among overweight adolescents with type 1 diabetes (T1D)
I Libman, KM Miller, LA DiMeglio, K Bethin, ML Katz, A Shah, JH Simmons, MJ Haller, S Raman, WV Tamborlane, J Coffey, AM Saenz, RW Beck


Patient-reported outcomes 1 year after randomization to laparoscopic adjustable gastric banding or intensive weight and diabetes management in obese patients with type 2 diabetes mellitus
DC Simonson, SA Ding, F Halperin, M Wewalka, K Foster, K Kelly, J Panosian, A Goebel-Fabbri, O Hamdy, K Clancy, D Lautz, A Vernon, AB Goldfine


Undermanagement of hyperlipidemia in young persons with type 1 diabetes (T1D)
ML Katz, GH Telo, JB Cartaya, CE Dougher, M Ding, LM Laffel


OR01-Clinical Issues in Type 1 and Type 2 Diabetes–Winner: Outstanding Abstract Award

18F-Flouride PET/CT and 18F-FDG labeled autologous leukocyte PET/CT for diagnosis of osteomyelitis in diabetic Charcot’s neuroarthropathy of foot
A Rastogi, A Bhansali


OR11-Thyroid Development, Clinical and Autoimmunity

Long-term outcomes and predictive factors of efficacy of ultrasound-guided ethanol injection for benign cystic thyroid lesions
E Papini, R Guglielmi, I Misischi, FM Graziano, A Persichetti, R Rendina, S Taccogna, G Bizzarri


OR11-Thyroid Development, Clinical and Autoimmunity–Winner: Outstanding Abstract Award

Novel insights into the effects of maternal thyroid function on child IQ reveal detrimental effects of high FT4 levels
TIM Korevaar, M Medici, H Tiemeier, E Visser, TJ Visser, RP Peeters


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

Kisspeptin signaling in the amygdala modulates reproductive hormone secretion
AN Comninos, J Anastasovska, M Sahuri-Arisoylu, X Feng Li, S Li, M Hu, CN Jayasena1, MA Ghatei, SR Bloom, P Matthews, K O’Byrne, JD Bell, WS Dhillo


PP09-Acromegaly

Biochemical control is maintained with pasireotide LAR in patients with acromegaly: Results from the extension of a randomized phase III study (PAOLA)
MR Gadelha, MD Bronstein, T Brue, MG Coculescu, L De Marinis, M Fleseriu, M Guitelman, V Pronin, G Raverot, I Shimon, J Fleck, A Kandra, AM Pedroncelli, A Colao


THR 113-137-Testis Cells: Control, Regulation and Functions

Effects of testosterone level on lower urinary tract symptoms
ED Crawford, W Poage, A Nyhuis, DA Price, SA Dowsett, D Muram

After massive weight gain, Cushing’s disease diagnosis saves man’s life – Health – TODAY.com

Donelle Trotman was only in his 30s when his health suddenly took a strange and frightening turn.

He was rapidly gaining weight — more than 100 pounds in one year. His upper torso was getting bigger, but not his legs. And he felt overwhelmingly tired.

“My body just started changing,” the Staten Island, New York, native told TODAY as part of a three-day series, “Medical Mysteries,” looking at people who have recovered from rare diseases.

It was especially puzzling because Trotman had never had weight issues before.

In school, Trotman was never a skinny kid, but he wasn’t overweight. He loved sports, playing both basketball and baseball.

So as he entered adulthood, he was active and in good shape. Then, three years ago, he suddenly began to gain weight.

“It was just specific places: My stomach, under my arms, my back of my neck, my face, the bottom of my back,” Trotman said. “My legs stayed the same for a long time.”

To lose the extra pounds, Trotman began running, working out and lifting weights. Nothing worked.

In the span of one year, Trotman gained more than 120 pounds, topping the scale at 366 pounds, twice the amount he weighed at 18.

“I doubled, like, I got a whole person on me,” he said.

There were other alarming changes. Trotman became so easily tired that he’d get out of breath just by chewing food. When he woke up seeing double three months ago, he knew it was time to go to the hospital.

Doctors ran a flurry of tests, but the results offered few clues, leaving everyone puzzled. Then one day, an intern noticed stretch marks all over Trotman’s body, a telltale sign that solved the mystery. Trotman had Cushing’s disease, a rare condition that affects fewer than 50,000 people in the U.S. every year.

Trotman’s weight gain was being caused by a tiny tumor at the base of his brain, prompting his body to produce too much of the hormone cortisol. He had some of the classic symptoms: major weight gain in his upper body, skin problems and acne, plus fatigue.

Dr. John Boockvar and Dr. Peter Costantino at New York’s Lenox Hill Hospital discovered Trotman had steroid levels ten times higher than normal.

“In Cushing’s disease, the pituitary gland has a small growth that releases a single hormone that causes the body to live with very high levels of steroids. The skin becomes very thin. You get increased acne. You can grow hair. You start sweating. You gain a lot of fat,” Boockvar said.

There was no time to lose: Untreated, Cushing’s is a fatal disease. Trotman was getting close to the point where doctors would not be able to reverse the changes, Costantino noted. He underwent surgery two weeks ago and had the growth successfully removed.

“The tumor was no bigger than the size of the tip of my pen,” Boockvar said. “And that something so small can cause a man to grow to 350 pounds and absolutely destroy his life is rather remarkable.”

These days, Trotman is feeling much better. His main focus now is to lose the weight he gained and regain an active lifestyle. He hopes to play basketball with his son soon.

“It’s wonderful. Every day it’s just like I feel a little stronger,” he said.

Doctors say Trotman will continue to lose weight and can shoot hoops with his son in about three months. There is an 8-10 percent chance the disease could come back, but Trotman said he knows what to look for now.

One of the reasons Trotman wanted to share his story is so others might recognize the symptoms of Cushing’s, although doctors stress it is a very rare illness.

 

Watch the video here: After massive weight gain, Cushing’s disease diagnosis saves man’s life – Health – TODAY.com.