OR17-Novel Aspects of Adrenal Tumors and the HPA Axis

Posted on March 6, 2015 by MaryO

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

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Myth: After a “cure” for Cushing’s, everyone heals and goes back to normal.

Posted on December 13, 2014 by MaryO

Myth: After a “cure” for Cushing’s, everyone heals and goes back to normal. All Cushing’s patients can easily heal with no repercussions after Cushing’s. After pituitary surgery or a Bilateral Adrenalectomy (BLA), life is great and being “cured” means having a “normal” life! After all, surgery is a “cure” and about 6 weeks later, you are back to normal. “Say, you had surgery XYZ long ago! Shouldn’t you be better by now?!!!!”

Fact: I can not even tell you how many people asked me “aren’t you better yet?!” after both of my surgeries! There are too many to count! There is a misperception that surgery means a cure and therefore, healing should happen magically and quickly. No! No! No! This is far from the truth.

The sad reality is that even some medical doctors buy into this myth and expect quick healing in their patients. However, they are not living in their patients bodies nor have they obviously read the extensive research on this. Research has shown that the healing process after surgery is a long and extensive one. One endocrinologist, expert from Northwestern, even referred to the first year after pituitary surgery for patients as “the year from hell”! He literally quoted that on a slide presentation.

It takes at least one year after pituitary surgery, for instance, to even manage hormones effectively. Surgery is invasive and hard. However, the hardest part comes AFTER surgery. This is when the body is compensating for all of the years of hormonal dysregulation and the patient is trying to get his/her levels back to normal.

There is a higher rate of recurrence of Cushing’s then we once thought. This means that after a patient has achieved remission from this illness, it is likely to come back. In these cases, a patient faces other treatments that may include radiation, the same type of surgery, or an alternative surgery.

For many pituitary patients who experience multiple recurrences, the last resort is to attack the source by removing both adrenal glands. This procedure is known as a Bilateral Adrenalectomy or BLA. In these cases, it is said that the patient “trades one disease for another”, now becoming adrenally insufficient and having Addison’s Disease. Both Pituitary and Adrenal patients are faced with a lifetime of either Secondary or Primary Adrenal Insufficiency.

Adrenal Insufficiency is also life threatening and adrenal crises can potentially lead to death. Additionally, research says that BLA patients take, on average, 3-5 years for their bodies to readjust and get anywhere near “normal”. Most patients will tell you that they never feel “normal” again!

Think of these facts the next time you feel tempted to ask your friend, family, or loved one, “why is it taking so long to get better after surgery?”. Remember that in addition to the aforementioned points; problems from Cushing’s can linger for years after surgery! One Cushing’s patient stated, “I’m 5 years post-op and I STILL have problems!” This mirrors the sentiments of many of us in the Cushing’s community. Please be conscious of this when supporting your loved one after treatment.

You can find more information in the following links:

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2011.04124.x/abstract;jsessionid=CC58CF32990A60593028F4173902EC47.f03t03?deniedAccessCustomisedMessage&userIsAuthenticated=false

http://press.endocrine.org/doi/abs/10.1210/jc.2013-1470

http://press.endocrine.org/doi/abs/10.1210/jc.2012-2893

This is another article that validates the aforementioned fact about the “cure myth”: http://home.comcast.net/~staticnrg/Cushing’s/resmini%20Cushing’s%20article-2.pdf

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Cushings Syndrome/Disease can be healed or cured through change in diet or exercise

Posted on December 10, 2014 by MaryO

Myth: Cushing’s Syndrome/Disease can be healed or cured through change in diet or exercise.

myth-busted

Fact: NO! Caloric intake or lack of exercise has NO impact on weight gain and/ or loss in persons with Cushing’s.

Saying that someone “cheated” on their diet may seem reasonable to some as a reason for weight gain but I assure you that a candy bar or a piece of pie does not make a person with Cushing’s gain weight or get sick. Excess cortisol is the reason for Cushing’s symptoms. Treating the disease is the only way to alleviate symptoms.

The first line of treatment with the highest rate of remission is currently surgery to remove the tumor (s) from the pituitary, adrenal gland, or ectopic source.

Filed under: adrenal, Cushing's, Myths and Facts, pituitary | Tagged: , , , , , , , , , , , | 1 Comment »

Long-term remission and recurrence rate in a cohort of Cushing’s disease: the need for long-term follow-up

Posted on June 9, 2014 by MaryO

Pituitary. 2014 Apr 19. [Epub ahead of print]


Aranda G1, Enseñat J, Mora M, Puig-Domingo M, Martínez de Osaba MJ, Casals G, Verger E, Ribalta MT, Hanzu FA, Halperin I.

Author information

 Abstract

OBJECTIVE:

Transsphenoidal surgery is the procedure of choice in Cushing disease (CD), with immediate post-operative remission rates ranging between 59 and 94 % and recurrence rates between 3 and 46 %, both depending upon the definition criteria and the duration of the follow-up. Our aim was to assess the rate of remission, recurrence and persistence of the disease after the first treatment and to identify predictors of remission in the CD population of our center.

METHODS:

Retrospective cohort study of the patients diagnosed of CD and with follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women and 6 men) with a mean age at diagnosis of 34 ± 13 years. The mean follow-up was 14 ± 10 years (range 1-37 years) and the median of follow-up period was 6.68 years.

RESULTS:

Thirty-five (85.4 %) patients underwent transsphenoidal surgery as first treatment option. Histopathological evidence of a pituitary adenoma was registered in 17 (48.5 %) patients. Thirty-two (78 %) patients achieved disease remission after the first treatment, 21 (65.6 %) of them presented disease recurrence. Persistent disease was observed in 9 (22 %) patients. Twelve (29.3 %) subjects developed post-surgical adrenal insufficiency, 7 of which (70 %) achieved stable remission. Two parameters were found to be significant predictors of remission after the first treatment: age at disease diagnosis and the development of adrenal insufficiency (cortisol ❤ μg/dl) in the immediate post-operative state.

CONCLUSIONS:

We report a high recurrence rate, at least partially attributable to the long follow-up time. Early post-surgery adrenal insufficiency predicts remission. Hypopituitarism was also very prevalent, and strongly associated with radiotherapy. These results lead us to the conclusion that CD needs a life-long strict follow-up.

PMID:

 

24748528

 

[PubMed – as supplied by publisher]

Filed under: adrenal crisis, Cushing's, pituitary, Treatments | Tagged: , , , , , , , , , | Leave a comment »

Cushing’s Awareness Challenge, Day 4

Posted on April 4, 2014 by MaryO
Another idea I borrowed from Robin – using a Wordle as inspiration for today’s post.
Even though I’m “in remission” since 1987, I’m still way too fatigued, napping every afternoon for several hours.  People think I should be normal since my pituitary surgery was so long ago.  Well, no.
me-tired
Just a few days ago, I posted this abstract on Severe fatigue in patients with adrenal insufficiency.  I don’t think that they needed to do this study at all.  Just ask any Cushie!
Giebels V1, Repping-Wuts H, Bleijenberg G, Kroese JM, Stikkelbroeck N, Hermus A.

Author information

Abstract

BACKGROUND:

Fatigue is a frequently experienced complaint in patients with adrenal insufficiency (AI) and may be influenced by cortisol levels.

AIM:

The objective of this study was to determine the prevalence of severe fatigue in adrenal insufficiency (AI) patients, to assess which dimensions contribute to fatigue severity and to determine the association between salivary cortisol levels and momentary fatigue.

SUBJECTS AND METHODS:

We performed a cross-sectional study in the outpatient department of a university hospital. Included were 27 patients with congenital adrenal hyperplasia (CAH), 26 patients with primary AI (PAI), 24 patients with secondary AI (SAI) and 31 patients with adrenal insufficiency after treatment for Cushing’s syndrome (Cush-AI). Measurements included computerised questionnaires to determine fatigue severity and physical and psychosocial contributors. Patients took four saliva samples at home, in which cortisol levels were measured.

RESULTS:

Severe fatigue was experienced by 41 % of the CAH patients, 42 % of the PAI patients, 50 % of the SAI patients and 42 % of the Cush-AI patients. Psychological distress, functional impairment, sleep disturbance, physical activity, concentration problems and social functioning contributed to the subjective experience of fatigue. Salivary cortisol levels were not correlated with momentary fatigue.

CONCLUSIONS:

A considerable proportion of AI patients experience severe fatigue. Salivary cortisol level is not a significant predictor for momentary fatigue in AI patients.

PMID:
24615365
[PubMed – in process]

From http://www.ncbi.nlm.nih.gov/pubmed/24615365

 

Back to my nap now…

maryo colorful zebra

Filed under: adrenal, Cushing's, pituitary | Tagged: , , , , , , , , , , , , | 3 Comments »

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