Metabolomic Biomarkers in Urine of Cushing’s Syndrome Patients

Int. J. Mol. Sci. 2017, 18(2), 294; doi:10.3390/ijms18020294 (registering DOI)
Department of Food Sciences, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
Laboratory of Environmental Chemometrics, Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
Department ofEnvironmental Analytics, Institute for Environmental and Human Health Protection, Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
Author to whom correspondence should be addressed.
Academic Editor: Ting-Li (Morgan) Han
Received: 5 December 2016 / Revised: 9 January 2017 / Accepted: 19 January 2017 / Published: 29 January 2017
(This article belongs to the Section Molecular Diagnostics)
Download PDF [1853 KB, uploaded 29 January 2017]

Abstract

Cushing’s syndrome (CS) is a disease which results from excessive levels of cortisol in the human body. The disorder is associated with various signs and symptoms which are also common for the general population not suffering from compound hypersecretion. Thus, more sensitive and selective methods are required for the diagnosis of CS.

This follow-up study was conducted to determine which steroid metabolites could serve as potential indicators of CS and possible subclinical hypercortisolism in patients diagnosed with so called non-functioning adrenal incidentalomas (AIs).

Urine samples from negative controls (n = 37), patients with CS characterized by hypercortisolism and excluding iatrogenic CS (n = 16), and patients with non-functioning AIs with possible subclinical Cushing’s syndrome (n = 25) were analyzed using gas chromatography-mass spectrometry (GC/MS) and gas chromatograph equipped with flame ionization detector (GC/FID). Statistical and multivariate methods were applied to investigate the profile differences between examined individuals. The analyses revealed hormonal differences between patients with CS and the rest of examined individuals.

The concentrations of selected metabolites of cortisol, androgens, and pregnenetriol were elevated whereas the levels of tetrahydrocortisone were decreased for CS when opposed to the rest of the study population. Moreover, after analysis of potential confounding factors, it was also possible to distinguish six steroid hormones which discriminated CS patients from other study subjects.

The obtained discriminant functions enabled classification of CS patients and AI group characterized by mild hypersecretion of cortisol metabolites. It can be concluded that steroid hormones selected by applying urinary profiling may serve the role of potential biomarkers of CS and can aid in its early diagnosis.

 

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

From http://www.mdpi.com/1422-0067/18/2/294

Froedtert and MCW researchers investigate Cushing syndrome incidence in bariatric surgery patients

Researchers at the Medical College of Wisconsin determined that Cushing syndrome, an endocrine disorder, may be the potential cause for weight gain and metabolic complications for patients who have undergone bariatric surgery for obesity. The study, published in the journal Obesity Surgery, was conducted by Ty B. Carroll, MD, assistant professor of endocrinology; James W. Findling, MD, FACP, professor of endocrinology ; and Bradley R. Javorsky, MD, assistant professor of endocrinology. The physicians practice at Froedtert Hospital in Wauwatosa and Community Memorial Hospital in Menomonee Falls.

Cushing syndrome can occur when the human body is exposed to high levels of cortisol for an extended period of time. Cortisol is a hormone in the body which affects blood pressure regulation and cardiovascular system functions. Cortisol also helps regulate the body’s conversion of proteins, carbohydrates and fats from diet into usable energy. However, when the level of cortisol becomes too high, Cushing syndrome can develop.

Cushing syndrome is associated with a variety of symptoms including weight gain and fatty tissue deposits in the body. According to the American Association of Neurological Surgeons, 10 to 15 million people are affected each year by Cushing syndrome.

Bariatric surgery is a procedure performed to help with extreme cases of obesity. Weight loss is achieved by reducing the size of the stomach with a gastric band, removal of a portion of the stomach or resecting and rerouting the small intestine to a small stomach pouch. Bariatric surgery is often used as an option for individuals unable to lose weight through diet and exercise, or have serious health problems caused by obesity.

According to the American Society for Metabolic and Bariatric Surgery, 179,000 bariatric surgeries were performed in the U.S. in 2013. However, despite successes in normal weight loss cases, bariatric surgery does not provide long term weight loss for individuals diagnosed with Cushing syndrome. Cushing syndrome often goes undiagnosed as a potential cause for weight gain and metabolic complications until after the surgery is performed.

MCW researchers in this study analyzed the incidence of Cushing syndrome in patients who underwent bariatric surgery for weight loss. During the investigation, the researchers performed a retrospective chart review on a series of 16 patients diagnosed with Cushing syndrome from five tertiary care centers in the U.S. who underwent bariatric surgery. The results from the study found 12 of the analyzed patients were not diagnosed with Cushing syndrome prior to their bariatric surgery. The remaining four patients had Cushing syndrome surgery prior to bariatric surgery, without recognition that their Cushing syndrome was persistent until after the weight loss surgery. The findings from the research indicate that Cushing syndrome may be often overlooked in patients undergoing bariatric surgery.

According to the researchers, testing for Cushing syndrome should be performed prior to bariatric surgery in patients with persistent hypertension, diabetes mellitus or excessive weight regain.

From http://www.lakecountrynow.com/usersubmittedstories/366480371.html

Cushing’s Syndrome Subtype Affects Postoperative Time to Adrenal Recovery

Berr CM. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2014-3632.

January 16, 2015

In patients undergoing curative surgical tumor resection for Cushing’s syndrome, the time to recovery of adrenal function is contingent upon the underlying etiology of the disease, according to recent findings.

In the retrospective study, researchers reviewed case records of 230 patients with Cushing’s syndrome. All patients were seen at a tertiary care center in Munich between 1983 and 2014, whose cases were documented in the German Cushing’s Registry. Patients were divided into three subgroups of Cushing’s syndrome: Cushing’s disease, adrenal Cushing’s syndrome and ectopic Cushing’s syndrome.

After applying various exclusion criteria, the researchers identified 91 patients of the three subgroups who were undergoing curative surgery at the hospital. The patients were followed for a median of 6 years. The researchers defined adrenal insufficiency as the need for hydrocortisone replacement therapy, and collected this information from patient records and laboratory results.

The duration of adrenal insufficiency was calculated as the interval between successful surgery and the completion of hydrocortisone replacement therapy. Cushing’s syndrome recurrence was defined as biochemical and clinical signs of hypercortisolism.

The researchers found a significant difference between Cushing’s syndrome subtypes in the likelihood of regaining adrenal function within 5 years of follow-up: The probability was 82% in ectopic Cushing’s syndrome, 58% in Cushing’s disease and 38% in adrenal Cushing’s syndrome (P=.001). Among the 52 participants who recovered adrenal function, the median type to recovery also differed between subtypes and was 0.6 years in ectopic Cushing’s syndrome, 1.4 years in Cushing’s disease and 2.5 years in adrenal Cushing’s syndrome (P=.002).

An association also was found between younger age and adrenal recovery in the Cushing’s disease participants (P=.012).

This association was independent of sex, BMI, symptom duration, basal adrenocorticotropic hormone and cortisol levels. No association was seen between adrenal recovery and length of hypercortisolism or postoperative glucocorticoid replacement dosage.

“It is the main finding of this series that the median duration of tertiary adrenal insufficiency was dependent on the etiology of [Cushing’s syndrome]: It was shortest in the ectopic [Cushing’s syndrome], intermediate in [Cushing’s disease] and longest in adrenal [Cushing’s syndrome] caused by unilateral cortisol producing adenoma,” the researchers wrote. “The significant difference to [Cushing’s disease] is an unexpected finding since by biochemical means cortisol excess is generally less severe in adrenal [Cushing’s syndrome]. If confirmed by others, our data have clinical impact for the follow-up of patients after curative surgery: Patients should be informed that adrenocortical function may remain impaired in benign conditions such as cortisol-producing adenoma.”

Disclosure: The study was funded in part by the Else Kröner-Fresenius Stiftung.

The original article is here: Healio

Some Lifestyle Tips for Cushing’s Syndrome

There are some ideas in the post below and some at http://www.cushings-info.com/index.php?title=Help_Yourself,_Part_1 (and also parts 2 and 3!)

Do you have any other helpful tips for the New Year?

Below is from https://www.endocrineweb.com/conditions/cushings-syndrome/4-lifestyle-tips-cushings-syndrome

As part of your overall Cushing’s syndrome treatment plan, there are some lifestyle tips you can incorporate to help you live well with Cushing’s syndrome.

Below are 4 lifestyle tips you can integrate into your recovery plan from Cushing’s syndrome. Have a conversation with your doctor before making any major changes, such as starting to exercise regularly.

  1. Eat smart. Make sure you’re eating nutritious foods. Of course, you should focus on eating fruits and vegetables, which are high in anti-oxidants, but also eat whole grains, lean protein, and healthy fats. These foods fuel your body by giving you healthy doses of energy.

    Also, be sure you get enough calcium and vitamin D in your diet. These nutrients help strengthen bones (important because bone loss is common with people who have Cushing’s syndrome). If you don’t get enough of these in your diet, talk to your doctor about taking calcium and vitamin D supplements.

    A registered dietitian (RD) can help you create a balanced meal plan—the key word here is “balanced.” Yes, you can still eat the foods you love (in moderation), but it’s important to eat foods that boost your health. An RD can also help you lose extra weight you gained from Cushing’s syndrome.

  2. Exercise gently. Exercise plays a significant role in any healthy lifestyle, but it’s important for you not to rush into it. Even if you think you’re feeling better, your body still needs time to heal.

    Start off slowly-you may want to try low—impact exercise, such as water aerobics, tai chi, or yoga. These exercises gently re-build your muscles and joints. From there, you can work up to a more moderate-paced exercise routine. You can also work with a personal trainer who can customize a workout plan for you.

    Exercising should be comfortable. If you experience pain or any new symptoms when exercising, talk to your doctor right away.

  3. Keep tabs on your mental health. Your mental health can take a toll when you have Cushing’s syndrome—depression is common. If you feel blue or you don’t feel like doing the things you used to and you’re not sure why, don’t ignore it. Talk to your doctor—he or she can recommend a psychologist who can help you cope with your feelings throughout your recovery.

    You may also want to keep a journal to record how you feel on a day-to-day basis.

  4. Give yourself a break. Don’t be hard on yourself as your body recovers from Cushing’s syndrome. It’s important to get plenty of rest, relaxation, and sleep. Treat yourself to a gentle massage, warm bubble bath, or listen to soothing music. Now’s not the time to push yourself—respect your body and its limits.

Incorporating these lifestyle tips into your routine can not only help you live well, but they can help you thrive with Cushing’s syndrome.

Cushing’s Syndrome Etiology Affects Adrenal Function Recovery

The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing’s disease (CD), adrenal CS and ectopic CS.

Design:

We performed a retrospective analysis based on the case records of 230 CS patients in our tertiary referral center treated from 1983 to 2014. The mean follow-up time was 8 years.

The probability of recovering adrenal function within a 5 years follow-up differed significantly between subtypes (p=0.001). It was 82 % in ectopic CS, 58 % in Cushing’s disease and 38 % in adrenal CS. In the total cohort with restored adrenal function (n=52) the median time to recovery differed between subtypes: 0.6 (IQR 0.03–1.1) years in ectopic CS, 1.4 (IQR 0.9–3.4) years in CD, and 2.5 (IQR 1.6–5.4) years in adrenal CS (p=0.002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio 0.896, 95% CI 0.822–0.976, p=0.012), independently of sex, BMI, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses.

Conclusions:

Time to recovery of adrenal function is dependent on the underlying etiology of CS.