Metabolomic Biomarkers in Urine of Cushing’s Syndrome Patients

Posted on January 29, 2026 by MaryO
Int. J. Mol. Sci. 2017, 18(2), 294; doi:10.3390/ijms18020294 (registering DOI)

Alicja Kotłowska 1,* , Tomasz Puzyn 2, Krzysztof Sworczak 3, Piotr Stepnowski 4 and Piotr Szefer 1

1 Department of Food Sciences, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
2 Laboratory of Environmental Chemometrics, Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
3 Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
4 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.

 

Keywords: Cushing’s syndrome; metabolomics; multivariate analysis; biomarkers; steroid hormones; urinary profiling; gas chromatography; linear discriminant analysis
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

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Cushing’s Syndrome Subtype Affects Postoperative Time to Adrenal Recovery

Posted on January 25, 2026 by MaryO

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

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COVID-19 May Be Severe in Cushing’s Patients

Posted on January 23, 2026 by MaryO

A young healthcare worker who contracted COVID-19 shortly after being diagnosed with Cushing’s disease was detailed in a case report from Japan.

While the woman was successfully treated for both conditions, Cushing’s may worsen a COVID-19 infection. Prompt treatment and multidisciplinary care is required for Cushing’s patients who get COVID-19, its researchers said.

The report, “Successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia,” was published in Endocrine Journal.

Cushing’s disease is caused by a tumor on the pituitary gland, which results in abnormally high levels of the stress hormone cortisol (hypercortisolism). Since COVID-19 is still a fairly new disease, and Cushing’s is rare, there is scant data on how COVID-19 tends to affect Cushing’s patients.

In the report, researchers described the case of a 27-year-old Japanese female healthcare worker with active Cushing’s disease who contracted COVID-19.

The patient had a six-year-long history of amenorrhea (missed periods) and dyslipidemia (abnormal fat levels in the body). She had also experienced weight gain, a rounding face, and acne.

After transferring to a new workplace, the woman visited a new gynecologist, who checked her hormonal status. Abnormal findings prompted a visit to the endocrinology department.

Clinical examination revealed features indicative of Cushing’s syndrome, such as a round face with acne, central obesity, and buffalo hump. Laboratory testing confirmed hypercortisolism, and MRI revealed a tumor in the patient’s pituitary gland.

She was scheduled for surgery to remove the tumor, and treated with metyrapone, a medication that can decrease cortisol production in the body. Shortly thereafter, she had close contact with a patient she was helping to care for, who was infected with COVID-19 but not yet diagnosed.

A few days later, the woman experienced a fever, nausea, and headache. These persisted for a few days, and then she started having difficulty breathing. Imaging of her lungs revealed a fluid buildup (pneumonia), and a test for SARS-CoV-2 — the virus that causes COVID-19 — came back positive.

A week after symptoms developed, the patient required supplemental oxygen. Her condition worsened 10 days later, and laboratory tests were indicative of increased inflammation.

To control the patient’s Cushing’s disease, she was treated with increasing doses of metyrapone and similar medications to decrease cortisol production; she was also administered cortisol — this “block and replace” approach aims to maintain cortisol levels within the normal range.

The patient experienced metyrapone side effects that included stomach upset, nausea, dizziness, swelling, increased acne, and hypokalemia (low potassium levels).

She was given antiviral therapies (e.g., favipiravir) to help manage the COVID-19. Additional medications to prevent opportunistic fungal infections were also administered.

From the next day onward, her symptoms eased, and the woman was eventually discharged from the hospital. A month after being discharged, she tested negative for SARS-CoV-2.

Surgery for the pituitary tumor was then again possible. Appropriate safeguards were put in place to protect the medical team caring for her from infection, during and after the surgery.

The patient didn’t have any noteworthy complications from the surgery, and her cortisol levels soon dropped to within normal limits. She was considered to be in remission.

Although broad conclusions cannot be reliably drawn from a single case, the researchers suggested that the patient’s underlying Cushing’s disease may have made her more susceptible to severe pneumonia due to COVID-19.

“Since hypercortisolism due to active Cushing’s disease may enhance the severity of COVID-19 infection, it is necessary to provide appropriate, multidisciplinary and prompt treatment,” the researchers wrote.

From https://cushingsdiseasenews.com/2021/01/15/covid-19-may-be-severe-cushings-patients-case-report-suggests/?cn-reloaded=1

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Cushing’s Syndrome Etiology Affects Adrenal Function Recovery

Posted on January 21, 2026 by MaryO
Abstract
Context:
Successful tumor resection in endogenous Cushing’s syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy.
Objective:

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.

Patients:
We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented follow-up after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analogue treatment, and malignant adrenal disease.
Results:

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.

Affiliations
  • 1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Germany;
  • 2Institut für Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universität München, Germany;
  • 3Chirurgische Klinik und Poliklinik – Innenstadt, Klinikum der Ludwig-Maximilians-Universität München, Germany;
  • 4Klinik für Neurochirurgie, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Germany;
  • 5IMSE, Klinikum rechts der Isar der TU München, München, Germany

From http://press.endocrine.org/doi/abs/10.1210/jc.2014-3632

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CV risk elevated in patients with adrenal incidentalomas, mild hypercortisolism

Posted on January 17, 2026 by MaryO

Patients with adrenal incidentalomas and mild hypercortisolism have an increased risk for cardiovascular events and mortality. This risk was evident even when clinical signs of overt hypercortisolism were not present, according to data published in The Lancet Diabetes & Endocrinology.

“Our findings are important because they add to the previously scant information about adrenal incidentalomas, which will be of use to doctors who are seeing an increasing number of patients with these masses,” Renato Pasquali, MD, of the S. Orsola-Malpighi Hospital in Bologna, Italy, said in a press release.

The retrospective study by Pasquali and colleagues assessed the adrenal incidentalomas of 198 outpatients treated every 18 to 30 months, with a mean follow-up of 7.5 years. At the time of follow-up, 114 patients demonstrated stable non-secreting adrenal incidentalomas (<50 nmol/L), 61 had either a stable intermediate phenotype (50 nmol/L-138 nmol/L) or subclinical Cushing’s syndrome (>138 nmol/L), and 23 patients had worsening pattern of secretion.

The incidence of CV events appeared higher in patients with a stable intermediate phenotype or subclinical Cushing’s syndrome (6.7% vs. 16.7%; P=.04) and in those with worsened secreting patterns (6.7% vs. 28.4%; P=.02) compared with patients with stable non-secreting adrenal incidentalomas, according to data.

In addition, CV events were independently related to changes in cortisol concentrations after the 1-mg dexamethasone suppression test (DST; HR=1.13; 95% CI, 1.05-1.21) from baseline to follow-up.

Patients with stable intermediate phenotype adrenal incidentalomas (57%) or subclinical Cushing’s syndrome (91.2%) tended to have lower survival rates for all-cause mortality (P=.005), researchers wrote. The main risk factors for all-cause mortality were age (HR=1.06; 95% CI, 1.01-1.12) and mean concentrations of cortisol after DST (HR=1.1; 95% CI, 1.01-1.19).

The unadjusted survival for CV-related mortality was lower in patients with either a stable intermediate phenotype (97.5%) or subclinical Cushing’s syndrome (78.4%; P=.02) vs. those with stable non-secreting adrenal incidentalomas (97.5%), and patients with worsened secreting patterns (60%; P=.01).

In an accompanying comment, Rosario Pivonello, MD, PhD, Maria Cristina De Martino, PhD, and Annamaria Colao, MD, PhD, of the Federico II University of Naples, Italy, wrote that the study supports the importance of long-term hormonal follow-up for clinical management of patients with adrenal incidentalomas.

“Furthermore, clinical monitoring of cardiometabolic risks seems to be important in these patients, particularly in those with subclinical Cushing’s syndrome and intermediate phenotype adrenal incidentalomas, for whom medical or surgical intervention could be needed,” they wrote.

They suggest long-term prospective studies to determine the frequency of new CV events and mortality in this patient population.

For more information:

Di Dalmazi G. Lancet Diabetes Endocrinol. 2014;doi:10.1016/S2213-8587(13)70211-0.

Pivonello R. Lancet Diabetes Endocrinol. 2014;doi:10.1016/S2213-8587(13)70190-6.

Disclosure: The researchers report no relevant financial disclosures.

This article is from http://www.healio.com/endocrinology/adrenal/news/online/%7B85f94352-9529-4cb7-9532-9c4518f77d80%7D/cv-risk-elevated-in-patients-with-adrenal-incidentalomas-mild-hypercortisolism

 

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