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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FDA Declines to Approve Relacorilant for Hypertension Linked to Hypercortisolism

Posted on January 6, 2026 by MaryO

Key takeaways:

  • The FDA issued a complete response letter for relacorilant to treat hypertension tied to hypercortisolism.
  • The investigational drug induced BP reductions for adults with hypertension in the phase 3 GRACE trial.

The FDA has issued a complete response letter for an oral selective glucocorticoid receptor antagonist under investigation for the treatment of hypertension secondary to hypercortisolism, according to an industry press release.

Corcept Therapeutics announced the FDA issued a complete response letter for relacorilant (Corcept Therapeutics). The drug is under investigation for the treatment of endogenous hypercortisolism, ovarian cancer and other disorders, according to the company.

As Healio previously reported, the phase 3 GRACE trial enrolled 152 adults with Cushing’s syndrome plus hypertension, hyperglycemia or both conditions. Participants received relacorilant for 22 weeks during an open-label phase. At 22 weeks, adults who met criteria for hypertension or hyperglycemia control entered a withdrawal phase where they were randomly assigned, 1:1, to continue relacorilant or switch to placebo for 12 weeks.

In the GRACE trial, adults with hypertension had a 7.9 mm Hg decrease in systolic blood pressure and a 5.1 mm Hg decline in diastolic BP at 22 weeks. During the randomized withdrawal phase, adults who remained on relacorilant had no change in systolic and diastolic BP, whereas those receiving placebo had a BP increase from the start of the phase to week 12.

In a press release from Corcept Therapeutics from 2024, the company announced results from the phase 3 GRADIENT trial, a randomized, double-blind, placebo-controlled trial where adults with Cushing’s syndrome caused by an adrenal adenoma or adrenal hyperplasia were randomly assigned, 1:1, to relacorilant or placebo for 22 weeks. According to the press release, the relacorilant group had a 6.6 mm Hg decline in mean systolic BP compared with baseline at 22 weeks. However, there was no significant difference in mean systolic BP change between the relacorilant and placebo groups.

As Healio previously reported, relacorilant was also assessed in a long-term extension study that enrolled adults who completed the GRACE and GRADIENT trials as well as a phase 2 hypercortisolism study. In that trial, relacorilant conferred a 10 mm Hg drop in 24-hour ambulatory systolic BP and a 7.3 mm Hg reduction in 24-hour ambulatory diastolic BP at 24 months.

In the company’s press release announcing receipt of the complete response letter, Corcept Therapeutics said the FDA acknowledged that the GRACE trial met its primary endpoint and that the GRADIENT trial provided “confirmatory evidence.” However, the FDA said it did not view relacorilant offered “a favorable benefit-risk assessment” without more data of its effectiveness, according to the press release.

“We are surprised and disappointed by this outcome,” Joseph K. Belanoff, MD, CEO of Corcept Therapeutics, said in a press release. “Our commitment to patients suffering from the effects of hypercortisolism is unwavering. I am confident we will find a way to get relacorilant to the patients it could help. We will meet with the FDA as soon as possible to discuss the best path forward.”

https://www.healio.com/news/endocrinology/20251231/fda-declines-to-approve-relacorilant-for-hypertension-linked-to-hypercortisolism?utm_source=selligent&utm_medium=email&utm_campaign=20251231ENDO&utm_content=20251231ENDO

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