Cushing Syndrome Test Choice Should Fit Patient Factors & Disease Stage

Posted on October 20, 2025 by MaryO

Caused by excessive exposure to the hormone cortisol, endogenous Cushing syndrome (CS) is difficult to diagnose. Currently available biochemical tests that assess cortisol production have limited diagnostic specificity and sensitivity, and their performance can vary depending on the patient, according to a review article in Current Opinion in Endocrinology, Diabetes and Obesity.

“Whether performed on blood, urine, saliva, or hair, all biochemical tests for CS have advantages and disadvantages. It is therefore essential to select them based on the individual characteristics of the patient and the stage of the disease in order to improve their diagnostic performance,” wrote corresponding author Antoine Tabarin, MD, and coauthor Amandine Ferriere, MD, of the University Hospital of Bordeaux in Pessac, France.

The Endocrine Society recommends initial screening of patients with suspected CS using 24-hour urinary-free cortisol (UFC), late-night salivary cortisol (LNSC), or the overnight dexamethasone suppression test (ONDST). To avoid false negatives from variability in cortisol production, UFC and LNSC tests should be performed twice.

Among the three screening options, meta-analysis findings suggest comparable diagnostic performance, the authors reported.

“However, they also concluded that these investigations should not be used indiscriminately,” the review continued, “and should be selected according to various circumstances.”

ONDST results can be affected by medications, age, a history of bariatric surgery, and even individual differences in dexamethasone metabolism, according to the review. UFC requires patient education and a complete 24-hour urine collection. LNSC testing, which biochemically assesses the loss of circadian rhythmicity consistent in CS, may not be appropriate for people with highly variable sleep schedules, including shift workers.

For early detection of Cushing disease (CD) recurrence after pituitary surgery, LNSC is the recommended first-line procedure for biochemical follow-up. LNSC is also the tool of choice for monitoring patients with CS treated with medication, the article reported.

For patients with adrenocorticotropic hormone (ACTH)-dependent CS, UFC offers high accuracy for assessing the likelihood of CD and ectopic adrenocorticotropin. However, for the diagnosis of cyclical or intermittent CS, repeat UFC tests are “cumbersome and nearly impossible,” the authors wrote.

LNSC, on the other hand, allows for frequent daily assessment of cortisol secretion which is helpful for identifying cyclical CS. Similarly, measurements of cortisol and cortisone levels in the hair can assess mid- to long-term tissular exposure to cortisol and signal cyclical CS as well, the review explained.

References

Ferriere A, et al. Curr Opin Endocrinol Diabetes Obes. 2025;32(5):233-239. doi:10.1097/MED.0000000000000923

From https://www.physiciansweekly.com/post/cushing-syndrome-test-choice-should-fit-patient-factors-disease-stage

Filed under: Cushing's, Diagnostic Testing | Tagged: , , , , | Leave a comment »

Osilodrostat-associated Adrenal Gland Shrinkage: a Case Series of Patients with ACTH-Dependent Cushing’s Syndrome

Posted on October 18, 2025 by MaryO

The Journal of Clinical Endocrinology & Metabolism, dgaf552, https://doi.org/10.1210/clinem/dgaf552

Abstract

Context

Medical therapy for Cushing’s syndrome (CS) is increasingly used. A potent adrenal steroidogenesis inhibitor, osilodrostat, has been rarely linked to prolonged adrenal insufficiency (AI).

Objective

We hypothesized that osilodrostat-induced adrenal insufficiency could be associated with adrenal gland shrinkage.

Design

Non-interventional, retrospective, longitudinal, IRB-approved study of patients with CS treated at Oregon Health and Science University between January 1, 2000 and July 1, 2025.

Setting

Ambulatory and inpatient, academic, quaternary medical center.

Patients or Other Participants

Patients with ACTH-dependent CS, treated with osilodrostat for >3 months, and CT imaging before and after osilodrostat available for adrenal volume (AV) measurement.

Intervention(s)

Age, sex, osilodrostat doses and duration, laboratory data and AI were recorded. AV was calculated using manual segmentation on CT images by a board-certified radiologist.

Main Outcome Measure(s)

AV before and after initiation of osilodrostat was expressed as percent reduction.

Results

10 patients (5 ectopic CS, 4 unknown ACTH source, 1 Cushing’s disease) were included. Osilodrostat mean starting, maximum and final doses: 7.7, 13.8 and 5.9 mg/day, respectively, over 23 months. Four patients received block-and-replace regimen, AI developed in 5. Adrenal gland volume decreased by 46.7±22.2% from 25.5±9.9 ml to 12.7±6.4 ml, p<0.001 over a median of 19 months. AV reduction positively correlated with maximum osilodrostat dose, r=0.626, p=0.027.

Conclusions

We found that in selected patients with ACTH-dependent CS, osilodrostat can induce significant adrenal shrinkage, with or without AI. Further confirmation by larger studies of different CS types and monitoring for AI is required for all patients.

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

Sleep Disturbances in Patients With Cushing Syndrome and Mild Autonomous Cortisol Secretion

Posted on October 16, 2025 by MaryO

The Journal of Clinical Endocrinology & Metabolism, dgaf553, https://doi.org/10.1210/clinem/dgaf553

Abstract

Context

The impact of active hypercortisolism on sleep is incompletely characterized. Studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate mild nocturnal hypercortisolism that could impact sleep.

Objectives

To characterize sleep abnormalities in patients with CS and MACS using the Pittsburgh Sleep Quality Index (PSQI), identify factors associated with poor sleep, and compare sleep abnormalities in patients with MACS versus referent subjects.

Methods

We conducted a single-center cross-sectional study of adults with active CS and MACS. Clinical and biochemical severity scores for hypercortisolism were calculated. Parallelly, we enrolled referent subjects. Quality of life was assessed using 1) Short Form-36 in all participants, and 2) Cushing QoL in patients with active hypercortisolism. Sleep quality was assessed using PSQI.

Results

PSQI was assessed in 154 patients with CS (mean 12, SD ±4.5), 194 patients with MACS (mean 11, SD 4.6), and 89 referents (mean 5, SD ±3.4). Patients with MACS exhibited shorter sleep duration, longer sleep latency, more severe daytime dysfunction, lower sleep efficiency, and a higher sleep medication use compared to referent subjects (P = <0.001 for all). Age-, sex, and BMI adjusted analysis demonstrated no differences in PSQI or its subcomponents between patients with CS and MACS (P >0.05 for all). In a multivariable analysis of patients with MACS, younger age, female sex and higher clinical hypercortisolism severity score were associated with impaired sleep. In patients with CS, only younger age was associated with poor sleep.

Conclusions

Patients with MACS demonstrate sleep impairment that is similar to patients with CS. Younger women with higher clinical severity of MACS are more likely to have impaired sleep.

Filed under: Cushing's, symptoms | Tagged: , , , | Leave a comment »

Millennial Woman Hasn’t Slept the Night in 19 Months—Viewers Shocked Why

Posted on October 14, 2025 by MaryO

“I haven’t had a proper night’s sleep in 19 months,” Aleksa Diaz told Newsweek. “Even if I’m physically exhausted, I can’t fall asleep. I wake up more than ten times a night—fully conscious. I only get about two to four hours of broken sleep.”

The 30-year-old from Austin, Texas, has shared her experience on TikTok (@aleksaheals) earning 94,000 views. During the video, she points out that she has not “crashed” once and wonders how her body is continuing to function.

Diaz says that her insomnia began in January 2024 and is linked to a benign tumor in her pituitary gland—a small, hormone-producing gland at the base of the brain—known as a pituitary adenoma.

According to the American Brain Tumor Association (ABTA), about 13,770 pituitary tumors are diagnosed each year in the U.S., accounting for roughly 17 percent of all primary tumors in the central nervous system (CNS).

Symptoms of Pituitary Tumors

Pituitary tumors and cysts typically arise from two main causes: pressure on the gland and surrounding structures, or overproduction of hormones. The severity and type of symptoms depend on the tumor’s size and the specific hormones involved.

The ABTA notes that when the tumor presses on the pituitary gland or nearby structures, it can lead to:

  • Headaches
  • Visual loss
  • Hair loss
  • Diminished libido
  • Weight fluctuations
  • Skin changes
  • Fatigue or low energy

Symptoms Caused by Excess Hormone Production

Approximately 70 percent of pituitary tumors are “secreting,” meaning they release excess hormones. These include:

  • Growth hormone: Overproduction can cause localized excess growth (‘acromegaly’) in adults and gigantism in children.
  • Prolactin: Leads to menstrual changes and abnormal milk production.
  • Sex hormones: Can cause menstrual irregularities and sexual dysfunction.
  • Thyroid hormones: Can trigger hyperthyroidism, with symptoms such as weight loss, heart rhythm changes, anxiety, bowel changes, fatigue, thinning skin and sleep problems.
  • Adrenal hormones: Excess can lead to Cushing’s disease, characterized by a moon-shaped face, excess body hair, easy bruising, menstrual irregularities and high blood pressure.

A Long Road to Diagnosis

Diaz told Newsweek that she has experienced many of these symptoms, beginning with severe hair loss at just 18.

“I started to feel off and suddenly began losing hair,” she recalled. “I was shedding over 300 hairs a day—just brushing my hair or running my fingers through it.”

Initially, doctors diagnosed her with polycystic ovary syndrome (PCOS). “I didn’t have any other symptoms, but I just thought it must be what they said,” Diaz explained.

By the time she turned 22, the hair loss was severe and unrelenting.

“It wasn’t stopping,” she said. “I went to a dermatologist and had a brain MRI—then they found a 5mm tumor on my pituitary gland.”

Around the same time, Diaz began gaining weight that wouldn’t budge despite dieting and regular exercise.

“I developed depression and always had a puffy, inflamed face,” she said. “The hair loss was causing me a lot of self-esteem issues.”

Over the years, Diaz’s symptoms multiplied—dry skin, dry eyes, low libido, anxiety, twitching legs and hip pain after exercise. She estimates she has consulted around 40 doctors and spent 500–600 hours researching her condition.

In 2018, she was formally diagnosed with a pituitary adenoma and prescribed metformin to lower hormone levels. “They told me to wait and see,” she said. When her insomnia worsened, Diaz suspected the tumor was causing multiple hormone-related conditions, but doctors did not confirm it.

By January 2024, she noticed new symptoms: vaginal dryness, hip pain and worsening sleep. Tests revealed her estrogen was abnormally low for her age.

“I take medication for that now and progesterone too,” she said. After years of trying everything—dermatologists, supplements and expensive hair treatments—she finally saw some hair regrowth.

Still, Diaz’s diagnosis of hypopituitarism means her pituitary gland underproduces several critical hormones.

The ABTA notes that doctors often recommend monitoring small tumors, since they typically grow slowly and cause no symptoms. But Diaz, whose tumor is 5 mm, disagrees.

She said: “Doctors believe that because the tumor is under 1 cm it can’t possibly be causing enough symptoms to risk doing surgery. The main risk is developing another hormone deficiency post-op.

“However, surgeons who do this surgery say it’s routine and not super risky, so it’s confusing as a patient.

“Cases like mine of mild hypopituitarism are often ignored, leading to a slow progression of hormone deficiencies—the very thing that is a risk of surgery.”

When she was 29, Diaz started taking hormone replacement therapy (HRT)—a treatment that replaces female hormones, mainly estrogen and progesterone, which fall to low levels during menopause.

She told Newsweek: “Doctors don’t understand why I’m basically in menopause. We don’t know the risks of long-term HRT. The medications make me feel better, but it’s not safe as a long-term solution.”

Living with the Emotional Toll

Alongside her physical symptoms, Diaz has developed severe depression and feels “literally running on empty.”

“I feel like I have hope for the future only when I manage a decent night’s sleep,” she said. “I don’t want to see anyone or socialize. I haven’t gone out in six months. It’s affected my job—I was almost fired in March.

“I’ve become very forgetful, I miss meetings and tasks and I sometimes can’t remember what I did yesterday. It’s like I have severe ADHD, but it’s not.”

A Call for Change in Treatment

Now financially and emotionally exhausted, Diaz fears what will happen if she continues to be denied further testing or surgical treatment.

“I’m worried something will happen to me,” she said. “I’ve reached my limit financially. My physical and mental health are exhausted.”

Diaz believes her struggle is far from unique. “From the time you have symptoms to when you get a diagnosis it can take 10 years,” she said.

“A lot of women have expressed they don’t feel like they are being taken seriously—and that has been my experience. Being young is a disadvantage. I’m on six medications now to manage my hormones. I’ve lost weight and my hair is growing back, so doctors think I must be fine. But they don’t see what’s really going on.”

Do you have a tip on a health story that Newsweek should be covering? Do you have a question about pituitary tumors? Let us know via health@newsweek.com.

https://www.newsweek.com/millennial-woman-sleep-insomnia-pituitary-tumor-10821739

Filed under: Interview, Rare Diseases | Tagged: , , , , , , , | Leave a comment »

The Impact of Adrenalectomy On Metabolic Outcomes of Patients Wwth Mild Autonomous Cortisol Secretion Defined by Low-Dose Dexamethasone Suppression Testing

Posted on October 12, 2025 by MaryO

Abstract

Background

Up to 50% of patients with adrenal incidentalomas have mild autonomous cortisol secretion, which may increase their cardiometabolic morbidity, compared with patients with nonfunctional adrenal tumors. Studies evaluating cardiometabolic outcomes of patients with mild autonomous cortisol secretion defined by 1-mg dexamethasone suppression testing (cortisol 1.8–5 μg/dL) have demonstrated mixed results. The aim of this study was to assess the metabolic outcomes of patients with mild autonomous cortisol secretion, defined by the 1-mg dexamethasone suppression testing criterion, compared with patients with nonfunctional adrenal tumors who underwent adrenalectomy.

Methods

We conducted a single-institution retrospective cohort study comparing adult patients who underwent unilateral adrenalectomy from November 30, 2011, to August 19, 2023, for mild autonomous cortisol secretion (1-mg dexamethasone suppression testing cortisol 1.8–5 μg/dL) or nonfunctional adrenal tumors (1-mg dexamethasone suppression testing cortisol <1.8 μg/dL). Preoperative prevalences and postoperative changes in diabetes mellitus, hypertension, dyslipidemia, and elevated body mass index (≥25) were assessed. Patients were followed from the time of surgery until their last outpatient visit. Multivariable logistic regression was pursued for outcomes that varied between cohorts.

Results

A total of 65 patients (53 mild autonomous cortisol secretion and 12 nonfunctional adrenal tumors) were analyzed. Patients with mild autonomous cortisol secretion were older and more likely to have diabetes mellitus than patients with nonfunctional adrenal tumors (odds ratio: 7.81, 95% confidence interval [0.94, 64.96], P = .04). Patients were followed for a median of 28.1 months [11.1, 55.3 months]. Patients with mild autonomous cortisol secretion were more likely to have postoperative weight improvement (odds ratio: 8.31, [0.97, 71.14], P = .03). After adjusting for clinically relevant variables, the 1-mg dexamethasone suppression testing cortisol was predictive of postoperative weight improvement (odds ratio: 1.88, [1.1, 3.65], P = .04).

Conclusion

Weight loss should be considered as a potential benefit of adrenalectomy in patients with mild autonomous cortisol secretion.

Introduction

Mild autonomous cortisol secretion (MACS) is the most common hormonal abnormality diagnosed in patients with adrenal incidentalomas, impacting 20%–50% of patients.1 Patients with MACS have biochemical evidence of adrenocorticotropic hormone (ACTH)-independent hypercortisolism but lack clinical stigmata commonly associated with overt hypercortisolism, such as facial plethora, abdominal adiposity, extremity weakness and wasting, and/or violaceous striae.2 Overt hypercortisolism is well recognized to cause cardiovascular, musculoskeletal, and metabolic disorders, which have variable resolution even after diagnosis and treatment.3 There is a growing body of evidence that patients with MACS also have increased cardiometabolic morbidity and mortality compared with patients with nonfunctional adrenal tumors,4 but this evidence is challenging to interpret given wide variability in diagnostic criteria that have historically been used.5, 6, 7
Recent guidelines have suggested that a diagnosis of MACS be applied to all patients with a morning (AM) serum cortisol of >1.8 μg/dL after low-dose (1-mg) dexamethasone suppression testing (DST) who lack overt features of hypercortisolism.8,9 However, prior studies comparing cardiometabolic outcomes between patients with MACS and nonfunctional adrenal tumors as well as between patients who underwent operative and nonoperative management have used a 1-mg DST AM serum cortisol of 1.8–5.0 μg/dL as a definition of mild (“subclinical”) hypercortisolism.10, 11, 12, 13, 14, 15, 16 Given that these studies have demonstrated mixed results,4 the primary aim of this study was to assess the metabolic outcomes of patients with MACS, as defined by a 1-mg DST AM cortisol of 1.8–5.0 μg/dL, compared with patients with nonfunctional adrenal tumors who underwent adrenalectomy.

Section snippets

Methods

This was a single-institution retrospective cohort study of patients aged ≥18 years who underwent initial unilateral adrenalectomy from November 30, 2011, to August 19, 2023. Patients were identified through a prospectively maintained database of all patients who underwent adrenalectomy at the study institution. Patients were excluded if they had a 1-mg DST AM serum cortisol of >5 μg/dL, ACTH-dependent hypercortisolism, primary aldosteronism, pheochromocytoma, primary bilateral macronodular

Results

Of the 460 patients who underwent adrenalectomy during the study period, 53 patients met criteria for MACS and 12 patients for nonfunctional adrenal tumors, yielding a cohort of 65 patients. Patients with MACS were older than those with nonfunctional adrenal tumors (MACS, median 60 years [IQR: 54, 68 years] vs nonfunctional adrenal tumors, 49 years [37, 57 years], P = .02) but were similar by sex, race, ethnicity, BMI, nodule size, laterality, and surgical approach (Table II). Among patients

Discussion

MACS is the most common hormonal abnormality diagnosed in patients with adrenal incidentalomas. Despite lacking clinical stigmata of overt hypercortisolism, patients with MACS appear to have increased cardiometabolic morbidity and mortality similar to patients with overt hypercortisolism. The optimal management of MACS is debated, and prior studies using a 1-mg DST AM serum cortisol of 1.8–5.0 μg/dL as a definition of mild hypercortisolism have demonstrated mixed results. Hence, this study

Funding/Support

This project is funded in part by the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through grant number UL1TR001436. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The grant supports the creation and maintenance of

CRediT authorship contribution statement

Alexa Lisevick Kumar: Writing – original draft, Visualization, Methodology, Formal analysis, Data curation, Conceptualization. Sophie Dream: Writing – review & editing, Validation, Supervision, Methodology, Investigation. Tahseen Shaik: Resources, Project administration, Investigation, Data curation. Kara Doffek: Resources, Project administration, Investigation, Data curation. Ryan Conrardy: Writing – review & editing, Methodology, Formal analysis. James W. Findling: Writing – review & editing,

Conflict of Interest/Disclosure

Dr Findling reports consulting for Corcept, Diurnal, Crinetics and serving as an investigator for Recordati. The rest of the authors reported no biomedical financial interests or potential conflicts of interest.

References (34)

  • T. Deutschbein et al.

    Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study

    Lancet Diabetes Endocrinol

    (2022)
  • A. Prete et al.

    Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches

    Nat Rev Endocrinol

    (2024)
  • L.K. Nieman

    Cushing’s syndrome: update on signs, symptoms and biochemical screening

    Eur J Endocrinol

    (2015)
  • S. Puglisi et al.

    Long-term consequences of cushing syndrome: a systematic literature review

    J Clin Endocrinol Metab

    (2024)
  • I.C.M. Pelsma et al.

    Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis

    Eur J Endocrinol

    (2023)
  • X. Ren et al.

    Evaluating the efficacy of surgical and conservative approaches in mild autonomous cortisol secretion: a meta-analysis

    Front Endocrinol (Lausanne)

    (2024)
  • M.M. Khadembashiri et al.

    Comparison of adrenalectomy with conservative treatment on mild autonomous cortisol secretion: a systematic review and meta-analysis

    Front Endocrinol

    (2024)
  • Y.S. Elhassan et al.

    Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess

    Ann Intern Med

    (2019)
  • M. Fassnacht et al.

    European society of endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European network for the study of adrenal tumors

    Eur J Endocrinol

    (2023)
  • L. Yip et al.

    American association of endocrine surgeons guidelines for adrenalectomy: executive summary

    JAMA Surg

    (2022)

 

Filed under: adrenal, Clinical trials | Tagged: , , , | Leave a comment »

« Previous Page — Next Page »