Recovery From Cushing Syndrome and Mild Autonomous Cortisol Secretion (MACS)

Cushing syndrome (CS) is an endocrine disorder caused by chronic exposure to glucocorticoid (GC) excess. Endogenous CS has an estimated incidence of 0.2 to 5.0 cases per million per year and prevalence of 39 to 79 cases per million in various populations. CS usually affects young women, with a median age at diagnosis of 41.4 with a female-to-male ratio of 3:1. Following a curative surgery for CS, patients develop adrenal insufficiency and require GC replacement postoperatively until the hypothalamic-pituitary-adrenal (HPA) axis recovery occurs. Factors, such as age, gender, BMI, subtypes of CS, duration of symptoms, clinical and biochemical severity and postoperative GC dose have been reported to affect the HPA recovery in small retrospective studies. Glucocorticoid withdrawal syndrome (GWS) is a withdrawal reaction due to decrease in supraphysiological GC concentrations, which occurs after a successful surgery of CS. Glucocorticoid withdrawal syndrome (GWS) is under-recognized entity in patients undergoing curative surgery for endogenous Cushing syndrome.

In this study we aim to determine pre- and post-surgical predictors of the duration and severity of glucocorticoid withdrawal in patients undergoing a curative surgery for cortisol excess and assess the effect of MUSE intervention on GWS severity in patients undergoing curative surgery for CS as compared to standard of care.

Study Overview

• Status: Recruiting
• Conditions: Cushing Syndrome
• Intervention / Treatment: Other: MUSE biofeedback

Detailed Description

Specific Aim 1: To determine pre- and post-surgical predictors of the duration and severity of glucocorticoid withdrawal in patients undergoing a curative surgery for cortisol excess Specific Aim 2: To characterize the timing and recovery of hypercortisolism-induced signs and symptoms, proximal myopathy and tissue accumulation of Advanced Glycation End products (AGEs) in patients after a curative surgery Specific Aim 3: To assess the effect of MUSE intervention on GWS severity in patients undergoing curative surgery for CS as compared to standard of care

1. Selection of study subjects and medical records review. We will prospectively recruit adult patients with CS of any three subtypes (pituitary, adrenal or ectopic CS) and MACS undergoing a curative surgery, from the pituitary clinic. Investigator will discuss participation in the study and obtain an informed consent. We will review data for any potential risk factors through clinical interview and review of medical record. Data will include demographics, behavioral factors (smoking and alcohol consumption), past medical history (history of AI, psychiatric disorder and recent GC usage), GWS related symptoms and signs (anorexia, nausea, emesis, lethargy, somnolence, arthralgia, myalgia, fever, hypotension), and lab tests.
2. Subjects: We will enroll 100 consecutive subjects in this study who will participate in this study for up to 2 years. Inclusion and exclusion criteria are as below. We plan to have 50 subjects participate in the intervention arm with MUSE in one year, without modifying other study procedures.

3. Step-by-Step methods:

   • Patients will be identified by their clinician. Permission will be obtained from the patient in order for one of the investigators to explain the study and obtain informed written consent.
   • Baseline history, physical examination, and the necessary baseline tests will be performed based on standard of care and as considered necessary by the treating physician.
   • Medical record will be reviewed for demographic information, comorbidities, medical therapy, imaging information and biochemical testing results
   • We will use a scoring system to quantify biochemical severity, and to classify clinical abnormalities as mild, moderate and severe ( based on existent laboratory and clinical parameters).
   • At baseline, all patients will be asked to complete the Cushing QoL questionnaire, SF36 and AddiQol questionnaires (forms are attached in Document). Patients will discuss the intervention with MUSE with the study investigator. If they agree to participate in the intervention arm, they will be instructed on its use.
   • At follow up, patients will complete AddQoL survey (weekly in the first 3 months, every 4 weeks in the next 6 months, every 3 months in the next 12 months, and then every 6 months until the end of the study) and SF36 survey (every 3 months) until the end of the study. (In-person, through a paper survey or electronically using external REDCap server (user name and password protected)).
   • For patients in the intervention group, in addition to the above, at the time of enrollment, the study coordinator will help set up the MUSE application on to iPad or iPhone or Android phone (we will use generic login name and password without protected health information included). The coordinator will also go over a few helpful hints and discuss the homework log, which will need to be completed throughout the course of the study. After the surgery, patients are asked to complete the 3 minute 'focusing' exercise daily until 12 weeks after the surgery. During this time frame we will download the data from our end on a weekly basis. After 12 weeks, the frequency of the usage will be at the participant's discretion although ongoing usage is encouraged and data download should continue. In addition, we ask that patients bring iPad, iPhone or Android phone to each of the clinical visit for an app interrogation.
   • Patient will participate in the study until one of the following: 1) 2 years of follow up completed, 2) patient withdraws consent, 3) HPA axis recovery is achieved and patient weans off GC, 4) completion of the study by the principal investigator.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Vanessa Fell, MA; Phone Number: 507-266-6068; Email: fell.vanessa@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Melinda Thomas; Phone Number: 507-293-6628; Email: thomas.melinda@mayo.edu
      • Principal Investigator: Irina Bancos, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Any male or female at least 18 years of age undergoing curative surgery for Cushing's Syndrome and MACS.

Description

Inclusion Criteria:

1. age 18 and above,
2. new diagnosis of CS of any of the three subtypes (pituitary, adrenal or ectopic CS), and MACS,
3. planning for a curative surgery
4. ability to provide informed consent.

Exclusion Criteria:

1. systemic supraphysiological GC for any reason within 1 month of enrollment, for more than 2 weeks,
2. inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Standard of care CS; Patients undergoing curative surgery for any type of CS who will be followed through standard of care after surgery
MUSE intervention CS; Patients undergoing curative surgery for any type of CS who will be introduced to and provided MUSE for use after surgery	Other: MUSE biofeedback; biofeedback through a headband

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life (SF36)	Score 0-100	periodic 0-24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HPA recovery	as measured by morning cortisol. Cortisol measurement will be performes every 6-12 weeks, 24h off glucocorticoid replacement therapy starting 4 weeks-8 weeks after surgery and until cortisol is 10 mcg/dl or above ( or HPA recovery is considered impossible by investigator)	0-24 months
Myopathy measurement	as measured by hand grip. Hand grip strength will be measured 3 times on left and right, and dominant hand grip strength will be considered as an average of 3 measurements.	0-24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AGE	measurement of AGE	0-24 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Irina Bancos, MD, MS, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2019
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Pituitary; Hypercortisolism; Cushing syndrome; Cushing disease
• Additional Relevant MeSH Terms: Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Adrenal Gland Diseases; Hypothalamic Diseases; Hyperpituitarism; Adrenocortical Hyperfunction; Pituitary Diseases; Pituitary ACTH Hypersecretion; Cushing Syndrome
• Other Study ID Numbers: 19-006003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No