Novel Mediators of the Lipodystrophy and Metabolic Consequences of Cushing's Disease

NCT ID: NCT03817840

Last Updated: 2024-06-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 8 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-07-16
• Study Completion Date: 2021-07-01

Brief Summary

This proposal will evaluate the glucocorticoid mediated changes in body fat distribution and metabolism that occur in patients with Cushing's disease. The objective is to identify the mechanisms that influence both the accumulation of lipodystrophic fat and also the changes in energy expenditure and metabolism that accompany them. The study is designed to determine if the high cortisol and AgRP levels in the blood of people living with Cushing's syndrome, either from taking steroid medications or from tumors, impact body fat and metabolism by turning off brown fat, which is a type of fat that increases one's metabolism.

Detailed Description

Cushing's disease (CD) is a disorder of chronic glucocorticoid (GC) excess that gives rise to a constellation of metabolic comorbidities and to a distinct lipodystrophic body habitus characterized by central adiposity, extremity wasting, and the accumulation of supraclavicular (SC) and dorsocervical (DC) fat in the region where human brown and beige adipose tissue is known to be concentrated. In spite of the recognized thermogenic capacity of select cervical adipocytes, the potential impact of lipomatous alterations in this depot on energy balance and metabolism in CD is unknown. To our knowledge, the "buffalo hump" and the supraclavicular fat pads - which are a sensitive physical finding for CD, have never been phenotypically characterized and the mechanisms underlying the GC mediated development of fat in these depots and the associated metabolic complications have not been explored in humans. The proposed research will advance our understanding of Cushing's lipodystrophy and its metabolic complications. Furthermore, it may lead to the identification of novel mediators and targetable pathways to attenuate the adverse effects of hypercortisolism on body composition and metabolism in CD, as well as in the significant population of patients treated with chronic GCs for an array of other clinical conditions. These findings may have important implications not only for those with Cushing's disease, but for the millions of Americans who are treated with chronic glucocorticoids for an array of clinical conditions.

Conditions

Cushing's Syndrome

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Treatment of Cushing's

Surgical resection of ACTH-secreting tumor to achieve cure of hypercortisolism

Intervention Type: PROCEDURE

Other Intervention Names

Medical treatment of hypercortisolism

Eligibility Criteria

Inclusion Criteria

1. Aged 18-70 yrs

2. Body mass index (BMI) <35 kg/m2

3. Urine free cortisol (UFC) ≥150ug/d

4. Pituitary tumor >6mm on MRI or an inferior petrosal sinus sampling with central to peripheral plasma adrenocorticotropic hormone (ACTH) gradient

5. Normal renal and thyroid function

6. HbA1c ≤8.0.

Exclusion Criteria

1. Smoking

2. Alcohol >2 drinks/day

3. Uncontrolled hypertension

4. HIV given potential for lipodystrophic confounding

5. Pregnancy and nursing

6. Use of beta-blockers, β-adrenergic or diabetes medications other than insulin

7. History of claustrophobia or difficulty lying flat

8. In-dwelling metal hardware.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York Obesity and Nutrition Research Center

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gabrielle Page-Wilson, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Neuroendocrine Unit

New York, New York, United States

Countries

United States

Other Identifiers

AAAR7901

Identifier Type: -

Identifier Source: org_study_id