The ARISE Trial Compares Whether Giving Routine Steroid Replacement or Using Targeted Blood Tests to Guide Replacement Better Protects Certain Patients From Adrenal Insufficiency After the Removal of a Diseased Adrenal Gland.

NCT07558135 | Not Yet Recruiting DMC

• 1 other identifier: IRAS 368153
• Study Type: interventional
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

Adrenalectomy is an operation to remove one of the adrenal glands. It is commonly performed to treat adrenal tumours or conditions that cause excess hormone production. The adrenal glands produce important hormones, including cortisol and aldosterone, which help regulate blood pressure, metabolism and the body's response to stress. After adrenalectomy, some patients may develop adrenal insufficiency, a condition in which the body does not produce enough of these essential hormones. In severe cases, this can lead to an Addisonian (adrenal) crisis, a life-threatening emergency that can cause shock, organ failure and death if not treated promptly. The risk of adrenal insufficiency after surgery depends largely on cortisol levels before the operation. In patients with Cushing's syndrome, where there is excessive cortisol production, the risk of adrenal insufficiency after adrenalectomy is almost 100%. For this reason, these patients routinely receive steroid replacement treatment after surgery to replace missing hormones and prevent adrenal crisis. For other patients undergoing adrenalectomy, the best management approach is less clear. Patients with mild autonomous cortisol secretion (MACS) have a moderate risk of adrenal insufficiency - around 50-65%. Patients with normal cortisol secretion (NCS) may also develop adrenal insufficiency because one adrenal gland has been removed, occurring in around 20-37% of cases. International medical guidelines currently disagree on how best to manage these patients after surgery. Some recommend measuring cortisol levels the morning after surgery and treating only if levels are low, while others recommend giving steroid treatment to all patients with mild cortisol excess. There is currently no clear guidance for patients with normal cortisol secretion. This study will compare these management strategies to determine which approach best reduces the risk of adrenal insufficiency after adrenalectomy. The study will be conducted at King's College Hospital and will run for approximately two years.

Conditions

Adrenal Gland Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of Sustained Adrenal Insufficiency at 3 Months

  The proportion of patients who fail a biochemical assessment of adrenal function. Adrenal insufficiency is defined as a peak cortisol level \<420 nmol/L following a 250 µg Short Synacthen Test (SST)

  3 months post-adrenalectomy

Study Arms (2)

Empirical Steroid Replacement (Standard Care)

ACTIVE COMPARATOR

Participants receive routine, empirical steroid replacement therapy following adrenalectomy regardless of post-operative cortisol levels. This follows the current King's College Hospital standard of care and European Society of Endocrinology / ENSAT guidance.

Drug: Empirical Hydrocortisone Protocol

Targeted Replacement (Intervention)

EXPERIMENTAL

Participants receive targeted steroid replacement based on biochemical assessment (Post-Operative Day 1 cortisol levels). Participants with normal cortisol levels do not receive steroid replacement. This follows American Association of Endocrine Surgeons guidelines.

Drug: Targeted Treatment Protocol

Interventions

Empirical Hydrocortisone Protocol DRUG

Routine administration of Hydrocortisone (e.g., 50mg-100mg IV followed by oral tapering doses) starting immediately post-adrenalectomy even in presence of normal \>300nmol/L cortisol reading on post-operative day 1.

Empirical Steroid Replacement (Standard Care)

Targeted Treatment Protocol DRUG

Administration of Hydrocortisone is withheld and the patient is monitored if Post-Operative Day 1 (POD1) serum cortisol level is \>300nmol/L and patient is asymptomatic.

Targeted Replacement (Intervention)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recommended for adrenalectomy following adrenal multidisciplinary discussion
• ≥18 years old
• Ability to consent

You may not qualify if:

• Overt Cushing's syndrome
• Pregnancy
• Pre-existing confirmed adrenal insufficiency
• Pre-existing steroid therapy (including high dose steroid inhalers)
• History of adrenalectomy
• Bilateral disease as assessed radiologically and clinically

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

MeSH Terms

Conditions

Adrenal Gland Diseases

Condition Hierarchy (Ancestors)

Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised controlled trial

Study Record Dates

• First Submitted: April 23, 2026
• First Posted: April 30, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04