Screening and Stimulation Testing for Residual Secretion of Adrenal Steroid Hormones in Autoimmune Addison's Disease

What Was Tested

In this not phased trial, researchers set out to test Cosyntropin.

In autoimmune adrenal insufficiency, or Addison's disease (AD), the immune system attacks the adrenal cortex.

As a result, the adrenal cells producing hormones such as cortisol and aldosterone are destroyed, leaving the body with insufficient levels to meet its needs.

The common perception is that upon diagnosis of Addison's disease, basically all adrenal hormone production has ceased.

It had eight arms (groups): Detectable levels of adrenal hormones (experimental), Controls with undetectable hormone levels (active comparator), Undetectable levels of adrenal hormones (no intervention), Congenital adrenal hyperplasia (CAH) control group (other) and Bilaterally adrenalectomized control group (other).

Patients with detectable serum levels of adrenal hormones will go through cosyntropin stimulation testing.

Twenty patients without detectable serum levels of adrenal hormones will serve as controls in cosyntropin stimulation testing.

Patients without detectable serum levels of adrenal hormones. Cosyntropin stimulation testing will not be performed.

The registry classes the interventions as device, diagnostic test and other.

More on the Plan

Autoimmune destruction of the adrenal cortex is the main cause of primary adrenal insufficiency (Addison's disease, AD).

Current dogma says that adrenal insufficiency ultimately is complete, that is the adrenal cortex stops producing steroids altogether.

However, several case reports indicate that there might be a subgroup of patients that retain some steroid production, even years after the diagnosis.

The objective of the study is to systematically assess to what extent patients with AAD have residual adrenocortical function, and to characterize this subgroup.

Who Took Part

Enrollment: 200 planned participants were the target.

It was open to people of any sex aged from 18 years up to 70 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Men and women with AAD, age 18-70 years old. This requires documented adrenal insufficiency and a positive test for 21-hydroxylase autoantibodies (biomarker for autoimmune cause) on at least one occasion. Provided written informed consent. In case of concomitant endocrine/autoimmune diseases, the patients should be on stable adequate treatment at least the last 3 months prior to the study period. For Norwegian AD patients: enrolled in ROAS. For Swedish AD patients: enrolled in the Swedish Addison registry.

The full record lists 5 inclusion and 7 exclusion criteria; among the exclusions: antihypertensive treatment, with the exception of doxazosin, verapamil, and moxonidine; active malignant disease, severe heart, kidney or liver failure; diabetes mellitus type 1.

How the Study Was Run

The set-up was non-randomized, parallel-group and open-label.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Everyone knew when Cosyntropin was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

It started in 2018-09-26 with completion listed for 2029-12-31.

It ran at 3 sites in Germany (1), Norway (1) and Sweden (1).

Its stated primary purpose is screening.

What Was Measured

The main thing measured (primary outcome): The percentage of included patients with residual secretion of cortisol and aldosterone (time frame: 1 day).

It also tracked 34 secondary outcomes, for example Medication-fasting adrenocorticotropic hormone (ACTH)-stimulated levels of metanephrines, Medication-fasting basal levels of cortisol, Medication-fasting basal levels of cortisol, Medication-fasting basal levels of cortisol, Medication-fasting basal levels of cortisol precursors and Medication-fasting basal levels of cortisol precursors.

What This Means in Plain Language

Put simply, this is a not phased, non-randomized trial of Cosyntropin in 200 people.

Its status is active not recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Cosyntropin compound page, all human trials.