NCT03793114

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

Residual Secretion of Adrenal Steroid Hormones in Addison's Disease

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: University of Bergen · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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. There have, however, been found a few individuals who preserve some residual secretion of cortisol even years after diagnosis. The objectives of this study is to find out how common it is, and to explore if residual function have impact on patient outcome. That is, do patients with and without residual function differ when it comes to quality of life, working ability, medication dosages, and risk of adrenal crisis?

Detailed description

Autoimmune destruction of the adrenal cortex is the main cause of primary adrenal insufficiency (Addison's disease, AD). Autoimmune AD (AAD) becomes clinically manifest when 90 % of cortex of adrenal gland is destroyed. 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. This ability could be beneficial as it could protect against adrenal crises, ease medication, and leave the patient with better quality of life. The objective of the study is to systematically assess to what extent patients with AAD have residual adrenocortical function, and to characterize this subgroup. The study will be an open non-randomized three-stage multicenter clinical trial comprising patients from the Norwegian Registry for organ-specific autoimmune disease (ROAS), the Swedish Addison registry, and Germany. In stage 1, patients will be asked to fill out questionnaires and deliver medication-fasting samples for analyses of adrenal steroids. In addition, patients with congenital adrenal hyperplasia (CAH) and bilaterally adrenalectomized will serve as negative controls for adrenal steroids. In stage 2, AAD patients with residual steroid production will be invited to a cosyntropin stimulation test to estimate the maximum steroid output from the adrenal glands. Twenty patients with no sign of residual function will also be tested as a control group. In stage 3, AAD patients with confirmed residual function will be invited to go through a 30-hour ambulatory sampling of interstitial fluid for investigation of diurnal variation in adrenocortical hormone levels. Also, newly diagnosed AAD patients will be invited to repeated cosyntropin testing as a means of delineating the natural progression of adrenocortical failure.

Conditions

• Primary Adrenal Insufficiency

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Cosyntropin stimulation test	Blood samples are taken before (0 min), and 30 and 60 min after intravenously administration of 250 µg cosyntropin (tetracosactide acetate) with the patient placed in the recumbent position. The test will be performed non-fasting (but medication-fasting) between 08:00 and 10:00 a.m.
DIAGNOSTIC_TEST	Baseline blood tests	Medication-fasting morning levels of adrenocortical hormones.
DEVICE	30-hour ambulatory sampling of intestinal fluid	30-hour ambulatory sampling of intestinal fluid for analysis of adrenocortical hormones.
OTHER	Blood test	Cardiovascular and inflammatory biomarker profiles

Timeline

• Start date: 2018-09-26
• Primary completion: 2025-12-01
• Completion: 2025-12-01
• First posted: 2019-01-04
• Last updated: 2023-11-29

Locations

3 sites across 3 countries: Germany, Norway, Sweden