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
1 other identifier
interventional
200
3 countries
3
Brief 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?
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Sep 2018
Longer than P75 for not_applicable
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 26, 2018
CompletedFirst Submitted
Initial submission to the registry
November 6, 2018
CompletedFirst Posted
Study publicly available on registry
January 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2025
CompletedNovember 29, 2023
November 1, 2023
7.2 years
November 6, 2018
November 28, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
The percentage of included patients with residual secretion of cortisol and aldosterone.
Percentage of included patients with detectable levels of adrenal steroid hormones.
1 day
Secondary Outcomes (34)
Medication-fasting adrenocorticotropic hormone (ACTH)-stimulated levels of metanephrines
1 day
Medication-fasting basal levels of cortisol
1 day
Medication-fasting basal levels of cortisol
1 day
Medication-fasting basal levels of cortisol
1 day
Medication-fasting basal levels of cortisol precursors
1 day
- +29 more secondary outcomes
Other Outcomes (4)
Adrenocortical hormones in congenital adrenal hyperplasia (CAH) controls
1 day
Adrenocortical hormones in bilaterally adrenalectomized controls
1 day
Change in response to cosyntropin testing
4 days
- +1 more other outcomes
Study Arms (8)
Detectable levels of adrenal hormones
EXPERIMENTALPatients with detectable serum levels of adrenal hormones will go through cosyntropin stimulation testing.
Controls with undetectable hormone levels
ACTIVE COMPARATORTwenty patients without detectable serum levels of adrenal hormones will serve as controls in cosyntropin stimulation testing.
Undetectable levels of adrenal hormones
NO INTERVENTIONPatients without detectable serum levels of adrenal hormones. Cosyntropin stimulation testing will not be performed.
Congenital adrenal hyperplasia (CAH) control group
OTHERMapping adrenal steroid profile in patients with congenital adrenal hyperplasia (CAH) with confirmed total deficiency of 21-hydroxylase.
Bilaterally adrenalectomized control group
OTHERMapping adrenal steroid profile in patients who are bilaterally adrenalectomized.
Diurnal variation in residual adrenocortical hormone levels
EXPERIMENTALPatients with detectable serum levels of adrenal hormones will go through a 30-hour ambulatory sampling of interstitial fluid for mapping of any diurnal variation in endogenous adrenocortical secretion.
Repeated cosyntropin testing in newly diagnosed patients
EXPERIMENTALNewly diagnosed patients will be invited to go through repeated cosyntropin testing to delineate the natural progression of adrenocortical failure.
Cardiovascular and inflammatory biomarkers
ACTIVE COMPARATORCompare cardiovascular and inflammatory biomarker profiles in patients with and without residual production of adrenocortical steroids
Interventions
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.
Medication-fasting morning levels of adrenocortical hormones.
30-hour ambulatory sampling of intestinal fluid for analysis of adrenocortical hormones.
Cardiovascular and inflammatory biomarker profiles
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Antihypertensive treatment, with the exception of doxazosin, verapamil, and moxonidine.
- Active malignant disease, severe heart, kidney or liver failure.
- Diabetes mellitus type 1.
- Pregnancy or breast feeding.
- Pharmacological treatment with glucocorticoids (except their usual cortisone or hydrocortisone replacement therapy) or drugs that interfere with cortisol and catecholamine metabolism (antiepileptics, rifampicin, St. Johns wart).
- Use of other glucocorticoid replacement medication than cortisone acetate or hydrocortisone.
- Intake of grapefruit, grapefruit juice, or and liquorice juice the last week before or during the study period.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Bergenlead
- Karolinska Institutetcollaborator
- Charite University, Berlin, Germanycollaborator
Study Sites (3)
Endokrinologie in Charlottenburg
Berlin, 10627, Germany
Haukeland University Hospital
Bergen, 5021, Norway
Karolinska Institutet
Stockholm, 171 77, Sweden
Related Publications (1)
Saevik AB, Akerman AK, Methlie P, Quinkler M, Jorgensen AP, Hoybye C, Debowska AJ, Nedrebo BG, Dahle AL, Carlsen S, Tomkowicz A, Sollid ST, Nermoen I, Gronning K, Dahlqvist P, Grimnes G, Skov J, Finnes T, Valland SF, Wahlberg J, Holte SE, Simunkova K, Kampe O, Husebye ES, Bensing S, Oksnes M. Residual Corticosteroid Production in Autoimmune Addison Disease. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2430-41. doi: 10.1210/clinem/dgaa256.
PMID: 32392298DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Eystein S Husebye, M.D, Prof
University of Bergen
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- SCREENING
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 6, 2018
First Posted
January 4, 2019
Study Start
September 26, 2018
Primary Completion
December 1, 2025
Study Completion
December 1, 2025
Last Updated
November 29, 2023
Record last verified: 2023-11
Data Sharing
- IPD Sharing
- Will not share
Upon informed and signed content, biological samples will be stored in the biobank for research on endocrine disorders. Any new analyses will not be performed without approval from the Regional committee for medical and health research ethics.