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?
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
SCREENING
Masking
NONE
Enrollment
200
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
Endokrinologie in Charlottenburg
Berlin, State of Berlin, Germany
Haukeland University Hospital
Bergen, Bergen, Norway
Karolinska Institutet
Stockholm, Stockholm County, Sweden
The percentage of included patients with residual secretion of cortisol and aldosterone.
Percentage of included patients with detectable levels of adrenal steroid hormones.
Time frame: 1 day
Medication-fasting adrenocorticotropic hormone (ACTH)-stimulated levels of metanephrines
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of cortisol
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of cortisol
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of cortisol
Levels in hair samples
Time frame: 1 day
Medication-fasting basal levels of cortisol precursors
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of cortisol precursors
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of cortisol precursors
Levels in hair samples
Time frame: 1 day
Medication-fasting basal levels of cortisol metabolites
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of cortisol metabolites
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of cortisol metabolites
Levels in hair samples
Time frame: 1 day
Medication-fasting basal levels of aldosterone
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of aldosterone
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of aldosterone precursors
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of aldosterone precursors
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of aldosterone metabolites
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of aldosterone metabolites
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of renin in patients with and without residual function.
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of renin in patients with and without residual function.
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of ACTH in patients with and without residual function.
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of ACTH in patients with and without residual function.
Levels in urine samples
Time frame: 1 day
Medication-fasting basal levels of metanephrines in patients with and without residual function
Levels in blood samples
Time frame: 1 day
Medication-fasting basal levels of metanephrines in patients with and without residual function
Levels in urine samples
Time frame: 1 day
Medication-fasting ACTH-stimulated levels of cortisol
Levels in blood samples
Time frame: 1 day
Medication-fasting ACTH-stimulated levels of cortisol precursors
Levels in blood samples
Time frame: 1 day
Medication-fasting ACTH-stimulated levels of cortisol metabolites
Levels in blood samples
Time frame: 1 day
Medication-fasting ACTH-stimulated levels of aldosterone
Levels in blood samples
Time frame: 1 day
Medication-fasting ACTH-stimulated levels of aldosterone precursors
Levels in blood samples
Time frame: 1 day
Medication-fasting ACTH-stimulated levels of aldosterone metabolites
Levels in blood samples
Time frame: 1 day
Cortisol replacement doses, including stress doses in patients with and without residual function.
Total daily dosage
Time frame: 1 day
Cortisol stress doses in patients with and without residual function.
No. stress doses the last week
Time frame: 1 day
Fludrocortisone replacement doses in patients with and without residual function.
Total daily dosage.
Time frame: 1 day
In patients with and without residual function: disease-specific quality-of-life
Total score ranging from 30 to 120 in disease-specific quality-of-life questionnaire, Addison Quality of Life (AddiQoL). For every question, scoring is translated in points (1 = 1 point, 2 and 3 = 2 points, 4 and 5 = 3 points, 6 = 4 points) and the algebraic sum of points is calculated. A higher score reflects better health-related quality-of-life.
Time frame: 1 day
In patients with and without residual function, generic health-related quality of life by the Short Form (36) Health Survey
The Short Form (36) Health Survey is a generic tool comprising 36 items evaluating patient reported quality of life concerning eight domains (physical functioning, role functioning physical, bodily pain, general health perception, vitality, social functioning, role functioning emotional, and mental health and general perception of change in health). Scores are expressed on a 0-100 scale with higher scores associated with better quality of life. The result of each domain is presented separately.
Time frame: 1 day
Number of adrenal crises pr. 100 patient years
Number of crises pr. 100 patient years for all included patients as well as in patients with versus without residual adrenal function
Time frame: 1 day
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