Predisposing Factors for the Incidence of Adrenal Crisis

Study Overview
=================
Brief Summary
-----------------
Within this clinical study patients with chronic adrenal insufficiency will be investigated by clinical and biochemical examination as well as questionnaire to identify predisposing factors for adrenal crisis.

Detailed Description
-----------------
Patients with chronic adrenal insufficiency (AI) are at risk of suffering from life-threatening adrenal crisis (AC), despite established hormone replacement therapies and patient education. Recent retrospective analyses observed different risk factors for AC, e.g. primary AI and comorbidities. Furthermore, patients that already experienced an AC seem to have an increased risk to develop further AC. The aim of the study is to evaluate potential risk factors/predisposing factors for AC in patients with chronic primary and secondary AI (PAI/SAI). Patients with chronic AI are assessed by clinical and biochemical examination and questionnaire to evaluate the quality of hormone replacement therapy with glucocorticoids, education status, cortisol-metabolism, catecholamine deficit, chronic inflammation and variations of the glucocorticoid receptor. AI patients with a high frequency of AC will be compared to matched controls (age, sex and cause of AI) with no AC or a low frequency of AC in the past.

Official Title
-----------------
Predisposing Factors for the Incidence of Adrenal Crisis in Chronic Adrenal Insufficiency

Conditions
-----------------
Adrenal Insufficiency

Intervention / Treatment
-----------------
* Diagnostic Test: Clinical and biochemical examination.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >18 years Patient´s written informed consent Ability to comply with the protocol procedures Patients with chronic primary or secondary adrenal insufficiency under established stable replacement therapy (disease duration at least 2 years) Exclusion Criteria: Age <18 years Pregnancy or breast feeding Intake of CYP3A4-inducting-drugs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High frequency of adrenal crisis<br>Patients with a high frequency of adrenal crisis in the past. Intervention: Clinical and biochemical examination (physical examination and blood-sampling before and after oral ingestion of glucocorticoids). | Diagnostic Test: Clinical and biochemical examination.<br>* Patients with chronic adrenal insufficiency were assessed by clinical and biochemical examination as well as questionnaire to evaluate the quality of hormone replacement therapy with glucocorticoids, education status, cortisol-metabolism, catecholamine deficit, chronic inflammation and variations of the glucocorticoid receptor.<br>|
| Low frequency of adrenal crisis<br>Patients with no adrenal crisis or a low frequency of AC in the past. Intervention: Clinical and biochemical examination (physical examination and blood-sampling before and after oral ingestion of glucocorticoids). | Diagnostic Test: Clinical and biochemical examination.<br>* Patients with chronic adrenal insufficiency were assessed by clinical and biochemical examination as well as questionnaire to evaluate the quality of hormone replacement therapy with glucocorticoids, education status, cortisol-metabolism, catecholamine deficit, chronic inflammation and variations of the glucocorticoid receptor.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic inflammation (hsCRP, Interleukin-6) | Measurement of hsCRP (mg/dl) and Interleukin-6 (pg/ml) levels. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit higher hsCRP and Interleukin-6 levels. | 1 day | 
| Cortisol metabolism | Measurement of cortisol-levels (mg/dl) before as well as 60 min and 120 min after ingestion of hydrocortisone. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis exhibit a faster hydrocortisone metabolism. | 1 day | 
| Replacement therapy with glucocorticoids | Evaluation of hormone replacement therapy with glucocorticoids by a clinical score. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement. | 1 day | 
| Replacement therapy with mineralocorticoids | Evaluation of hormone replacement therapy with mineralocorticoids by a clinical and biochemical assessment. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis suffer from under-replacement. | 1 day | 
| Glucocorticoid-receptor-polymorphisms | Evaluation of glucocorticoid-receptor-polymorphisms (ER 22/23 EK, N363S, bcl1, 9beta, Tth3l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a higher prevalence of glucocorticoid-receptor-polymorphisms. | 1 day | 
| Catecholamine-levels | Evaluation of catecholamine-levels (ng/l). Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a more pronounced catecholamin-deficit. | 1 day | 
| Patient education | Evaluation of patient education by questionnaire. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a worse education status. | 1 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
predisposing factors, adrenal crisis