Predisposing Factors for the Incidence of Adrenal Crisis

• Conditions: Adrenal Insufficiency
• Interventions: Diagnostic Test: Clinical and biochemical examination.

• Registration Number: NCT03410160
• Lead Sponsor: Wuerzburg University Hospital

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.

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2018-01-18
• Study First Submitted QC: 2018-01-18
• Study First Posted: 2018-01-25
• Primary Completion: 2018-06
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-11
• Last Update Posted: 2019-10-14
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 71

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
High frequency of adrenal crisis	Clinical and biochemical examination.	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).
Low frequency of adrenal crisis	Clinical and biochemical examination.	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).

Primary Outcome Measures

Name	Time	Method
Patient education	1 day	Evaluation of patient education by questionnaire. Hypothesis: Patients with chronic adrenal insufficiency and a high frequency of adrenal crisis have a worse education status.
Chronic inflammation (hsCRP, Interleukin-6)	1 day	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.
Glucocorticoid-receptor-polymorphisms	1 day	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.
Cortisol metabolism	1 day	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.
Replacement therapy with glucocorticoids	1 day	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.
Replacement therapy with mineralocorticoids	1 day	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.
Catecholamine-levels	1 day	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.

Trial Locations

Locations (1)

University Hospital Wuerzburg, Dept. of medicine I; 🇩🇪 Wuerzburg, Germany