Clinical trial NCT03410160: Predisposing Factors for the Incidence of Adrenal Crisis
Official title: Predisposing Factors for the Incidence of Adrenal Crisis in Chronic Adrenal Insufficiency
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Adrenal Insufficiency
Keywords: adrenal crisis
predisposing factors
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
First posted: 2018-01-25
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with chronic adrenal insufficiency under hormone replacement therapy with glucocorticoids.

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.

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

Primary outcomes:
measure: Chronic inflammation (hsCRP, Interleukin-6)
timeFrame: 1 day
measure: Cortisol metabolism
timeFrame: 1 day
measure: Replacement therapy with glucocorticoids
timeFrame: 1 day
measure: Replacement therapy with mineralocorticoids
timeFrame: 1 day
measure: Glucocorticoid-receptor-polymorphisms
timeFrame: 1 day
measure: Catecholamine-levels
timeFrame: 1 day
measure: Patient education
timeFrame: 1 day
Secondary outcomes:
Other outcomes:
Locations:
city: Wuerzburg
country: Germany
facility: University Hospital Wuerzburg, Dept. of medicine I
Study officials:
affiliation: Univesity Hospital Wuerzburg
name: Stefanie Hahner, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.
citation: Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015 Mar;172(3):R115-24. doi: 10.1530/EJE-14-0824. Epub 2014 Oct 6.
citation: Reisch N, Willige M, Kohn D, Schwarz HP, Allolio B, Reincke M, Quinkler M, Hahner S, Beuschlein F. Frequency and causes of adrenal crises over lifetime in patients with 21-hydroxylase deficiency. Eur J Endocrinol. 2012 Jul;167(1):35-42. doi: 10.1530/EJE-12-0161. Epub 2012 Apr 18.
citation: Reincke M, Ritzel K, Osswald A, Berr C, Stalla G, Hallfeldt K, Reisch N, Schopohl J, Beuschlein F. A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome. Eur J Endocrinol. 2015 Oct;173(4):M23-32. doi: 10.1530/EJE-15-0265. Epub 2015 May 20.
citation: Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan;84(1):17-22. doi: 10.1111/cen.12865. Epub 2015 Aug 27.
citation: Hahner S, Arlt W, Allolio B. [Adrenal crisis. Diagnostic and therapeutic management of acute adrenal cortex insufficiency]. Internist (Berl). 2003 Oct;44(10):1243-52. doi: 10.1007/s00108-003-1050-1. German.