Counterregulatory Hormone Production in Adrenal Insufficiency and Diabetes Type I

As patients with adrenal insufficiency also exhibit an adrenomedullary dysfunction and patients who suffer from both, adrenal insufficiency and type I diabetes more frequently report hypoglycemia, particularly after strenuous activities this study investigates the counter-regulatory hormonal response to physical stress and the impact on cognitive function in subjects with and without Addison's disease, type I diabetes and healthy subjects. Patients will perform ergometer training with an individualized intensity and fulfill cognitive function testing (stroop test and fatigue inventories) before and after strenuous activity.

• Spiroergometry (Procedure): At visit 1 determination of the individual VO2max (maximal oxygen uptake) by spiroergometry after first testing of cognitive function. At visit 2: Spiroergometry with 3 min warm up followed by 5 min 50% VO2max and 15 min at the individual respiratory compensation point (RCP).

Primary outcomes

• difference in cognitive function before and after physical stress [testing is performed at first visit (baseline, duration 5 min) and second visit (at least 48 hours after visit1). The second test is performed 5 min after strenous activity of 23 min duration, test duration again 5 min)]: study participants are tested with three standardized tests: stroop-task, symptom rating scale and a short term memory test. First testing is performed at visit 1 at rest, the second test at visit 2 after strenuous activity at a bicycle ergometer.

Secondary outcomes

• differences in counterregulatory hormonal response to physical stress [at visit 2, blood sampling over 180 min starting 10 min before spiroergometry]: blood samples for determination of blood glucose, catecholamines and other counterregulatory hormones (cortisol, growth hormone) are collected before, during and after physical activity.

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* Diagnosis of Addison's disease and/or diabetes mellitus type I or healthy control with normal adrenal function and normal glucose regulation
* Age ≥ 18 years
* Ability to comply with the study protocol
* Capability to perform spiroergometry

Exclusion Criteria:

* Any contraindication for performing spiroergometry according to the guidelines of the German Cardiac Society:

  * acute myocardial infarction
  * instable angina pectoris
  * symptomatic arrhythmia
  * severe and symptomatic stenosis of the aortic valve
  * decompensated heart failure
  * acute pulmonary embolism
  * Acute myocarditis
  * Acute pericarditis
  * Acute aortic dissection
  * main coronary artery disease
  * valvulopathies
  * electrolyte disturbance
  * arterial hypertension (systolic blood pressure > 200 mm Hg, diastolic BP > 110 mm Hg)
  * Tachyarrhythmia or Bradyarrhythmia
  * Hypertrophic cardiomyopathy and other forms of obstructive heart disease
  * second or third degree atrioventricular block
* Fever
* Diabetes mellitus Type 2
* Diseases or medication influencing the endogenous levels of plasma catecholamines(e. g. pheochromocytoma, paraganglioma, antidepressants, levodopa)
* Glucocorticoid-pharmacotherapy

• Bruno Allolio, MD, Study chair, University of Wuerzburg
• Stefanie Hahner, MD, Principal investigator, University of Wuerzburg