Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH

Study Overview
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Brief Summary
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Individuals with CAH produce lower levels of epinephrine (adrenalin) than controls. This can be correlated to the CYP21A2 genotype and is most pronounced in the classic forms. Individuals with CAH have an increased risk of developing hypoglycemia because both cortisol and epinephrine are important counter regulatory hormones. Stress dosing is essential in situations of increased physical stress such as infections with fever for example. Glucocorticoid treatment and stress dosing cannot compensate fully during physical stress neither for the reaction to psychological stress. This may render various types of difficulties in the individual's life. We aim to investigate if the deficient epinephrine production can be confirmed and if it is related to the increased level of anxiety and vulnerability to stress that we observe in the patients. Specific aims of the study: Analyse the epinephrine/adrenalin production in patients with CAH using measurements of epinephrine and metanephrine in blood, during an exercise test Assess stress vulnerability and anxiety using validated questionnaires Correlate the results to severity of disease, CYP21A2 genotype Investigate if psychological and somatic stress symptoms are related to the epinephrine production capacity.

Detailed Description
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After written informed consent study subjects, patients and controls, are invited to fill in a web based survey with the validated questionnaires. A link to the survey, expected to take 30 - 60 minutes to complete, is mailed to to the subjects . A subgroup of study subjects are invited to perform an ergo-spirometri test followed by the exercise test at the hospital. They are asked not to eat for 6 hours or drink any coffe during the day before the test. A venous catheter is used for blood sampling during the exercise. ECG, an orthostatic blood pressure test and a the ergo-spirometry test are performed before the subject is asked to do the exercise test, a cycling maximum test. Blood glucose, lactate, are followed every 4 minutes. Adrenal androgens, cortisol, insulin and methoxy-catecholamine are measured before and when the subject has reached maximum effort load and the test is ended. The physical capacity, orthostatic blood pressure and the blood test results are related to the severity of CAH and to the maximum level of methoxy-cathecholamine produced by each individual. In the larger group of individuals, not taking part in the exercise test but completing the survey the genotype is correlated to the questionnaire results.

Official Title
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Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH

Conditions
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Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Diagnostic Test: physical exercise as a standardized high intensity exercise test
* Behavioral: Stress vulnerability


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CAH due to 21-hydroxylase deficiency, Exclusion Criteria: Cardiovascular disease

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SW CAH<br>Patients with 21-hydroxylase deficiency, salt wasting form. | Diagnostic Test: physical exercise as a standardized high intensity exercise test<br>* High intensity exercise test, cycling, performed at the Karolinska University Hospital<br>Behavioral: Stress vulnerability<br>* Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire<br>* Other names: Validated questionnaires;|
| SV CAH<br>Patients with 21-hydroxylase deficiency, simple virilising form. | Diagnostic Test: physical exercise as a standardized high intensity exercise test<br>* High intensity exercise test, cycling, performed at the Karolinska University Hospital<br>Behavioral: Stress vulnerability<br>* Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire<br>* Other names: Validated questionnaires;|
| NC CAH<br>Patients with 21-hydroxylase deficiency, non-classic form. | Diagnostic Test: physical exercise as a standardized high intensity exercise test<br>* High intensity exercise test, cycling, performed at the Karolinska University Hospital<br>Behavioral: Stress vulnerability<br>* Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire<br>* Other names: Validated questionnaires;|
| Carrier CAH<br>Healthy individuals, heterozygous carriers a mutation in the CYP21A2 gene. Recruited among parents of patients with CAH. | Diagnostic Test: physical exercise as a standardized high intensity exercise test<br>* High intensity exercise test, cycling, performed at the Karolinska University Hospital<br>Behavioral: Stress vulnerability<br>* Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire<br>* Other names: Validated questionnaires;|
| Control<br>Healthy sex and age matched controls | Diagnostic Test: physical exercise as a standardized high intensity exercise test<br>* High intensity exercise test, cycling, performed at the Karolinska University Hospital<br>Behavioral: Stress vulnerability<br>* Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire<br>* Other names: Validated questionnaires;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| epinephrine level | Measured methoxy-catecholamine at maximum exercise test, cycling test. | 2022 December 31 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Anxiety Depression Scale | stress vulnerability | 2022 December 31 | 
| Mental Fatigue scale | stress vulnerability | 2022 December 31 | 
| Liebowitz anxiety scale | stress vulnerability | 2022 December 31 | 
| Karolinska Exhaustion disorder scale | stress vulnerability | 2022 December 31 | 
| sleep questionnaire | stress vulnerability | 2022 December 31 |