Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Congenital Adrenal Hyperplasia
• Intervention / Treatment: Diagnostic test: physical exercise as a standardized high intensity exercise test; Behavioral: Stress vulnerability

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• Sweden
  • (State)
    • Stockholm, (State), Sweden, 17176
      • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Men and women with congenital adrenal hyperplasia due to 21-hydroxylase deficienc. Sex and age matched controls.

Description

Inclusion Criteria:

• CAH due to 21-hydroxylase deficiency,

Exclusion Criteria:

• Cardiovascular disease

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SW CAH; Patients with 21-hydroxylase deficiency, salt wasting form.	Diagnostic test: physical exercise as a standardized high intensity exercise test; High intensity exercise test, cycling, performed at the Karolinska University Hospital; Behavioral: Stress vulnerability; Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire; Other Names: Validated questionnaires
SV CAH; Patients with 21-hydroxylase deficiency, simple virilising form.	Diagnostic test: physical exercise as a standardized high intensity exercise test; High intensity exercise test, cycling, performed at the Karolinska University Hospital; Behavioral: Stress vulnerability; Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire; Other Names: Validated questionnaires
NC CAH; Patients with 21-hydroxylase deficiency, non-classic form.	Diagnostic test: physical exercise as a standardized high intensity exercise test; High intensity exercise test, cycling, performed at the Karolinska University Hospital; Behavioral: Stress vulnerability; Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire; Other Names: Validated questionnaires
Carrier CAH; 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; High intensity exercise test, cycling, performed at the Karolinska University Hospital; Behavioral: Stress vulnerability; Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire; Other Names: Validated questionnaires
Control; Healthy sex and age matched controls	Diagnostic test: physical exercise as a standardized high intensity exercise test; High intensity exercise test, cycling, performed at the Karolinska University Hospital; Behavioral: Stress vulnerability; Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire; Other Names: Validated questionnaires

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Orthostatic blood pressure	Blood pressure measured lying down and standing for 10 minutes	2022 December 31
CYP21A2 genotype	mutation analysis	2022 December 31

Collaborators and Investigators

• Sponsor: Region Stockholm
• Investigators: Study Director: Fredrika Gauffin, MDPhD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: December 5, 2021
• First Submitted That Met QC Criteria: December 17, 2021
• First Posted (ACTUAL): December 20, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome
• Other Study ID Numbers: CAH and epinephrine

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No