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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SW CAH | Patients with 21-hydroxylase deficiency, salt wasting form. |
| |
| SV CAH | Patients with 21-hydroxylase deficiency, simple virilising form. |
| |
| NC CAH | Patients with 21-hydroxylase deficiency, non-classic form. |
| |
| Carrier CAH | Healthy individuals, heterozygous carriers a mutation in the CYP21A2 gene. Recruited among parents of patients with CAH. |
| |
| Control | Healthy sex and age matched controls |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| physical exercise as a standardized high intensity exercise test | Diagnostic Test | High intensity exercise test, cycling, performed at the Karolinska University Hospital |
|
| Measure | Description | Time Frame |
|---|---|---|
| epinephrine level | Measured methoxy-catecholamine at maximum exercise test, cycling test. | 2022 December 31 |
| Measure | Description | Time Frame |
|---|---|---|
| Hospital Anxiety Depression Scale | stress vulnerability | 2022 December 31 |
| Mental Fatigue scale | stress vulnerability | 2022 December 31 |
| Measure | Description | Time Frame |
|---|---|---|
| Orthostatic blood pressure | Blood pressure measured lying down and standing for 10 minutes | 2022 December 31 |
| CYP21A2 genotype | mutation analysis |
Inclusion Criteria:
Exclusion Criteria:
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Men and women with congenital adrenal hyperplasia due to 21-hydroxylase deficienc. Sex and age matched controls.
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| Name | Affiliation | Role |
|---|---|---|
| Fredrika Gauffin, MDPhD | Karolinska University Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Karolinska University hospital | Stockholm | (State) | 17176 | Sweden |
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| ID | Term |
|---|---|
| D000312 | Adrenal Hyperplasia, Congenital |
| ID | Term |
|---|---|
| D047808 | Adrenogenital Syndrome |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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Blood tests
| Stress vulnerability | Behavioral | Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire |
|
|
| Liebowitz anxiety scale | stress vulnerability | 2022 December 31 |
| Karolinska Exhaustion disorder scale | stress vulnerability | 2022 December 31 |
| sleep questionnaire | stress vulnerability | 2022 December 31 |
| 2022 December 31 |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D043202 | Steroid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |