SAT284 Is Stress Vulnerability In CAH Related To Epinephrine Deficiency And CYP21A2 Genotype?
Authors: Nordenstrom Anna , Ekbom Kerstin , Said Ragad , Strandqvist Anna , Lönnberg Hanna , Lindberg Maria , Bertman Noah , Hirschberg Angelica Linden , Falhammar Henrik , Rickenlund Anette 
Published: October 2023

Disclosure: A. Nordenstrom: None. K. Ekbom: None. R. Said: None. A. Strandqvist: None. H. Lönnberg: None. M. Lindberg: None. N. Bertman: None. A.L. Hirschberg: None. H. Falhammar: None. A. Rickenlund: None.

Introduction: Primary adrenal insufficiency due to CYP21A2 deficiency results in epinephrine deficiency.The lack of a sufficient increase in epinephrine during high intensity exercise has been described, and increased hydrocortisone doses cannot compensate and normalize glucose response. Clinically patients with CAH seem vulnerable to stress. A possible role of epinephrine deficiency for stress vulnerability has not been studied previously.

Research question: Do patients with CAH show increased stress sensitivity, depression and anxiety compared to healthy controls? Is stress sensitivity related to the severity of CAH, e.g. CYP21A2 genotype? Can vulnerability to different types of stress be correlated to the individual’s capacity to produce epinephrine?

Methodology: 26 patients, aged 18-52 years, (13 F, 13 M) and 14 sex-matched controls. Plasma metanephrines (metabolites of catecholamines) were measured at start and at the peak of physical exertion on a maximum work test using ergometer cycle. All participants answered validated questionnaires regarding perceived stress (PSS), depression and anxiety (HADS), signs of fatigue syndrome (KEDS).Plasma metanephrine (metabolite of epinephrine) was correlated to CYP21A2 genotype. The results of the psychological questionnaires were correlated to the metanephrine levels and to the CYP21A2 genotype.

Results: Patients with CAH had lower metanephrine levels than controls and it was related to CYP21A2 genotype. The few included patients with null genotype had virtually no metanephrin and lower levels than individuals with I2G genotype which has not been shown before.The patients scored higher on anxiety and stress and for risk of fatigue syndromed than controls. However, the men with null genotype did not report increased anxiety and depression compared to controls. Men with I2G genotype had lower scores than I172N genotype.There was a clear sex difference in that women had higher scores than men and women with severe genotypes, null and I2G, had more signs of depression and anxiety. There were no differences for perceived stress.

Interpretation/Conclusions: Over all the results for the patients on the questionnaires showed a similar pattern with increasing signs of stress vulnerability with milder genotype and increasing, but deficient, metanephrine levels. An interesting finding was that a total epinephrine deficiency, as in null genotype, with less somatic effects of stress (increased heart rate etc), may be beneficial for some aspects of perceived stress tolerance. However, it may put these patients at increased risk of fatigue or burn out syndrome. The psychological effects of the virilization due to CAH per se may partly overshadow the effects of the epinephrine deficiency in women with CAH.

Larger studies are needed to be able to study what role the capacity to produce epinephrine, has for the psychological stress vulnerability in CAH.

Presentation: Saturday, June 17, 2023