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Increased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study
Abstract
CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. OBJECTIVE: This study aimed to study cardiovascular and metabolic morbidity in CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. MAIN OUTCOME MEASURES: To study cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
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“Adjustments in glucocorticoid (and fludrocortisone) dose are usually necessary, especially in the third trimester (134), similar to pregnancies in women with primary adrenal insufficiency (668,669).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [668]
In the citing paper
“In a Swedish cohort of 588 CAH patients, there was a higher frequency of hypertension, hyperlipidemia, diabetes, and venous thromboembolism compared to controls.95”
From Congenital adrenal hyperplasia (2017) · cites this paper as [95]
In the citing paper
“A Swedish population-based study of 588 patients with CAH found an increased prevalence of obesity, type 2 diabetes mellitus, obstructive sleep apnoea, hypertension, elevated lipids, atrial fibrillation and venous thromboembolism compared with control individuals83.”
From Management challenges and therapeutic advances in congenital adrenal hyperplasia (2022) · cites this paper as [83]
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Self-citation
Metadata
- Authors
- Falhammar, H., Frisén, L., Hirschberg, A. L., Norrby, C., Almqvist, C., Nordenskjöld, A., & Nordenström, A.
- Affiliations
- Karolinska University Hospital (SE)
- Corresponding author
- Falhammar, Henrik
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-09
- Volume
- 100
- Issue
- 9
- Pages
- 3520-3528
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1890257176
- Cited by
- 204
- References
- 36
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 17 · 2023: 20 · 2022: 24 · 2021: 20 · 2020: 20 · 2019: 19 · 2018: 21 · 2017: 19 · 2016: 8 · 2015: 3
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion)
- Open Archive (Karolinska Institutet) (submittedVersion)
- Funders
- Karolinska Institutet
- Stockholms Läns Landsting (340‐2013‐5867)
- Vetenskapsrådet (340–2013-5867)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- congenital adrenal hyperplasia, 21-hydroxylase deficiency, cardiovascular morbidity, glucocorticoid therapy, hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, type 2 diabetes, obstructive sleep apnea, hypothyroidism, thyrotoxicosis, salt-wasting CAH, sex differences, newborn screening
- MeSH terms
- Adolescent, Adrenal Hyperplasia, Congenital, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Child, Child, Preschool, Female, Genotype, Humans, Infant, Infant, Newborn, Male, Metabolic Diseases, Middle Aged, Risk, Steroid 21-Hydroxylase, Cohort Studies, Prevalence, Neonatal Screening, Young Adult
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