Cited by 204Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

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Increased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study

Falhammar, Henrik, Frisén, Louise, Hirschberg, Angelica Linden, Norrby, Christina, Almqvist, Catarina, Nordenskjöld, Agneta, Nordenström, Anna·2015·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2015-2093

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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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Self-citation

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
ORCID: Falhammar, Henrik
Frisén, Louise
Almqvist, Catarina
Nordenskjöld, Agneta
Nordenström, Anna
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
DOI: 10.1210/jc.2015-2093
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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Increased Cardiovascular and Metabolic Morbidity in Patients With 21-Hydroxylase Deficiency: A Swedish Population-Based National Cohort Study

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