Henrik Falhammar1, Louise Frisén1, Angelica Linden Hirschberg1, Christina Norrby1, Catarina Almqvist1, Agneta Nordenskjöld1, Anna Nordenström1. 1. Department of Endocrinology, Metabolism and Diabetes (H.F.), Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Department of Molecular Medicine and Surgery, SE-171 76 Karolinska Institutet (H.F.), Stockholm, Sweden; Department of Clinical Neuroscience (L.F.), Karolinska Institutet, SE-171 77 Stockholm, Sweden; Child and Adolescent Psychiatry Research Center (L.F.), SE-113 30 Stockholm, Sweden; Department of Obstetrics and Gynaecology (A.L.H.), Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Department of Women's and Children's Health (A.L.H., Ag.N., An.N.), SE-171 76 Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics (C.N., C.A.), Karolinska Institutet, SE-171 77 Stockholm, Sweden; Lung and Allergy Unit (C.A.), Astrid Lindgren Children's Hospital, Karolinska University Hospital, SE-171 64 Stockholm, Sweden; Center for Molecular Medicine (Ag.N.), Karolinska Institutet, SE-171 76 Stockholm, Sweden; and Paediatric Surgery (Ag.N.) and Department of Paediatric Endocrinology (An.N.), Astrid Lindgren Children's Hospital, Karolinska University Hospital, SE-171 64 Stockholm, Sweden.
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.
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.
Authors: Kyriakie Sarafoglou; Gregory P Forlenza; O Yaw Addo; Jennifer Kyllo; Aida Lteif; P C Hindmarsh; Anna Petryk; Maria Teresa Gonzalez-Bolanos; Bradley S Miller; William Thomas Journal: Clin Endocrinol (Oxf) Date: 2017-03-28 Impact factor: 3.478
Authors: Diala El-Maouche; Deborah P Merke; Maria G Vogiatzi; Alice Y Chang; Adina F Turcu; Elizabeth G Joyal; Vivian H Lin; Lauren Weintraub; Marianne R Plaunt; Pharis Mohideen; Richard J Auchus Journal: J Clin Endocrinol Metab Date: 2020-08-01 Impact factor: 5.958