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

Abstract Context Fertility in males with 21-hydroxylase deficiency (21OHD) is unclear. Objective Study fertility outcome in males with congenital adrenal hyperplasia. Design, Setting, and Participants Males ≥15 years old with 21OHD (n = 221) were compared with controls matched for sex and year and place of birth (n = 22,024). Data were derived by linking national population-based registers. Subgroup analyses were performed regarding phenotype [salt-wasting (SW), simple virilizing (SV), and nonclassic (NC)] and CYP21A2 genotype (null, I2 splice, I172N, and P30L) and stratified by the introduction of neonatal screening. Main Outcome Measures Number of biological and adopted children. Results Males with 21OHD were less likely to be fathers of biological children [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.4 to 0.7; after adjusting for socioeconomic characteristics: OR, 0.4; 95% CI, 0.2 to 0.5]. This was true for SW, SV, I2 splice, and I172N, but not for NC, null, and P30L groups (all adjusted). Among patients born before the neonatal screening introduction, fewer were fathers (adjusted OR, 0.3; 95% CI, 0.2 to 0.5), but this normalized in those born afterward. Adoption was more common in the 21OHD males (OR, 2.9; 95% CI, 1.0 to 7.9) and the SV and I172N subgroups. Age at becoming a father, marriage, region of residence, and education were similar, but fewer patients had high incomes. NC and I172N groups had, however, higher academic degrees and NC patients were more often married, whereas SW and I2 splice patients were more often divorced. Conclusions 21OHD was associated with a reduced frequency of biological children and an increased frequency of adopted children, suggesting impaired fertility, although some subgroups had normal fertility.

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Increased Prevalence of Fractures in Congenital Adrenal Hyperplasia: A Swedish Population-Based National Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab712 ◽

2021 ◽

Author(s):

Henrik Falhammar ◽

Louise Frisén ◽

Angelica Lindén Hirschberg ◽

Agneta Nordenskjöld ◽

Catarina Almqvist ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Population Based ◽

Place Of Birth ◽

Adrenal Hyperplasia ◽

Mineral Density ◽

Hydroxylase Deficiency ◽

Swedish Population ◽

Classic Phenotype ◽

National Cohort ◽

21 Hydroxylase Deficiency

Abstract Context Low bone mineral density has been reported in individuals with congenital adrenal hyperplasia (CAH), but the prevalence of fractures is unclear. Objective To study the prevalence of fractures in CAH. Design, Setting, and Participants: Patients with CAH (n=714, all 21-hydroxylase deficiency) were compared with controls matched for sex and year and place of birth (n=71,400). Data were derived by linking National Population-Based Registers. . Main Outcome Measures Number and type of fractures. Results Mean age was 29.8±18.4 years. Individuals with CAH had more fractures compared to controls (23.5% vs. 16.1%, OR 1.61, 95%CI 1.35-1.91), and this was found in both sexes (females: 19.6% vs. 13.3%, OR 1.57, 95%CI 1.23-2.02; males: 28.7% vs. 19.6%, OR 1.65, 95%CI 1.29-2.12). Fractures were significantly increased in patients born before the introduction of neonatal screening but not in those born afterwards. Any major fracture associated with osteoporosis (spine, forearm, hip or shoulder) was increased in all individuals with CAH (9.8% vs. 7.5%, OR 1.34, 95%CI 1.05-1.72). The highest prevalence of fractures was seen in SV phenotype and I172N genotype while non-classic phenotype and I2 splice genotype did not show increased prevalence. A transport accident as a car occupant and fall on the same level were more common in patients with CAH, both sexes, than in controls. Conclusions Patients with CAH had an increased prevalence of both any fracture and fractures associated with osteoporosis (both sexes) but not for patient neonatally screened. We conclude that fracture risk assessment and glucocorticoid optimization should be performed regularly.

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Non-infectious comorbidity in patients with multiple sclerosis: A national cohort study in Sweden

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217320947761 ◽

2020 ◽

Vol 6 (3) ◽

pp. 205521732094776

Author(s):

Anna Castelo-Branco ◽

Flaminia Chiesa ◽

Camilla E Bengtsson ◽

Sally Lee ◽

Neil N Minton ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cohort Study ◽

Improve Patient Care ◽

Bowel Dysfunction ◽

Population Based ◽

Incidence Rates ◽

Swedish Population ◽

Comorbidity Burden ◽

National Cohort ◽

Rate Ratios

Background Comorbidity is of significant concern in multiple sclerosis (MS). Few population-based studies have reported conditions occurring in MS after diagnosis, especially in contemporary cohorts. Objective To explore incident comorbidity, mortality and hospitalizations in MS, stratified by age and sex. Methods In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years) and 61,828 matched MS-free individuals were identified between 1 January 2008 and 31 December 2016, using national registers. Incidence rates (IRs) and incidence rate ratios (IRRs) with 95% CI were calculated for each outcome. Results IRs of cardiovascular disease (CVD) were higher among MS patients than MS-free individuals, (major adverse CVD: IRR 1.42; 95% CI 1.12–1.82; hemorrhagic/ischemic stroke: 1.46; 1.05–2.02; transient ischemic attack: 1.65; 1.09–2.50; heart failure: 1.55; 1.15–2.10); venous thromboembolism: 1.42; 1.14–1.77). MS patients also had higher risks of several non-CVDs such as autoimmune conditions (IRR 3.83; 3.01–4.87), bowel dysfunction (2.16; 1.86–2.50), depression (2.38; 2.11–2.68), and fractures (1.32; 1.19–1.47), as well as being hospitalized and to suffer from CVD-related deaths ((1.91; 1.00–3.65), particularly in females (3.57; 1.58–8.06)). Conclusion MS-patients experience a notable comorbidity burden which emphasizes the need for integrated disease management in order to improve patient care and long-term outcomes of MS.

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