Total, autoimmune, and cardiometabolic comorbidity burden across turner syndrome karyotypes: a nationwide danish cohort study

Balle Camilla M; Simon Chang; Kirstine Stochholm; Agnethe Berglund; Claus H Gravholt

doi:10.1530/endoabs.118.OC2.1

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Endocrine Abstracts (2026) 118 OC2.1 | DOI: 10.1530/endoabs.118.OC2.1

IDSD2026 Oral Communication Abstracts Session 2 (8 abstracts)

Total, autoimmune, and cardiometabolic comorbidity burden across turner syndrome karyotypes: a nationwide danish cohort study

Camilla M Balle ^1,2 , Simon Chang ^1,2,3 , Kirstine Stochholm ^1,2 , Agnethe Berglund ⁴ & Claus H Gravholt ^1,2,3

Author affiliations

¹Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; ² Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; ³ Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; ⁴ Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. Correspondence to: [email protected]

Background: Turner syndrome (TS) is associated with increased morbidity across the lifespan, yet the cumulative diagnostic burden and variation by karyotype remain insufficiently characterized. This study aimed to quantify diagnostic accumulation in TS and compare comorbidity burden across karyotype groups, with separate analyses of total, autoimmune, and cardiometabolic diagnostic burden.

Methods: We conducted a nationwide cohort study based on Danish national registries, including all females with a karyotype consistent with TS. Karyotypes were classified into three mutually exclusive groups: Monosomy TS (non-mosaic 45,X), Variant TS (structural X-chromosomal abnormalities and/or Y-chromosomal material), and Mosaic TS (mosaic karyotypes including a 45,X cell line). Outcomes included the cumulative number of ICD-10 subchapter diagnoses, as well as specific autoimmune and cardiometabolic diagnoses. Diagnostic accumulation was assessed using multiple-failure Cox regression models estimating hazard ratios (HRs). Age-specific cumulative incidence functions (CIFs) were estimated for participants born in or after 1977.

Results: The cohort comprised 1,381 women with TS: 468 with Monosomy TS (33.9%), 386 with Variant TS (27.9%), and 527 with Mosaic TS (38.2%); median follow-up was 40.6 years. Overall diagnostic accumulation was similar in Variant TS and Monosomy TS (HR 1.00, 95% confidence interval (CI) 0.91-1.10), but lower in Mosaic TS (HR 0.71, 95% CI 0.65-0.78). Autoimmune burden was higher in Variant TS (HR 1.46, 95% CI 1.08-1.97) and lower in Mosaic TS (HR 0.47, 95% CI 0.33-0.66) than in Monosomy TS. Cardiometabolic accumulation was lower in Mosaic TS (HR 0.62, 95% CI 0.47-0.83), whereas Variant TS showed a higher point estimate (HR 1.31, 95% CI 1.00-1.72). In the subcohort born in or after 1977 (n = 703), cumulative incidence curves showed that many women with TS reached ≥10 ICD-10 subchapter diagnoses before age 40, although this generally occurred later in Mosaic TS.

Conclusions: Women with TS accumulate substantial comorbidity across the lifespan. Although diagnostic burden differ by karyotype and is lowest in Mosaic TS, all groups were markedly affected. Variant TS resembled Monosomy TS overall, but showed higher autoimmune burden and a possible increase in cardiometabolic morbidity. These findings support lifelong, systematic follow-up with screening and management of comorbidities in girls and women with TS.