The Natural History of Metabolic Comorbidities in Turner Syndrome from Childhood to Early Adulthood: Comparison between 45,X Monosomy and Other Karyotypes

Abstract

ObjectivePatients with Turner syndrome (TS) are at increased risk for metabolic disorders. We aimed to delineate the occurrence and evolution of metabolic comorbidities in TS patients and to determine whether these differ in 45,X monosomy and other karyotypes.MethodsA longitudinal and cross-sectional retrospective cohort study was conducted in a tertiary pediatric endocrine unit during 1980–2016. Ninety-eight TS patients, 30 with 45,X monosomy were followed from childhood to early adulthood. Outcome measures included weight status, blood pressure (BP), glucose metabolism, and lipid profile.ResultsLongitudinal analysis showed a significant change in body mass index (BMI) percentiles over time [F(3,115) = 4.8, P = 0.003]. Age was associated with evolution of elevated BP [systolic BP: odds ratio (OR) = 0.91, P = 0.003; diastolic BP: OR = 0.93, P = 0.023], impaired glucose metabolism (HbA1c: OR = 1.08, P = 0.029; impaired glucose tolerance: OR = 1.12, P = 0.029), and abnormal lipid profile (cholesterol: OR = 1.06, P = 0.01; low-density lipoprotein cholesterol: OR = 1.07, P = 0.041; high-density lipoprotein cholesterol: OR = 1.07, P = 0.033). The occurrence of metabolic comorbidities was similar in 45,X monosomy and other karyotypes. Coexistence of multiple metabolic comorbidities was significantly higher in 45,X monosomy [F(1,72) = 4.81, P = 0.032]. BMI percentiles were positively correlated with metabolic comorbidities (occurrence and number) in each patient (r = 0.35, P = 0.002 and r = 0.383, P = 0.001, respectively).ConclusionOur longitudinal study provides unique insights into the evolution of weight gain and metabolic disorders from childhood to early adulthood in TS patients. Since overweight and increasing age aggravate the risk for metabolic comorbidities, careful surveillance is warranted to prevent and control obesity already from childhood. The more prominent clustering of metabolic comorbidities in 45,X monosomy underscores the importance of a more vigorous intervention in this group.

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

“…Most cases of overt diabetes in Turner syndrome occur in adult women (Lebenthal et al, ; Sybert & McCauley, ). However, since current data do not always present age‐specific frequency and risk factors, it is necessary to include girls and younger women in this discussion.…”

“…However, since current data do not always present age‐specific frequency and risk factors, it is necessary to include girls and younger women in this discussion. Impaired glucose tolerance is seen in 10–40% of girls and women with Turner syndrome, a prevalence that is significantly higher than that seen in both healthy controls and age‐and weight‐matched women with ovarian failure due to other causes (Bakalov et al, ; Lebenthal et al, ). Epidemiologic studies indicate that the relative risk of T2D in adult women with Turner syndrome is three to fivefold higher than controls (Bakalov et al, ; Gravholt, Juul, Naeraa, & Hansen, ) with prevalence estimates ranging from 12.4 to 25% (Bakalov et al, ; Ibarra‐Gasparini et al, ).…”

“…Estimates of diabetes risk are influenced by several factors including age, body weight, use of hormone therapy (GH, HRT), whether the diagnosis of diabetes is based on known cases reported in national registries, or whether screening tests are employed. Age appears to be the strongest independent predictor of diabetes in Turner syndrome (Ibarra‐Gasparini et al, ; Lebenthal et al, ). Incidence of impaired glucose tolerance shows a stepwise increase from 10% of children to 16% in adolescents and 41% in adults with Turner syndrome (Lebenthal et al, ).…”

“…Age appears to be the strongest independent predictor of diabetes in Turner syndrome (Ibarra‐Gasparini et al, ; Lebenthal et al, ). Incidence of impaired glucose tolerance shows a stepwise increase from 10% of children to 16% in adolescents and 41% in adults with Turner syndrome (Lebenthal et al, ). Genetic mechanisms have been invoked to explain this phenomenon, with the hypothesis that it arises from haploinsufficiency of genes involved in insulin signal transduction and β‐cell function that are located on the X chromosome (Sun et al, ).…”

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“…5,6 Metabolic syndrome is a cluster of common disorders that include visceral adiposity, hypertension, insulin resistance, and dyslipidemia and may lead to the development of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease. 7 Although several studies have reported an increased prevalence of each of the MetS components in TS, 4,5,8,9 few studies have determined the global prevalence of MetS in TS. 10,11 In addition, most of these studies have methodological deficiencies such as different age ranges.…”