Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity

Abstract

Objective: Adverse body compositional features and low bone mineral density (BMD) are the characteristic of patients with active Cushing's syndrome (CS). The aim of this study was to evaluate body composition and BMD in women with CS in long-term remission and the influence of polymorphisms in genes affecting glucocorticoid (GC) sensitivity on these end-points. Design, patients and methods: This was a cross-sectional, case-controlled study, including 50 women previously treated for CS and 50 age and gender-matched controls. Median (interquartile range) remission time was 13 (5-19) years. Body composition and BMD were measured with dual-energy X-ray absorptiometry. Five polymorphisms in four genes associated with GC sensitivity were analysed using TaqMan or Sequenom single-nucleotide polymorphism genotyping. Results: Patients with CS in remission had increased abdominal fat mass (P!0.01), whereas BMD was not significantly different at any site between patients and controls. In patients, the NR3C1 Bcl1 polymorphism was associated with reduced total (P!0.05) and femur neck BMD (P!0.05). The polymorphism rs1045642 in the ABCB1 gene was associated with increased abdominal fat mass (P!0.05) and decreased appendicular skeletal muscle mass (P!0.05). GC replacement was associated with reduced total BMD (P!0.01), BMD at lumbar spine (P!0.05) and increased abdominal fat (P!0.01). Conclusion: Ongoing GC replacement therapy together with polymorphisms in two genes related with GC sensitivity is associated with abdominal obesity and adverse skeletal health in patients with CS in long-term remission.

Impact of hypercortisolism on skeletal muscle mass and adipose tissue mass in patients with adrenal adenomas

“…To what extent these common genetic variants may influence glucocorticoid sensitivity and regional differences in body composition measurements in patients with CS remains to be further investigated. 28 In our study, when we adjusted for major cofounding factors (age, sex and BMI), the V/T fat ratio was increased in patients with overt CS when compared to NFAT which is in agreement with other studies. 16 Surprisingly, we have observed that VAT and V/S were lower in patients with MACE when compared to NFAT.…”

“…Finally, several polymorphisms (ie, NR3C1 and Bc11) in the GC receptor are described that may either increase or decrease GC sensitivity. To what extent these common genetic variants may influence glucocorticoid sensitivity and regional differences in body composition measurements in patients with CS remains to be further investigated . In our study, when we adjusted for major cofounding factors (age, sex and BMI), the V/T fat ratio was increased in patients with overt CS when compared to NFAT which is in agreement with other studies .…”

Metabolic comorbidities in Cushing's syndrome

“…They also found that the difference in patients' muscle mass between active disease and remission disappeared when disregarding post-menopausal women, suggesting a role of the oestrogen deprivation as well (99). Furthermore, a long-term follow-up study demonstrated that patients with CS had reduced limb skeletal muscle mass, but similar total lean body mass, compared to age-and gendermatched controls (103). Muscle fibre conduction is also altered in CS patients.…”

“…Correction of hypercortisolism is generally associated with a reduction of VAT and SAT mass, although adverse metabolic profile and increased cardiovascular risk can persist after remission (1,100,101). Although CS patients experience loss of weight and fat in the short-medium term after remission (102), long-term follow-up demonstrated increased abdominal fat mass compared to age-and gender-matched controls (103). In another study, long-term cured CS patients had total fat mass and trunk fat mass comparable to patients with active disease and higher than gender-, age-and BMImatched healthy controls (104).…”

Trabecular bone score as one of the new methods of non-invasive evaluation of bone microarchitecture in patients with Cushing’s syndrome

“…Распространенность низкотравматичных перело-мов у пациентов с ЭГ варьирует от 20 до 70% [8][9][10][11][12]. Несмотря на тяжелое течение и высокую частоту переломов, показатели минеральной плотности ко-сти (МПК) у пациентов с эндогенным и экзогенным гиперкортицизмом в ряде случаев соответствуют лишь остеопении или даже остаются нормальными [13]. Оценка TBS наряду с показателями МПК у па-циентов с гиперкортицизмом может дать суще-ственную дополнительную информацию о наруше- нии микроархитектоники костной ткани у этих больных.…”