Effects of Child- and Adolescent-Onset Endogenous Cushing Syndrome on Bone Mass, Body Composition, and Growth: A 7-Year Prospective Study Into Young Adulthood

Abstract

The long-term effects on bone and fat mass in children with endogenous CS are unknown. In 14 children followed for 3-7 years into young adulthood after cure of CS, whereas bone mass largely recovered, persisting increases in total body and visceral fat suggests an increase risk of the metabolic syndrome.Introduction: Endogenous Cushing syndrome (CS) is associated with decreased bone mass and increased central fat mass. Whereas bone mass seems to improve after successful treatment, little is known about whether central fat persists. Materials and Methods:This was a prospective study of 14 children (10 girls and 4 boys) and adolescents with CS who were successfully treated and remained eucortisolemic. Growth, puberty, bone mass, and body composition were evaluated at baseline and during regular follow-up for 3 years and in seven children for a further 4 years of remission to assess final adult height (FH), BMI, bone mass, and body composition. Results: CS compromised growth, leading to about a −0.8 SD loss of FH and 0.9 SD increase in weight and BMI. BMD apparent density (BMAD) SD Score (SDS) at the lumbar spine (LS) at diagnosis were −1.8 and −1.25, respectively, and after 3 years of follow-up approached the mean with no further increase apparent up to 7 years of follow-up. Whereas hip BMD SDS increased from −1.3 at diagnosis to −0.40 at 3 years and 0 at 7 years of follow-up, femoral neck BMAD remained at or around 0 SDS at diagnosis and during follow-up. BMI was >25 kg/m 2 in five of seven adult subjects, most of whom were women. Total body fat and the ratio of visceral to subcutaneous was abnormally high in the majority of these subjects, whereas LS volumetric BMD was −0.7 SDS. Conclusions: Despite remission of CS, children and adolescents have significant alterations in body composition that result in a small but significant decrease in bone mass and increase in visceral adiposity. Although bone mass largely recovers after endogenous CS, changes in total and visceral fat suggest these subjects are at increased risk of the metabolic syndrome. Therefore, long-term monitoring of body fat and bone mass is mandatory after treatment of CS.

Management of Cushing syndrome in children and adolescents: experience of a single tertiary centre

“…Several studies have reported a high BMI SDS and visceral fat mass after several years of follow-up post-cure [7,17]. In our patients, end of growth stature was available for four individuals, two of whom proved to be GH deficient, albeit only one of them received GH therapy.…”

“…Other pediatric reports have suggested that, despite effective therapy, CS results in a reduction in final height [7,17], increased prevalence of hypertension [21], increased visceral fat mass [7,17] and reduced quality of life [15]. Growth effects may be due to the adenoma itself, surgery, radiotherapy or glucocorticoid exposure [12].…”

Metabolic comorbidities in Cushing's syndrome

“…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). Similarly, studies on prolonged follow-up of CD children and adolescents reported persistence of increased total body fat, ratio of VAT to SAT and waist circumference (105,106). The effects of exogenous hypercortisolism on body composition can be different from those seen in endogenous CS.…”

Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment

“…Many patients remain obese with high BMI SDS 3.9 yrs post cure (58). A long-term followup study of childhood and adolescent CD patients showed that total body fat was abnormally high 7 years after cure, with an elevated ratio of visceral to subcutaneous fat (60). Bone mineral density (BMD) is often but not universally reduced in children and adolescents with CD (61).…”