Background: Muscle weakness may persist in patients with Cushings syndrome (CS) long-term after resolution of hypercortisolism, but mechanisms determining this sustained impairment are not known. We hypothesized that alteration of muscle structure, due to fatty infiltration, is associated with muscle dysfunctions in these patients.
Patients & methods: Twenty-six CS women [mean(±S.D.) age 49±12 years; mean(±S.D.) BMI 27±4 Kg/m2; mean(±S.D.) duration of remission, 132±87 months], and 24 age- and BMI-matched controls were studied. The degree of fatty infiltration of the thigh muscles was measured using magnetic resonance imaging (MRI), ultrashort multiecho T2-weighted and 3-point Dixon sequences in the anterior, posterior, and anterior+posterior compartments. T2 signal intensity was classified as high (corresponding to fat), medium (muscle), low (macromolecules-muscle). The following muscle function tests were also performed: gait speed velocity (GS), timed up and go (TUG), 30-second chair stand and hand grip strength in both hands.
Results: Mean muscle fat fraction (%) in the posterior compartment, as determined by 3-point Dixon, was increased in patients as compared with control group (22.8±6.4% vs 18.7±3.4%; P=0.025), indicating greater muscle fatty infiltration in the former. There was a tendency towards higher mean muscle fat fraction in anterior+posterior compartments of the tight in patients as compared with controls (21.8±6.1% vs 18.2±4.5%; P=0.052). Greater mean muscle fat fraction in the posterior compartment was associated with slower GS (r=−0.43, P=0.025), and poorer performance on both TUG (r=0.63, P<0.001) and 30-second chair stand (r=−0.57, P=0.002) in patients only. An increase in the percent of high-T2 signal in overall tight muscles, suggesting increased intramuscular fat tissue, was associated with slower GS (ρ=−0.049, P=0.025) and worse performance on TUG (ρ=0.58, P=0.007) in patients only. In a multiple linear regression model, mean muscle fat fraction in the posterior compartment predicted TUG in patients, after adjusting for age and BMI (ß 0.64, P<0.001).
Conclusion: Rate of fatty infiltration in thigh muscles is increased in patients with CS in remission and is related to impaired muscle function. Muscle MRI could be a reliable biomarker to follow up treated CS patients who are at risk of developing muscle dysfunction. Future studies are needed to elucidate the mechanisms underlying the relationship between altered muscle structure and function after correction of hypercortisolism.
18 - 21 May 2019
European Society of Endocrinology