NCT03673761

Muscle in Acromegaly and Cushing's Syndrome

Role of Myosteatosis in the Occurrence and Persistence of Residual Muscle Weakness in Patients With Acromegaly and Cushing's Syndrome. Study of the Mechanisms Involved

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 120 (estimated)
• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau · Academic / Other
• Sex: Female
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

Cushing's syndrome (CS) and acromegaly determine myopathy and muscle weakness which persist long-term after control of hormone excess. Fatty infiltration in skeletal muscle (myosteatosis) is associated with muscle atrophy, frailty, and increased morbidity and mortality in several human models. The study is aimed at evaluating muscle structure in patients with controlled CS and acromegaly, and correlate it with functional tests of muscle strength. In addition, circulating molecules potentially mediating persistent myopathy in these patients will also be assessed.

Detailed description

Prior chronic exposure to glucocorticoids or growth hormone (GH) determines fat infiltration and persistent impairment of muscle structure in "cured" patients with CS or acromegaly, respectively. All this leads to irreversible changes in muscle strength and performance, markedly affecting morbidity and quality of life of these patients. In particular, muscle weakness would contribute significantly to the development of severe arthropathy associated with excess GH, as well as deterioration of bone status and increased risk of fracture, as described in patients with either CS or acromegaly in remission. Our aim is to evaluate whether muscular MRI is a useful tool for the assessment of myopathy and myosteatosis in these patients. If this is the case, we would have identified a non-invasive test that would allow the follow-up of patients at risk of developing functional motor problems, anticipating the onset of muscle weakness or fatigue and consequent deterioration of their quality of life. On the other hand, we will examine the role of microRNAs, which can suppress the process of myogenic differentiation, as potential modulators of myopathy in these conditions. Indeed, microRNAs could be used in clinical practice as markers to identify patients at risk of myopathy, and develop strategies for their prevention. Clarifying the impact of muscle fat infiltration on muscle strength would allow us to better understand the interaction between muscle and adipose tissue, encouraging research on potential mediators of this relationship, such as myostatin (MSTN) (able to direct the mesenchymal cell muscle towards the formation of adipocytes at the expense of myocytes) and adiponectin (ApN) (which keeps the levels of fat in the muscle low while favoring the formation and regeneration of muscle tissue).

Conditions

• Cushing Syndrome
• Acromegaly

Interventions

Type	Name	Description
OTHER	MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing	3.Dixon, T2 mapping MRI microRNAs

Timeline

• Start date: 2018-02-01
• Primary completion: 2019-10-31
• Completion: 2020-01-31
• First posted: 2018-09-17
• Last updated: 2019-02-25

Locations

1 site across 1 country: Spain