Muscle in Acromegaly and Cushing's Syndrome (MAC)

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Status: Unknown

Conditions: Acromegaly; Cushing Syndrome

Treatments: Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

Study type: Observational

Funder types: Other

Identifiers

NCT03673761

IIBSP-MIO-2017-41

Details and patient eligibility

About

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.

Full 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).

Enrollment: 120 estimated patients

Sex: Female

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients with Cushing's syndrome or acromegaly who have been in remission for at least 5 years.

Exclusion criteria

• Pregnancy, breastfeeding, chronic liver/kidney disease, chronic treatment with glucocorticoids.

Trial design

120 participants in 3 patient groups

Cushing's syndrome

Description:

a) Patients with Sd Cushing (SC): 40 women (25-60 years) with SC, with controlled hypercortisolism after treatment and without clinical / biochemical signs of relapse for more than 5 years. This group will under go the following procedures: * muscle MRI * dual-energy x-ray absorptiometry * muscle ultrasounds * blood testing

Treatment:

Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

acromegaly

Description:

b) Patients with acromegaly: 40 patients of both sexes (25-60 years) with GH / Insulin-like-Growth Factor (IGF-I) controlled after treatment and without clinical / biochemical signs of relapse for more than 5 years. This group will under go the following procedures: * muscle MRI * dual-energy x-ray absorptiometry * muscle ultrasounds * blood testing

Treatment:

Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

Healthy controls

Description:

Controls: n = 40; normal healthy control paired by age, sex and BMI will be included. This group will under go the following procedures: * muscle MRI * dual-energy x-ray absorptiometry * muscle ultrasounds * blood testing

Treatment:

Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing