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Myopathy in endogenous Cushing’s Syndrome: Type II muscle fiber atrophy and its association with age and circulating IGF-1.
Endocr. Connect., DOI: 10.1530/ec-26-0355 (2026)
Context
Patients with endogenous Cushing syndrome (CS) exhibit reduced muscle
strength compared with healthy individuals and frequently experience a
further postoperative decline despite remission.
Objective
To evaluate the histological and immunohistochemical patterns underlying
myopathy in patients with active and remitted CS.
Patients and methods
We included nine patients with active CS and eight patients with CS in
remission, prospectively enrolled at XXX Hospital. Patients in remission
had curative tumor surgery and biochemical remission for ≥24 months.
Biopsies of the vastus lateralis muscle were obtained surgically and
analyzed by histology, immunohistochemistry, and electron microscopy.
IGF-1 concentrations were determined by IDS-iSYS analyzer.
Results
In active CS, the mean cross-sectional area of type II muscle fibers was
reduced. Nicotinamide-adenine-dinucleotide staining revealed mild
moth-eaten fiber patterns in four patients, accompanied by
ultrastructural pathologies on electron microscopy, including increased
subsarcolemmal mitochondrial aggregates that were also present in
remitted CS. In active CS circulating absolute IGF-1 concentrations
positively (rs=0.8, p=0.014) and age inversely (rs= -0.77, p=0.021)
correlated with mean cross-sectional area of type II muscle fibers. In
remission from CS, type II fiber atrophy was not present in most
patients. No substantial associations were found between the severity of
glucocorticoid-excess and histological alterations during active or
remitted disease.
Conclusion
Active CS is characterized by type II fiber atrophy and is associated
with circulating IGF-1 and age. In remission type II fiber atrophy was
not present, whereas mitochondrial ultrastructural alterations could be
observed. These findings indicate sustained muscle alterations and
highlight the need for mechanistic studies to guide targeted therapies.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Atrophy ; Myopathy ; Context (archaeology) ; Vastus Lateralis Muscle ; Immunohistochemistry ; Muscle Atrophy ; Mitochondrial Myopathy ; Skeletal Muscle
ISSN (print) / ISBN
2049-3614
e-ISSN
2049-3614
Journal
Endocrine Connections
Publisher
BioScientifica
Publishing Place
Bristol