Myopathy in endogenous Cushing's syndrome: type II muscle fiber atrophy and its association with age and circulating IGF-1.

Abstract

Context: Patients with endogenous Cushing's 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 LMU 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 using an 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.