Endocrinol Metab.  2021 Jun;36(3):564-571. 10.3803/EnM.2021.1069.

Cushing Syndrome Associated Myopathy: It Is Time for a Change

• Reincke M

• KMID: 2517645
• DOI: http://doi.org/10.3803/EnM.2021.1069

Abstract

Cushing syndrome is the result of excessive levels of glucocorticoids. Endogenous Cushing syndrome is rare with an incidence of two to three cases per million per year. Clinically, the presentation consists of a characteristic phenotype including skin symptoms and metabolic manifestations. A frequent co-morbidity with high impact on quality of life is Cushing syndrome associated myopathy. It characteristically affects the proximal myopathy, impairing stair climbing and straightening up. The pathophysiology is complex and involves protein degradation via the forkhead box O3 (FOXO3) pathway, intramuscular fat accumulation, and inactivity-associated muscle atrophy. Surgical remission of Cushing syndrome is the most important step for recovery of muscle function. Restoration depends on age, co-morbidities and postoperative insulin-like growth factor concentrations. At average, functionality remains impaired during the long-term compared to age and sex matched control persons. Growth hormone therapy in individuals with impaired growth hormone secretion could be an option but has not been proved in a randomized trial.

Keyword

Glucocorticoids; Quality of life; Cushing syndrome; Growth hormone; Stair climbing; Muscular atrophy; Somatomedins; Phenotype; Bodily secretions; Muscles

Figure

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  Fig. 1 Biopsy of left musculus gastrocnemius of a patient with florid Cushing syndrome. (A) H&E stain reveals disseminated atrophic muscle fibres with mild fibrosis and increase in connective tissue. Myonucleii are somewhat more internalised and single fibres show subsarcolemmal vacuolization. (B) Trichrome Gömori staining displays no protein aggregation or ragged red fibres. Anti-myosin fast (C) and slow (D) stainings show a pronounced type-2 fibre atrophy; however, some type-1 fibres are also atrophic. Oxidative stainings (E, nicotin amide adenine dinucleotide [NADH]; F, cytochrome C oxidase/succinate dehydrogenase [COX/SDH] double staining) shows central reduction of oxidative enzymes in some fibres, pointing at an energy level alteration in those myofibres (×25).

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