From the Guidelines
There is a significant overlap between Cushing's syndrome and connective tissue diseases (CTD), with Cushing's syndrome affecting connective tissues throughout the body due to cortisol's impact on collagen synthesis and degradation. This overlap is evident in the development of thin, fragile skin, easy bruising, purple striae, poor wound healing, and muscle weakness in patients with Cushing's syndrome, all of which are manifestations of connective tissue deterioration 1. Additionally, Cushing's patients often develop osteoporosis, another connective tissue disorder affecting the bone matrix. The relationship between Cushing's syndrome and CTD is complex, with long-term glucocorticoid treatment for CTD potentially inducing iatrogenic Cushing's syndrome, further complicating the clinical picture.
Some key points to consider in the overlap between Cushing's syndrome and CTD include:
- The impact of cortisol on collagen synthesis and degradation, leading to reduced collagen content and structural integrity in skin, blood vessels, and other connective tissues 1
- The development of osteoporosis in Cushing's patients, which can be exacerbated by glucocorticoid treatment for CTD 1
- The potential for Cushing's syndrome to mimic other CTD, creating diagnostic challenges 1
- The importance of considering Cushing's syndrome in patients with unexplained connective tissue abnormalities, particularly in those with a history of glucocorticoid treatment for CTD 1
In terms of screening for CTD in patients with Cushing's syndrome, the evidence suggests that early detection of pulmonary involvement and accurate diagnosis of interstitial lung disease (ILD) are essential for informed treatment decisions and prognosis 1. However, clear guidelines on screening for ILD in patients with CTD are lacking, and a multidisciplinary approach is recommended to define best practices in ILD screening in the context of autoimmune rheumatic diseases 1.
The most recent and highest quality study on this topic is from 2025, which highlights the importance of early detection and accurate diagnosis of ILD in patients with CTD 1. This study recommends a multidisciplinary approach to screening and monitoring for ILD in patients with CTD, including those with Cushing's syndrome. Therefore, it is recommended that patients with Cushing's syndrome be screened for CTD, particularly ILD, and that a multidisciplinary approach be taken to diagnose and manage these conditions.
From the Research
Overlap between Cushing's Syndrome and Connective Tissue Diseases
- There is limited direct evidence on the overlap between Cushing's syndrome and connective tissue diseases (CTD) in the provided studies.
- However, studies on overlap syndromes and mixed connective tissue disease suggest that overlap between different connective tissue diseases is common, with up to 25% of CTD patients presenting with an overlap syndrome 2.
- The term "overlap syndrome" refers to a heterogeneous group of disorders that present with features of multiple connective tissue diseases, such as systemic lupus erythematosus, systemic sclerosis, and polymyositis 2, 3.
- Specific autoantibodies have been identified in some overlap syndromes, supporting the hypothesis that these syndromes are distinct clinical entities with specific clinical characteristics 3.
- While there is no direct evidence on the overlap between Cushing's syndrome and CTD, the study on Cushing's syndrome and mild autonomous cortisol secretion suggests that patients with Cushing's syndrome can present with a variable phenotypic landscape, including comorbidities and clinical signs that may overlap with those seen in CTD 4.
Clinical Implications
- The diagnosis and treatment of overlap syndromes and CTD can be challenging due to the complexity and variability of clinical presentations 2, 3, 5, 6.
- The identification of specific autoantibodies and clinical characteristics can help guide diagnosis and treatment decisions in patients with overlap syndromes and CTD 3.
- Further research is needed to fully understand the relationship between Cushing's syndrome and CTD, and to develop effective diagnostic and therapeutic strategies for patients with these conditions.