Autoimmune Diseases in Patients with Cushing’s Syndrome after Resolution of Hypercortisolism: Case Reports and Literature Review

Abstract

Introduction Cushing's syndrome (CS) is a clinical condition characterized by excessive cortisol production, associated with metabolic complications, such as diabetes mellitus, dyslipidemia, metabolic syndrome, hypertension, and cardiovascular diseases. Nowadays, the occurrence of autoimmune diseases in CS have not been completely evaluated in the previous studies. Objective The aim of this study was to evaluate the occurrence of autoimmune diseases in CS patients after successfully treated. Materials and Methods From January 2001 to December 2017, in our Secondary Hypertension Unit, we evaluated 147 CS patients (91 with ACTH-independent disease, 54 with ACTH-dependent disease, and 2 patients with ectopic ACTH production. Results 109 CS patients (74.1%) were surgically treated (67 ACTH-independent CS patients (61.5%) undergone adrenalectomy and 42 ACTH-dependent CS (38.5%) undergone transsphenoidal surgery) and evaluated after 6, 12, and 24 months after clinical and biochemical remission of disease. In 9 (8.3%) of overall treated CS patients (8.3%), during follow-up, we observed the onset of some manifestations of autoimmune diseases. In particular, one patient had a systemic lupus erythematosus, one patient had rheumatoid arthritis, 4 patients reported autoimmune thyroiditis (Basedow-Graves' disease and Hashimoto's thyroiditis), one patient had clinical features of psoriasis, one patient showed myasthenia gravis, and one patient had giant cell arteritis. Conclusions Our results demonstrate that patients successfully treated for CS could develop autoimmune diseases. Therefore, after treatment, CS patients need to be strictly monitored in order to evaluate the possible onset of autoimmune diseases.

Management of thyrotoxicosis occurring after surgery for Cushing’s disease: a case series

“…Thyroid autoimmune diseases (GD and painless thyroiditis) are the major causes of thyrotoxicosis, according to the few published cases (5,(13)(14)(15)(16)(17)(18), although one case of de Quervain's thyroiditis has been reported (28). However, the underlying mechanism for the development of thyroid autoimmunity in patients showing remission of CD has not been established.…”

“…Colao et al (5) briefly mentioned two cases of thyrotoxicosis resulting from thyroiditis after surgery. In addition, a further six patients were reported to have developed thyrotoxicosis because of Graves' disease after surgery for CD (13,(15)(16)(17)(18). Apart from this, several isolated cases of other conditions upon resolution of hypercortisolism have also been reported and call attention to a wider spectrum of immune dysfunctions, including rheumatoid arthritis (19), seronegative arthritis (20), systemic lupus erythematous (21), etc.…”

Case of Cyclic Cushing’s Disease with Improvement of Psoriatic Skin Lesions During a Period of Hypercortisolemia

“…Psoriasis is an immune-mediated inflammatory disease that is treated by immunosuppressive or immunomodulatory agents [ 11 ]. It is also known that autoimmune-related diseases, such as Graves’ disease, rheumatoid arthritis, and psoriasis, may occur after resolution of hypercortisolemia due to CS [ 3–5 ]. However, to the best of our knowledge, there have been no reports of improvement in an autoimmune-related disease during a period of cortisol hypersecretion in cyclic CS.…”

“…The episodes of hypercortisolism can occur in intercyclic phases ranging from days to months [ 2 ]. It has also been demonstrated that some patients with CS develop an autoimmune disease, such as autoimmune thyroid disease, rheumatic disease, and psoriasis, after resolution of the hypercortisolism [ 3 ]. At least 3 cases of psoriasis that became apparent after resolution of hypercortisolism in CS have been reported [ 3–5 ].…”

Glucocorticoid excess and COVID-19 disease

“…The correlation between CS and rheumatic disease is complex: on the one hand the presence of primitive hypercortisolism could mask expression of a rheumatic disease [87]; on the other hand, exogenous administration of GCs in rheumatic diseases could induce a iatrogenic form of CS. The scientific rationale for the use of GCs in inflammatory and/or autoimmune diseases is their anti-inflammatory and immunosuppressive effect.…”