From the Guidelines
Cushing's syndrome is caused by at least five main etiologies, including exogenous glucocorticoid administration, ACTH-secreting pituitary adenomas, ectopic ACTH syndrome, adrenal tumors, and adrenal hyperplasia, as supported by recent guidelines and evidence 1. The most common cause of Cushing's syndrome is exogenous glucocorticoid administration, where patients take steroid medications like prednisone, dexamethasone, or hydrocortisone for conditions such as asthma or rheumatoid arthritis. ACTH-secreting pituitary adenomas (Cushing's disease) represent about 70% of endogenous cases, where a benign tumor in the pituitary gland produces excess ACTH, stimulating the adrenal glands to produce cortisol, as noted in a recent consensus guideline update 1. Ectopic ACTH syndrome occurs when tumors outside the pituitary, commonly in the lungs (small cell lung cancer) or pancreas, secrete ACTH, with an incidence of 2% in patients with Cushing’s syndrome 1. Adrenal tumors, either benign adenomas or malignant carcinomas, can autonomously produce cortisol independent of ACTH control, with malignancy suspected if the tumor is larger than 5 cm or is inhomogeneous with irregular margins and/or local invasion 1. Finally, adrenal hyperplasia, where the adrenal glands enlarge and produce excess cortisol, can be caused by genetic conditions like primary pigmented nodular adrenocortical disease or macronodular adrenal hyperplasia, as discussed in a recent review of neuroendocrine tumors 1. These various etiologies lead to the classic symptoms of Cushing's syndrome, including:
- Central obesity
- Moon face
- Buffalo hump
- Purple striae
- Hypertension
- Glucose intolerance It is essential to determine the underlying cause of Cushing's syndrome to provide appropriate treatment and management, as outlined in recent guidelines and consensus statements 1.
From the FDA Drug Label
The diurnal rhythm of the HPA axis is lost in Cushing's disease, a syndrome of adrenocortical hyperfunction characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc The same clinical findings of hyperadrenocorticism may be noted during long-term pharmacologic dose corticoid therapy administered in conventional daily divided doses. development of cushingoid state, diabetes mellitus (new onset or manifestations of latent), The following adverse reactions have been reported with prednisone or other corticosteroids: ... development of cushingoid state,
The causes of Cushing's syndrome include:
- Adrenocortical hyperfunction
- Long-term pharmacologic dose corticoid therapy
- Daily divided doses of corticosteroids
- Development of cushingoid state due to corticosteroid use
- Diabetes mellitus (new onset or manifestations of latent) which may be associated with Cushing's syndrome 2 2
From the Research
Causes of Cushing's Syndrome
The following are some of the causes of Cushing's syndrome:
- Exogenous steroid use, which is the most frequent cause of Cushing syndrome 3
- Endogenous overproduction of cortisol, which can be caused by:
- Pituitary tumors (Cushing disease), occurring in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production 3
- Ectopic adrenocorticotropic hormone (ACTH) secretion from non-pituitary tumors, such as bronchial neuroendocrine neoplasia, small cell lung cancer, pancreatic neuroendocrine neoplasia, thymic neuroendocrine neoplasia, medullary thyroid cancer, and pheochromocytoma 4
- Adrenal tumors, which can cause autonomous cortisol overproduction by the adrenal glands (ACTH-independent cases) 5, 6
- Other rare causes, such as:
- Coexistence of pituitary microadenoma and meningioma, which is an extremely rare comorbidity 7
Classification of Cushing's Syndrome
Cushing's syndrome can be classified into two main categories: