ACTH Producing Adenomas: Cushing’s Disease

Abstract

Cushing’s syndrome is a rare disorder characterized by prolonged exposure to excessive concentrations of glucocorticoids. Endogenous Cushing’s syndrome, which will be the focus of this chapter, is usually divided into adrenocorticotropic hormone (ACTH)-dependent and ACTH-independent causes. ACTH-dependent Cushing’s syndrome accounts for approximately 80–85% of all cases and is primarily due to excess ACTH production from a pituitary adenoma. This is also called Cushing’s disease. In Cushing’s disease, pituitary adrenocorticotropic hormone (ACTH) oversecretion (from corticotrophs) prompts bilateral adrenocortical hyperplasia, excess production of cortisol, adrenal androgens, and 11-deoxycorticosterone which together cause the clinical and biological features of this disease. The most common clinical features of Cushing’s syndrome include central obesity, diabetes, hypertension, moon facies, facial plethora, proximal muscle weakness, and reddish purple striae and in children, impaired growth with concomitant weight gain.

Testing for Cushing’s disease first serves to confirm a diagnosis of Cushing’s syndrome or hypercortisolemia, then to differentiate the location of the hypersecretory adenoma. Tests used to screen for Cushing’s syndrome include measurement of random serum cortisol and ACTH, urine free cortisol, late night salivary cortisol, and a 1 mg dexamethasone suppression test. Tests used to differentiate Cushing’s disease from other forms of Cushing’s syndrome include an 8 mg high-dose dexamethasone suppression test, a corticotrophin-releasing hormone (CRH) stimulation test, pituitary MRI, and petrosal sinus sampling.

The optimal treatment for Cushing’s disease is removal of the culprit pituitary adenoma. However, other treatments exist such as pharmacological therapies. Several medications are available that act at different levels, some on the adenoma itself, others blocking the cortisol receptor sites or inhibiting steroidogenesis at the level of the adrenal glands. In cases of persistent or recurrent Cushing’s disease, bilateral adrenalectomy may be performed as a definitive treatment; however, this has long-term implications such as lifelong dependence on replacement glucocorticoids and mineralocorticoids. Pituitary irradiation can be used in cases of recurrent or persistent Cushing’s disease.

Cushing’s disease is not only associated with increased morbidity and mortality during active disease, but this increased risk may also persist in remission. Cushing’s disease is also associated with impaired quality of life, with patients reporting numerous impacts on daily life such as fatigue, interference with family life and relationships with partners, changes in physical appearance, among others. Biochemical remission is typically associated with a small improvement in quality of life impairments when compared to remission of disorders associated with other pituitary adenomas. The nurses’ role is vital in the process of patient assessment, postoperative and long-term monitoring and management of these issues.