From the Guidelines
The most common cause of Cushing's disease is an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor, specifically microadenomas. These tumors produce excessive amounts of ACTH, which stimulates the adrenal glands to overproduce cortisol, leading to the characteristic symptoms of Cushing's disease, including central obesity, moon face, buffalo hump, purple striae, thin skin, easy bruising, muscle weakness, hypertension, and glucose intolerance 1. It's essential to distinguish Cushing's disease (pituitary cause) from Cushing's syndrome, which refers to excess cortisol from any cause, including adrenal tumors, ectopic ACTH production from tumors elsewhere in the body, or exogenous steroid use.
Some key points to consider:
- Cushing's disease accounts for 75–80% of cases of Cushing's syndrome in children and adolescents, with a male predominance in prepubertal patients 1.
- Microadenomas are the most common cause of Cushing's disease, accounting for 98% of cases in children and adolescents, with the adenoma diameter frequently being ≤2 mm 1.
- Treatment typically involves transsphenoidal surgery to remove the pituitary tumor, which is successful in 70-90% of cases, with selective adenomectomy being the first-line treatment of choice for children and adolescents with Cushing's disease 1.
- If surgery fails, options include radiation therapy, medication to block cortisol production (such as ketoconazole, metyrapone, or mitotane), or bilateral adrenalectomy in severe cases 1.
The most recent and highest-quality study, published in 2024, provides strong evidence for the diagnosis and management of pituitary adenomas in childhood and adolescence, including Cushing's disease 1. This study recommends selective adenomectomy as the first-line treatment for Cushing's disease and highlights the importance of lifelong follow-up for children treated for Cushing's disease.
From the Research
Causes of Cushing's Disease
- The most common cause of Cushing's disease is a pituitary tumor secreting corticotropin (ACTH), leading to cortisol excess 2, 3, 4, 5, 6.
- This condition is responsible for approximately 70% of cases of endogenous Cushing's syndrome 2, 4.
- The excess secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol 5.
Pathophysiology
- Cushing's disease is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma 5.
- The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death 5.
Diagnosis and Treatment
- The diagnosis of Cushing's disease is complex and includes two separate steps: establishing the presence of pathologic hypercortisolism and identifying the underlying cause 2.
- The management of Cushing's disease usually includes transsphenoidal pituitary surgery (TSS) as the primary form of therapy 2, 3, 6.
- Medical therapy has recently acquired an emerging role, with the availability of several drugs with different therapeutic targets, efficacy and safety profiles 4.