Understanding Cushing Syndrome: Diagnosis and Treatment Pathways

Cushing syndrome is a complex endocrine disorder characterized by excessive levels of cortisol in the body. The diagnosis begins with assessing baseline serum cortisol levels, followed by administering high-dose dexamethasone—16 mg over 48 hours. In patients with ACTH-secreting pituitary adenomas, this treatment often results in a significant suppression of cortisol levels. This response helps differentiate between Cushing disease, caused by pituitary adenomas, and other sources of ACTH, such as ectopic tumors.

The effectiveness of the high-dose dexamethasone suppression test varies, with less than 50% suppression indicating a potential ectopic source of ACTH. Serum ACTH levels are often higher in ectopic tumors, although this method is not entirely reliable. For a more accurate diagnosis, venous sampling from the inferior petrosal sinus can be conducted. This invasive procedure, performed by interventional radiologists, evaluates the hormone's levels in the petrosal sinus after CRH stimulation, helping to identify the origin of ACTH secretion.

A clear ACTH gradient from the inferior petrosal sinus to peripheral blood suggests that the source is the anterior pituitary. However, it’s crucial that glucocorticoid excess is confirmed during this testing to avoid misinterpretation. Once the source is established, imaging techniques such as MRI for the anterior pituitary and CT scans for the adrenal glands can be employed to identify tumors or other abnormalities.

Treating Cushing syndrome is vital, as it significantly increases the risk of cardiovascular disease and premature mortality. The primary aim is to normalize cortisol production and restore the body’s natural rhythms. Surgical options include unilateral adrenalectomy for adrenal adenomas and trans-sphenoidal surgery for pituitary adenomas, with the latter being performed by specialized surgeons. In cases where surgery isn’t feasible, medical therapy options like metyrapone are available to inhibit glucocorticoid secretion.

In the postoperative phase, patients often experience relative adrenal insufficiency due to the body’s adaptation to high cortisol levels. Hydrocortisone replacement therapy is typically required until the hypothalamic–anterior pituitary–adrenal axis normalizes. For inoperable cases or when surgery fails, pituitary radiotherapy can be an effective treatment option, providing a pathway to manage this complex condition. Understanding the nuances of diagnosis and treatment in Cushing syndrome is essential for effective patient care.