Cushing’s disease is a specific type of Cushing’s syndrome and is caused by a pituitary adenoma, which is a benign tumor in the pituitary gland. This tumor secretes excess amounts of adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal glands to produce excessive cortisol, leading to the symptoms of Cushing’s syndrome.
Surgical management of Cushing disease
Corticotropin (adrenocorticotropic hormone [ACTH])-secreting pituitary adenomas are a primary cause of Cushing syndrome, characterized by excessive adrenal secretion of cortisol. These adenomas are usually benign microadenomas (≤10 mm in diameter), occasionally macroadenomas, and rarely carcinomas. The treatment of choice for these tumors is transsphenoidal selective adenectomy, aiming for Cushing syndrome cure while preserving anterior and posterior pituitary function.
The most common surgical approach is the endonasal approach, utilizing an endoscope through the sphenoid sinus and sella floor. Corticotroph adenomas are basophilic and exhibit positive ACTH staining on immunohistochemistry. Cure rates range from 80% to 90% for microadenomas that are preoperatively localized using MRI or inferior petrosal sinus sampling. Challenges in achieving a cure include the adenoma’s small size or inaccessible location, such as the cavernous sinus.
MRI, preferably with a high-strength magnet and gadolinium enhancement, is essential for preoperative tumor localization. However, only about half of ACTH-secreting tumors are large enough for MRI detection. Additionally, around 10% of healthy individuals might display an apparent microadenoma on MRI, making it non-specific for a corticotroph adenoma. Cure rates for macroadenomas are lower (about 60%) due to potential cavernous sinus involvement inhibiting complete resection.
On the day of surgery, patients should receive an intravenous dose of glucocorticoid (e.g., hydrocortisone 100 mg). Post-surgery, the serum cortisol concentration is measured to confirm a short-term cure, indicated by a low serum cortisol level (e.g., <1.8 μg/dL). If symptoms of acute glucocorticoid withdrawal arise, stress dosages of glucocorticoids are administered.
Patients are typically discharged on exogenous orally administered glucocorticoids at twice the standard replacement therapy dosage (e.g., prednisone 10 mg in the morning and 5 mg in the afternoon), gradually tapering to a standard replacement dose over 4 to 6 weeks. This gradual reduction is crucial to prevent severe steroid withdrawal symptoms and to allow recovery of hypothalamic corticotropin-releasing hormone neurons and atrophic anterior pituitary corticotrophs, which may take months post-surgery. Most patients eventually tolerate a single dose of a short-acting glucocorticoid (e.g., 15-20 mg of hydrocortisone every morning) starting 8 to 12 weeks after surgical cure.
Postoperative Management of Pituitary-Dependent Cushing Syndrome
After surgery for pituitary-dependent Cushing syndrome, patients typically need exogenous glucocorticoids for about 12 months. The 8 am serum cortisol concentration should be measured every 6 weeks, with blood samples taken before the morning hydrocortisone dose. When serum cortisol levels rise above 10 μg/dL from initially undetectable levels, the hydrocortisone dosage can be gradually tapered and discontinued over a 2-week period. The signs and symptoms of Cushing syndrome often take around 6 months to resolve post-surgery.
Despite low postoperative serum cortisol levels, there is still a risk of recurrent disease. If some adenomatous corticotroph cells remain after surgery, they can multiply and potentially lead to recurrent Cushing syndrome, usually within 3 to 4 years. Hence, annual follow-ups are crucial to monitor for disease recurrence.
Patients with Cushing syndrome face an increased risk of thromboembolic events perioperatively. Prophylactic measures, such as early ambulation starting the day after surgery, are recommended to prevent complications like deep venous thrombosis.
If transsphenoidal surgery does not effectively cure Cushing syndrome, alternative treatments include a second transsphenoidal surgery or bilateral laparoscopic adrenalectomy. Other less common treatment options are radiation therapy targeting the sella or pharmacotherapy aimed at reducing adrenal cortisol production. The choice of these treatments depends on the specific case and the presence of residual or recurrent tumor tissue.