SAT-489 - When Standard Therapy Fails: A Challenging Case of Cushing'S Disease

Background:
Around 40-50% of patients with Cushing's disease have pituitary adenomas that are too small to be visualized on conventional MRI. When transsphenoidal surgery fails to achieve remission, second-line therapeutic options may interfere with fertility planning, especially in females of reproductive age. In those cases, a patient-centered treatment strategy is required.

Case description:
A 36-year-old female presented to the clinic with: sixty-pound weight gain in one-year, elevated blood pressure, purple striae on her abdomen and thighs, central obesity, and supraclavicular fat pads. Her initial workup revealed an elevated urinary cortisol level of 132 mcg/24 hours (reference range: 4-50 mcg/24 hours), cortisol post-dexamethasone of 5.6 ug/dL, and 3 consecutive late-night salivary tests elevated: 0.34 mcg/dL, 0.46 mcg/dL, and 0.18 mcg/dL, respectively. ACTH was elevated at 63 pg./mL (reference range). MRI did not show any pituitary abnormalities. CT chest and abdomen revealed no adrenal adenoma or any other lesions suggesting ectopic ACTH secretion, and the high-dose dexamethasone suppression test suppressed adequately. Inferior petrosal sinus sampling (IPSS) demonstrated a significant central-to-peripheral ratio of ACTH, suggesting central/pituitary production of excess ACTH as well as a left-to-right gradient. The patient had endonasal transsphenoidal pituitary surgery, but remission was not achieved. Repeat IPSS suggested a left-sided gradient, and gadolinium–68 dotatate scan revealed focal sellar radiotracer uptake corresponding to residual pituitary tissue. She underwent repeat endonasal transsphenoidal approach for left-sided hemi-hypophysectomy, which once again did not achieve remission of her Cushing’s disease. After discussing the advantages and disadvantages of all treatment options, patient opted for elective bilateral adrenalectomy to preserve fertility., Hydrocortisone and Fludrocortisone were started post-operatively. A couple of months after surgery, the patient developed hyperpigmentation and diplopia, and an MRI of the brain revealed an 8 mm lesion within the left posterolateral aspect of the pituitary gland extending into the cavernous sinus. She subsequently underwent a third endoscopic endonasal transsphenoidal approach for resection of this tumor within the left cavernous sinus. ACTH stain was indeterminate. Tumor cells were positive for TPIT. The patient is currently on Hydrocortisone and Fludrocortisone and is trying to conceive.

Conclusion:
Bilateral adrenalectomy is an option for patients with Cushing's disease after noncurative surgery, severe ACTH-dependent disease, or for females desiring fertility preservation. Patients may develop Nelson’s syndrome (NS), which consists of radiographically visible corticotroph tumor progression as shown here. Lifelong surveillance is required with MRI and ACTH.

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