Introduction: Cushing’s disease is a condition of cortisol overproduction caused by an ACTH-producing tumor. Corticotroph cells surrounding an ACTH-producing tumor usually undergo Crooke’s hyaline change, where cytokeratin filaments accumulate in the cytoplasm in response to glucocorticoid excess. These changes are thought to be a mechanism of feedback inhibition and thus facilitate a suppression of ACTH. However, in a subtype of ACTH-secreting tumors known as Crooke’s cell adenomas (CCA), the ACTH-producing cells also undergo these hyaline changes. This would be expected to suppress hormone secretion but these cells are still able to release significant amounts of ACTH.
Case presentation: A 32-year-old woman presented to the hospital after an episode of syncope. On head MRI, she was found to have a 2 cm sellar mass with optic chiasm compression. Labs showed low TSH, free FT4, T3, FSH, and LH. She was also pre-diabetic with an HgbA1c of 6.2%. Her baseline cortisol of 20.6 µg/dL did not suppress after 1 mg of dexamethasone. After receiving 4 mg of dexamethasone, her cortisol suppressed to 5.2 µg/dL. She was diagnosed with hypopituitarism except for cortisol and a likely ACTH-producing pituitary macroadenoma. She completed a transsphenoidal pituitary resection and pathology revealed Crooke’s hyaline changes with immunohistochemical stains positive for ACTH. The immunostain for the proliferation marker Ki67 showed a relatively low proliferation index. Her course was complicated by diabetes insipidus. She was ultimately discharged on 20 mg hydrocortisone each morning, 10 mg hydrocortisone each afternoon, desmopressin 0.05 µg daily, and levothyroxine 125 µg daily. Two weeks later, the patient was sent to the emergency room by her endocrinologist for hyperglycemia up to 288 mg/dL. She was also found to be newly diabetic with an HgbA1c of 6.5%. A fasting morning cortisol was collected during her admission and showed a cortisol level of <1.0 µg/dL, proving she was cured of Cushing’s disease. However, she will need close endocrinology follow up and MRI imaging of her pituitary for this aggressive type of pituitary adenoma.
Discussion: We have come across an interesting case of a young woman who presented for syncope and was found to have a pituitary macroadenoma with pathology consistent with CCA. This type of ACTH-producing tumor is known for aggressive patterns including high rates of recurrence with rates of up to 60% reported in literature, persistent disease after surgery, malignant transformation, and metastases. Despite presentation and symptoms similar to those of other ACTH-producing adenomas, the dangerous pattern of Crooke’s cell adenomas necessitate long-term follow-up in affected patients.