Sustained hypercortisolemia after bilateral adrenalectomy in Cushing's disease

INTRODUCTION: Cushing's disease caused by pituitary corticotropin (ACTH)-secreting tumors. These tumors are almost always benign and are usually microadenomas. In 30 to 40 percent, the microadenoma is so small that it is not detectable by magnetic resonance imaging (MRI). Primary therapy consists of transsphenoidal surgery or pituitary irradiation. Patients who fail this first approach can be treated either by repeat transsphenoidal surgery, medical therapy, radiotherapy, or, as a final resort, surgical or medical adrenalectomy. CLINICAL CASE: A 38-year-old male patient presented with headache and fatigue. The laboratory examinations reviewed ACTH depending Cushing's syndrome. A suspicious lesion in the pituitary with no contrast enhancement was observed in Sella MRI. Cavernous sinus sampling consistent with central sources. He was operated in 2018 for pituitary Cushing's disease. Reticulin framework disrupted compatible with adenoma but, ACTH could not be stained in immunohistochemical staining for technical reasons. Due to the high cortisol levels of the patient in the postoperative follow-up, the patient underwent bilateral adrenalectomy in 2019. Because of active Cushing's disease, patient was re-evaluated in 2022. In laboratory examinations, HGB 16.6 g/dL, WBC 6400 /uL, NEU 3200 /uL, PLT 228000 uL, cre 0.76 mg/dL, TSH 1.5 mIU/L, FT4 1.2 ng/dl, FSH 4.6 U/L, LH 7.98 U/L, PTH 23.7 ng/L, PRL 17 µg/L, Total Testosterone 571 ng/dl, Progesterone 0.06 µg/L, GH 0.04 ug/L, IGF1 83 µg/L were detected. Basal cortisol was 35 ug/dl and ACTH 67 ng/L. Cortisol with 1 mg of DST resulted in 28 ug/dl. 2 mg DST resulted in cortisol 38 ng/L. Free cortisol in the urine was found to be 281 mg/day (n<130 mg/day). Empty sella was observed in sella MR. No prominent contoured lesion was observed in the pituitary gland. Adrenal gland was not observed in the Abdominal MRI. No tumor was detected in Thorax CT. The patient's pasireotide 0.3 mg 1×1 treatment was continued. Metyropane 250 mg 2×1 was added to the treatment. CONCLUSION: In Cushing's disease, the ACTH-secreting adenoma may be too small to be detected. [Figure: see text]