Introduction: 55-year-old male with Nelson's Syndrome was originally diagnosed with Cushing’s disease 5 years prior after the identification of a 15 x 13 mm pituitary adenoma and ACTH 174 pg/mL. He had typical symptoms including proximal weakness, easy bruising, abdominal striae, weight gain, and atraumatic vertebral fractures. Pathology following TSRPT at that time showed an ACTH-producing tumor with MIB1 index 20%. He had initial improvement of his Cushing's stigmata but one year later developed proximal muscle weakness, hypokalemia requiring replacement, worsening diabetes, and weight gain. Repeat MRI was negative for new/recurring lesion.
Case Description: One and a half years after initial TSRPT, he started on ketoconazole 400 mg three times daily and cabergoline 1 mg TID as a repeat MRI showed a recurring pituitary lesion measuring 13 x 14 x 9 mm with corresponding ACTH level 159 pg/mL. He underwent radiotherapy with 20 Gy in one fraction and two months later underwent bilateral adrenalectomy with cessation of ketoconazole and cabergoline.
Two years later, his ACTH level increased to 1,342 pg/mL and he underwent another fraction of radiotherapy of 20 Gy. A repeat MRI showed a decrease in the size of pituitary lesion. However, eight months later, his ACTH levels peaked at 45,510 pg/mL and he underwent a second TSRPT and a stereotactic radiosurgery series of >54 Gy in 30 fractions over three months. Surgical pathology showed a low-grade neuroendocrine neoplasm without any mitotic figures and an MIB-1 index 15%.
Two months following the SRS series, his ACTH levels peaked at 188,567 pg/mL. He presented to the ED for abdominal pain and CT Abdomen showed possible metastatic lesions in the liver, one of which was subsequently biopsied and positive for pituitary carcinoma. He is currently undergoing capecitabine chemotherapy and an SRS series to the liver with plans to add temozolomide upon completion of the SRS.
Discussion: A key learning point is to suspect metastatic disease with drastic ACTH increases. PET scan imaging is recommended in a patient with rapid or significant increase in ACTH level with or without progression of a lesion centrally. Additionally, although the original histology did not show carcinoma, the elevated MIB-1 index should raise the suspicion for malignant possibility and therefore, increased surveillance. Functional pituitary carcinoma has the twofold task of treating the excess hormone production and controlling the spread of metastatic disease. Given the rarity of this type of cancer, a multi-disciplinary approach best serves the patient including endocrinology, oncology, (neurological) surgery, and radiation oncology. More data and studies are needed to definitively assess efficacy of chemotherapeutics including capecitabine and temozolomide for these types of tumors.
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