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Chemotherapy-Induced Regression of an Adrenocorticotropin-Secreting Pituitary Carcinoma Accompanied by Secondary Adrenal Insufficiency

DOI: 10.1155/2013/675298

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Abstract:

Purpose. Adrenocorticotropin- (ACTH-) secreting pituitary carcinomas are rare and require multimodality treatment. The aim of this study was to report the response to various therapies and discuss the potential development of secondary adrenal insufficiency with cytotoxic chemotherapy. Methods. This report describes a man with a large silent corticotroph adenoma progressing to endogenous hypercortisolism and metastatic ACTH-secreting pituitary carcinoma over a period of 14 years. Results. Seven years after initial presentation, progressive tumor enlargement associated with the development of hypercortisolism mandated multiple pituitary tumor debulking procedures and radiotherapy. Testing of the Ki-67 proliferation index was markedly high and he developed a hepatic metastasis. Combination therapy with cisplatin and etoposide resulted in a substantial reduction in tumor size, near-complete regression of his liver metastasis, and dramatic decrease in ACTH secretion. This unexpectedly resulted in symptomatic secondary adrenal insufficiency. Conclusions. This is the first reported case of secondary adrenal insufficiency after use of cytotoxic chemotherapy for metastatic ACTH-secreting pituitary carcinoma. High proliferative indices may be predictive of dramatic responses to chemotherapy. Given the potential for such responses, the development of secondary adrenal insufficiency may occur and patients should be monitored accordingly. 1. Introduction Pituitary carcinomas are rare, constituting less than 1% of patients with pituitary tumors [1]. Aggressive pituitary tumors are characterized by invasion of the parasellar region including the cavernous sinus, bone, and subarachnoid space of the suprasellar region. The diagnosis of pituitary carcinoma usually requires evidence of either intracranial or extracranial metastases [2]. Adrenocorticotropin- (ACTH-) secreting pituitary tumors are the most common secretory subtype which undergo malignant transformation [3, 4]. The majority of ACTH-secreting pituitary carcinomas present with clinical and biochemical features of Cushing’s syndrome and can occasionally manifest after bilateral adrenalectomy for Cushing’s disease (Nelson’s syndrome) [4]. However, some corticotroph carcinomas develop from “silent” corticotroph adenomas which secrete precursors of ACTH from the prohormone proopiomelanocortin (POMC) detected in ACTH immunoassays. Some of these “silent” corticotroph tumors may undergo malignant transformation to elaborate biologically active ACTH and endogenous hypercortisolism may ensue [3]. Pituitary carcinomas

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