Session: SUN 29-49-Congenital Adrenal Hyperplasia & Ectopic Cushing's
Poster Board SUN-39
Adrenal pheochrmocytoma (PCS) are catecholamine-(CA) secreting tumor arising from chromaffin cells, which originally derives from neural crests, of the adrenal medulla and it is also capable of secreting a variety of hormones such as corticotropin releasing hormone, corticotrophin and vasopressin as well as cytokines. Here we report a rare case of ectopic ACTH syndrome caused by a PCS that exhibited diabetic ketoacidosis with Cushing features. Importantly, in vivo and vitro analysis revealed that Cushing syndrome (CS) was pathophysiologically enhanced by a paradoxical response of ectopic ACTH secretion to glucocorticoids (GC) in a positive feedback loop via GR expression in tumor cells.
A 56-year-old female with severe clinical features of CS presented the impaired consciousness due to serious diabetic ketoacidosis and then was admitted to our hospital. Endocrinological investigation showed the ectopic ACTH production with high level of cortisol and revealed markedly elevated urinary catecholamine, leading to the diagnosis of PCS. Consistently, CT scan and magnetic resonance imaging displayed a 5.6 cm of left adrenal tumor and MIBG and FDG-PET represented abnormal accumulation in tumor. Interestingly, we found that ectopic ACTH secretion and CA production were blocked by metyrapone treatment, suggesting the possibility of positive feedback loop of ACTH and CA regulation by GC. Indeed, the administration of metyrapone and phentolamine drastically improved hormonal status and stabilized the general condition of patient. Thus, left adrenalectomy was performed safely under stabilized conditions and resulted in remission of CS and PCS completely.
In vitro Analysis
Immunohistological analysis clarified that the tumor consists of functionally distinct two types of cells; one is chromogranin-positive cells, a major components of tumor, stained with tyrosine hydroxylase (TH) and PNMT. Another is minor population of ACTH-positive cells with negative staining of TH and PNMT. Notably, both cells are positive for GR staining. In addition, gene expression analysis of tumor tissue and primary culture cells confirmed the expression of POMC, TH, PNMT and GR mRNA and demonstrated that the dexamethasone treatment markedly increased the secretion of CA and ACTH in medium as well as induction of TH, PNMT and POMC mRNA.
Thus, we describe a case of ectopic ACTH syndrome associated with PCS caused by two different tumor cell linage, and positive feedback of glucocorticoid-inducible ACTH secretion may contribute to aggravate the patient’s condition.
Nothing to Disclose: SH, IS, TT, NH, AS, HN, SS, HK, TY, IT, KY, TT
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