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  • Title: Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors.
    Author: Arnaldi G, Mancini T, Kola B, Appolloni G, Freddi S, Concettoni C, Bearzi I, Masini A, Boscaro M, Mantero F.
    Journal: J Clin Endocrinol Metab; 2003 Dec; 88(12):5834-40. PubMed ID: 14671177.
    Abstract:
    A 56-yr-old woman was referred with a diagnosis of Cushing's disease. Hypertension and severe hypokalemia were present and high urinary free cortisol/cortisone ratio was detected, raising a suspicion of an ectopic ACTH syndrome. Inferior petrosal sinus sampling, thoracic computed tomography, and octreotide scans were negative. Remission and relapse periods lasting 3-4 months were observed during the 3.5 yr of follow-up. Finally a thoracic computed tomography scan showed a basal paracardic nodule in the left lung. After surgery, a well-differentiated neuroendocrine tumor (typical bronchial carcinoid) was diagnosed, staining positively for ACTH. RT-PCR revealed expression of proopiomelanocortin, CRH receptor, and V3 vasopressin receptor. Somatostatin receptor type 1, 2, 3, and 5 mRNA was detected only in tumoral tissue. Interestingly, we observed the simultaneous presence of ghrelin and both GH secretagogue (GHS) receptors (1a and 1b) mRNA in tumoral tissue but not in the normal lung. This finding correlates with the in vivo ACTH hyperresponsiveness to hexarelin (a GHS). This is the first report of a cyclical ectopic ACTH-secreting tumor with an in vivo ACTH response to hexarelin coupled with the tumoral expression of ghrelin and GHS receptors. This finding might imply an autocrine/paracrine modulatory effect of ghrelin in bronchial ACTH-secreting tumors.
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