PubMed · 16191499
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Lal K Tanwani, SriPrakash L Mokshagundam. Visual vignette. Dynamic MRI.. https://doi.org/10.4158/ep.11.5.351
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Cushing disease (CD) is a life-threatening disorder attributed to excess pituitary tumor-derived adrenocorticotrophic hormone (ACTH) and adrenal steroid secretion caused by pituitary tumors. Whereas CD was first described in 1932, the underlying genetic basis driving tumor growth and ACTH secretion remains unsolved. Here, we show that testicular orphan nuclear receptor 4 (TR4, nuclear receptor subfamily 2, group C, member 2) is overexpressed in human corticotroph tumors as well as in human and mouse corticotroph tumor cell lines. Forced overexpression of TR4 in both human and murine tumor cells increased proopiomelanocortin transcription, ACTH secretion, cellular proliferation, and tumor invasion rates in vitro. Conversely, knockdown of TR4 expression reversed all phenotypes. Mechanistically, we show that TR4 transcriptionally activates proopiomelanocortin through binding of a direct repeat 1 response element in the promoter, and that this is enhanced by MAPK-mediated TR4 phosphorylation. In vivo, TR4 overexpression promotes murine corticotroph tumor growth as well as enhances ACTH and corticosterone production, whereas TR4 knockdown decreases circulating ACTH and corticosterone levels in mice harboring ACTH-secreting tumors. Our findings directly link TR4 to the etiology of corticotroph tumors, hormone secretion, and cell growth as well as identify it as a potential target in the treatment of CD.
This is the first report of a silent corticotroph cell pituitary adenoma arising in a struma ovarii. The patient, a 79-year-old woman, was found to have an asymptomatic left-sided adnexal mass confirmed by vaginal sonography to be a complex cystic and solid tumor. Pathological analysis demonstrated an 8-cm partially cystic struma ovarii in which there was a focus of predominantly basophilic adenohypophyseal cells arranged in a diffuse pattern, adjacent to mature neural tissue containing numerous Herring bodies. The epithelial lining cells of the colloid-filled small and cystic follicles were immunoreactive for thyroglobulin. The pituitary cells were predominantly immunoreactive for adrenocorticotropic hormone, in addition to synaptophysin.
OBJECTIVE: Transnasal endoscopic surgery is the most common approach to removal of pituitary tumors. This study evaluated the transnasal transethmosphenoidal approach (TTES) in terms of its operative manipulability and the postoperative status of the paranasal cavities. METHODS: A total of 132 patients with pituitary tumors underwent surgery by one of the following three approaches: (1) bilateral TTES, in which the surgical procedures were performed via the bilateral paranasal cavities, (2) unilateral TTES, in which the procedures were performed via one side only, and (3) unilateral TTES and resection of the posterior portion in the nasal septum approach (RPS), which is a modification of approach (2) and enables performance of the procedures from both sides. RESULTS: The degree of freedom for the surgical procedures with each of the approaches decreased in the following order: bilateral TTES, unilateral TTES and RPS, and unilateral TTES. The postoperative CT images and endoscopic findings were good with each of the surgical approaches, but the incidences of olfactory disturbance and nasal dryness were significantly higher with the bilateral TTES compared with the unilateral TTES and RPS and the unilateral TTES. CONCLUSION: The unilateral TTES and RPS was for us most suitable approach of the three methods. In the case of advanced tumors, the bilateral TTES should be selected because it permits superior operative manipulability. Finally, the unilateral TTES is most appropriate for removal of tumors that are deviated to one side and localized within the sella.