PMC:3724972 / 1925-4047 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3724972","sourcedb":"PMC","sourceid":"3724972","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3724972","text":"Introduction\nCushing’s disease (CD) is a condition of hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. While rare, it is associated with significant morbidity and mortality [1–3].\nPituitary secretion of ACTH is normally regulated by hypothalamic and paracrine signals, and through negative feedback by glucocorticoids [4]. Systemic ACTH levels also exhibit a circadian rhythm, controlled by the suprachiasmatic nucleus and entrained by light–dark cycles [4]. Superimposed on this circadian rhythm is an ultradian cycle of pulsatile ACTH release, which is closely mimicked by cortisol levels (Fig. 1a) [5–7]. In patients with CD, both basal and peak ACTH levels are elevated (Fig. 1b), and ACTH and cortisol levels are uncoordinated [5–10].\nFig. 1 24-hour plasma levels of ACTH (dotted line) and cortisol (solid line) in a normal female (a) and a female patient with Cushing’s disease (b). Note that in CD, both basal and peak cortisol levels are elevated, and cortisol secretion is less synchronized to ACTH levels. From Roelfsema F, Pincus SM, Veldhuis JD (1998) J Clin Endocrinol Metab, volume 83, page 690 [7]. Reproduced with permission\nFor most patients with CD, primary treatment is transsphenoidal surgery to remove the pituitary adenoma. However, success rates are variable (reported as 65 to 90 %) and dependent on the surgeon’s expertise [11]. Published 5- and 10-year recurrence rates are as high as 25 and 56 %, respectively [12, 13], and many patients develop deficiencies of other pituitary hormones post-surgery [11]. Patients who fail to achieve or maintain remission require secondary treatment, including radiotherapy and/or adrenalectomy—both of which are associated with subsequent hormone deficiencies [11]. Thus, additional treatment options for patients with CD are required.\nWhile there are several potential CD therapeutic targets, there is relatively little clinical experience with most medical treatments. Recently, however, prospective studies have demonstrated promise for pituitary-directed medical interventions targeting the underlying adenoma.","divisions":[{"label":"title","span":{"begin":0,"end":12}},{"label":"p","span":{"begin":13,"end":224}},{"label":"p","span":{"begin":225,"end":1185}},{"label":"figure","span":{"begin":785,"end":1185}},{"label":"label","span":{"begin":785,"end":791}},{"label":"caption","span":{"begin":792,"end":1185}},{"label":"p","span":{"begin":792,"end":1185}},{"label":"p","span":{"begin":1186,"end":1843}}],"tracks":[{"project":"2_test","denotations":[{"id":"23673515-8187313-63233576","span":{"begin":219,"end":220},"obj":"8187313"},{"id":"23673515-16698415-63233576","span":{"begin":219,"end":220},"obj":"16698415"},{"id":"23673515-20829610-63233576","span":{"begin":219,"end":220},"obj":"20829610"},{"id":"23673515-165214-63233577","span":{"begin":647,"end":648},"obj":"165214"},{"id":"23673515-3031116-63233577","span":{"begin":647,"end":648},"obj":"3031116"},{"id":"23673515-9467594-63233577","span":{"begin":647,"end":648},"obj":"9467594"},{"id":"23673515-165214-63233578","span":{"begin":778,"end":779},"obj":"165214"},{"id":"23673515-3031116-63233578","span":{"begin":778,"end":779},"obj":"3031116"},{"id":"23673515-9467594-63233578","span":{"begin":778,"end":779},"obj":"9467594"},{"id":"23673515-219007-63233578","span":{"begin":778,"end":779},"obj":"219007"},{"id":"23673515-3017037-63233578","span":{"begin":778,"end":779},"obj":"3017037"},{"id":"23673515-9150699-63233578","span":{"begin":778,"end":779},"obj":"9150699"},{"id":"23673515-9467594-63233579","span":{"begin":1155,"end":1156},"obj":"9467594"},{"id":"23673515-18413427-63233580","span":{"begin":1394,"end":1396},"obj":"18413427"},{"id":"23673515-16268808-63233581","span":{"begin":1483,"end":1485},"obj":"16268808"},{"id":"23673515-18056770-63233582","span":{"begin":1487,"end":1489},"obj":"18056770"},{"id":"23673515-18413427-63233583","span":{"begin":1573,"end":1575},"obj":"18413427"},{"id":"23673515-18413427-63233584","span":{"begin":1769,"end":1771},"obj":"18413427"}],"attributes":[{"subj":"23673515-8187313-63233576","pred":"source","obj":"2_test"},{"subj":"23673515-16698415-63233576","pred":"source","obj":"2_test"},{"subj":"23673515-20829610-63233576","pred":"source","obj":"2_test"},{"subj":"23673515-165214-63233577","pred":"source","obj":"2_test"},{"subj":"23673515-3031116-63233577","pred":"source","obj":"2_test"},{"subj":"23673515-9467594-63233577","pred":"source","obj":"2_test"},{"subj":"23673515-165214-63233578","pred":"source","obj":"2_test"},{"subj":"23673515-3031116-63233578","pred":"source","obj":"2_test"},{"subj":"23673515-9467594-63233578","pred":"source","obj":"2_test"},{"subj":"23673515-219007-63233578","pred":"source","obj":"2_test"},{"subj":"23673515-3017037-63233578","pred":"source","obj":"2_test"},{"subj":"23673515-9150699-63233578","pred":"source","obj":"2_test"},{"subj":"23673515-9467594-63233579","pred":"source","obj":"2_test"},{"subj":"23673515-18413427-63233580","pred":"source","obj":"2_test"},{"subj":"23673515-16268808-63233581","pred":"source","obj":"2_test"},{"subj":"23673515-18056770-63233582","pred":"source","obj":"2_test"},{"subj":"23673515-18413427-63233583","pred":"source","obj":"2_test"},{"subj":"23673515-18413427-63233584","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#d793ec","default":true}]}]}}