Ectopic (Inappropriate) Hormone Production by Tumors: Mechanisms Involved and the Biological and Clinical Implications*

Baylin, Stephen B.; Mendelsohn, Geoffrey

doi:10.1210/edrv-1-1-45

Cited by 172 publications

(58 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The EAS occurs in around 5-10% of all cases of ACTH-dependent hypercortisolism (5,6). Different from Cushing's disease, which presents a predominance of 75-80% in the female sex, the EAS is only slightly more frequent in women.…”

Section: Introductionmentioning

confidence: 93%

Ectopic ACTH syndrome: our experience with 25 cases

Fragoso²,

et al. 2006

View full text Add to dashboard Cite

Objective: Ectopic ACTH syndrome (EAS) occurs in about 5-10% of all patients with ACTH-dependent hypercortisolism with most of them caused by intrathoracic neoplasms. It may be associated with overt malignancies or with occult and indolent tumors. We assessed the accuracy of dynamic tests, inferior petrosal sinus sampling (IPSS) using desmopressin, and imaging in the work-up diagnosis of EAS. Design and subjects: Tumor markers, imaging, and outcome data from 25 patients (13F/12M) aged 18-72 years. High dexamethasone suppression test (HDDST), desmopressin test, GHRP-6 test, corticotropin-releasing hormone (CRH) test, IPSS, computed tomography (CT), magnetic resonance imaging (MRI), and 111 In-pentetreotide scintigraphy were revised. Results: In 5 out of 20 patients HDDST was positive. In 13 patients who underwent desmopressin test, ACTH-and cortisol-positive responses were seen in six and five patients respectively. GHRP-6 test was positive in two out of three cases. Two patients underwent CRH test with negative response. In the seven patients submitted to IPSS using desmopressin in six of them, none had ACTH gradients. CT was positive in 15 out of 21 patients and MRI in 8 out of 17 cases.111 In-pentetreotide scintigraphy was positive in three out of five patients. Fourteen patients had intrathoracic tumors, five had pheochromocytomas, three had pancreatic tumors, one had a glomic tumor, and had three occult tumors. Six out of 11 patients with metastasis died and 3 others without metastasis died. Conclusions: IPSS with desmopressin was helpful for differential diagnosis. Patients initially harboring occult carcinoids may also exhibit severe hypercortisolism and those harboring tymic carcinoids had poor prognoses when compared with bronchial carcinoids and pheocromocytomas.European Journal of Endocrinology 155 725-733

show abstract

Section: Introductionmentioning

confidence: 93%

Ectopic ACTH syndrome: our experience with 25 cases

Fragoso²,

et al. 2006

View full text Add to dashboard Cite

show abstract

“…SCLC makes up 20% of all human lung cancers, and has a very poor prognosis, with widespread early metastases. SCLC is thought to result from malignant transformation of a primitive progenitor cell that then undergoes a pattern of dysdifferentiation (Baylin & Mendelsohn 1980).…”

Section: Introductionmentioning

confidence: 99%

Analysis of co-factor function in a glucocorticoid-resistant small cell carcinoma cell line

Waters¹,

Stevens²,

White³

et al. 2004

Journal of Endocrinology

View full text Add to dashboard Cite

Human small cell lung carcinoma (SCLC) tumours exhibit neuroendocrine differentiation, secreting hormones such as ACTH and related peptides. While glucocorticoids inhibit ACTH secretion from the pituitary, this does not occur in SCLC tumours and SCLC cell lines. Failure of glucocorticoids to suppress ACTH peptides is accompanied by a global lack of glucocorticoid action in a number of SCLC cell lines.In the human SCLC cell line, COR L103, activation of a human tyrosine aminotransferase (TAT3)-luciferase reporter gene is resistant to glucocorticoids despite similar glucocorticoid receptor (GR) expression to the glucocorticoid-sensitive A549 human lung cancer cell line; moreover, the GR is free of deleterious mutations. Overexpression of a wild-type GR restores glucocorticoid regulation of TAT3-luciferase, and this is enhanced when the activation function (AF)-2 domain is deleted but much reduced when the AF-1 domain is deleted. This suggests aberrant AF-2 activation domain function. We identified defective steroid receptor co-activator 1 (SRC1) recruitment to the GR AF-2 in COR L103 cells, although SRC1 was successfully recruited to the steroid X receptor with rifampicin, suggesting a defect in the GR. Analysis of other GR C-terminal co-factors identified increased expression of nuclear co-repressor (NCoR) in COR L103 cells. To determine the impact of this, NCoR was over-expressed in A549 cells, where it reduced GR transactivation by 55%.In summary, glucocorticoid resistance is associated with altered SRC protein recruitment and increased expression of NCoR in these SCLC cells, suggesting that glucocorticoid sensitivity may be modified by subtle changes in co-factor recruitment.

show abstract

“…Invariably, clinically manifested endocrine abnormalities in patients with lung tumors are associated with small cell carcinoma (156). For some time now, the lung K cell has been considered the cell of origin for lung small cell carcinomas and bronchial carcinoid tumors (14,(157)(158)(159)(160)(161)(162). This concept was based on the fact that these tumors revealed ultrastructural features, i.e., the presence of dense-core vesicles, and cytochemical properties which are similar to pulmonary K cells (14,112,157,159,163,164).…”

Section: Pathobiologymentioning

confidence: 99%

“…This concept was based on the fact that these tumors revealed ultrastructural features, i.e., the presence of dense-core vesicles, and cytochemical properties which are similar to pulmonary K cells (14,112,157,159,163,164). An "endocrine cell hypothesis" was formulated to explain ectopic hormone production in various organs (153,154,157,165,166). According to this hypothesis, tumors which synthesize ectopic hormones are derived from endocrine cells which previously had made a different hormone.…”

Section: Pathobiologymentioning

confidence: 99%