PubMed · 9172543
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K Tanaka, M Toriumi, S Itoh, Y Ogino. 1997. [CRH-test].. https://pubmed.ncbi.nlm.nih.gov/9172543/
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The ectopic ACTH syndrome results from the transcription of the proopiomelanocortin (POMC) gene in non pituitary tumors. To determine its mechanisms, we examined in the human bronchial carcinoma cell line DMS-79 transacting factors binding to the human POMC gene promoter. Three binding sites were identified in the proximal promoter and proteins were studied by gel-shift assays. One of them is a binding site for Nur77/Nurr1 proteins in corticotroph cells but is bound in DMS-79 cells by factor(s) distinct from these proteins. The remaining two binding sites bound yet unidentified proteins and were both functionally active in DMS-79 cells. We also showed that DMS-79 cells lacked a factor required for tissue-restricted POMC gene expression in corticotroph cells. Altogether, our results indicate that POMC gene expression in DMS-79 cells is achieved without several of the corticotroph factors and provide a preliminary characterization of some factors involved in this process. They also reveal that DMS-79 cells are deficient in proteins involved in the regulation by cAMP and glucocorticoids.
Bilateral diffuse lung uptake of In-111 pentetreotide (OCT) was observed during a whole-body scan performed in a 68-year-old woman with Cushing's syndrome and suspected ectopic adrenocorticotropic hormone secretion. A few days later, she was found to have bilateral bacterial pneumonia (of mixed anaerobic origin). Cushing's syndrome was finally proved to be of pituitary origin. The OCT lung uptake in pneumonia probably resulted from tracer binding by somatostatin receptors on the inflammatory leukocytes. Although the rapid wash-out from experimentally induced abscesses does not make OCT a suitable tracer for detecting acute infections, the images and data here reported suggest that infectious lung disease should be excluded before diagnosing lung involvement by neuroendocrine tumors.
The clinical, biochemical, and radiological features of pituitary ACTH-dependent Cushing's syndrome (CS) [Cushing's disease (CD)] are often indistinguishable from those of occult ectopic ACTH-dependent CS (oEAS). We have evaluated, retrospectively, the results of simultaneous bilateral inferior petrosal sinus (IPS) ACTH sampling before and after CRH stimulation in 128 patients with ACTH-dependent CS: 107 patients with CD, 6 with oEAS, 1 with an adrenal adenoma, 1 with a pituitary gangliocytoma, and 1 with Nelson's syndrome; while, in the remaining 12, the source remains unclear. One hundred seven patients received human-sequence CRH (hCRH), and 11 received ovine CRH; another 6 patients underwent stimulation with desmopressin and hCRH, and 4 with desmopressin alone. A successful bilateral IPS catheterization and sampling (IPSCS) rate of 87.5% was obtained only after considerable experience had been gained. Sixty-nine patients with CD underwent successful bilateral IPSCS: the IPS-to-peripheral ratio of plasma ACTH value (IPS/P) rose from 9.5 +/- 1.4 to a maximum ratio of 55.8 +/- 7.5 in 67 patients, after CRH stimulation. The maximum ratio was obtained at 5 min in 60 of the 69 patients with CD; however, all 69 patients obtained a ratio of more than 2, at that time. In contrast, the 6 patients with occult ACTH-secreting neoplasms had a maximal IPS/P ratio of 1.3 +/- 0.16, and this did not change after CRH stimulation. A bilateral IPS/P ratio more than 2, obtained 5 min after CRH stimulation, had a sensitivity of 97% and a specificity of 100% in diagnosing CD. Two patients with proven active CD had an IPS/P ratio of less than 2. After successful bilateral IPSCS, the gradients between the IPS ACTH concentrations [IPS ACTH gradient (IPSG)] of more than 1.4, at 5 min after CRH stimulation, had a sensitivity of 83% in correctly lateralizing the pituitary microadenoma, compared with 72% sensitivity for magnetic resonance imaging (MRI) scanning. Furthermore, when IPSG and MRI findings were contradictory, IPSG was more often correct than MRI scanning. Although oEAS is a relatively uncommon cause of ACTH-dependent hypercortisolism (5.5% in our series), the accurate diagnosis of ACTH-dependent CS and localization of an intrapituitary microadenoma requires bilateral IPSCS with CRH stimulation, provided that the appropriate technical experience is available. hCRH is as effective a secretagogue as ovine CRH, and either may be used. The value of the combination of CRH and desmopressin stimulation requires more detailed investigation.