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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reviewed 31 patients in whom both bilateral inferior petrosal sinus sampling without CRH stimulation, and a CT scan of the lungs were done. Twenty-five had normal lung CT scans, of whom 23 had a higher inferior petrosal sinus: peripheral ACTH ratio > or = 1.5. After careful follow-up, none was subsequently shown to have ectopic ACTH syndrome. Six had abnormal lung CT scans, of whom two had ratios > or = 1.5. In these two patients, other investigations suggested pituitary disease, and pituitary surgery led to apparent cure. Of the remaining four patients, who had ratios < 1.5, two had incidental lung findings, and pituitary abnormalities were demonstrated at pituitary surgery. The third underwent bilateral adrenalectomy, and no evidence of ectopic ACTH syndrome has emerged as yet after 4 years follow-up. The fourth had a small-cell carcinoma of the lung, confirmed histologically. Our series suggests that whole-lung CT scanning is only necessary in cases of ACTH-dependent Cushing's syndrome where bilateral inferior petrosal sinus sampling has not demonstrated a significant increase in petrosal sinus ACTH levels as compared with the peripheral level. Thus, in our experience the test is now only necessary in those patients (approximately 25%) where the ratio is < or = 1.5.
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PMID:Is whole-lung CT scanning still necessary in all cases of ACTH-dependent Cushing's syndrome in the era of petrosal sinus sampling? 1061 9

Because high circulating levels of glucocorticoids impair immunity and predispose to infections, we evaluated whether indices of cortisol (F) production could predict infections in patients with Cushing syndrome (CS) caused by ectopic production of ACTH (EA). Charts of 54 consecutive patients with untreated EA, without underlying diagnosis of small cell carcinoma of the lung, were reviewed, and types of infections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydroxysteroid/g creatinine excretion (17OHS)], were recorded. Thirty-five patients had no or clinically mild infection; the remaining 19 patients had severe, systemic infection (n = 13) and/or sepsis (n = 6), including either bacterial or opportunistic pathogens or both (73.7%, 42.1%, and 13.8%, respectively). The latter group of patients had significantly higher indices of hypercortisolism (F, UFC, and 17OHS) than those with mild or no infections, but these indices did not correlate with temperature or WBC count. Thresholds for identifying severe infection were selected for maximal positive predictive value and were: F, 43.1 microg/dL; UFC, 2000 microg/day; and 17OHS, 35 mg/g creatinine. The most accurate discriminator for severe infection was 17OHS, based on a positive predictive value of 64.7%. Our data strongly suggests that the likelihood for a bacterial or opportunistic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The predictive value of total WBC count or the presence of an elevated temperature is not sufficient to identify patients with severe, life-threatening infection.
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PMID:Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. 1115 75

Ectopic POMC syndrome remains one of the most challenging differential diagnoses in endocrinology. Recent progress in the understanding of the tissue specific regulation of POMC gene expression and new insights into the processing of the POMC peptide in nonpituitary tissues has helped elucidate some of the molecular events leading to ectopic expression and secretion of POMC peptides. Corticotropin and other POMC-derived peptides have diverse effects on adrenal steroidogenesis, growth, and extra-adrenal tissues. Differences in POMC gene regulation in the corticotrope versus ectopic POMC-producing tumors provides a scientific framework for the clinical distinction between eutopic and ectopic Cushing's syndrome. In an attempt to revisit recent basic and clinical advances in the diagnosis of ectopic POMC syndrome the authors undertook an extensive literature review of 530 cases in 197 published papers and provided a molecular biologic, demographic and diagnostic update. According to this review, the four most common causes of ectopic POMC syndrome are the small cell carcinoma of the lung (27%), bronchial carcinoids (21%), islet cell tumor of the pancreas (16%), and thymic carcinoids (10%). Although the clinical features of patients with ectopic POMC syndrome are similar to those with Cushing's disease, subgroup analysis reveals a broad spectrum of severity and progression of signs and symptoms of hypercortisolism. The endocrine workup of a patient with suspected ectopic POMC syndrome includes the establishment of pathologic hypercortisolism, diagnosis of corticotropin dependency, and the differential diagnosis of corticotropin-dependent Cushing's syndrome. The use of a variety of baseline endocrine values, dynamic endocrine testing, and invasive procedures leads to the correct diagnosis in the majority of patients with ectopic POMC syndrome. Diagnostic imaging, including conventional radiological techniques and somatostatin receptor scintigraphy, aids in the correct localization and eventual treatment of ectopic POMC production.
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PMID:Ectopic pro-opiomelanocortin syndrome. 1205 89

DNA microarray techniques were used to compare gene expression in an adrenocorticotropin (ACTH)-producing human small cell lung carcinoma line (DMS-79) with six other small cell lung cancer (SCLC) lines that do not produce ACTH. Twelve genes were expressed at more than five-fold higher levels in DMS-79 cells. Two transcription factors were the genes that exhibited the most remarkable over-expression: T-box 3 mRNA was detected at levels 19.37 +/- 3.78 times those observed in the SCLCs. Thyroid transcription factor (TTF-1, T/ebp, Nkx2.1) was expressed at 14.24 +/- 3.41-fold higher in DMS-79 cells. Seven genes were identified whose expression levels were at least five-fold lower in the ACTH-producing cell line. Variation in culture medium formulation did not significantly affect the gene expression profile of DMS-79 cells and expression data observed in microarray experiments were corroborated by northern blot analysis of RNA from the same cell lines. These experiments reveal new candidate genes that could be involved in the dysregulation of POMC gene expression manifested by ACTH-producing nonpituitary tumors.
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PMID:Gene expression phenotyping of an ACTH-producing small cell lung cancer line. 1514 32

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. Over-expression 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.
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PMID:Analysis of co-factor function in a glucocorticoid-resistant small cell carcinoma cell line. 1553 25

Hepatic carcinoid tumors are very uncommon; most are clinically non-functional and very few present with the symptoms of carcinoid syndrome. ACTH-producing carcinoid tumors most commonly originate in the lung or thymus and present insidiously with bronchospasm and/or chest mass. Occasionally, ectopic ACTH syndromes have been reported in association with pancreatic islet cell tumors, medullary thyroid cancer, pheochromocytoma, small-cell lung carcinoma, and rarely, ovarian and prostate tumors. We report here a patient with an ectopic ACTH-secreting primary hepatic carcinoid tumor who presented with cushingoid appearance, profound proximal muscle weakness, severe lower extremity edema, and markedly elevated urinary free cortisol. ACTH levels were in the low normal range. A solitary vascular hepatic lesion was found on magnetic resonance imaging, which was isodense with the surrounding liver on octreotide scan and photopenic on an 18-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) scan. Following surgical resection of the hepatic tumor, histopathology confirmed an ACTH-secreting neuroendocrine tumor (NET), the patient had complete resolution of hypercortisolemic symptoms and remains in remission, now 4 yr after hepatic tumor resection. This case reports the first ACTH-secreting primary hepatic NET presenting as ectopic Cushing's syndrome. Interesting aspects of this case include the presence of a pituitary incidentaloma, the low normal ACTH, and photopenia on 18FDG-PET imaging.
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PMID:Primary hepatic carcinoid tumor presenting as Cushing's syndrome. 1755 71

Muscle weakness is a common complaint in clinical practice. If this symptom is combined with focal liver lesions there is a broad spectrum of differential diagnoses for the gastroenterologist to consider. Tumors of neuroendocrine origin such as small-cell lung carcinoma (SCLC) produce a wide array of peptide hormones and are common causes of paraneoplastic syndromes. We report on a 68-year-old woman who presented with progressing muscle fatigue and multiple liver lesions on ultrasonography. Hypertension, hyperglycemia, hypokalemia and metabolic alkalosis prompted consideration of underlying hypercortisolism. Further work-up demonstrated an acute ectopic ACTH syndrome as paraneoplastic manifestation of a small cell lung carcinoma. The woman deteriorated rapidly and finally died from intracranial tumor spread and septic complications. This case stresses the diagnostic and therapeutic difficulties of acute ectopic ACTH syndrome in the setting of SCLC.
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PMID:Making sense of muscle fatigue and liver lesions. 1762 Feb 25

Cushing's syndrome is rare and remains a challenge to diagnose. Particularly difficult are the differentiation between Cushing's syndrome and Pseudo-Cushing's states and between the two forms of ACTH dependent Cushing's: Cushing's disease and ectopic ACTH syndrome. We report the case of a patient diagnosed with a metastatic small cells lung carcinoma associated with ectopic ACTH-syndrome. Hypokalaemia was a clue to diagnosis. We focus on critical questions addressing diagnosis and differential diagnosis of Cushing's syndrome and we explain the mechanism of hypokalaemia.
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PMID:[Ectopic ACTH syndrome and severe hypokalaemia]. 1762 26

Severe psychosis in patients with Cushing's syndrome is rare and generally difficult to treat. We report a 46-yr-old woman suffering from Cushing's syndrome caused by an inoperable ACTH-producing lung carcinoma. She was initially treated with chemotherapy and radiotherapy. Six months later she presented with severe psychosis. Laboratory findings revealed a severe hypokalemia and metabolic alkalosis, which was caused by extremely high serum ACTH (788 ng/l) and cortisol (4.2 micromol/l). She was unresponsive to treatment with conventional antipsychotic drugs; she was therefore sedated and intubated. Treatment was started i.v. with etomidate, which blocks the cortisol synthesis, and orally by nasogastric tube with mifepristone, which competes with cortisol for binding to their receptors. To counteract adrenal insufficiency, she received corticosteroids. After 5 days there was a normalization of the ACTH, cortisol levels, and the metabolic disorders. After discontinuing etomidate she was extubated; there were no signs of psychosis observed. Computed tomography (CT) scan of the brain showed no metastasis, however CT scan of the abdomen showed liver metastasis and bilateral adrenal enlargement. Unfortunately, the clinical situation worsened and the patient died due to progression of the metastasis. This case report demonstrates the efficacy of a treatment of mifepristone with etomidate in a patient with an ectopic ACTH-producing Cushing's syndrome.
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PMID:Treatment of severe psychosis due to ectopic Cushing's syndrome. 1799 71

Once the diagnosis of Cushing's syndrome (CS) has been established, the main step is to differentiate between ACTH dependent and independent disease. In adults, 80% of CS is due to ACTH-dependent causes and 20% due to adrenal causes. ACTH-secreting neoplasms cause ACTH-dependent CS. These are usually anterior pituitary microadenomas, which result in the classic Cushing's disease. Non-pituitary ectopic sources of ACTH, such as a small-cell lung carcinoma or carcinoid tumours, are the source of the remainder of ACTH-dependent disease. In the majority of patients presenting with clinical and biochemical evidence of CS, modern non-invasive imaging can accurately and efficiently provide the cause and the nature of the underlying pathology. Imaging is essential for determining the source of ACTH in ectopic ACTH production, locating the pituitary tumours and distinguishing adrenal adenomas, carcinomas and hyperplasias. In our chapter we review the adrenal appearances in ACTH-dependent and ACTH-independent CS. We also include a discussion on the use of MRI and CT for the detection and management of pituitary ACTH secreting adenomas. CT of the chest, abdomen and pelvis with intravenous injection of contrast medium is the most sensitive imaging modality for the identification of the ectopic ACTH source and detecting adrenal pathology. MRI is used for characterising adrenal adenomas, problem solving in difficult cases and for detecting ACTH-secreting pituitary adenomas.
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PMID:Imaging in Cushing's syndrome. 1820 70


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