Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 72-year-old man was admitted to a general hospital with progressive liver dysfunction, hypokalemia, hyperglycemia, and nodules in the lung and liver and then transferred to our institution on the seventh hospital day. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol, and neuron-specific enolase concentrations were extremely high. He developed acute liver failure, his consciousness and general condition deteriorated rapidly, and he died on Day 11. At the postmortem examination, he was found to have extensive metastases from small-cell lung cancer, including advanced hepatic metastases. This is the first reported case of acute liver failure caused by metastases derived from an ACTH-producing pulmonary small-cell carcinoma.
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PMID:Acute Liver Failure Due to Severe Hepatic Metastasis of Small-cell Lung Cancer Producing Adrenocorticotropic Hormone Complicating Ectopic Cushing Syndrome. 3124 30

: Hypopituitarism includes all clinical conditions that result in partial or complete failure of the anterior and posterior lobe of the pituitary gland's ability to secrete hormones. The aim of management is usually to replace the target-hormone of hypothalamo-pituitary-endocrine gland axis with the exceptions of secondary hypogonadism when fertility is required, and growth hormone deficiency (GHD), and to safely minimise both symptoms and clinical signs. Adrenocorticotropic hormone deficiency replacement is best performed with the immediate-release oral glucocorticoid hydrocortisone (HC) in 2-3 divided doses. However, novel once-daily modified-release HC targets a more physiological exposure of glucocorticoids. GHD is treated currently with daily subcutaneous GH, but current research is focusing on the development of once-weekly administration of recombinant GH. Hypogonadism is targeted with testosterone replacement in men and on estrogen replacement therapy in women; when fertility is wanted, replacement targets secondary or tertiary levels of hormonal settings. Thyroid-stimulating hormone replacement therapy follows the rules of primary thyroid gland failure with L-thyroxine replacement. Central diabetes insipidus is nowadays replaced by desmopressin. Certain clinical scenarios may have to be promptly managed to avoid short-term or long-term sequelae such as pregnancy in patients with hypopituitarism, pituitary apoplexy, adrenal crisis, and pituitary metastases.
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PMID:Management of Hypopituitarism. 3181 11

Pituitary adrenocorticotropic hormone-dependent Cushing's syndrome due to ectopic production of corticotropin-refeasing hormone (CRH) or bombesin (gastrin-releasing peptide) is an extremely rare cause of pituitary adrenocorticotropic hormone (ACTH) hypersecretion. We report a patient with elevated ACTH and cortisol levels due to ectopic secretion of both bombesin and CRH by metastatic medullary carcinoma of the thyroid (MCT). A 45-year-old man was investigated because of diabetes insipidus and visual field disturbances due to suprasellar metastasis of the MCT. On physical examination, he was a chronically ill man with a body mass index of 18.5 and was darkly pigmented but without other features typical of Cushing's syndrome. Hypogonadotropic hypogonadism, thyroid-stimulating hormone (TSH) deficiency, and hyperprolactinemia were due to pituitary stalk disorder, in light of these deficiencies, we were surprised to find elevated plasma ACTH, cortisol, and growth hormone (GH) levels throughout the day. Plasma ACTH at 9AM was 118 pg/ml and plasma cortisol was 859 nmol/L. At 12PM, ACTH was 89 pg/ml whereas plasma cortisol was 540 nmol/L. Urinary 17 OH CS were elevated (38 nmol/24 hr). The mean of the four-point day curve for GH was elevated. Plasma electrolytes were normal. The presence of both CRH and bombesin was documented by immunocytologic studies in the metastases (lymph node and suprasellar biopsy). ACTH was not found in any of the metastases. Because of the close proximity of the suprasellar metastasis to the portal pituitary circulation, CRH and bombesin could have been readily provided to the pituitary corticotrophs.
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PMID:Elevated adrenocorticotropic hormone and cortisol levels in a patient with medullary carcinoma of the thyroid containing ectopic immunoreactive corticotropin-releasing hormone and bombesin. 3235 21

Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain-tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.
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PMID:The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management. 3242 87

Ectopic ACTH-secretion causing Cushing's syndrome is unusual and its diagnosis is frequently challenging. The presence of high-molecular-weight precursors throughout pro-opiomelanocortin (POMC) translation by these tumors is often not reported. We present the case of a 49-year-old woman with a 3-month history of proximal muscular weakness, skin pigmentation, and weight loss. Upon initial evaluation, she had a full moon face, hirsutism, and a buffalo hump. Laboratory workup showed hyperglycemia, hypokalemia and metabolic alkalosis. ACTH, plasma cortisol, and urinary free cortisol levels were quite elevated. Serum cortisol levels were not suppressed on dexamethasone suppression testing. An octreo-SPECT scan showed enhanced nucleotide uptake in the liver and pancreas. Transendoscopic ultrasound-guided biopsy confirmed the diagnosis of a pancreatic ACTH-secreting neuroendocrine tumor (NET). Surgical excision of both pancreatic and liver lesions was carried out. Western blot analysis of the tumor and metastases revealed the presence of a high-molecular-weight precursor possibly POMC (at 30 kDa) but not ACTH (normally 4.5 kDa). ACTH-precursor secretion is more frequent in ectopic ACTH-secreting tumors compared with other causes of Cushing's syndrome. Hence, the measurement of such ACTH precursors warrants further evaluation, especially in the context of ACTH-dependent hypercortisolism.
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PMID:High Molecular Weight ACTH-Precursor Presence in a Metastatic Pancreatic Neuroendocrine Tumor Causing Severe Ectopic Cushing's Syndrome: A Case Report. 3290 71


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