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

o,p'-DDD, administered by mouth in doses of 1 to 7 grams daily for 5 to 42 days, was found to lower serum uric acid concentration in each of eight normouricemic patients (one with Cushing's disease and seven with metastatic cancer). The decrease ranged from 21 to 53% (average 39%) and the maximum effect was apparent in five to ten days. Urinary uric acid excretion showed no change, indicating that uric acid production was unaffected and that the hypouricemic effect resulted from an increase in the renal clearance of uric acid. The present findings introduce a new type of chemical compound to the group of known hypouricemic agents.
 ...
PMID:The hypouricemic effect of o,p'-DDD. 51 67

Knowledge of clinico-pathological correlations in canine Cushing's disease is rather poor. Therefore we describe, clinically and pathologically, a case of pituitary tumour-dependent Cushing's disease in an 8-year old female cocker spaniel. Based on our results, the tumour was defined as a non-dexamethasone-suppressive, corticotrophic adenocarcinoma characterized by some new findings such as intracerebral metastases of anti-ACTH-labelled tumour cells and combined alpha-, beta- and gamma 3-MSH immunoreactivity in the tumour.
 ...
PMID:A clinico-pathological study of canine Cushing's disease caused by a pituitary carcinoma. 166 39

A 53-yr-old man with Cushing's disease was found to have a pituitary carcinoma with metastases to the liver and lung which produced both CRH and ACTH simultaneously. Despite removal of the pituitary tumor, his Cushing's disease worsened. Endocrinological examination then demonstrated elevated plasma CRH and markedly elevated plasma ACTH, beta-lipotropin, and cortisol concentrations, increased urinary 17-hydroxycorticosteroid and 17-ketosteroid excretion, and no suppression of serum cortisol after low or high dose dexamethasone administration. Urinary 17-hydroxycorticosteroid excretion increased in response to metyrapone, and lysine vasopressin elicited a striking increase in plasma ACTH. A computed tomographic scan of abdomen revealed multiple hypodense areas in the liver and bilateral adrenal hyperplasia. Postmortem histological examination revealed a necrotic hemorrhagic pituitary carcinoma with metastases to the liver, lung, and olfactory bulb. Immunohistochemical staining, gel filtration, and Northern blot analysis of liver and lung metastases revealed evidence of the production of both CRH and ACTH in these metastases. We concluded that the patient's pituitary carcinoma produced both CRH and ACTH.
 ...
PMID:Corticotropin-releasing hormone- and adrenocorticotropin-producing pituitary carcinoma with metastases to the liver and lung in a patient with Cushing's disease. 169 98

We report the history, laboratory and histological findings in a man who presented with Cushing's disease. Despite removal of the primary pituitary tumour, his disease progressed and after bilateral adrenalectomy, he became pigmented and plasma ACTH levels remained elevated. He had further pituitary surgery and radiotherapy, to relieve compression of the optic chiasma. Plasma ACTH levels remained elevated. He developed liver, bone and lymph gland metastases and after an acute paraparesis due to spinal metastases he died. Immunoperoxidase staining techniques demonstrated ACTH in the pituitary recurrence and metastases. The combination of bone, liver and lymph node metastases has not previously been reported, nor has ACTH been reported before in metastases from a primary intrasellar tumour.
 ...
PMID:An intrasellar pituitary tumour producing metastases in liver, bone and lymph glands and demonstration of ACTH in the metastatic deposits. 300 76

Pituitary carcinoma is defined as a malignant pituitary tumour associated with blood- or lymph-borne metastases. Cushing's disease is frequently present in patients with this condition. After adrenalectomy for Cushing's disease, a 37-year-old man developed Nelson's syndrome resulting from a pituitary carcinoma with metastases to the spinal cord, cauda equina, heart, liver, and pancreas. The primary tumour and its metastases showed immunocytochemical staining for ACTH, beta-lipotrophin, and variably for beta-endorphin and alpha-melanocyte stimulating hormone (alpha-MSH). A coincidental glioblastoma was also present. Nine cases of Cushing's disease associated with pituitary carcinoma, including the present patient, are documented in the literature. The case reported is only the second in which immunohistochemical staining of the primary pituitary tumour and its metastases was performed, and the first in which ACTH-related peptides, in addition to ACTH itself, were demonstrated in the carcinoma cells.
 ...
PMID:Pituitary pro-opiomelanocortin-cell carcinoma occurring in conjunction with a glioblastoma in a patient with Cushing's disease and subsequent Nelson's syndrome. 302 76

109 cases of surgery on the adrenal glands are reported. 8 cases (7.3%) were reoperated because of relapse. This was Cushing's disease in 5 cases, malignant neuroblastoma in 2 cases and benign pheochromocytoma in 1 case. Only the latter and 1 with Cushing's disease were cured. Reoperation revealed carcinoma in 3 cases of Cushing's disease, though microscopic examination did not show malignancy in the specimen taken at the first operation. In another case microscopic examination again failed to show malignancy, but the patient died from her metastases. 2 cases of malignant neuroblastoma were reoperated for palliation.
 ...
PMID:[Problems and results of reinterventions on the adrenal gland]. 321 78

In the present study, the effects of o,p'-DDD on plasma levels of pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone, 11-deoxycorticosterone, deoxycortisol, corticosterone, cortisol, androstenedione and testosterone were studied in 6 patients with adrenal carcinoma (3 with Cushing's syndrome, 2 with adrenogenital syndrome, one without clinical manifestation) and 6 with Cushing's disease. Plasma levels of these steroids were decreased in all of the patients with adrenal carcinoma. The decrement of progesterone and 17 alpha-hydroxyprogesterone was greater than that of pregnenolone and 17 alpha-hydroxypregnenolone. These results indicate that o,p'-DDD inhibits both cholesterol cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase system. Plasma levels of pregnenolone and 17 alpha-hydroxypregnenolone showed a twofold increase on the 7th day after consecutive administrations of o,p'-DDD in patients with Cushing's disease. Plasma levels of cortisol were decreased to normal one month after continuous o,p'-DDD treatment. Urinary 17-OHCS and 17-KS have been decreased out of proportion to the decrease in plasma cortisol in the first week of o,p'-DDD treatment. Such a disparity suggests that o,p'-DDD might affect the extra-adrenal metabolism of cortisol. However, no evidence was found for the inhibition of hepatic C17-20lyase and glucuronyl transferase. Regression of pulmonary metastases was observed in one case with Cushing's syndrome due to adrenal carcinoma, suggesting that o,p'-DDD causes necrosis of the metastatic adrenal carcinoma. A remission of the disease was obtained in one patient with Cushing's disease after 6 months of continuous o,p'-DDD treatment. The usefulness of o,p'-DDD for the treatment of adrenal carcinoma with metastases and Cushing's disease was confirmed.
 ...
PMID:[The effects of o,p'-DDD on human adrenal steroid synthesis]. 609 74

A 36 year old woman with hypercorticism and markedly elevated blood ACTH levels underwent pituitary ablation because of suspected hypophysial Cushing's disease. Since no adenoma was detected in the anterior lobe and the hypercorticism persisted, a bilateral adrenalectomy was performed. Four months later lymph node and mediastinal metastases of an anaplastic small cell carcinoma, with the presence of argyrophil granulation, as well as immunoreactive 19-39ACTH, beta-LPH and alpha-endorphin, were found. The primary site of ectopic ACTH production was not revealed. A light and electron microscopic study of the adrenals, in addition to cortical hyperplasia, disclosed numerous small cells associated with nonmyelinated sympathetic nerve fibers and containing cytoplasmic inclusions indistinguishable from Reinke crystals. The Leydig-like cell-nonmyelinated nerve complexes, noted in both the adrenal cortex and medulla, showed perivascular localization, and their morphologic features were similar to those of hilus cells of the ovaries or extraglandular Leydig cells of the testis. The underlying mechanism accounting for the development of Leydig-like cells remained obscure; cytodifferentiation from pluripotent mesenchymal cells, possibly mediated by secretory products of sympathetic nerve fibers, may provide an explanation for their formation.
 ...
PMID:Leydig-like cells in the adrenals of a woman with ectopic ACTH syndrome. 719 May 43

Ectopic ACTH syndrome represents a cancer-induced amplification of a property [proopiomelanocortin (POMC) peptides production] normally present in the cells from which the cancer originated but with aberrant posttranslational processing of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic ectopic ACTH-producing tumors described in the 1960s were highly malignant but more recently slowly growing tumors such as carcinoids are reported with increasing frequency. Clinical features of patients with ectopic ACTH were analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal sinus ACTH sampling before and after oCRH. Among the tumor markers examined, elevation of ACTH precursors was uniformly present followed by increased output of calcitonin, gut hormones, oncofetal and placental hormones in decreasing order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and chromogranins are very useful. The imaging procedures for localization of the tumor ranged from chest X-rays to computed tomography and magnetic resonance of the chest and abdomen. Abdominal ultrasonography was also useful. Finally somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors and/or metastases, even when the tumors were occult. The ACTH content, immunostaining for APUD markers and altered POMC processing were evaluated in ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4-6 months of symptoms without the emergence of an obvious source was reviewed. Since the tumors are often clinically and biochemically undistinguishable from pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6 published cases) leading to excessive stimulation of the pituitary which became hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12 published cases and 1 unreported patient with ectopic CRH-ACTH tumors were reviewed, the majority being metastatic small cell lung carcinomas, bronchial and thymic carcinoids.
 ...
PMID:Ectopic ACTH syndrome. 762 46

In pediatric patients, endogenous Cushing syndrome is an infrequent condition almost always due to one of two conditions. 1) Adrenal gland tumors account for 70% of Cushing syndromes in young pediatric patients. They cause rapidly progressive hypercorticism not due to increased ACTH production (elevated plasma and urine cortisol levels, very low ACTH and LPH levels unchanged by dexamethasone, metyrapone or CRH). Imaging techniques determine the side and spread of the tumor and look for metastases. Following surgical removal, patients with indicators of malignant disease (tumor weight above 30 g, extracapsular spread or metastases, independently from pathological data) are given op'DDD. 2) Cushing disease occurs in peripubertal patients and causes overweight with delayed statural gain. ACTH production is increased (positive dexamethasone suppression test and provocative metopirone and CRH tests) as a result of a pituitary adenoma which should be looked for by magnetic resonance imaging and whose removal ensures recovery in 50% of cases. Other therapeutic tools include op'DDD, radiation to the pituitary, and bilateral adrenalectomy as the last resort given the high risk of post-adrenalectomy pituitary tumor (50% of pediatric patients). Other causes are exceedingly rare: primary nodular hyperplasia of the adrenal glands and production of ACTH by a nonpituitary tumor. Corticosteroid treatment is the most common cause of Cushing syndrome in children.
 ...
PMID:[Cushing syndrome in children]. 823 97


1 2 3 4 Next >>