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)

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.
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PMID:[Cushing syndrome in children]. 823 97

A 62-year-old male with small cell lung cancer (SCLC) associated with Cushing's syndrome and diabetes insipidus (DI) is reported. The patient was referred to our hospital for treatment of SCLC. A diagnosis of paraneoplastic Cushing's syndrome was made on the basis of an elevated serum ACTH (623.5 pg/ml) level, elevated excretion of urinary 17-OHCS (18.01 mg/day), obesity, hypertension, hyperglycemia, persistent hypokalemia, alkalosis, and no history of diabetes mellitus. He was also diagnosed as having DI based on polyuria and polydipsia, low specific gravity of the urine (1.007-1.010), low serum ADH (1.4 pg/ml) level, normal plasma osmolarity (29 mOsm/kg H2O), and the results of water deprivation test. DI and a left visual field defect was suggestive of metastasis to the pituitary region, but no lesion was detected by either CT scan or MRI scan. The patient failed to show a good response to intensive chemotherapy, and died of the tumor five months after commencing chemotherapy. Post-mortem examination revealed metastases to the hypothalamic-neurohypophyseal region, lungs, liver, adrenal glands, bone, bone marrow, and hilar and mediastinal lymph nodes.
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PMID:[A case of small cell lung cancer associated with diabetes insipidus and Cushing's syndrome]. 839 May 89

The radiological features of 14 patients with Cushing's syndrome due to 'occult' ectopic ACTH syndrome have been reviewed. In 11 of the 14 patients (79%), the ACTH-producing tumour was located in the thorax. Bronchial carcinoid tumours (eight patients) were the single most common source of 'occult' ectopic ACTH production with thymic carcinoid tumours (two patients) and mediastinal metastases from a medullary carcinoma of the thyroid gland (one patient) accounting for the other intrathoracic tumours. The tumours were usually small with five of the eight bronchial carcinoid tumours measuring between 4 and 10 mm in diameter. Since it remains difficult to distinguish between pituitary-dependent Cushing's disease and 'occult' ectopic ACTH-dependent Cushing's syndrome both clinically and biochemically, the role of radiology remains vital.
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PMID:The radiological investigation of occult ectopic ACTH-dependent Cushing's syndrome. 839 21

An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is reported. The patient was a 63-yr-old man with multiple bone metastases from an undetermined primary site. Hyperpigmentation was observed at the terminal stage. The plasma levels of ACTH, cortisol, chromogranin A, and urinary 17-hydroxy-corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine tumor was diagnosed. In addition, plasma CRH was high. Autopsy revealed that the patient had primary thymic carcinoid with extensive metastases. Remarkable hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the pituitary gland were consistent with Cushing's syndrome by ectopic ACTH production. There were multiple CRH-producing cells without degenerative changes in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger ribonucleic acid were detected in the tumor cells by an in situ hybridization method. Expression of PC2 was considered to induce hyperpigmentation by producing alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor cells, hypothalamic CRH cells were not atrophic. This case is a good example to demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal axis as well as hyperpigmentation in Cushing's syndrome.
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PMID:Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone. 855 Jul 83

A 63-year-old man was admitted to Sendai Red Cross Hospital complaining of chest and back pain associated with Cushing's syndrome. Based on the abnormally high levels of ACTH, cortisol, and CRH in plasma the patient was suspected of having ectopic ACTH syndrome. Histological examination of an extirpated rib and pleural tumor led to the diagnosis of atypical carcinoid tumor, with ribbon and festoon formation, immunoreactivity to ACTH, NSE, Chg-A, and argyrophilia in the tumor cells. Anti-cancer chemotherapy was not effective, and the patient died within a year after the onset of Cushing's syndrome. An autopsy revealed that the patient had an ACTH- and CRH-producing thymic carcinoid with metastases to many organs. The pituitary was atrophic with Crooke's hyaline change. There were many CRH-positive cells in the paraventricular nuclei of the hypothalamus, where no remarkable pathologic changes were seen.
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PMID:[Thymic carcinoid associated with ectopic ACTH syndrome]. 869 71

We report a 73-year-old woman with rapidly developing symptoms and signs of Cushing's syndrome and high urinary free cortisol. She was virilized and hirsute with testosterone levels which became exceptionally high. ACTH was suppressed and CT scan of the adrenals and pelvis showed no abnormality. Ultrasound scanning showed enlargement of the left ovary. Venous catheter studies suggested a left ovarian source. A 2-cm diameter lipid cell tumor was removed from the left ovary laparoscopically. Histology was initially benign, and clinical and biochemical cure of Cushing's syndrome was rapid. However, the neoplastic nature of the ovarian tumour was demonstrated 12 months later when peritoneal metastases were detected and there was then clinical and biochemical relapse.
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PMID:An ovarian lipid cell tumour causing virilization and Cushing's syndrome. 875 86

The effects of somatostatin and its analogs have been studied in different subclasses of patients with Cushing's syndrome (due to Cushing's disease, ectopic corticotropin [ACTH]- and/or corticotropin-releasing hormone [CRH]-secreting tumors, or ACTH-independent Cushing's syndrome) and in patients with Nelson's syndrome. In most patients with untreated Cushing's disease, octreotide does not suppress ACTH release, a finding that is supported by in vitro studies. However, octreotide or somatostatin inhibits pathological ACTH secretion in Nelson's syndrome. Short-term octreotide treatment has caused a significant initial response (decreased serum cortisol, ACTH, and cortisoluria) in 24 of 38 (64%) patients with ectopic ACTH/CRH Cushing's syndrome, and long-term treatment caused a persistent response in 10 of 14 (71%) cases. Pentetreotide scintigraphy may help to identify those patients with ectopic ACTH/CRH tumors who will have an initial response to octreotide, and is useful for locating ectopic ACTH/CRH-secreting tumors and their metastases. To date, octreotide has been shown to temporarily suppress gastric inhibitory peptide (GIP)-induced cortisol secretion in GIP-dependent (ACTH-independent) Cushing's syndrome, but has not shown any therapeutic benefit in other forms of ACTH-independent Cushing's syndrome.
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PMID:Is there a role for somatostatin and its analogs in Cushing's syndrome? 876 91

In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2-26). The compounds were tested in vitro for inhibition of the three targets enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition P450 18 (bovine adrenal mitochondria), P450 scc (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vitro, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre-and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found; 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone (4) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin (12) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12, the 6-OCH3 derivative (compound 11) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone (13) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin (17) as well 2-(imidazol-1-ylmethyl)-tetralin (16) and 7-OCH3-2-imidazol-1-yl-3, 4-dihydronaphthalene (25) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests.
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PMID:Synthesis and evaluation of azole-substituted tetrahydronaphthalenes as inhibitors of P450 arom, P450 17, and P450 TxA2. 877 34

The non-neoplastic and neoplastic lesions in adrenals, thyroids, pituitary, uterus, ovaries, testes and mammary gland of senile untreated Sprague-Dawley rats were evaluated. The correlation between the neoplastic and non-neoplastic lesions in the pituitary gland and those in the target organs was made. The pituitary gland of the senile Sprague-Dawley rats had focal or diffuse hyperplasia and/or hypertrophy of PRL, STH, and ACTH cells. Approximately 47% of the males and 62% of the females had pituitary adenomas. Multiple adenomas in the same pituitary were noted in 7% of the males and in 11% of the females. Although many adenomas contained pleomorphic foci and quite a number of mitotic figures and were locally invasive, no evidence of distant metastases was discovered; therefore carcinoma was not diagnosed in the present material. The adenomas observed were divided into different types on the basis of the cytological characteristics of the cellular elements. Single cell-type adenomas such as PRL-, ACTH-, STH-, TSH-, immature- gonadotrophin-cell adenomas, and mixed cell (more than one cell type) adenomas were diagnosed. The adenomas containing PRL cells were the predominant type of neoplasms and they represented 30% and 34% of the total pituitary neoplastic lesions observed in males and females, respectively. The cytological changes in the hypophyseal cell types in senile Sprague-Dawley rats were usually accompanied by spontaneous non-neoplastic and neoplastic lesions in adrenals, thyroids, testes, ovaries, and mammary gland. The possible role of the hypophyseal hormones in the induction of the non-neoplastic and neoplastic lesions in the target organs is discussed. The combination of the spontaneous endocrine tumors could be associated both with aging and with genetic background of the animals. In addition, this polyglandular proliferative lesion in Sprague-Dawley rats might represent a potential model of mixed MEN syndrome.
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PMID:Neoplastic and non-neoplastic lesions in the mammary gland, endocrine and genital organs in aging male and female Sprague-Dawley rats. 878 9

This paper reports the experience of five Belgian surgical teams with 18 videoendoscopic adrenalectomies performed on 16 patients between October 1993 and May 1995. The adrenal gland diseases were pheochromocytoma (4 patients), primary hyperaldosteronism (2 cases), Cushing's adenoma (2 cases), Cushing's disease (1 case), nonfunctional adenoma (3 cases), single metastasis from adenocarcinoma (2 cases), functional adenoma with dehydro-epiandrostenedione (DHEAS) and cortisol hypersecretion (1 case), ACTH secreting metastases from a thymoma (1 case) Two patients underwent bilateral adrenalectomies. Eleven left and three right adrenal glands were removed in 14 other patients. The eight women and eight men range in age from 17 to 72 years (median 47). Six patients demonstrated a body mass index greater than 30. Median tumor size was 3 cm (range 1.3 - 5). Laparoscopic adrenalectomy was successful in 14 patients (87%). The median duration of the procedure was 132 minutes (range 59-360). The median postoperative stay was 6 days (range 2-13). No patient required blood transfusion. We conclude that the videoscopic approach can safely be used for surgical removal of adrenal lesions. However this approach should be performed by surgeons well versed in the techniques of open adrenalectomy for endocrine disorders, but also well trained in videoendoscopic surgery.
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PMID:Videoendoscopic adrenalectomy: multicentric study from the Belgian Group for Endoscopic Surgery (BGES). 880 96


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