Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential efficacy of early repeat transsphenoidal surgery for persistent Cushing's disease has not previously been examined. On 222 patients with no prior pituitary treatment and a preoperative diagnosis of Cushing's disease, 29 (13%) remained hypercortisolemic after an initial transsphenoidal pituitary exploration. Seventeen of these 29 patients underwent further surgery 7 to 46 days after the initial transsphenoidal approach in order to completely excise suspected residual tumor. Patients were followed for 4 to 84 months (mean +/- standard deviation, 34 +/- 25 months) to document sustained remission or recurrence of Cushing's disease (a urine free cortisol level > 90 micrograms/day was considered evidence of recurrence). Of the 17 patients with repeat surgery, 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 micrograms/dl); however, in three of these 12, hypercortisolism recurred 5, 12, and 24 months later. In 14 patients a lesion that appeared to be a tumor was identified during the initial procedure or on histological examination. Of these, 12 had immediate resolution of hypercortisolism and nine are still in remission. Three patients, in whom no adenoma could be identified during the initial surgery or an examination of the partial hypophysectomy specimen from the initial surgery, had persistent Cushing's syndrome after the second operation. Seven (41%) of the 17 patients developed hypopituitarism requiring treatment with thyroid hormone, gonadal steroid, or vasopressin replacement. The low incidence of identification of an adenoma on computerized tomography or magnetic resonance images (three of 17 patients), the failure to find a corticotrophic adenoma during the initial surgery (10 of 17 patients), and the failure of these 17 patients to respond to the initial transsphenoidal surgery suggest that they may comprise a subset of patients who are more difficult to treat successfully with surgery than most patients with Cushing's disease. Despite that, early reoperation induced immediate remission of hypercortisolism in 71% of cases, but did so at the expense of a high risk of hypopituitarism. However, since the alternative treatments (such as radiation therapy, long-term drug therapy, or bilateral adrenalectomy) also have potential adverse effects, early reoperation deserves consideration for the management of persistent Cushing's disease, especially when an adrenocorticotrophic hormone-secreting adenoma was partially excised during the first surgery.
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PMID:Early repeat surgery for persistent Cushing's disease. 827 Oct 20

Cushing's syndrome occurs rarely; in analyzing 50 cases studied at our institution we discuss the following aspects: syndromatic diagnosis, etiologic differentiation into the 3 categories of the syndrome, and therapeutic strategies for each variety. We postulate that non-endocrinologists should be responsible for the syndromatic diagnosis, easily done by using 2 simple tools: the measurement of basal free urinary cortisol and the performance of an overnight suppression of the adrenal axis with 1 mg of dexamethasone (Nugent's test). In contrast, the etiologic diagnosis and the therapeutic interventions should be strictly restricted to highly specialized institutions having well seasoned endocrinologists, a reliable endocrine laboratory, easy access to computed tomographies of the brain and abdomen as well as to nuclear resonance imaging of the brain. The usefulness of our in-house devised vasopressin challenge following overnight dexamethasone suppression for the etiologic diagnosis is highlighted. Neurosurgical expertise in the transsphenoidal approach to the pituitary gland as well surgeons well experienced in adrenal surgery are a must to offer a reasonable chance of success to patients with the syndrome. Forty one (82%) of the series were female patients, 78% were pituitary-dependent and 22% pituitary-independent Cushings. Six out of 8 (75%) of the adrenal tumors were carcinomas. Only 3 patients (6%) qualified as ectopic ACTH syndromes. The easiest variety to diagnose and treat was the adrenal adenoma (2 cases); adrenal carcinomas were always incurable. The ectopic ACTH syndrome was amenable to successful medical treatment with ketoconazole or surgical resolution with complete resection of the offending tumor (1 of 3 cases) or bilateral adrenalectomy (2 of 3 cases) Pituitary-dependent Cushings are quite tricky to diagnose and difficult to treat. Transsphenoidal resection of the offending microadenoma was successful in only 43.5% (10/23) of cases and we experienced 3 recurrences of the syndrome even after 8 years of successful removal of the pituitary adenoma. The remainder had to be cured by bilateral adrenalectomy. Seven out of 39 patients with Cushing's disease (18%) ultimately died for a variety of reasons; six out of 6 patients (100%) with adrenal carcinoma died of dissemination; two out of 2 adrenal adenomas cured and 1 out of the 3 ectopic ACTH syndromes died of dissemination of a malignant thymic carcinoma. We conclude that Cushing's syndrome is a serious, underdiagnosed disorder, which should be suspected and diagnosed by the non specialized physician and then referred to a specialized center for expert etiologic diagnosis and surgical therapy.
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PMID:[Cushing's syndrome: review of a national caseload]. 852 77

Vasopressin is an important regulator of hypothalamo-pituitary-adrenal axis activation, primarily acting through the V3 receptor (V3R). Many patients with ACTH-secreting pituitary adenomas, but not normal individuals, respond to desmopressin, a relatively V2-specific vasopressin agonist, with increased ACTH and cortisol levels. We have searched for mutations of the V3R gene in ACTH-secreting pituitary adenomas and one ectopic ACTH-secreting tumor. No abnormalities were found in 12 tumors studied by PCR-single strand conformation polymorphism (PCR-SSCP) analysis. We then verified by RT-PCR whether the response to desmopressin was due to overexpression of the V3R or abnormal expression of the V2R in the pituitary tumor. We found that the V2R gene was expressed in a number of corticotroph tumors and in the ACTH-secreting ectopic tumor, and that the V3R gene appears to be overexpressed in these tumors. We conclude that V3R mutations are unlikely to be present in the ACTH-secreting tumors we examined, but that the V2R gene is expressed in the majority of the samples tested, and the V3R is expressed in all of these tumors. We speculate that the response to the desmopressin test observed in patients with Cushing's disease may be due to abnormal expression of V3R or V2R in ACTH-secreting tumors.
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PMID:Vasopressin receptor expression and mutation analysis in corticotropin-secreting tumors. 862 31

To assess the ability of desmopressin to differentiate between pituitary and ectopic ACTH-dependent Cushing's syndrome and to determine whether diagnostic accuracy could be improved by administering it together with human sequence CRH, we examined its effects on cortisol and ACTH secretion when given alone or in combination with CRH in patients with Cushing's syndrome of varied etiology and compared these data to the results of a standard CRH test in the same individuals. Each patient was studied on three occasions, in random order, separated by at least 48 h. At 0900 h, via an indwelling forearm cannula, 10 micrograms desmopressin, 100 micrograms CRH, or a combination of the two were given as an iv bolus; thereafter, blood was drawn every 15 min for 2 h. The responses to the individual agents were determined according to the timing and calculation criteria suggested by Nieman et al. (1993). A total of 25 patients with Cushing's syndrome were studied: 17 patients with pituitary-dependent Cushing's syndrome, Cushing's disease (CD); 5 patients with occult ectopic ACTH secretion (EC); and 3 patients with primary adrenal (ACTH-independent) Cushing's syndrome. In this series, the best discrimination among ACTH-dependent patient groups was achieved using the combined test. Using the responses of plasma cortisol, all 17 patients with CD showed a rise greater than any of the 5 patients with EC, whereas 1 patient with CD showed a plasma ACTH response within the range seen in the patients with EC. Plasma cortisol responses to desmopressin alone were seen in 14 of 17 patients with CD and 1 of 5 patients with EC and, after CRH alone, in 15 of 17 patients with CD but in no patient with EC. In contrast, plasma ACTH responses after CRH alone were seen in 14 of 17 patients with CD and 2 of 5 patients with EC and, after desmopressin alone, in 12 of 17 with CD and 3 of 5 with EC, thus indicating overlapping responses between the groups and poorer discrimination. No responses were seen in the ACTH-independent group. These data indicate that desmopressin causes the secretion of ACTH and cortisol in patients with ACTH-dependent Cushing's syndrome, and that in combination with CRH, it may provide an improvement over the standard CRH test in the differential diagnosis of ACTH-dependent Cushing's syndrome. Furthermore, these data suggest that there may be abnormalities in vasopressin receptor function or number in ACTH-secreting tumors.
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PMID:A combined test using desmopressin and corticotropin-releasing hormone in the differential diagnosis of Cushing's syndrome. 898 55

To investigate the expression of CRF receptor (CRF-R) in human corticotropic adenoma (hCA) cells, we analyzed messenger RNA (mRNA) levels of type-1 CRF-R (CRF-R1). Adenomas were obtained from 10 patients with Cushing's disease. Northern blot analysis using a rat CRF-R1 complementary RNA probe revealed a main hybridization band of 2.7 kilobases in all the hCAs. The CRF-R1 mRNA level significantly increased after 1 h, reached 15-fold the basal level at 8 h, and remained elevated 24 h after the addition of 10 nmol/L CRF in vitro. Dose dependency of the stimulatory effect of CRF was also demonstrated in hCA cells, whereas CRF down-regulated CRF-R1 mRNA levels in rat anterior pituitary (AP) cells. Treatment with dexamethasone or vasopressin decreased the CRF-R1 mRNA level in hCA cells, as observed in rat AP cells. In conclusion, we detected CRF-R1 mRNA in all hCAs tested. The CRF-R1 mRNA level was up-regulated by CRF itself in cultured hCA cells, in contrast to the down-regulation in rat AP cells.
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PMID:Corticotropin-releasing factor up-regulates its own receptor gene expression in corticotropic adenoma cells in vitro. 910 Jun

Simultaneous bilateral inferior petrosal sinus (IPS) sampling has been repeatedly proposed to be a highly specific approach for the diagnosis of Cushing's disease and 100% sensitivity in detecting autonomous pituitary ACTH secretion by an adenoma has been reported in a large series. We now report on a patient suffering from ACTH-dependent Cushing's syndrome in whom repeated bilateral IPS sampling failed to detect a central/peripheral gradient diagnostic for autonomous pituitary ACTH secretion during initial evaluation. Applying lysine vasopressin as the corticotroph secretatogue, the maximum central/peripheral gradient was 1.0 before and 1.1 following stimulation. Moreover, results of high dose dexamethasone and corticotrophin releasing hormone administration suggested ectopic ACTH secretion. Since thorough diagnostic procedures failed to localise a suspected carcinoid tumour, occult ectopic Cushing's syndrome was diagnosed. Eight years later, a pituitary macroadenoma was detected by magnetic resonance imaging (MRI), IPS catheterisation then revealed a maximal central/ peripheral gradient of 9.3 before and 20.4 after the intravenous administration of lysine vasopressin. Resected tumour tissue was classified as a typical densely granulated ACTH cell adenoma. We conclude that repeated MRI scans should be included in the follow-up of patients with a diagnosis of occult ectopic Cushing's syndrome to avoid the risk of overlooking 'occult eutopic Cushing's syndrome'.
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PMID:Occult eutopic Cushing's syndrome--failure of simultaneous bilateral petrosal sinus sampling to diagnose pituitary-dependent Cushing's syndrome. 924 5

A desmopressin-induced ACTH increase has been recently suggested to be specific for pituitary-dependent Cushing's disease. We present the case of a 47-year-old woman with Cushing's syndrome due to ectopic ACTH production by a bronchial carcinoid. While CRH failed to induce an ACTH or cortisol response, intravenous administration of desmopressin led to a 47% increase in serum ACTH and a 42% increase in serum cortisol concentration. After surgical removal of the tumour, the desmopressin response became negative. In vitro, ACTH production by tumour cells obtained at surgery was also stimulated by desmopressin but not by CRH. Additional receptor mRNA expression studies using RT-PCR revealed expression of both V2 and V3 vasopressin receptor subtypes in the carcinoid tumour at a level comparable to that recently described in pituitary corticotroph adenomas. This case illustrates that ACTH stimulation by desmopressin is not specific for pituitary-dependent Cushing's syndrome as vasopressin receptor subtypes known to interact with desmopressin may also be found in ectopic tumours producing ACTH.
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PMID:Ectopic ACTH production by a bronchial carcinoid tumour responsive to desmopressin in vivo and in vitro. 942 3

We evaluated the usefulness of a desmopressin (DDAVP) test in the diagnosis of ACTH-dependent Cushing's syndrome. After an intravenous injection of 5 microg DDAVP, plasma ACTH levels increased to more than 200% of the basal levels in 10 of 10 patients with Cushing's disease, but remained less than 150% in all of 11 normal subjects, 3 patients with Addison's disease, 5 cases of Cushing's disease in remission, and 3 patients with ectopic ACTH syndrome. Peak levels of plasma cortisol after the DDAVP stimulation were 159 +/- 14% in the patients with Cushing's disease, and less than 150% of the basal levels in the other 5 groups. We also found a case of Cushing's disease with periodicity which responded to DDAVP only in the active stage. In vitro studies revealed that DDAVP directly stimulates ACTH release from corticotropic adenoma cells through V1b but not V2 vasopressin receptors. In conclusion, the DDAVP stimulation test, i.e., determination of plasma ACTH levels after 5 microg DDAVP injection, seems useful for discriminating Cushing's disease from normality, and may serve to facilitate the differentiation between Cushing's disease and ectopic ACTH syndrome.
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PMID:Desmopressin stimulation test for diagnosis of ACTH-dependent Cushing's syndrome. 946 24

We studied the putative role of the vasopressin receptors in the phenotypic response of steroid-secreting adrenocortical tumors. A retrospective analysis of a series of 26 adrenocortical tumors responsible for Cushing's syndrome (19 adenomas and 7 carcinomas) showed that vasopressin (10 IU, i.m., lysine vasopressin) induced an ACTH-independent cortisol response (arbitrarily defined as a cortisol rise above baseline of 30 ng/mL or more) in 7 cases (27%). In comparison, 68 of 90 patients with Cushing's disease (76%) had a positive cortisol response. We then prospectively examined the expression of vasopressin receptor genes in adrenocortical tumors of recently operated patients (20 adenomas and 19 adrenocortical carcinomas). We used highly sensitive and specific quantitative RT-PCR techniques for each of the newly characterized human vasopressin receptors: V1, V2, and V3. The V1 messenger ribonucleic acid (mRNA) was detected in normal adrenal cortex and in all tumors. Its level varied widely between 2.0 x 10(2) and 4.4 x 10(5) copies/0.1 microgram total RNA, and adenomas had significantly higher levels than carcinomas, although there was a large overlap. Among the 6 recently operated patients who had been subjected to the vasopressin test in vivo, the tumor V1 mRNA levels were higher in the 4 responders (9.5 x 10(3) to 5.0 x 10(4)) than in the 2 nonresponders (2.0 x 10(2) and 1.8 x 10(3)). One adenoma that had a brisk cortisol response in vivo, also had in vitro cortisol responses that were inhibited by a specific V1 antagonist. In situ hybridization showed the presence of V1 mRNA in the normal human adrenal cortex where the signal predominated in the compact cells of the zona reticularis. A positive signal was also present in the tumors with high RT-PCR V1 mRNA levels; its distribution pattern was heterogeneous and showed preferential association with compact cells. RT-PCR studies for the other vasopressin receptors showed a much lower signal for V2 and no evidence for V3 mRNA. We could not establish whether the V2 mRNA signal observed in normal and tumoral specimens was present within adrenocortical cells or merely within tissue vessels. We conclude that the vasopressin V1 receptor gene is expressed in normal and tumoral adrenocortical cells. High, and not ectopic, expression occurs in a minority of tumors that become directly responsive to vasopressin stimulation tests.
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PMID:Variable expression of the V1 vasopressin receptor modulates the phenotypic response of steroid-secreting adrenocortical tumors. 962 35

Preclinical studies of inflammatory and autoimmune illnesses have demonstrated the importance of central components of the HPA axis in disease pathophysiology. The implications of these data for human illness are poorly understood. We have studied the pathophysiology of the hypercortisolism seen in two human illnesses involving the central nervous system, multiple sclerosis (MS) and depression, and looked for demonstrable somatic changes that may be associated with such hypercortisolism. Data from a study of medication-free patients with multiple sclerosis not in acute exacerbation suggest that compared with depression, MS is associated with increased prominence of hypothalamic vasopressin secretion (p < 0.05). Data from studies of depressed patients with mild to moderate hypercorticolism (assessed by 24-hour urinary free cortisol excretion) demonstrate marked reductions in bone mineral density compared to healthy, carefully matched controls (p < 0.001), as well as changes in markers of bone metabolic activity similar to those seen in patients with Cushing's disease or exogenous glucocorticoid treatment (p < 0.05). Taken together, these studies suggest HPA axis dysregulations demonstrated in preclinical models of autoimmune and inflammatory illness also occur in human illness and may have important and lasting somatic sequelae.
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PMID:Pathophysiologic and somatic investigations of hypothalamic-pituitary-adrenal axis activation in patients with depression. 962 98


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