Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 39-year-old Chinese man with hypertension being evaluated for elevated serum alkaline phosphatase (SAP) levels was found to have an incidental right adrenal mass. The radiological features were characteristic of a large adrenal myelolipoma. This mass was resected and the diagnosis confirmed pathologically. His blood pressure normalised after removal of the myelolipoma, suggesting that the frequently observed association between myelolipomas and hypertension may not be entirely coincidental. Persistent elevation of the SAP levels and the discovery of hypercalcaemia after surgery led to further investigations which confirmed primary hyperparathyroidism due to a parathyroid adenoma. The patient's serum biochemistry normalised after removal of the adenoma. The association of adrenal myelolipoma with primary hyperparathyroidism has been reported in the literature only once previously. Although unconfirmed by genetic studies this association may possibly represent an unusual variation of the multiple endocrine neoplasia type 1 syndrome.
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PMID:The elevated serum alkaline phosphatase--the chase that led to two endocrinopathies and one possible unifying diagnosis. 1006 58

Prevention of secondary hyperparathyroidism (SHPTH) and treatment of the moderate cases by small p.os doses of Vitamin D has not been thoroughly investigated on the long term, while large doses of Vitamin D have been successful in the short term treatment of this entity. We administered calcitriol p.os 0.5-1.0 microgram, according to iPTH levels, after each dialysis session, in 19 patients (group A) for 36 months. They were ten men and nine women, 63 years old (43-81), with iPTH levels > 4N (419 +/- 185 pg/mL). Seven adenomas were found in five of them (group A1). Serum Ca, phosphate (P) and alkaline phosphatase (AP) were measured every 15-30 days. Serum iPTH and aluminum as well as echogram or scanning of the parathyroid glands were checked every 6 months. Ten additional dialysis patients, seven men and three women, 54.5 years old (36-68), non-significantly different to group A in iPTH levels (290 +/- 225 pg/mL) with three adenomas in two of them (group B1) received no calcitriol and served as controls (group B). Calcitriol treatment significantly lowered serum iPTH levels in group A patients (from 419 +/- 185 to 173 +/- 142 pg/mL, p < 0.0001, delta iPTH: -246 +/- 161 pg/mL); iPTH remained stable in group B patients (delta iPTH: +7.9 +/- 116 pg/mL) with an intergroup significant difference at P < 0.0001. All other parameters measured did not show any significant change. No significant correlation of iPTH to Ca, P or AP was found in A. Initial iPTH levels were higher in A1 and B1 patients and decreased by calcitriol in A1 group. Adenomas in A1 patients did not change in number and size in contrast to B1 where new adenomas appeared (5 patients, 10 glands). Small doses of vitamin D lower high iPTH levels and prevent parathyroid gland hyperplasia. Existing hypertrophy is stabilized under calcitriol treatment both morphologically and biologically.
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PMID:Long-term effects of small doses of calcitriol in hemodialysis patients with moderate secondary hyperparathyroidism. 1008 80

The hydrolysis of sphingomyelin generates key molecules regulating cell growth and inducing apoptosis. Data from animal cancer models support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. In the intestinal tract, a sphingomyelinase with an optimum alkaline pH has been identified. We recently found that the activity of alkaline sphingomyelinase is significantly decreased in colorectal adenocarcinomas, indicating a potential anticarcinogenic role of this enzyme. To further examine whether the reduction of sphingomyelinase is present already in the premalignant state of neoplastic transformation, we measured sphingomyelinase activities in patients with familial adenomatous polyposis (FAP) and in sporadic colorectal tubulovillous adenomas. Tissue samples were taken from adenomas and surrounding macroscopically normal mucosa from 11 FAP patients operated with ileorectal anastomosis, from three FAP patients with intact colon, from 13 patients with sporadic colorectal adenomas and from 12 controls. Activities of acid, neutral and alkaline sphingomyelinase were measured together with alkaline phosphatase. In FAP adenoma tissue, alkaline sphingomyelinase activity was reduced by 90% compared to controls (P < 0.0001), acid sphingomyelinase by 66% (P < 0.01) and neutral sphingomyelinase by 54% (P < 0.05). Similar reductions were found in the surrounding mucosa. In sporadic adenoma tissue, only alkaline sphingomyelinase was reduced significantly, by 57% (P < 0.05). Alkaline phosphatase was not changed in FAP adenomas, but decreased in the sporadic adenomas. We conclude that the markedly reduced levels of alkaline sphingomyelinase activities in FAP adenomas and in the surrounding mucosa may be a pathogenic factor that can lead to unrestrained cell proliferation and neoplastic transformation.
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PMID:Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key factor to the unrestrained cell proliferation? 1049 47

Multiple endocrine neoplasia type 1 was diagnosed in a 12-year-old male crossbred dog. Relevant history included polyuria and polydipsia of four months' duration. Physical examination revealed abdominal enlargement, seborrhoea and polypnoea. Diagnostic tests indicated hypercalcaemia, elevated serum alkaline phosphatase and alanine aminotransferase, an exaggerated response to adrenocorticotropic stimulation of the adrenal gland, lack of cortisol suppression with a low dose dexamethasone suppression test and suppression of cortisol secretion with a high dose dexamethasone test. An enlarged right parathyroid gland was removed surgically and confirmed histopathologically to be a parathyroid adenoma. The pituitary-dependent hyperadrenocorticism was treated successfully with mitotane for 14 months before the patient was euthanased for an unrelated problem.
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PMID:Multiple endocrine neoplasia type 1 in a crossbred dog. 1070 Nov 89

In primary hyperparathyroidism, adenoma size is a major determinant of disease severity and manner of presentation, but the reason for the large variation in size (>100-fold) is unknown. One factor could be the level of vitamin D nutrition, because in India, where vitamin D deficiency is endemic, adenomas are larger and the disease more severe than in the U.S. Accordingly, we determined the relationship between vitamin D nutrition, as measured by serum levels of 25-hydroxyvitamin D (25OHD), and parathyroid gland weight, expressed on a logarithmic scale, in 148 U.S. patients with primary hyperparathyroidism. A significant inverse relationship was found between log gland weight as dependent variable and serum 25OHD as independent variable (r = -0.365; P < 0.0001). The only other influence on gland weight was a weak inverse correlation with age. Log gland weight as an independent variable was significantly related to adjusted calcium, PTH, and alkaline phosphatase (AP) as dependent variables. In 51 patients with serum 25OHD levels less than 15 ng/mL, gland weight, PTH, AP, and adjusted calcium were each significantly higher than in 97 patients with 25OHD levels of 15 ng/mL or more, but 1,25-dihydroxyvitamin D levels were similarly increased in both groups. In the former group the response of adjusted calcium to PTH was blunted, and the response of AP was enhanced, based on significant differences in regression slopes (P = 0.0004 and 0.0022, respectively). Suboptimal vitamin D nutrition stimulates parathyroid adenoma growth by a mechanism unrelated to hypocalcemia or 1,25-dihydroxyvitamin D deficiency and reduces the calcemic response to PTH, so that a higher PTH level and more parathyroid cells are needed to raise the patient's serum calcium to the level corresponding to the increased set-point that is characteristic of the disease. Improved vitamin D nutrition in the population is partly, perhaps largely, responsible for the historical changes in disease severity and manner of presentation that have occurred over the last 50 yr.
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PMID:Effect of vitamin D nutrition on parathyroid adenoma weight: pathogenetic and clinical implications. 1134 51

Vitamin D3 is believed to reduce the risk of colon cancer, and serum levels inversely correlate with colorectal cancer incidence. The active metabolite, 1alpha,25-dihydroxyvitamin D3, has previously been shown to inhibit growth and promote differentiation of colon cancer cells. The vitamin D analogue, EB1089, is currently under clinical trial in a variety of cancers because of its growth-inhibitory effects in vitro and reduced hypercalcemic effects in vivo. The mechanism of growth inhibition by EB1089, however, remained to be determined. In this study we examined the effects of alpha,25-dihydroxyvitamin D3 and EB1089 on five colorectal tumor cell lines (two adenoma and three carcinoma) to determine the mechanism of growth inhibition and to ascertain whether premalignant adenoma cells were responsive to these agents. 1alpha,25-Dihydroxyvitamin D3 and EB1089 induced p53-independent apoptosis in adenoma and carcinoma cell lines in a dose-dependent manner between 10(-10) and 10(-6) M. EB1089, as well as inducing apoptosis, increased the proportion of cells in the G1 phase, particularly in the adenoma cell lines. In two of the three carcinoma cell lines (SW620 and PC/JW), levels of apoptosis induced by EB1089 were similar or greater than those induced by 1alpha,25-dihydroxyvitamin D3. Although the carcinoma cell line HT29 was relatively resistant to apoptosis induced by EB1089 compared with 1alpha,25-dihydroxyvitamin D3, EB1089 markedly inhibited cell yields. These observations offer promise for the clinical use of EB1089. To determine whether the induction of apoptosis by 1alpha,25-dihydroxyvitamin D3 and EB1089 was potentially via a differentiation pathway, alkaline phosphatase activity was measured as a marker of differentiation. Induction of alkaline phosphatase was observed in the floating apoptotic cells as well as in the adherent population. A link between the induction of differentiation and apoptosis by 1alpha,25-dihydroxyvitamin D3 and EB1089 is suggested by the occurrence of apoptosis subsequent to the induction of differentiation. To investigate the molecular pathway to apoptosis induction, members of the Bcl-2 family of proteins were examined (Bcl-2, Bcl-x, Bax, and Bak). Decreased Bcl-2 was observed in some cell lines, particularly in response to EB1089, but was not essential for apoptosis. Levels of the proapoptotic protein Bak, however, were consistently increased in all of the five cell lines in association with apoptosis induced by either agent. The results implicate Bak protein in the induction of apoptosis by 1alpha,25-dihydroxyvitamin D3 or its analogue EB1089. The ability of EB1089 to induce apoptosis in colorectal carcinoma cells suggests that this or other vitamin D analogues may prove clinically effective for the treatment of colorectal cancer. Furthermore, the fact that it induces cell cycle arrest and apoptosis in the premalignant adenoma cells may suggest an application in colorectal cancer chemoprevention.
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PMID:Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. 1078 99

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.
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PMID:Postoperative elevated serum levels of intact parathyroid hormone after surgery for parathyroid adenoma: sign of bone remineralization and decreased calcium absorption. 1103 1

Humans may be exposed to 2-aminoanthracene (2-AA), a substituted polycyclic aromatic hydrocarbon, and a recognized mutagen and carcinogen, through oral and respiratory routes from contact with a variety of environmental sources. For the present study, we sought to evaluate hepatic damage and recovery in Fischer 344 rats following multiple i.p. injections of 5 mg of 2-AA. Rats were injected weekly for up to 5 weeks. Subgroups were then allowed to recover for 1, 5, or 9 weeks, and biochemical and pathologic changes were evaluated. We observed that weight gains were reduced relative to controls for all groups receiving > or = 2 injections. Serum enzyme levels indicative of liver damage were evident and included alterations in serum aspartate aminotransferase, alkaline phosphatase, total protein, albumin, and globulin. These alterations usually returned to normal by 5 weeks following cessation of 2-AA administration. In contrast, histologic liver changes, including hepatocyte hypertrophy, biliary hyperplasia with oval cell proliferation, altered foci, nodular hyperplasia, and one hepatocellular adenoma became more severe with time. This experiment demonstrates patterns of hepatic damage and recovery in rats exposed to 2-AA.
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PMID:Hepatic toxicity and recovery of Fischer 344 rats following exposure to 2-aminoanthracene by intraperitoneal injection. 1144 19

A 35-year-old woman with neurofibromatosis 1 and thoracic kyphoscoliosis had incomplete paraplegia. She had a history of hyperparathyroidism due to a parathyroid adenoma which had been excised 4 years previously. Plain radiographs of the spine revealed kyphoscoliosis from the third to sixth thoracic vertebrae. Kyphosis and scoliosis angles were 86 degrees and 28 degrees, respectively. Radiographs of the skull and hands showed radiological changes suggestive of hyperparathyroidism. Laboratory tests showed low-normal serum calcium, hypophosphatemia, elevated serum alkaline phosphatase, and low serum 25-hydroxyvitamin D. Retrospective review of the patient's laboratory data showed that she had osteomalacia at the time of diagnosis of primary hyperparathyroidism. The patient had been treated by anterior and posterior decompression and fusion with posterior instrumentation through a single posterior approach. The postoperative kyphosis and scoliosis angles were 30 degrees and 12 degrees, respectively. Neurological recovery and spinal fusion had been achieved. Osteomalacia responded well to vitamin D therapy. This is the first case of coexisting neurofibromatosis 1, primary hyperparathyroidism due to parathyroid adenoma and osteomalacia to be reported in the literature. The osteomalacia in this patient could be related to primary hyperparathyroidism, and not to neurofibromatosis 1. A drop in melatonin level after parathyroidectomy may have been the cause of spinal curvature progression in this patient.
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PMID:The association of neurofibromatosis 1 and spinal deformity with primary hyperparathyroidism and osteomalacia: might melatonin have a role? 1148 9

We present the case of a 25-year-old woman who developed a large central liver adenoma after 8 years of continuous oral contraceptive use. The first diagnosis was made by ultrasonography, after a rise in plasmatic gamma-glutamyl-transpeptidase and alkaline phosphatase levels was noted. Withdrawal of the oral contraceptive was followed by shrinkage of the adenoma, with complete disappearance 9 months after the diagnosis. Hepatic adenoma (HA) still presents problems in terms of differential diagnosis and clinical management. There are reports of complete or partial regression of an HA after discontinuation of oral contraceptives, but they are poorly documented. To our knowledge, a patient with such rapid disappearance of a large HA has never been reported.
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PMID:Rapid disappearance of hepatic adenoma after contraceptive withdrawal. 1150 Jun 16


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