Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary hyperparathyroidism (SH) and hyperplasia of the parathyroid glands (PTG) are universal complications in patients with CRF. In early renal failure, reduction in serum calcitriol and moderate decreases in ionized calcium contribute to greater synthesis and secretion of PTH. As renal disease progresses, a reduction in parathyroid expression of vitamin D receptor and calcium receptor renders the PTG more resistant to both calcitriol and calcium. High dietary phosphorus (P), independent of calcium and calcitriol, further enhances uremia-induced PTG hyperplasia and PTH synthesis and secretion, the latter by posttranscriptional mechanisms. Once SH develops, dietary P restriction can return the high serum PTH levels toward normal, however, parathyroid hyperplasia persists. Studies in our laboratory identified 2 of the mechanisms involved in the opposing effects of high and low dietary P content on PTG growth. Whereas high dietary P increases parathyroid expression of transforming growth factor alpha (TGFalpha), a growth promoter, P restriction induces the cyclin-dependent kinase inhibitor p21, an inducer of growth arrest. Both effects of P are specific for the PTG. No increase in either protein was observed in liver or intestine. TGFalpha induction of hyperplasia involves binding to the epidermal growth factor receptor and activation of mitogen activated protein (MAP) kinases cascades. p21 blocks progression through the cycle and cell division by inactivating cyclin/cyclin-dependent kinase complexes. Preventing hyperphosphatemia and elevated Ca x P product in renal failure not only ameliorates the progression of SH and bone disease but also the morbidity and mortality resulting from vascular calcification.
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PMID:Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. 1115 62

Parathyroid gland carcinoma is a rare malignancy. The tumor is mostly functioning, causing severe hyperparathyroidism, with high serum calcium level and severe bone disease. Non-functioning parathyroid carcinomas are extremely rare. We report on a 60-year-old male patient admitted to ENT Department due to a large neck tumor mass compressing the thyroid and trachea. Preoperatively, thyroid hormone, parathyroid hormone (PTH) and calcium serum levels were normal. The following immunohistochemical markers (DAKO, Denmark) were used: bcl-2; CD-10; Chromogranin-A; Cyclin-D1; EMA; Ki-67; Mdm-2; p-53; PGP-9,5; RCC; Synaptophysin; Thyroglobulin; and TTF-1. Immunohistochemical analysis indicated the diagnosis of a primary parathyroid gland carcinoma. Tumor cells showed diffusely positive immunohistochemical staining with chromogranin-A and PGP-9,5, positive staining of variable intensity with synaptophysin, and weakly positive reaction with EMA. Also, the cytoplasm of tumor cells was diffusely positively stained with bcl-2, while the nuclei showed positive reaction with p-53 oncogene and TTF-1. The remaining markers (CD-10, cyclin-D1, Ki-67, Mdm-2, RCC and thyroglobulin) were negative. Four years after the surgery, the patient died from renal carcinoma pulmonary metastases and liver cirrhosis complications. In conclusion, non-functioning parathyroid gland carcinoma is a very rare disease. Detailed immunohistochemical analysis is needed to distinguish it from other thyroid and parathyroid neoplasms and metastatic carcinoma. Surgical treatment is presently the best mode of therapy.
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PMID:Non-functioning parathyroid gland carcinoma: case report. 2226 88