Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteocalcin is initially synthesized as an 11 kD molecule consisting of a 23-residue translocation signal peptide that is cleaved during translation, a 26-residue propeptide that targets the protein for gamma-carboxylation, and the 49-residue mature protein. Although the majority of newly synthesized osteocalcin is deposited into bone matrix, a small amount can be detected in blood, and it is this characteristic that has led to its current clinical use as a specific index of osteoblastic activity. Nothing is known, however, about the fate of the propeptide. If osteocalcin and the propeptide are cosecreted, then the concentration of the propeptide could also be useful as a marker of osteoblastic function and, further, may be superior to osteocalcin because it would be unaffected by binding to bone. To test this hypothesis, we synthesized a peptide corresponding to 21 residues of the osteocalcin propeptide from humans and produced a polyclonal antibody to this peptide. Human sera were screened for the presence of the propeptide, and the human osteosarcoma cell line MG-63 was tested for secretion of the propeptide. We could not detect any osteocalcin propeptide in sera from normal adults or individuals with renal failure or primary hyperparathyroidism or those on long-term coumadin therapy. Likewise there was no propeptide present in media from cells grown in the presence of vitamin K, 1,25-(OH)2D3, warfarin, or warfarin plus 1,25-(OH)2D3. In contrast, the cell extract, characterized by high-performance liquid chromatography, contained mature osteocalcin, free propeptide, and the proosteocalcin precursor when cells were grown in the presence of 1,25-(OH)2D3 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The osteocalcin propeptide is not secreted in vivo or in vitro. 154 60

We report a two-step immunochemical method for estimating serum intact PTH, as defined by immunochemical methods, and its validation by a newly developed osteosarcoma cell adenyl cyclase stimulation assay for PTH bioactivity. The first step involves extraction and concentration of serum PTH moieties with solid phase amino-terminal PTH antibodies; in the second step, the initial PTH immunoextract is analyzed with a sensitive midregion immunoassay. Intact PTH can thus be detected in virtually all normal subjects. Intact PTH levels in our group of primary hyperparathyroid persons average nearly 20 times higher than normal and do not overlap the normal range. Intact PTH is also elevated in chronic renal disease, but less dramatically than in primary hyperparathyroidism. Since total PTH immunoreactivity (intact plus fragments) is much higher in renal disease patients than in persons with primary hyperparathyroidism, serum intact PTH in renal disease apparently comprises a much smaller fraction of total circulating PTH immunoreactivity than in primary hyperparathyroidism. The finding that intact PTH accounts for a large portion of total circulating PTH immunoreactivity in primary hyperparathyroidism is contrary to published reports by us and others. Some of the possible reasons for the differences between our present results and previous reports are examined.
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PMID:Estimation of biologically active intact parathyroid hormone in normal and hyperparathyroid sera by sequential N-terminal immunoextraction and midregion radioimmunoassay. 631 57

The authors treated 18 patients with Paget's disease of bone (12 men and 6 women, age 65 +/- 5 years) with pamidronate (bisphosphonate of the second generation). Three patients from this group were treated previously without success with calcitonin or bisphosphonate of the first generation (etidronate) 50% of the patients suffered from the polyostotic form of the disease. In one patient a rare combination of primary hyperparathyroidism with Paget's bone disease was found and in another patient later an osteosarcoma developed in the affected bone. To all patients sodium pamidronate was administered (Aredia, Ciba-Geigy) 30 mg per day by i.v. infusion for 2 hours during three days. Four patients developed fever, two patients phlebitis at the site of injection. These side-effects are described by the manufacturer. Two patients developed transient regional alopecia, not described so far. Subjective pain relief of the affected skeleton occurred in one patient after one month of treatment, after three months in 78%. Laboratory manifestations of activity of the disease (serum activity of alkaline phosphatase, tartrate resistant acid phosphatase and hydroxyprolinuria) declined gradually from the 1st to the 6th month after onset of treatment. There was a less marked decline of the osteocalcin serum concentration. The concentration of calcium, phosphorus and vitamin D metabolites did not change markedly. Twelve months after treatment 14.7% of the patients were inactive according to laboratory tests, 73% however experienced another rise of parameters of osteoresorption and osteoformation. Pamidronate treatment in patients with Paget's disease of bone is effective and safe.
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PMID:[Paget's disease of bone and treatment with pamidronate]. 837 65

A 69-year-old woman was diagnosed with a malignant tumor of the right proximal femur. She had primary hyperparathyroidism and chronic elevation of parathyroid hormone levels (PTH > 1,000 pg/ml). She underwent resection of the bone lesion; histological analysis showed a high-grade fibroblastic osteosarcoma. In addition, she underwent curative resection of a large left superior parathyroid adenoma. To our knowledge, this is the third reported clinical case of osteosarcoma arising in association with hyperparathyroidism.
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PMID:Osteosarcoma of bone in apatient with primary hyperparathyroidism: a case report. 1251 Aug 19

The American Food and Drug Administration approval of parathyroid hormone (PTH) administration for osteoporosis as well as the possibility for its future therapeutic applications requires an examination of the suggested association between PTH and cancer, particularly osteosarcomas. The objective was to evaluate such a connection by collecting observational data from two groups of patients, designated as "studies by nature". Cohort 1: Medical records of all patients with primary hyperparathyroidism that were treated in a referral center during a 12-year period were retrospectively reviewed for malignancy before, at the time or after diagnosis. Cohort 2: Records of patients with osteosarcomas that were treated in referral centers during 15 years were retrospectively reviewed for hyperparathyroidism, as indicated by history or laboratory results. There were 582 patients with primary hyperparathyroidism. While 56 (9.6%) had malignancy, 47 (8%) developed cancer after diagnosis with hyperparathyroidism during 6.1 years of documentation. This rate did not exceed the incidence of developing cancer among the general population. Although thyroid cancer was about 4 times the incidence in the general population, this may be attributed to a high level of detection while work-up, treating and following the parathyroid disease. None had osteosarcoma. None of the 126 patients with osteosarcoma had documentation of primary hyperparathyroidism or had biochemical evidence of hyperparathyroidism. No obvious association was found between primary hyperparathyroidism and cancer. Similarly, there was no demonstrable relationship between osteosarcomas and hyperthyroidism biochemical stigmata. Since PTH may contribute to tumor invasiveness, screening for existing neoplasms, especially prostate and breast, before PTH treatment may be of importance.
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PMID:Primary hyperparathyroidism and malignancy: "studies by nature". 1653 Apr 96

Although bone disease and stone disease are the universally accepted classical manifestations of primary hyperparathyroidism, clinical parathyroid bone disease is rarely seen today in the United States (<5% of patients) and Western Europe. Nevertheless, in a given patient, classical skeletal involvement can be the first sign of primary hyperparathyroidism, but not recognized because it is not usually included, anymore, in the differential diagnosis of this manifestation of skeletal disease. We describe four cases of primary hyperparathyroidism in which the first clinical manifestation of the disease was a pathological fracture that masqueraded as a malignancy. The presence of large osteolytic lesions gave rise to the initial diagnosis of a primary or metastatic cancer. In none of the reported cases was primary hyperparathyroidism with osteitis fibrosa considered as the diagnosis. It would seem to us that this course is best explained by the fact that in many countries such manifestations of primary hyperparathyroidism have become a rarity. In fact, the incidence of osteitis fibrosa among patients with primary hyperparathyroidism in the US is estimated as so rare, that in majority of medical centers routine x-ray examinations of the bones in these patients is not recommended. The X-ray or computed tomography scan findings of osteitis fibrosa cystica include lytic or multilobular cystic changes. Multiple bony lesions representing brown tumors may be misdiagnosed on computed tomography scan as metastatic carcinoma, bone cysts, osteosarcoma, and especially giant-cell tumor. Distinguishing between primary hyperparathyroidism and malignancy is made readily by the concomitant measurement of parathyroid hormone which in primary hyperparathyroidism, again, will be markedly elevated. In the hypercalcemias of malignancy, such elevations of parathyroid hormone are virtually never seen.
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PMID:Osteitis fibrosa cystica-a forgotten radiological feature of primary hyperparathyroidism. 2890 Aug 35