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)

Cinacalcet is a type II calcimimetic agent which is an allosteric modulator of the calcium-sensing receptor (CaR) located on the surface of the parathyroid cells. Cinacalcet increases the sensitivity of CaR via binding to the transmembrane region of CaR. Increasing sensitivity of CaR causes reduced secretion of parathyroid hormone (PTH) and suppression of serum calcium levels. Cinacalcet has recently been approved by Federal Drug Administration (FDA) for the treatment of patients with secondary hyperparathyroidism on maintenance dialysis and hypercalcemia in patients with parathyroid cancer. It is used also in Europe for both indications. Several controlled studies have shown that cinacalcet is effective in normalizing serum calcium levels also in primary hyperparathyroidism. Cinacalcet is metabolized primarily in the liver by N-dealkylation leading to carboxylic acid and oxidation of naphthalene ring to form dihydrodiols. The safety and optimal dosage of the drug in hypercalcemic patients with liver impairment remains unclear. We present a patient with Child-Pugh B class primary biliary cirrhosis who presented with moderate hypercalcemia and was diagnosed as primary hyperparathyroidism. As she refused having parathyroid surgery for her parathyroid adenoma at first, her hypercalcemia was treated successfully with 30 mg/day cinacalcet for 6 months. Cinacalcet was discontinued after 6 months. Her calcium level increased gradually. As she accepted surgery this time, her parathyroid adenoma was removed by minimally invasive parathyroidectomy. Parathyroid adenoma was confirmed pathologically. Her calcium levels maintained within the normal ranges after surgery.
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PMID:Hypercalcemia of primary hyperparathyroidism was treated by cinacalcet in a patient with liver cirrhosis. 1856 Oct 96

HRPT2 and parafibromin studies improved the diagnostic accuracy in two patients with primary hyperparathyroidism (PHPT) referred to us after surgery, in whom the clinical data were at variance with the pathological diagnosis of adenoma and carcinoma, respectively. Patients were referred to us after parathyroidectomy. Patient #1 had had a 1.5-cm tumor easily removed with a histological diagnosis of parathyroid carcinoma and normocalcemia for 2 years. Re-examination of the histology showed no cardinal signs of parathyroid cancer. Patient #2, with severe PHPT, had had the removal of a 3.5-cm tumor described histologically as adenoma. Ten years later PHPT recurred and persisted despite removal of two mildly enlarged parathyroid glands that were histologically normal. Re-review of the initial histology showed a trabecular pattern, fibrous bands, and atypical mitoses, suggesting an atypical adenoma. Because of the suspicion that case #1 could be an atypical adenoma and case #2 a carcinoma further molecular studies were performed. No HRPT2 and parafibromin abnormalities were identified in patient #1, strongly indicating a benign lesion. In patient #2, an HRPT2 germline mutation was found (E115X in exon 4) and associated with no parafibromin staining. These data, together with the clinical features, supported the suspicion of a parathyroid carcinoma that was confirmed by histological examination of further slides of the tumor, showing capsular and vascular invasion. A lung 1.5-cm nodule detected by computed tomography was excised. Histology showed a metastasis of parathyroid carcinoma. HRPT2 gene studies improved the diagnostic accuracy in 2 parathyroid tumors that are of uncertain type.
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PMID:Hyperparathyroidism 2 gene (HRPT2, CDC73) and parafibromin studies in two patients with primary hyperparathyroidism and uncertain pathological assessment. 1909 96

Parathyroid carcinoma is a rare neoplasm that accounts for only 1-3% of cases of primary hyperparathyroidism. Parathyroid carcinoma is a well-differentiated tumor that is sometimes difficult to differentiate histopathologically from its benign counterpart, parathyroid adenoma. The molecular mechanism of parathyroid carcinogenesis remains unknown, and investigators have reported that abnormalities of the p53 gene do not play a significant role in parathyroid carcinogenesis, unlike in other human malignancies. The present report describes parathyroid carcinoma with anaplastic transformation of differentiated parathyroid carcinoma in a patient with primary hyperparathyroidism. Nuclear accumulation of p53 protein was found in anaplastic carcinoma cells but not in differentiated carcinoma cells. Polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing showed that anaplastic carcinoma cells carried a missense mutation at codon 248 (CGG to CAG) of the p53 gene, while the remaining differentiated carcinoma cells had the wild-type p53 gene. These findings suggest that the p53 gene mutation is associated with anaplastic transformation of parathyroid carcinoma.
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PMID:Parathyroid carcinoma with anaplastic feature: association of a p53 gene mutation with anaplastic transformation. 1915 65

We report a 47-year-old women who presented to her general practitioner and our hospital with weight loss of unknown etiology. Eight years previously she had undergone a hemithyroidectomy for nodular goiter with one cold nodule. Laboratory results revealed hypercalcemia, evidence of primary hyperparathyroidism and computer tomography of the thorax showed bilateral pulmonary metastasis. After undergoing CT-guided biopsy of a metastasis, histology revealed an endocrine primary tumor with low parathyroid hormone expression. In view of the history, clinical and biochemical findings we diagnosed a recently metastasized functioning parathyroid carcinoma, which eight years previously has been labeled as a benign atypical thyroid adenoma. The patient underwent surgical resection of all detected metastases. Afterwards the serum calcium and parathyroid hormone levels normalized. Parathyroid carcinoma is an uncommon tumor. In the absence of pathognomonic diagnostic criteria a definitive pathological diagnosis of parathyroid carcinoma often is not possible. The treatment of parathyroid carcinoma is essentially surgical. Patients with parathyroid carcinoma mostly die from uncontrollable hypercalcemia rather than from other tumor-related complications.
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PMID:[Rare cause of hypercalcemia]. 1921 66

Primary hyperparathyroidism (PHP) is a known endocrine disorder. Many years ago, the most frequent forms of clinical presentation were symptomatic renal or skeletal disease with moderate or severe hypercalcemia; however, currently, most patients have few symptoms and mild hypercalcemia. The last NIH Workshop on Asymptomatic PHP developed criteria for the management of this disease. Multiple endocrine neoplasia (MEN) types 1 and 2 are two genetic syndromes caused by different types of molecular abnormalities. PHP is the most common manifestation of MEN-1 and is the last feature to appear in MEN 2A. Parathyroid carcinoma (PC) is a rare neoplasm and an uncommon cause of parathyroid hormone (PTH)-dependent hypercalcemia. In this report, the treatment of PHP in MEN syndrome and PC are reviewed. Special attention is paid to a new class of drugs called "calcimimetics", which are powerful compounds that may be highly useful in the treatment of both conditions.
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PMID:[Primary hyperparathyroidism in special situations: multiple endocrine neoplasia syndromes and parathyroid cancer]. 1962 59

Parathyroid carcinoma is a rare malignancy, and only accounts for 0.5-2% of cases of primary hyperparathyroidism. Less than 10% of parathyroid carcinomas are non-functional, and as such, they have been rarely reported in the literature. Importantly, margin status at resection is related to prognosis, and only a handful of case reports of non-functional carcinoma note this important parameter. Here we report the first case of non-functional parathyroid carcinoma with negative margins, and review the literature on this rare entity. Whether functional or non-functional, parathyroid carcinoma can often be difficult to differentiate from benign parathyroid adenoma. While diagnosis has been based on clinical and histological criteria, recent data concerning the molecular underpinnings of parathyroid carcinoma may allow for improved accuracy in distinguishing benign and malignant parathyroid tumors.
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PMID:Non-functional parathyroid carcinoma: a review of the literature and report of a case requiring extensive surgery. 1964 46

Most cases of primary hyperparathyroidism (80 to 90%) are caused by a parathyroid adenoma; most of the rest are caused by either parathyroid gland hyperplasia or multiple adenomas. Parathyroid carcinoma can be the cause of primary hyperparathyroidism in 1 to 5% of patients. When the appropriate clinical scenario is presented, it must be considered in the differential diagnosis. We describe the case of a 72-year-old woman with a long history of hypercalcemia and arthritic shoulder and neck pain who was admitted with an elevated calcium level and acute renal failure secondary to bilateral obstructing ureteral calculi. A sestamibi scan and magnetic resonance imaging detected the presence of what appeared to be a right inferior parathyroid adenoma. Her intact parathyroid hormone (PTH) level was 2,257 pg/ml. Following placement of bilateral ureteral stents and adequate hydration, the patient was taken to the operating room for a neck exploration and removal of a parathyroid adenoma with rapid intraoperative PTH monitoring. A 4 x 2.5-cm, 10-g mass was removed from the right inferior pole of the thyroid gland. Following excision, her intraoperative PTH level dropped from 1,103 to 110 pg/ml. Her ionized calcium levels fell from a high of 8.4 mg/dl preoperatively to 4.7 mg/dl. On final pathologic examination, the mass was confirmed to be a parathyroid carcinoma.
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PMID:Parathyroid carcinoma: a rare cause of primary hyperparathyroidism. 1975 Apr 62

Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism-jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a new class of small, non-coding RNAs implicated in development of cancer, since their deregulation can induce aberrant expression of several target genes. The aim of the present study was to identify differentially expressed microRNAs in parathyroid cancers compared with normal tissues. We performed a TaqMan low-density array profiling of four parathyroid cancers harboring CDC73 inactivating mutations and negative for parafibromin immunostaining. Their microRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human microRNAs assayed, 279 (77%) were successfully amplified. Fourteen and three microRNAs were significantly down- and over-expressed in parathyroid cancers respectively. Of these, miR-296 and miR-139 were down-regulated, and miR-503 and miR-222 were over-expressed with a null false discovery rate. Carcinomas could be discriminated from parathyroid adenomas by a computed score based on the expression levels of miR-296, miR-222, and miR-503 as miR-139 was similarly down-regulated in both cancers and adenomas. Finally, miR-296 and miR-222 levels negatively correlated with mRNA levels of the hepatocyte growth factor receptor-regulated tyrosine kinase substrate and p27/kip1 levels respectively. These results suggest the existence of an altered microRNA expression pattern in PaCs together with a potential role of miR-296 as novel oncosuppressor gene in these neoplasia.
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PMID:Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue. 1992 10

Primary hyperparathyroidism (PHPT) due to parathyroid carcinoma is rare, and affects more frequently women in their 4th-5th decades of life. Parathyroid cancer (PC) accounts for 0.5% up to 5% of the patients with primary hyperparathyroidism (PHPT). Diagnosis of PC is not easy, and a lot of patients with PHPT receive no pre-operative or intra-operative diagnosis of malignancy. Most of PC are hyperfunctioning, with marked serum PTH levels, and symptoms occurs more frequently than in benign disease. We report the case of a 52 years old woman that underwent a single parathyroidectomy for hyperfunctioning gland. Histological examination revealed carcinoma. Parathyroid carcinoma is rare and surgery represent the only curative approach, although there can be a local recurrence of the disease. A pre-operative diagnosis is not easy, and many features that suggest the diagnosis of malignancy are controversial. According to the literature, we think that the cure of the parathyroid cancer is difficult to achieve. After two years of follow- up, our patient is in good conditions and has no evidence of disease. A careful follow up is of primary importance to diagnose the local recurrence of disease and perform a second surgical treatment, to achieve the control of hypercalcemia, which causes severe metabolic alterations and visceral lesions until the death.
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PMID:Parathyroid cancer as rare cause of primary hyperparathyroidism. Case report and review of the literature. 1995 85

Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism (PHPT), this disease is often misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion preoperatively and early intraoperative recognition with en bloc surgical resection are crucial for favorable outcome. Owing to the rarity of the disease, little is known about the molecular pathogenesis of parathyroid carcinoma. Here, we review the literature to present current understanding of the disease and provide new information on gene expression and use of intraoperative parathyroid hormone (PTH) monitoring in the surgical management of this rare malignancy. Specifically, using microarray transcriptome analysis of an unequivocal case of parathyroid carcinoma and a biopsy from the same patient's normal parathyroid gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes in parathyroid carcinoma. Further, using case records from four cases of unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of these patients to 475 patients with benign PHPT, and show that intraoperative PTH monitoring is accurate in predicting postoperative normocalcemia in initial en bloc operations for parathyroid carcinoma.
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PMID:Parathyroid carcinoma: current understanding and new insights into gene expression and intraoperative parathyroid hormone kinetics. 2005 78


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