Mechanism of parathyroid tumourigenesis in uraemia.
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Clonal analysis has shown that in renal hyperparathyroidism (2-HPT), parathyroid glands initially grow diffusely and polyclonally after which the foci of nodular hyperplasia are transformed to monoclonal neoplasia. There is a great deal of information about genetic abnormalities contributing to the tumourigenesis of parathyroid neoplasia in primary hyperparathyroidism. It is speculated that allelic loss of the MEN1 suppressor gene and overexpression of cyclin D1 induced by rearrangement of the parathyroid hormone gene may be the major genetic abnormality in sporadic parathyroid adenoma but not in 2-HPT. The pathogenesis of 2-HPT, abnormality of the Ca2+-sensing receptor (CaR) gene and the vitamin D receptor gene may possibly contribute to parathyroid tumourigenesis in 2-HPT. However, this is not yet clear and heterogeneous and multiple genetic abnormalities may be responsible for the progression of secondary parathyroid hyperplasia. (+info)
The elevated serum alkaline phosphatase--the chase that led to two endocrinopathies and one possible unifying diagnosis.
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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. (+info)
A large intrathoracic parathyroid adenoma.
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A case is described in which an unusually large parathyroid adenoma was visible on the plain chest radiograph taken during the investigation of hypercalcaemia. This was diagnosed preoperatively and a scheme is suggested whereby such a disgnosis can now readily be made. The differential diagnosis is discussed ant the literature is reviewed. (+info)
Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma.
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BACKGROUND: In primary hyperparathyroidism, certain genetic abnormalities responsible for parathyroid tumorigenesis are proposed, and it has been reported that the overexpression of PRAD1/cyclin D1 induced by a DNA rearrangement of the parathyroid hormone (PTH) gene is one of the genetic disorders in a number of primary parathyroid adenomas. However, in secondary hyperparathyroidism caused by uremia, the mechanism of monoclonal proliferation in nodular parathyroid hyperplasia is not well understood. To elucidate the mechanism, we examined the expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in primary adenoma and secondary hyperplasia. METHODS: In adenomas (N = 15) and associated glands (N = 7) with normal histology obtained from patients with primary hyperparathyroidism and in diffuse (N = 14), multinodular (N = 58), and single nodular (N = 28) glands from patients who underwent parathyroidectomy for renal hyperparathyroidism, the expression of these cell cycle regulators was evaluated by immunohistochemical technique. A labeling index was used to define the proportion of cells with positive nuclear staining by each antibody. RESULTS: In 6 out of 15 (40%) primary adenomas, PRAD1/cyclin D1 was overexpressed (a labeling index of more than 500), possibly because of the PTH gene rearrangement, but not in secondary hyperplasia, including single nodular glands. Compared with diffuse hyperplasia, nodular hyperplasia showed a significantly higher expression of PRAD1/cyclin D1 (P < 0.05), retinoblastoma gene products (P < 0.05), and Ki67 (P < 0.05). However, no statistically significant correlation between the expression of PRAD1/cyclin D1 and that of Ki67 was observed in both primary adenoma and secondary hyperplasia. CONCLUSIONS: These results suggest that in secondary hyperplasia caused by uremia, at least remarkable overexpression of PRAD1/cyclin D1 induced by PTH gene rearrangement may be not the major genetic abnormality responsible for tumorigenesis. Heterogenous genetic changes seem to contribute to monoclonal proliferation of parathyroid cells induced by the expression of PRAD1/cyclin D1 or by some other mechanism independent of the amplification of the proto-oncogene. (+info)
We report the case of a 63-year-old woman admitted to hospital because of bilateral hemothorax associated with acute respiratory failure and laterotracheal neoformation. A right thoracoscopy biopsy revealed a paratracheal parathyroid adenoma which was responsible for bilateral hemothorax and primary hyperparathyroidism. A curative resection was successfully performed by cervicotomy. (+info)
Ultrasound-guided unilateral neck exploration for sporadic primary hyperparathyroidism: is it worthwhile?
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The role of preoperative localisation tests before initial neck exploration for primary hyperparathyroidism (PHP) remains controversial, as does the optimal surgical approach. We report our experience with preoperative ultrasound (US) and the operative management of sporadic PHP between 1990 and 1995. Preoperative US was carried out by an experienced radiologist. Three surgeons adopted a policy of 'selective' US-guided unilateral neck exploration (UNE); the fourth surgeon performed routine bilateral neck exploration (BNE). There were 72 patients: 26 men and 46 women, with a mean age of 57.4 +/- 12.5 years (range 21-80 years). All patients underwent initial neck exploration for 'sporadic' PHP, of whom 63 had preoperative US. This was positive in 52 patients; 27 of whom underwent a UNE, 23 had a BNE, and two patients had a UNE converted to a BNE. Patients with 'negative' US (n = 11), and those receiving no preoperative localisation test (n = 90) underwent a BNE. The sensitivity, specificity and accuracy of US were 80% (52/65), 100% (61/61), and 90% (113/126), respectively. Comparable success rates were achieved (BNE: 97% (33/34) vs UNE: 93% (27/29), P < 0.05), with very low morbidity. Failures with the scan-guided UNE were caused by missed contralateral adenomas. An experienced radiologist and a low incidence of multiglandular disease (MGD) are essential prerequisites for the scan-guided unilateral approach. An experienced surgeon, on the other hand, is the only prerequisite for the 'gold standard' bilateral approach. (+info)
Identification of a novel activated form of the keratinocyte growth factor receptor by expression cloning from parathyroid adenoma tissue.
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Parathyroid adenomas are benign tumors in the parathyroid glands, whose pathogenesis is largely unknown. We utilized an expression cDNA cloning strategy to identify oncogenes activated in parathyroid adenomas. An expression cDNA library was prepared directly from a clinical sample of parathyroid adenoma tissue, transfected into NIH3T3 cells, and foci of morphologically transformed cells were isolated. Following plasmid rescue, we identified cDNAs for the keratinocyte growth factor receptor at a high frequency. Interestingly, approximately half of the clones encoded a variant receptor containing an altered C-terminus. Analysis of the transforming activity of the variant receptor revealed that the altered C-terminus up-regulated the transforming activity in a ligand-independent manner. The higher transforming activity was not accompanied by increase of dimerization or overall autophosphorylation of the receptor. However, tyrosine phosphorylation of downstream receptor substrates, including Shc isoforms and possibly FRS2, are increased in the transfectants expressing the parathyroid tumor-derived receptor. Genomic analysis showed that a previously unidentified exon was used to form the novel isoform. This alternative splicing appears to occur preferentially in parathyroid adenomas. (+info)
Hyperfunctional parathyroid glands with 99mTc-MIBI scan: semiquantitative analysis correlated with histologic findings.
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The purpose of this study was to correlate the semiquantitative analysis of 99mTc-methoxyisobutyl isonitrile (MIBI) scan with histologic findings of hyperfunctional parathyroid glands. METHODS: Early and delayed cervical images of MIBI scans were reviewed in 31 patients who eventually underwent parathyroidectomies because of biochemically suspected hyperparathyroidism ([HPT], primary, n = 13; secondary, n = 18). The sensitivity of a scan for localizing the diseased glands was determined by comparing scan findings with pathologic findings, which were considered the gold standard. The average ratio of parathyroid-to-thyroid (P/T) count was compared between glands with large and small areas of whole gland, chief cell, oxyphil cell or cellular components. The mean areas of whole gland, chief cells and oxyphil cells were also compared between glands detected by MIBI scan and those that the scan missed. RESULTS: There were 99 resected lesions, including 9 parathyroid adenomas and 61 hyperplastic parathyroids. The sensitivity for localizing the diseased glands in patients with primary HPT (91%) was higher than that in patients with secondary HPT (83%). Significantly greater average P/T counts ratio on both early and delayed images was observed in the diseased glands with greater areas of whole gland, chief cells, oxyphil cells or cellular components. Fifty-nine MIBI-positive glands had significantly greater average areas of whole gland (P < 0.001) and chief cell (P = 0.002) than did 11 MIBI-negative glands. CONCLUSION: The uptake of MIBI in hyperfunctional parathyroid is dependent on gland size and the amount of cellular components, chief cells and oxyphil cells. However, the amount of oxyphil cells does not clearly affect the results of MIBI parathyroid scintigraphy, because it is small in most hyperfunctional glands. (+info)