Hypercalcemia associated with parathyroid hormone-related protein produced by B-cell type primary malignant lymphoma of the kidney

 A patient with primary non-Hodgkin's (B-cell type) lymphoma of the kidney developed hypercalcemia at the terminal stage of the disease. Although the plasma parathyroid hormone level was low, urinary cyclic AMP excretion was elevated. Serum osteocalcin (BGP) was suppressed and the plasma level of 1,25(OH)₂D was within the normal range. Serum concentrations of PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) were elevated, and the tissue concentration of PRP-LI in the postmortem lymph node showed high level along with elevated serum PRP-LI, furthermore the production of PTHrP by the tumor was demonstrated by immunohistochemistry and Northern blotting analysis. These findings indicate that the hypercalcemia of the patient was caused by the PTHrP-producing B-cell lymphoma. Hypercalcemia was restored to normocalcemia by bisphosphonate treatment. Our case will add further information on humoral hypercalcemia in B-cell lymphoma, which rarely has been demonstrated to produce PTHrP. Received: 17 July 1997 / Accepted: 2 February 1998     

Giant Cell Lesions Associated with Primary Hyperparathyroidism

Aims and Objective

To evaluate the prevalence, clinical features, diagnostic laboratory values and treatment outcome of giant cell lesions (brown tumors) associated with primary hyperparathyroidism (PHPT) in oral and maxillofacial region.

Study Design

A 5 year retrospective data was analyzed wherein all histopathologically proven cases of giant cell lesions involving oral and maxillofacial region were evaluated. Out of these cases, those associated with PHPT were tabulated. Correlation was established with other concomitant clinical features and also with the laboratory values of altered serum calcium, phosphate, alkaline phosphate and parathormone. Follow up of these cases after the correction of PHPT was also noted.

Result

Out of 85 cases of histopathologically proven giant cell lesions, five cases were associated with PHPT. There was involvement of maxilla and mandible in one case each. Only frontal bone was involved in two cases. Fifth case had multiple lytic lesions in maxilla and frontal bone. All patients consistently showed very high values of alkaline phosphate and parathormone. Hypercalcemia and hypophosphatemia was noted in four cases. All cases showed regression of the lytic lesion after parathyroidectomy obviating the need for surgical excision of the jaw lesions.

Conclusion

Giant cell lesions (brown tumors) associated with PHPT in oral and maxillofacial region are rare clinical entities. The prevalence of PHPT associated giant cell lesions is 5.9 %. They are clinically, radiologically and histopathologically similar to any other peripheral or central giant cell tumor. Relevant history may alert the clinician and altered biochemical values may help in correlating the oral and maxillofacial findings with the underlying systemic disease. At times, the brown tumor maybe the only presenting sign leading to the diagnosis of PHPT.     

Multiple brown tumor revealing primary hyperparathyroidism associated with Behçet’s disease: A case report

BackgroundPrimary hyperparathyroidism (PHP) is defined as hypercalcemia that may remain asymptomatic for years and cause lesion in skeletal system such as brown tumor (BT). Endocrine involvement in Behçet’s Disease (BD) regarding various systems can be seen.Case reportWe report an association between BD and PHP in a 45-year-old female. She had complained of inflammatory pain in the lower limb. Plain x-ray showed a lytic lesion on the upper tibia. Laboratory investigations revealed hypercalcemia (3.32 mmol/L), hypophosphatemia (0.48 mmol/L), a high parathyroid hormone (PTH) level (2278 pg/L) and a low vitamin D level (8.1 μg/L). An adenoma in the right lower parathyroid has been shown on scintigraphy, a vertebral fracture was present on lumbar spine X-ray and salt and pepper skull was shown on the lateral skull X-ray. Severe osteoporosis was present on the lumbar bone mineral density (t score ?3.3), and multiple BT were revealed on bone scan. The patient was operated on and developed Hungry Bone Syndrome (HBS) following surgery. Therefore, she received high doses of calcium with favorable outcome.ConclusionThis case is a leading report for the coexistence of BD with PHP. This case provides further evidence that BD should be considered as an autoimmune process, which may be associated with endocrine involvement including PHP. On the other hand, musculoskeletal manifestations of PHP including BT still seen in daily practice require continued vigilance on the part of the physician.     

p38丝裂原活化蛋白激酶信号途径在鼠破骨细胞生成和骨吸收中的作用

目的研究p38丝裂原活化蛋白激酶(p38MAPK)信号途径在甲状旁腺素相关肽(PTHrP)诱导的破骨细胞生成和骨吸收中的作用。方法取小鼠骨髓细胞,在PTHrP(45ng/ml)的刺激下,在不同试验组中分别入0.1、1.0及10μmol/L的p38MAPK抑制剂Fr167653,继续培养6d。抗酒石酸染色,进行破骨细胞计数。在小鼠颅骨部位注射PTHrP建立骨吸收和高钙血症动物模型。每日给予p38MAPK抑制剂Fr16765330mg/kg,每日2次,X线片观察骨吸收面积,组织学检查计算单位面积内破骨细胞数目,采集血样观察全血内游离钙水平。结果PTHrP刺激下,大量破骨细胞生成(118.9±28.3)个/孔;加入0.1μmol/LFr167653可以部分抑制破骨细胞的生成(79.6±28.0)个/孔,加入10μmol/LFr167653几乎全抑制了破骨细胞生成(7.4±0.4)个/孔,每日给予Fr16765330mg/kg,每日2次,可以明显抑制骨吸收,表现为X线片上骨吸收面积减少,单位面积内破骨细胞数目减少,但是并不能有效地抑制高钙血症。结论抑制p38MAPK信号途径可以抑制破骨细胞的分化和局部骨吸收。