X-linked hypophosphatemia: Normal renal function despite medullary nephrocalcinosis 25 years after transient vitamin D2-induced renal azotemia

Myeloma causes a devastating and unique form of osteolytic bone disease. Although osteoclast activation is responsible for bone destruction, the precise mechanisms by which myeloma cells increase osteoclast activity have not been defined. An animal model of human myeloma bone disease would help in clarification of these mechanisms. Multiple myeloma occurs spontaneously in aging C57 BL/KaLwRij mice and has all of the features of the disease in humans, including the characteristic bone lesions. The disease can be induced in normal C57 BL/KaLwRij mice by inoculation of fresh marrow-derived cells from mice with myeloma, but this model is difficult to study because of variability in the number of myeloma cells in marrow-derived preparations. To develop a better animal model of human myeloma bone disease. we have established and subcloned a cell line from this murine myeloma and found that it causes osteolytic bone lesions in mice characteristic of human myeloma bone disease. The cell line produces interleukin-6, but grows independent of exogenous interleukin-6. Mice inoculated intravenously with the cultured cells predictably develop an identical disease to the mice injected intravenously with fresh bone-marrow-derived myeloma cells, including monoclonal gammopathy and radiologic bone lesions. We found that some of the mice became hypercalcemic, and the bone lesions are characterized by increased osteoclast activity. We found identical results when we inoculated Nu/Bg/XID mice with cultured murine myeloma cells. Because we can inoculate mice with precise numbers of cells and predict accurately when the mice will develop bone lesions, become hypercalcemic, and die, this should be a convenient model for determining the mechanisms by which the myeloma cells cause osteoclast activation in this model of human myeloma bone disease.     

Differences in vitamin D status and calcium intake: Possible explanations for the regional variations in the prevalence of hypercalcemia in tuberculosis

The prevalence of hypercalcemia in patients with untreated tuberculosis (TB) varies widely between countries. Since the vitamin D status and calcium intake are important determinants of hypercalcemia in TB, these two factors were compared among four populations (U.K., Hong Kong, Malaysia, Thailand) with a low prevalence (<3%) and two populations (Sweden, Australia) with a high prevalence (>25%). In the three Asian countries, the circulating vitamin D levels are abundant, but the calcium intakes are low. Subjects from the U.K. have the lowest circulating vitamin D level of all, although their calcium intake is high. In Sweden and Australia, both the circulating vitamin D levels and calcium intakes are high. Since serum 1,25(OH)₂D concentration will only be raised if its substance for extrarenal conversion, 25(OH)D, is plentiful and the effect of a given serum 1,25 (OH)₂D concentration on serum calcium is determined by the calcium intake, it is postulated that the regional variation in the prevalence of hypercalcemia in TB may be due to differences in the circulating vitamin D levels and calcium intakes in these populations. Received: 18 March 1996 / Accepted: 17 June 1996     

Calcium free hemodialysis: an effective therapy in hypercalcemic crisis — report of 4 cases

Hypercalcemic crisis respresents a medical emergency. If conservative treatment is ineffective, low calcium bath or zero calcium bath hemodialysis are good alternatives. We report 4 patients treated with calcium free acetate hemodialysis because of hypercalcemic crisis due to breast cancer, hepatocellular carcinoma, cirrhosis of the liver and immobilisation with hydrochlorothiazids' medication. Following 3 h of hemodialysis, serum calcium concentrations fell from a mean value of 3.96 (range 3.53–4.46) mmol/l to 2.71 (2.28–3.12) mmol/l. In 2 patients rapid clinical improvement was achieved and in one oliguric patient diuresis started spontaneously during hemodialysis. One patient died from gram-negative sepsis. In 3 cases the subsequent conservative treatment was sufficient to maintain serum calcium levels within the normal range. Together with the previously reported cases (5 patients treated by hemodialysis with low dialysate calcium and 3 patients by hemodialysis with calcium free dialysate) our experience indicates that hemodialysis is an effective and safe therapy for hypercalcemic crisis.     

Kalziumfreie Hämodialyse — Stellenwert in der Therapie der hyperkalzämischen Krise

Summary If conservative treatment of hypercalcemic crises is ineffective, low calcium bath or zero calcium bath hemodialysis represent good alternatives. We report 5 patients (from 54 to 82 years old) treated with calcium free acetate hemodialysis because of hypercalcemic crises due to breast cancer with bone metastases, thiazids' medication and immobilisation, liver cirrhosis, hepatocellular carcinoma and hyperparathyroidism. By 3 hours' therapy calcium concentration could be reduced from a mean value of 3,74 mmol/l (3,13–4,46) to 2,47 mmol/l (1,38–3,12). In 3 cases rapid clinical improvement was achieved and in 4 cases the subsequent conservative therapy was sufficient to maintain serum calcium levels within reference range. In accordance to other investigators we consider hemodialysis as an effective method of low risk in hypercalcemic crises. Calcium rebound may occure in patients with hyperparathyroidism.

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Abkürzungsverzeichnis PTH Parathormon     

Successful palliation of hypercalcemia secondary to metastatic parathyroid cancer: an unusual indication for hepatic resection

Primary carcinoma of the parathyroid gland is a rare disease. It is often diagnosed after recurrence of hyperparathyroidism following resection for presumed adenomatous disease. Local and distant recurrence is high and aggressive resection is advocated. Patients with parathyroid cancer are frequently plagued by severe hypercalcemia, which is often refractory to medical therapy. Herein we describe the case of a patient with metastatic parathyroid cancer localized to the liver. The patient was treated with a palliative hepatic resection for the management of persistent and refractory hypercalcemia. Intraoperative parathyroid hormone levels were utilized as an adjunct to determine successful metastatectomy. Our case highlights the importance of an aggressive approach to patients with metastatic parathyroid cancer, as well as the utility of intraoperative parathyroid hormone levels to confirm successful extirpation of disease. the authors declare no conflicts of interest     

Chronotherapy of high-dose active vitamin D<Subscript>3</Subscript>: is evening dosing preferable?

Oral Vitamin D(3) is usually administered to children with chronic renal failure in the morning. Is there enough evidence that evening dosing is more beneficial with respect to suppression of parathyroid hormone and reduction of side effects such as hypercalcemia?     

唑来磷酸治疗恶性肿瘤引起高钙血症的临床研究

目的评价唑来磷酸（择泰）治疗恶性肿瘤引起高钙血症的有效性和安全性。方法入组患者共有17例,均为校正血钙值〉2．7mmol／L的肿瘤患者,以唑来磷酸4mg,静脉滴注15min,观察28d内的校正血钙值。结果本组17例患者均可评价疗效及安全性,有效率为94．1％（16／17）,仅1例无效。有效患者的校正血钙均值于用药后第4天第1次复查时即降至正常,于第14人达到最低点,各观察日校正血钙值与疗前比较均明显下降,差异有统汁学意义（P均〈0．01）。主要不良反应为发热（29．4％,5／17）、低钙性抽搐（11.8％,2／17）和轻度早搏（5．9％,1／17）。结论唑来磷酸治疗恶性肿瘤性高钙血症疗效确切,不良反应轻,耐受性好。     

Congenital mesoblastic nephroma associated with polyhydramnios and hypercalcemia

Congenital mesoblastic nephroma (CMN) can present with atypical clinical and imaging findings. A premature male neonate was born to an 18-year-old woman after 33 weeks’ gestation, which was complicated by polyhydramnios and placenta abruptio. A right abdominal mass was diagnosed antenatally. From the 1st day of life, the newborn had hypercalcemia with initially normal parathormone levels and polyuria for the first hours of life and normal urine output afterwards. Ultrasonographic study and magnetic resonance imaging of the abdomen showed at the upper pole of the right kidney a heterogeneous, solid, poorly defined mass, partially surrounded by a subcapsular fluid collection mimicking malignant rhabdoid tumor of the kidney. Surgical resection revealed a CMN of mixed, classic, and in areas, cellular type. One year after the resection, the patient is asymptomatic and normocalcemic. In conclusion, CMN may present with atypical clinical and imaging findings, necessitating an extensive work-up in order to exclude highly malignant renal tumors of the neonatal period. Received: 12 December 2000 / Revised: 1 May 2001 / Accepted: 9 October 2001     

他克莫司对肾移植术后患者血钙水平的远期影响

目的探讨他克莫司对肾移植术后患者血钙水平的远期影响。方法将我院2002-2004年接受肾移植手术的124例患者,按免疫抑制方案不同随机分两组:观察组(他克莫司 MMF 强的松,n=58);对照组(环孢素A MMF 强的松,n=66)。比较两组患者肾移植2年后的血钙水平及高钙血症发生率。结果FK506治疗组和环孢素A组肾移植术后高钙血症发生率分别为5.17%和13.63%,两组比较具有显著性差异(P<0.01)。结论肾移植患者术后应用他克莫司比环孢素A可有效降低高钙血症的发生率。     

A case of multiple skeletal lesions of brown tumors, mimicking carcinoma metastases

Brown tumor is not a true tumor, being an unusual reactive lesion in association with primary or secondary hyperparathyroidism. We report a 23-year-old woman, who initially presented with lower back pain caused by ureterolithiasis. The initial diagnosis of brown tumor was delayed, but later pain in her leg worsened and a sacral lesion was incidentally discovered on lumbar magnetic resonance imaging (MRI); multiple destructive bone lesions were then found radiologically. The radiological features of the multiple bone lesions, which mimicked multiple metastatic tumors, seemed to be those of the terminal stage of malignancy. However, pathological examination and abnormal laboratory data showing elevated serum calcium, alkaline phosphatase, and parathyroid hormone and low serum phosphate confirmed the diagnosis of brown tumor. Adenoma in the parathyroid gland was confirmed and surgically resected. The clinical symptoms of bone pain, and abnormal radiological findings and laboratory data were resolved 6 months after surgery. Synthetic analysis of the clinical, radiological, and laboratory findings was necessary for the definite diagnosis of brown tumor.