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Hypercalcaemia
Kinds of Hypercalcaemia Selected AbstractsVacuolar H+ -ATPase expression is increased in acid-secreting intercalated cells in kidneys of rats with hypercalcaemia-induced alkalosisACTA PHYSIOLOGICA, Issue 4 2007W. Wang Abstract Aims:, Hypercalcaemia is known to be associated with systemic metabolic alkalosis, although the underlying mechanism is uncertain. Therefore, we aimed to examine whether hypercalcaemia was associated with changes in the expression of acid,base transporters in the kidney. Methods:, Rats were infused with human parathyroid hormone (PTH, 15 ,g kg,1 day,1), or vehicle for 48 h using osmotic minipumps. Results:, The rats treated with PTH developed hypercalcaemia and exhibited metabolic alkalosis (arterial HCO: 31.1 ± 0.8 vs. 28.1 ± 0.8 mmol L,1 in controls, P < 0.05, n = 6), whereas the urine pH of 6.85 ± 0.1 was significantly decreased compared with the pH of 7.38 ± 0.1 in controls (P < 0.05, n = 12). The observed alkalosis was associated with a significantly increased expression of the B1-subunit of the H+ -ATPase in kidney inner medulla (IM, 233 ± 45% of the control level). In contrast, electroneutral Na+ -HCO cotransporter NBCn1 and Cl,/HCO anion exchanger AE2 expression was markedly reduced in the inner stripe of the outer medulla (to 26 ± 9% and 65 ± 6%, respectively). These findings were verified by immunohistochemistry. Conclusions:, (1) hypercalcaemia-induced metabolic alkalosis was associated with increased urinary excretion of H+; (2) the increased H+ -ATPase expression in IM may partly explain the enhanced urinary acidification, which is speculated to prevent stone formation because of hypercalciuria and (3) the decreased expression of outer medullary AE2 suggests a compensatory reduction of the transepithelial bicarbonate transport. [source] Requesting patterns for serum calcium concentration in patients on long-term lithium therapyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2009B. J. Jones Summary Aim:, Long-term lithium therapy is associated with hypercalcaemia in 10,60% of patients, but unlike creatinine and thyroid stimulating hormone (TSH), monitoring by general practitioners of serum calcium for patients on lithium is not a requirement of the Qualities and Outcomes Framework (QOF) of 2004. We aimed to assess requesting patterns for serum calcium in patients on long-term lithium therapy and subsequent diagnosis of hypercalcaemia. Methods:, We identified 100 patients on long-term lithium therapy, as indicated by regular monitoring of lithium levels in our laboratory for at least 1 year. We determined how many of these patients had had serum calcium analysed, noting the assay date, concentration, source of request and clinical details stated. Results:, Forty-three out of hundred patients had serum calcium analysed during the course of their treatment including 28 in the previous 15 months. Twenty-one patients had serum calcium analysed by their GP, including 12 in the previous 15 months. Hypercalcaemia was diagnosed in five patients (11.6%). Conclusion:, A significant proportion of patients in whom calcium was checked developed hypercalcaemia on lithium therapy. However, only 12% of the patients had serum calcium requested by their GP in the previous 15 months, which compares unfavourably with TSH and creatinine, for which monitoring approaches 100%. We recommend that serum calcium be checked every 15 months along with creatinine and TSH. This might be achieved by incorporating appropriate targets into the QOF, or by reflective or reflex adding-on of calcium to lithium specimens from patients who have not had calcium analysed in the previous 15 months. [source] Hypercalcaemia of malignancy: an undiagnosed and undertreated diseaseJOURNAL OF INTERNAL MEDICINE, Issue 1 2001O. Lamy Lamy O, Jenzer-Closuit A, Burckhardt P (University Hospital, Lausanne, Switzerland). Hypercalcaemia of malignancy: an undiagnosed and undertreated disease. J Intern Med 2001; 250: 73,79. Background.,Hypercalcaemia of malignancy, a relatively frequent phenomenon, seems to be insufficiently recognized and treated. Its symptoms are not specific, but they affect the quality of life. Methods.,A prospective study to analyse the influence of symptoms caused by hypercalcaemia on the decision of the admitting physician, the motivation for treatment, and the effect of the treatment on the given symptoms in hospitalized patients with oncologic disease in progression, where confounding causes of similar symptoms such as cerebral metastasis, radiotherapy, treatment with opioids, etc., were excluded. Results.,A total of 71 patients, mean age 65 + 11 years, fulfilled the strict inclusion criteria. About 42% were hospitalized because of symptoms caused by hypercalcaemia, but none of the medical reports mentioned hypercalcaemia as reason for hospitalization. Specific antihypercalcaemic therapy was given to only 37% of patients, and only 25% got an adequate rehydratation. Antihypercalcaemic treatment was guided by the severity of hypercalcaemia (>3.00 mmol L,1), not by the symptoms. Polyuria-polydipsia, nausea-vomiting and constipation were correlated with hypercalcaemia. These symptoms, as well as confusion-stupor and bone pains improved significantly when calcaemia was normalized. Patients with calcaemia normalized returned home most frequently (P < 0.03). Conclusions.,Malignant hypercalcaemia remains mostly undiagnosed in medical praxis. Specific treatment occurs in too small fractions of the patients. As the normalization of calcaemia significantly improves the symptoms because of hypercalcaemia and the quality of life, rapid rehydration and specific calcium lowering treatments should be part of palliative measures in all patients with malignant hypercalcaemia. [source] Expression of 25-hydroxyvitamin D3 -1,-hydroxylase in subcutaneous fat necrosisBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009A. Farooque Summary Background, The most serious complication of subcutaneous fat necrosis (SCFN), a rare condition of the newborn characterized by indurated purple nodules, is hypercalcaemia. However, the mechanism for this hypercalcaemia remains unclear. Objectives, To determine whether the hypercalcaemia associated with SCFN involves expression of the vitamin D-activating enzyme 25-hydroxyvitamin D3 -1,-hydroxylase (1,-hydroxylase) in affected tissue. Methods, Skin biopsies from two male patients with SCFN and hypercalcaemia were taken. The histological specimens were assessed using a polyclonal antibody against 1,-hydroxylase. Results, Histology in both cases showed strong expression of 1,-hydroxylase protein (brown staining) within the inflammatory infiltrate associated with SCFN. This was consistent with similar experiments in other granulomatous conditions. Conclusions, Hypercalcaemia in SCFN appears to be due to abundant levels of 1,-hydroxylase in immune infiltrates associated with tissue lesions. This is consistent with previous observations of extrarenal 1,-hydroxylase in skin from other granulomatous conditions such as sarcoidosis and slack skin disease. [source] Vacuolar H+ -ATPase expression is increased in acid-secreting intercalated cells in kidneys of rats with hypercalcaemia-induced alkalosisACTA PHYSIOLOGICA, Issue 4 2007W. Wang Abstract Aims:, Hypercalcaemia is known to be associated with systemic metabolic alkalosis, although the underlying mechanism is uncertain. Therefore, we aimed to examine whether hypercalcaemia was associated with changes in the expression of acid,base transporters in the kidney. Methods:, Rats were infused with human parathyroid hormone (PTH, 15 ,g kg,1 day,1), or vehicle for 48 h using osmotic minipumps. Results:, The rats treated with PTH developed hypercalcaemia and exhibited metabolic alkalosis (arterial HCO: 31.1 ± 0.8 vs. 28.1 ± 0.8 mmol L,1 in controls, P < 0.05, n = 6), whereas the urine pH of 6.85 ± 0.1 was significantly decreased compared with the pH of 7.38 ± 0.1 in controls (P < 0.05, n = 12). The observed alkalosis was associated with a significantly increased expression of the B1-subunit of the H+ -ATPase in kidney inner medulla (IM, 233 ± 45% of the control level). In contrast, electroneutral Na+ -HCO cotransporter NBCn1 and Cl,/HCO anion exchanger AE2 expression was markedly reduced in the inner stripe of the outer medulla (to 26 ± 9% and 65 ± 6%, respectively). These findings were verified by immunohistochemistry. Conclusions:, (1) hypercalcaemia-induced metabolic alkalosis was associated with increased urinary excretion of H+; (2) the increased H+ -ATPase expression in IM may partly explain the enhanced urinary acidification, which is speculated to prevent stone formation because of hypercalciuria and (3) the decreased expression of outer medullary AE2 suggests a compensatory reduction of the transepithelial bicarbonate transport. [source] Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidismDIABETIC MEDICINE, Issue 10 2009F. Tassone Abstract Aims, An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients. Subjects and methods, One hundred and twenty-two consecutive pHPT patients without known DM were investigated [age (mean ± sd) 59.3 ± 13.6 years, body mass index (BMI) 25.7 ± 4.2 kg/m2; serum calcium 2.8 ± 0.25 mmol/l; PTH 203.2 ± 145.4 ng/l]. Sixty-one control subjects were matched, according to the degree of glucose tolerance, in a 2 : 1 patient:control ratio. Fasting- and oral glucose tolerance test-derived estimates of insulin sensitivity and secretion were determined by means of the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite. Results, Both the QUICKI and ISI composite were lower in pHPT patients than control subjects (P < 0.03 and P < 0.05, respectively) after adjusting for age, systolic blood pressure and BMI. Conversely, all insulin secretion estimates were significantly increased in pHPT patients than in control subjects (P < 0.04 and P < 0.03, respectively) and after adjusting for age, systolic blood pressure and BMI. Log serum calcium levels were negatively associated with the QUICKI and log ISI composite (R = ,0.30, P = 0.001; R = ,0.23, P = 0.020, respectively) in pHPT patients. Serum calcium levels significantly and independently contributed to impaired insulin sensitivity in multivariate analysis (QUICKI as dependent variable: , = ,0.31, P = 0.004, R2 = 0.15; log ISI composite as dependent variable: , = ,0.29, P = 0.005, R2 = 0.16). Conclusions, Our study confirms a reduction in both basal and stimulated insulin sensitivity in primary hyperparathyroidism, in spite of increased insulin secretion. Moreover, our data show for the first time a significant relationship between hypercalcaemia and insulin sensitivity in this condition. [source] Validation and clinical utility of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone in the horseEQUINE VETERINARY JOURNAL, Issue 3 2003J. C. ESTEPA Summary Reasons for performing study: Parathyroid hormone (PTH) plays a critical role in the regulation of mineral metabolism in mammals. Until recently, the standard method for PTH measurement has been the 2nd generation intact-PTH (I-PTH) assay. Current evidence indicates that the I-PTH assay binds to the PTH molecule and to an inactive N-terminally truncated PTH fragment that tends to accumulate in the blood of uraemic patients. Therefore, a new 3rd generation PTH assay that detects only the whole PTH molecule (W-PTH; cyclase-activating PTH [CAP]) has been developed. Objectives: To validate this more specific W-PTH assay for measurement of equine PTH and evaluate its clinical utility. Methods: W-PTH and I-PTH were measured in plasma samples from normal horses (adults and foals) and horses with nutritional secondary hyperparathyroidism (N2HPT) and with chronic renal failure (CRF). Replicate measurements and dilutional paralellism were used for assay validation. Changes in blood ionized calcium were induced by EDTA and CaCl2 administration. Results: Performance of the W-PTH assay (accuracy, sensitivity, specificity and ability to detect changes in PTH in response to changes in calcium) was similar to that of the I-PTH assay. Surprisingly, the relative W-PTH concentration in normal horses and foals was higher than the relative I-PTH concentration. W-PTH values remained higher than I-PTH during acute hypo- and hypercalcaemia. An increase in both W-PTH and I-PTH concentrations was found in horses with N2HPT. In horses with CRF, W-PTH and I-PTH values were very low and no increase in I-PTH was observed. Conclusions: The W-PTH assay can be used for measurement of equine PTH. Potential relevance: The use of W-PTH assay is likely to improve the diagnosis of mineral metabolism in horses. [source] The role of calcimimetics in the treatment of hyperparathyroidismEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2007R. P. Wüthrich Abstract Calcimimetics reduce serum levels of parathyroid hormone (PTH) and calcium, with a leftward shift in the set-point for calcium-regulated PTH secretion. The aim of this publication is to review the data available for calcimimetics in primary, secondary and tertiary hyperparathyroidism (HPT). Parathyroidectomy (PTX) is currently the only curative treatment for primary HPT, and recommended for patients with moderate-to-severe disease, as defined by a 2002 National Institute's of Health summary statement. In general, patients with primary HPT not meeting these surgical criteria, as well as those with contraindication or refusal for surgery, are monitored for signs and symptoms of primary HPT. There are currently no non-surgical therapies approved for use in primary HPT, although bisphosphonates are used in some patients, in an effort to control serum calcium levels. Calcimimetics decrease PTH and calcium levels and are a potential alternative for patients contraindicated for PTX, or who have failed previous PTX and have recurrent primary HPT. Secondary HPT develops early in chronic kidney disease and is present virtually in all patients with end-stage renal disease (ESRD). Secondary HPT is a progressive disease and is associated with several systemic complications, including renal osteodystrophy, soft tissue and vascular calcifications, and adverse cardiovascular outcomes. In ESRD patients, calcimimetics were shown to simultaneously reduce PTH, calcium, phosphate and calcium × phosphate product. In addition, observational analyses of use of calcimimetics in the ESRD population have shown a reduction of important clinical outcomes. In renal allograft recipients with tertiary HPT and hypercalcaemia, calcimimetics are a promising treatment option to control the parameters of calcium phosphate metabolism and may be a valid alternative to PTX. Based on its unique mechanism of action, the calcimimetic cinacalcet may play a role in the medical treatment of primary and tertiary forms of HPT, in addition to the registered indication for the treatment of secondary HPT. [source] Requesting patterns for serum calcium concentration in patients on long-term lithium therapyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2009B. J. Jones Summary Aim:, Long-term lithium therapy is associated with hypercalcaemia in 10,60% of patients, but unlike creatinine and thyroid stimulating hormone (TSH), monitoring by general practitioners of serum calcium for patients on lithium is not a requirement of the Qualities and Outcomes Framework (QOF) of 2004. We aimed to assess requesting patterns for serum calcium in patients on long-term lithium therapy and subsequent diagnosis of hypercalcaemia. Methods:, We identified 100 patients on long-term lithium therapy, as indicated by regular monitoring of lithium levels in our laboratory for at least 1 year. We determined how many of these patients had had serum calcium analysed, noting the assay date, concentration, source of request and clinical details stated. Results:, Forty-three out of hundred patients had serum calcium analysed during the course of their treatment including 28 in the previous 15 months. Twenty-one patients had serum calcium analysed by their GP, including 12 in the previous 15 months. Hypercalcaemia was diagnosed in five patients (11.6%). Conclusion:, A significant proportion of patients in whom calcium was checked developed hypercalcaemia on lithium therapy. However, only 12% of the patients had serum calcium requested by their GP in the previous 15 months, which compares unfavourably with TSH and creatinine, for which monitoring approaches 100%. We recommend that serum calcium be checked every 15 months along with creatinine and TSH. This might be achieved by incorporating appropriate targets into the QOF, or by reflective or reflex adding-on of calcium to lithium specimens from patients who have not had calcium analysed in the previous 15 months. [source] Normalization of serum calcium by cinacalcet in a patient with hypercalcaemia due to a de novo inactivating mutation of the calcium-sensing receptorJOURNAL OF INTERNAL MEDICINE, Issue 2 2006H. J. L. M. TIMMERS Abstract. Familial benign hypocalciuric hypercalcaemia (FHH) results from a heterozygous inactivating mutation of the calcium-sensing receptor (CaR) and is characterized by hypercalcaemia, hypocalciuria and inappropriately normal plasma levels of parathyroid hormone. In a minority of patients, a loss of function mutation of the CaR results in severe hypercalcaemia associated with complications for which no effective surgical or medical treatment is available. We investigated the effects of the calcimimetic agent cinacalcet, an allosteric modulator of the CaR, in a 26-year-old man presenting with hypercalcaemia due to a de novo inactivating mutation of the CaR. Complicating features were recurrent psychosis and progressive severe osteoporosis. A single dose of either 30 or 60 mg of cinacalcet resulted in a 63,88% decline in plasma parathyroid hormone levels within 2 h of administration of the agent, reverting to baseline levels after 12 h. Normalization of serum calcium was more gradual but sustained for up to 12 months of treatment with a maintenance twice-daily oral dose of 60 + 30 mg cinacalcet. In addition to its beneficial effects in primary and secondary hyperparathyroidism, cinacalcet may open new therapeutic avenues in the management of a subset of patients with severe hypercalcaemia due to inactivating mutations of the CaR. [source] Surviving extreme hypercalcaemia , a case report and review of the literatureJOURNAL OF INTERNAL MEDICINE, Issue 1 2005K. MARIENHAGEN Abstract. We report a case of extreme hypercalcaemia associated with a parathyroid adenoma in a young man. The patient presented with classical symptoms of a hypercalcaemic syndrome, and serum calcium and parathyroid hormone levels were 6.92 mmol L,1 and 70.2 pmol L,1 respectively. After stabilizing the patient and reducing the calcium level, a parathyroidectomy was performed. The postoperative course was uneventful with rapidly resolving clinical symptoms. Hypercalcaemic crisis is a rare but life-threatening complication of primary hyperparathyroidism. It should be suspected in acutely ill patients complaining of muscular weakness, gastrointestinal and cerebral symptoms. To reduce mortality, it is essential to correctly diagnose the condition without delay and provide appropriate emergency management correcting hypercalcaemia and dehydration. Successful parathyroidectomy quickly relieves symptoms and prevents recurrence. [source] Primary hyperparathyroidism: new concepts in clinical, densitometric and biochemical featuresJOURNAL OF INTERNAL MEDICINE, Issue 1 2005J. P. BILEZIKIAN Abstract. Primary hyperparathyroidism (PHPT) is characterized most commonly now as an asymptomatic disorder with hypercalcaemia and elevated levels of parathyroid hormone (PTH). The elevation in PTH is detected by both the standard immunoradiometric assays (IRMA) and a more recent IRMA that detects only the 1,84 full-length PTH molecule. The serum calcium concentration is usually <1 mg dL,1 above normal. Recently, another variant of PHPT (normocalcaemic PHPT) has been described in which the serum calcium is normal but the serum PTH is elevated, in the absence of any secondary cause for PTH elevation. Although usually sporadic, PHPT also occurs in inherited syndromes. Skeletal manifestations are appreciated by densitometry showing a typical pattern in which cancellous bone of the lumbar spine is reasonably well preserved whilst the cortical bone of the distal third of the radius is preferentially reduced. Although reduced in incidence, renal stones remain the most common overt complication of PHPT. Other organs are theoretical targets of PHPT such as the neurobehavioural axis and the cardiovascular system. Vitamin D looms as an important determinant of the activity of the PHPT state. The 2002 NIH Workshop on asymptomatic PHPT has led to revised guidelines to help doctors determine who is best advised to have parathyroid surgery and who can be safely followed without surgery. New information about the natural history of PHPT in those who did not undergo surgery has helped to define more precisely who is at-risk for complications. At the NIH workshop, a number of items were highlighted for further investigation such as pharmacological approaches to controlling hypercalcaemia, elevated PTH levels and maintaining bone density. [source] Hypercalcaemia of malignancy: an undiagnosed and undertreated diseaseJOURNAL OF INTERNAL MEDICINE, Issue 1 2001O. Lamy Lamy O, Jenzer-Closuit A, Burckhardt P (University Hospital, Lausanne, Switzerland). Hypercalcaemia of malignancy: an undiagnosed and undertreated disease. J Intern Med 2001; 250: 73,79. Background.,Hypercalcaemia of malignancy, a relatively frequent phenomenon, seems to be insufficiently recognized and treated. Its symptoms are not specific, but they affect the quality of life. Methods.,A prospective study to analyse the influence of symptoms caused by hypercalcaemia on the decision of the admitting physician, the motivation for treatment, and the effect of the treatment on the given symptoms in hospitalized patients with oncologic disease in progression, where confounding causes of similar symptoms such as cerebral metastasis, radiotherapy, treatment with opioids, etc., were excluded. Results.,A total of 71 patients, mean age 65 + 11 years, fulfilled the strict inclusion criteria. About 42% were hospitalized because of symptoms caused by hypercalcaemia, but none of the medical reports mentioned hypercalcaemia as reason for hospitalization. Specific antihypercalcaemic therapy was given to only 37% of patients, and only 25% got an adequate rehydratation. Antihypercalcaemic treatment was guided by the severity of hypercalcaemia (>3.00 mmol L,1), not by the symptoms. Polyuria-polydipsia, nausea-vomiting and constipation were correlated with hypercalcaemia. These symptoms, as well as confusion-stupor and bone pains improved significantly when calcaemia was normalized. Patients with calcaemia normalized returned home most frequently (P < 0.03). Conclusions.,Malignant hypercalcaemia remains mostly undiagnosed in medical praxis. Specific treatment occurs in too small fractions of the patients. As the normalization of calcaemia significantly improves the symptoms because of hypercalcaemia and the quality of life, rapid rehydration and specific calcium lowering treatments should be part of palliative measures in all patients with malignant hypercalcaemia. [source] ORAL PHOSPHATE BINDERS FOR THE MANAGEMENT OF SERUM PHOSPHATE LEVELS IN DIALYSIS PATIENTSJOURNAL OF RENAL CARE, Issue 2009Ismail Mohammed MBBS, MRCP SUMMARY Hyperphosphataemia is an inevitable consequence of end stage chronic kidney disease and is present in the majority of dialysis patients. Hyperphosphataemia is statistically associated with increased cardiovascular mortality among dialysis patients. Dietary restriction of phosphate and current dialysis modalities are not sufficiently effective to maintain serum phosphate levels within the recommended range so that the majority of dialysis patients require oral phosphate binders. However, benefits of achieving the recommended range have yet to be demonstrated prospectively. Unfortunately, conventional phosphate binders are not reliably effective and are associated with a range of limitations and side effects. Aluminium containing agents are highly efficient but no longer widely used because of well-established and proven toxicity. Calcium-based salts are inexpensive, effective and most widely used but there is now concern about their association with hypercalcaemia and vascular calcification. Sevelamer hydrochloride and lanthanum carbonate are non-aluminium, calcium-free phosphate binders. They are effective and reasonably well tolerated, but still do not control phosphate levels in all patients. Patient education programmes have been shown to be a useful and effective method of improving achievement of serum phosphate targets. [source] Metastatic malignant melanoma presenting with hypercalcaemia and bone marrow involvementJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2006JA Batsis Abstract We report a 75-year-old female patient with a background of malignant melanoma who presented with hypercalcaemia to our institution. She was aggressively treated but declined clinically. Computed tomography head and X-ray studies were suggestive of multiple myeloma, but bone marrow examination was significant for metastatic malignant melanoma. Very few patients with melanoma present with these features, and it further exemplifies the importance of close follow-up and the aggressive nature of this disease process. [source] Outcome of parathyroidectomy for patients with renal disease and hyperparathyroidism: predictors for recurrent hyperparathyroidismANZ JOURNAL OF SURGERY, Issue 5 2009Tsu-Hui (Hubert) Low Abstract Background:, A small group of patients with renal disease-related secondary or tertiary hyperparathyroidism require surgical parathyroidectomy. Among them, 5,20% require further re-exploration and excision of parathyroid tissue because of recurrent disease. The aims of the present study were to review the characteristics and outcomes of patients undergoing parathyroidectomy for renal disease related hyperparathyroidism and to identify the risk factors for recurrent hyperparathyroidism. Methods:, Review of data from a dedicated head and neck database at Royal Prince Alfred Hospital between 1988 and 2004. Results:, There were 115 patients of whom 68 (59%) patients were treated with subtotal parathyroidectomy (STP), 43 (37%) were treated with total parathyroidectomy (TP) and 4 (3%) were treated with TP with autotransplant. Of those, 11 (9.6%) patients developed recurrent hyperparathyroidism (9 had STP, 1 had TP and 1 had TP with autotransplant). On re-exploration, persistent hyperplastic parathyroid tissue was located at the site of partially excised parathyroid gland (64%), autotransplanted parathyroid tissue (9%), anterior mediastinum (18%) and intrathyroidal parathyroid (9%). Predictors for recurrent hyperparathyroidism are STP (P= 0.049), preoperative symptom of calciphylaxis or calcinosis (P= 0.024), elevated preoperative calcium level (P= 0.007) and elevated post-operative PTH levels (P= 0.014). Post-operative PTH levels less than 10 pmol/L has a positive predictive value of 97.5% for cure (P= 0.02). Conclusion:, More aggressive surgical approach could be indicated in patients with preoperative hypercalcaemia and calcinosis/calciphylaxis. Post-operative PTH can be utilized as a marker for cure after parathyroidectomy in hyperparathyroidism of renal disease. [source] HN08P AUDIT OF 115 CONSECUTIVE PARATHYROIDECTOMIES IN PATIENTS WITH RENAL HYPERPARATHYROIDISMANZ JOURNAL OF SURGERY, Issue 2007T. H. Low Objectives To review the characteristics and outcomes of patients undergoing parathyroidectomy for renal (secondary and tertiary) hyperparathyroidism. Methods Review of prospectively collected data from a dedicated head and neck database at RPAH between 1988 and 2004. A total of 115 patients underwent exploratory parathyroidectomy. Results Common indications for parathyroidectomy included hypercalcaemia, renal osteodystrophy, calciphylaxis and calcinosis, bone or joint pain, and pruritus. Sixty-nine patients had subtotal parathyroidectomy (STP), 47 had total parathyroidectomy (TP) of which 4 had total parathyroidectomy with autotransplant (TPA). Ten patients required re-exploration for recurrent hyperparathyroidism at a median time to reoperation of 55 months. Of those, 8 had STP, 1 had TP, and 1 had TPA. Predictors of recurrent hyperparathyroidism included higher post operative PTH level (median of 22.5 pmol/L vs 3.4 pmol/L) and higher total parathyroid weight (median of 7.75 gm vs 2.9 gm). 97% of patients reported resolution of symptoms on follow-up. The average length of hospital admission was 4.4 days. Morbidity of this series included wound infection (0.8%), temporary vocal cord paralysis (0.8%), seizure due to severe hypocalcaemia (0.8%) and neck haematomas requiring evacuation (0.8%). Conclusions Parathyroidectomy is effective in the management of renal hyperparathyroidism. Subtotal parathyroidectomy is associated with a higher re-exploration rate. Predictors for recurrent hyperparathyroidism include total parathyroid weight and post-operative PTH level. [source] CALCIPHYLAXIS AND ITS SURGICAL SIGNIFICANCEANZ JOURNAL OF SURGERY, Issue 5 2005Stephanie Bardsley Calciphylaxis is a rare but significant condition. It is associated with a high degree of morbidity and is fatal in between 60% and 80% of patients. It occurs most commonly in patients with endstage renal failure and is associated with hypercalcaemia or hyperphosphataemia or both (elevated calcium-phosphate product). Secondary hyperparathyroidism is also common. Clinically, patients develop rapidly progressive, necrotic skin ulcers that are extremely painful. They, universally, respond poorly to usual ulcer therapies. Some surgeons advocate parathyroidectomy for patients with calciphylaxis. Evidence is inconclusive regarding this treatment; however, some trials have shown improved rates of ulcer healing and overall survival in patients treated with parathyroidectomy. [source] Teriparatide (Biosynthetic Human Parathyroid Hormone 1,34): A New Paradigm in the Treatment of OsteoporosisBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2004Kim T. Brixen Biosynthetic human parathyroid hormone 1,34 (teriparatide) was recently approved in the EU and the USA as the first anabolic treatment of osteoporosis. The effects of teriparatide are mediated by the G-protein-dependent, parathyroid hormone receptor-1 in the cell membrane. The binding of the ligand to the receptor activates adenylate cyclase and a number of phospholipases (A, C, and D) and increases intracellular levels of cAMP and calcium. Intermittent teriparatide increases the number of osteoblasts and bone formation by activation of pre-existing osteoblasts, increased differentiation of lining cells, and reduced osteoblast apoptosis. Anabolic effects of teriparatide on bone have been demonstrated in several species. It increases bone mass, structural integrity, bone diameter, and bone strength. Clinical efficacy was demonstrated in a randomized study comprising 1637 post-menopausal women with osteoporosis showing a 65% and 35% reduction of the relative risk of vertebral and appendicular fractures, respectively, during 18 months of treatment. Moreover, bone mineral density in the lumbar spine and hip increased by 9.7% and 2.6%, respectively. Similar effects on bone mineral density have been reported in men with osteoporosis and in glucocorticoid-induced osteoporosis, however, fracture data are limited in these groups. Direct comparison with alendronate revealed that teriparatide has a more pronounced effect on bone mineral density. Teriparatide should be used in combination with calcium plus vitamin D, and may be combined with hormonal replacement therapy. In contrast, alendronate attenuates the effect of teriparatide. The efficacy of other combinations remains uncertain. After termination of teriparatide, bone mineral density of the lumbar spine is reduced by approximately 2,3% after 2 1/2 years. This decrease is prevented by treatment with bisphosphonates. The most frequent adverse effects with teriparatide are nausea, headache, dizziness, and leg cramps, however, only the latter two differed significantly between the groups receiving teriparatide 20 ,g/day and placebo. In the pivotal clinical study, reduced dosage or termination of therapy due to hypercalcaemia was necessary in 3% and 0.2%, respectively. In a rat toxicology study, in which teriparatide was administered in high dosages for an extended period of time, osteosarcoma was seen in a significant number of animals. However, none of the approximately 2800 patients in clinical trials has developed osteosarcoma. Teriparatide constitutes a break-through in the treatment of severe osteoporosis, although a number of issues about the optimal use of teriparatide remains unsettled. The published data provide proof of concept on anabolic therapy which changes several paradigms of bone physiology. Other parathyroid hormone analogues are being investigated in clinical trials and the development of non-peptide, small molecules targeted at the parathyroid hormone receptor may be envisaged. [source] Expression of 25-hydroxyvitamin D3 -1,-hydroxylase in subcutaneous fat necrosisBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009A. Farooque Summary Background, The most serious complication of subcutaneous fat necrosis (SCFN), a rare condition of the newborn characterized by indurated purple nodules, is hypercalcaemia. However, the mechanism for this hypercalcaemia remains unclear. Objectives, To determine whether the hypercalcaemia associated with SCFN involves expression of the vitamin D-activating enzyme 25-hydroxyvitamin D3 -1,-hydroxylase (1,-hydroxylase) in affected tissue. Methods, Skin biopsies from two male patients with SCFN and hypercalcaemia were taken. The histological specimens were assessed using a polyclonal antibody against 1,-hydroxylase. Results, Histology in both cases showed strong expression of 1,-hydroxylase protein (brown staining) within the inflammatory infiltrate associated with SCFN. This was consistent with similar experiments in other granulomatous conditions. Conclusions, Hypercalcaemia in SCFN appears to be due to abundant levels of 1,-hydroxylase in immune infiltrates associated with tissue lesions. This is consistent with previous observations of extrarenal 1,-hydroxylase in skin from other granulomatous conditions such as sarcoidosis and slack skin disease. [source] Topical PTH (1,34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trialBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003M.F. Holick Summary Background There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth. Objectives A programme was initiated to determine whether an agonist of this peptide's receptor, PTH (1,34), could be developed as a drug to treat psoriasis. Methods PTH (1,34) was formulated in Novasome A® cream. Fifteen adult patients with chronic plaque psoriasis who had failed to respond to at least one standard treatment were enrolled in a randomized double-blinded placebo self-controlled trial. The patients topically applied to a 25-cm2 psoriatic lesion 0·1 g of either Novasome A® cream or Novasome A® cream that contained 20 ,g of PTH (1,34) twice a day for 2 months. At the end of the double-blind study, patients were enrolled in an open large area study. Ten patients applied PTH (1,34) (50 ,g per 0·1 g) once daily to their psoriatic lesions. The patients were evaluated for their global improvement and calcium metabolism. Results Novasome A® cream enhanced the percutaneous absorption of PTH (1,34) in human skin in comparison with formulations in propylene glycol or normal saline. Psoriatic lesions treated with PTH (1,34) showed marked improvement in scaling, erythema and induration. There was a 67·3% improvement in the global severity score for the lesion treated with PTH (1,34) compared with the placebo-treated lesion, which only showed a 17·8% improvement. Ten patients topically applied PTH (1,34) on all of their lesions in a stepwise manner. A Psoriasis Area and Severity Index score analysis of all the patients revealed improvement of 42·6% (P < 0·02). None of the patients experienced hypercalcaemia or hypercalciuria or developed any side-effect to the medication. Conclusions Patients who were resistant to at least one standard therapy for psoriasis had a remarkable improvement in their psoriasis when they applied PTH (1,34) to their lesion(s). No untoward toxicity was observed in any of the subjects. This pilot study suggests that topical PTH (1,34) is a safe and effective novel therapy for psoriasis. [source] Burkitt lymphoma presenting as posterior reversible encephalopathy syndrome secondary to hypercalcaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2009Edmond S. K. Ma No abstract is available for this article. [source] Cutaneous sarcoid with varied morphology associated with hypercalcaemia and renal impairmentCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 8 2009H. Miida Summary Sarcoidosis is a multisystem disorder of unknown aetiology, which presents with hilar lymphadenopathy, pulmonary infiltration, and ocular and cutaneous involvement. Cutaneous lesions often present as erythema nodosum, maculopapular, plaque, scar, subcutaneous nodule or lupus pernio. Most patients with cutaneous involvement have a single type of skin lesion, but some cases may have , 2 types. We report a case of sarcoidosis presenting with various types of skin lesions. The case was also complicated by hypercalcaemia and renal dysfunction, and was successfully treated with oral corticosteroids. Presentation of various skin lesions may indicate systemic organ involvement requiring treatment with systemic corticosteroid. [source] Comparative therapeutic effects of orally administered 1,25-dihydroxyvitamin D3 and 1alpha-hydroxyvitamin D3 on type-1 diabetes in non-obese diabetic mice fed a normal-calcaemic dietCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2008J. P. Driver Summary Frequent injections of the hormonal form of vitamin D3, 1,25 dihydroxyvitamin D3 (1,25D3) reportedly inhibits autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by correcting some of the abnormalities in antigen-presenting cells which contribute the development of pathogenic T cell responses. This route of administration greatly elevates the levels of these compounds in the bloodstream for hours after treatment, which requires mice to be fed diets formulated to contain much reduced levels of Ca to avoid the toxic effects of hypercalcaemia. In the current work, we demonstrate that feeding 1,25D3 or its synthetic precursor, 1alpha(OH) vitamin D3 (1alphaD3), as part of a T1D supportive chow diet containing normal levels of Ca, is an effective means of reducing the incidence of disease in NOD mice, but the doses required for protection elicited hypercalcaemia. However, T1D protection elicited by D3 analogue feeding appears, at least partially, to have an immunological basis, as splenic T cells from treated mice had a decreased capacity to adoptively transfer disease. Protection is associated with an increased proportion of T cells with CD4+ forkhead box P3+ regulatory phenotype within the islet infiltrate of treated animals. The 1alphaD3 precursor is converted rapidly to the active 1,25D3 isoform in vivo. However, feeding the 1alphaD3 analogue elicited stronger T1D protection than the 1,25D3 compound, but also induced more severe hypercalcaemia. In future, the dietary supplementation of novel low-calcaemic D3 analogues may enable their continuous delivery at levels that inhibit T1D development in susceptible humans consuming normal levels of Ca. [source] Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patientsCLINICAL ENDOCRINOLOGY, Issue 5 2008Antongiulio Faggiano Summary Background, In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. Objective, To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. Patients, Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. Design, The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. Measurements, Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. Results, After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62·5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37·5%). Conclusion, Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP. [source] Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium-sensing receptor geneCLINICAL ENDOCRINOLOGY, Issue 3 2007Judit Tõke Summary Introduction, Neonatal severe hyperparathyroidism (NSHPT) is induced by inactivating mutations of human calcium-sensing receptor (CaSR). Only three heterozygous de novo inactivating mutations of CaSR causing NSHPT have been described. We report the case of a now 11-year-old boy with NSHPT and we characterize a novel inactivating mutation along with the results of some functional analyses. Patient and methods, As a neonate the patient presented the clinical syndrome of NSHPT. At 6 years of age persisting hypercalcaemia without clinical symptoms was documented, and the patient remained completely symptom free without parathyroid surgery until his present age of 11 years. The entire coding region of the CaSR gene of the patient and his family members was sequenced. Functional investigation was performed in HEK-293 cells, transiently transfected with wild type and mutant CaSR plasmid constructs. Results, Sequence analysis revealed a novel de novo heterozygous mutation at codon 551 (AGG,AAG), predicting a change of arginine to lysine (R551K) and a known heterozygous polymorphism (A986S) on the same allele, which was inherited from the father. We demonstrated that the novel R551K mutation significantly reduced the calcium sensitivity of CaSR (EC50: from 3·38 ± 0·62,6·10 ± 0·83 mmol/l), which was not alleviated by the simultaneous presence of A986S polymorphism. Conclusions, We present the fourth NSHPT case induced by a novel de novo heterozygous inactivating mutation (R551K) of the CaSR gene. The disease gradually reverted to a symptomless, benign condition resembling familial hypocalciuric hypercalcaemia without any surgical intervention. [source] Novel mutation of the calcium sensing receptor gene in familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidismCLINICAL ENDOCRINOLOGY, Issue 6 2006Simone Caixeta de Andrade No abstract is available for this article. [source] Failure to normalize parathyroid hormone during treatment of vitamin D deficiency in Asian patientsCLINICAL ENDOCRINOLOGY, Issue 5 2004Steven R. Peacey Summary objective, Vitamin D deficiency and osteomalacia remain commonplace within the Asian community in Bradford. The treatment of vitamin D deficiency and osteomalacia is cheap and effective, but there are few data on long-term outcomes. Studies have suggested that a minority of patients fail to normalize parathyroid hormone (PTH) levels during therapy with vitamin D. This study aimed to determine what proportion of Asian patients with vitamin D deficiency and secondary hyperparathyroidism normalize PTH levels following therapy with oral vitamin D and to examine reasons for failure to normalize PTH. design, This study examined the impact of an oral regimen of vitamin D 800 i.u. (20 micrograms) and calcium 1000 mg daily, on PTH levels within an endocrinology outpatient clinic. patients, 51 (4M:47F) Asian patients, median age 39 years (range 16,77 years) with vitamin D deficiency (25-hydroxyvitamin D < 25 nmol/l) and secondary hyperparathyroidism (PTH > 5·7 pmol/l). measurements, All patients had at least one follow-up measurement of PTH and calcium during treatment. A subgroup of patients gave consent for examination of GP-prescribing records to indirectly asses adherence to therapy. results, PTH normalized in only 28/51 (55%) patients (group N) and failed to normalize in 23/51 (45%) patients (group F). Baseline patient characteristics including: age, basal serum 25-hydroxyvitamin D (25OHD), basal serum PTH, basal serum calcium and post treatment serum calcium, were similar in groups N and F. Mild hypercalcaemia occurred in only two (3·9%) patients. The proportion of prescriptions collected by patients in group N was 75 (17,100)% and in group F was 17 (0,100)%, P < 0·0001. conclusions, This study has demonstrated that long-term oral treatment with vitamin D and calcium, fails to normalize PTH in a significant proportion of patients with vitamin D deficiency and osteomalacia. This is most likely related to lack of adherence to long-term treatment. Improved ways of treating this condition need to be explored. [source] Update on genetic and clinical aspects of primary hyperparathyroidismCLINICAL ENDOCRINOLOGY, Issue 5 2003S. Miedlich Summary Primary hyperparathyroidism (pHPT) is a common endocrine disorder that predominantly affects postmenopausal women. It is mostly caused by solitary tumours within the parathyroid glands. Although the pathophysiology of pHPT is still incompletely understood, recent studies provide new clues on the development and cellular growth of tumours within the parathyroids associated with hypersecretion of parathyroid hormone and hypercalcaemia. The natural course of pHPT is rather benign. Nowadays, it has become an oligo- or asymptomatic disease often only detected by routine blood tests. These facts raise the question whether to perform parathyroidectomy on oligo- and asymptomatic patients with pHPT or whether it is possible to monitor these patients without surgery. The aim of this article is to review the literature as regards (i) the pathophysiological mechanisms that underlie parathyroid neoplasia and (ii) the defective calcium-sensing in patients with pHPT (iii) environmental and/or genetic risk factors that predispose to or promote parathyroid neoplasia, as well as (iv) alternative approaches to treat oligo- and asymptomatic patients with pHPT medically. [source] Impaired GH secretion to provocative stimuli in two families with hypocalciuric hypercalcaemiaCLINICAL ENDOCRINOLOGY, Issue 5 2003Elisabetta Cecconi Summary objective, To determine whether hypercalcemia per se might be responsible for an impairment in GH secretion. design, Prospective study. patients, Six subjects of two unrelated families with familial hypocalciuric hypercalcaemia (FHH), an autosomal dominant disorder due to inactivating mutations in the calcium receptor gene, leading to an increase in serum calcium levels and inappropriately normal serum PTH concentrations. Forty normal subjects, matched for sex and age served as controls. measurements, Serum GH concentrations were measured after GHRH-Arginine (GHRH-Arg) stimulation test; serum IGF-I, ACTH, cortisol, FT4, FT3, TSH, PRL, LH, FSH levels were measured under basal conditions. results, All subjects (two male, four female, age range 24,74 years) had increased serum ionized calcium levels (range 1·36,1·56 mmol/l) and five of six patients had normal PTH levels (range for all patients was 14,68 ng/l). Basal serum GH concentrations ranged from 0·1 to 7·0 µg/l. Mean serum GH secretory peak after GHRH-Arg stimulation test was reduced in five subjects (mean 9·3 ± 3·6 µg/l, P < 0·006 vs. Controls, mean 67·0 ± 44·0 µg/l, cut-off, 16·0 µg/l) and normal in one subject (38·7 µg/l). However, serum IGF-I levels were reduced only in two patients (29 and 57 µg/l) and normal in four subjects (range 127,208 µg/l). The basal secretion of the other anterior pituitary hormones was within their normal ranges. conclusions, The results of the present study support the concept that elevated serum calcium levels impair GH secretion. However, the clinical relevance of GH deficiency in FHH remains to be elucidated. [source] | |||||||||||||||||||||||||