Normal Serum Calcium Levels Research Articles

Vitamin D3 supplementation to improve fatigue in patients with advanced cancer.

9097 Background: Fatigue is one of the most common symptoms of patients diagnosed with cancer. Vitamin D deficiency has been associated with an increased risk of mortality in oncology patients. We conducted a prospective vitamin D (cholecalciferol) supplementation study to analyse the response to oral D3 supplementation on fatigue in this population of chemo-naïve patients. Methods: Eligibility critera included life expectancy ≥ 6 months, ECOG PS 0-3, low serum 25-hydroxyvitamin D3 at the time of diagnosis (using cutoff value of 32 ng/mL), and normal serum calcium level. Cancer related fatigue was measured with the Functional Assessment of Cancer Therapy Fatigue module (FACT-F). Patients were randomized to receive oral supplementation with 2,000 IU of Vitamin D3 daily for 3 months with standard cancer treatment or to continue standard treatment without vit D3 supplementation. Primary endpoint was changes in the FACT-F scale. Secondary endpoints was improvement of vitamin D serum levels and safety. Results: 69 vit D deficient patients enrolled in the this study between November 2009 and November 2011 returned a baseline FACT-F. The mean serum 25(OH)D levels were 18.7 ng/ml (SD = 7.4) at baseline. Patients in experimental arm showed marked improvement from baseline in fatigue (p<0.05) and vitamin D serum levels after 3 months (p<0.001). There were significant difference in fatigue score in patients with experimental arm and control arm after 3 months of treatment (p< 0.001). Conclusions: Vitamin D supplementation resulted in a significant increase in Fatigue score and serum 25(OH)D levels in vitamin D deficient patients. Fatigue improve rapidly but remain worse in control arm. The safety profile of vitamin D in combination with chemotherapy or BSC was acceptable. [Table: see text]

Normocalcemic primary hyperparathyroidism: one-year follow-up in one hundred postmenopausal women

Routine measurement of parathormone (PTH) has lead to the identification of high PTH levels without hypercalcemia. This situation, which is known as normocalcemic hyperparathyroidism [1], was defined by Wills in 1962 and is established after ruling out the main causes of secondary hyperparathyroidism. There are conflicting data about its bone effects and clinical course. The aims of our study was to evaluate the frequency of normocalcemic hyperparathyroidism in postmenopausal, to analyse parameters related to bone metabolism, and to assess changes after one-year follow-up. We conducted a prospective study conducted in a cohort of 100 healthy postmenopausal women. Clinical and biochemical data and bone mass by quantitative ultrasound (QUS) were determined at baseline and after 1 year. The study protocol was approved by the ethical review board of our hospital and was done conformed to the ethics guidelines for research in humans. All the participants in the study provided written informed consent. Baseline characteristics of the study groups are shown in Table 1. 16 patients had high PTH levels, one woman with criteria of primary hyperparathyroidism (PTH 109 pg/ml and calcium 11.2 mg/dl) who was excluded from the study and 15 of them with normal calcium serum levels (PTH 78 ± 13 pg/ml and serum calcium 9.3 ± 0.3 mg/dl). In this group, six patients had high PTH with 25-OH vitamin D [30 ng/ml and were classified as normocalcemic primary hyperparathyroidism. There were no differences in biochemical and clinical variables between women with secondary hyperparathyroidism and normocalcemic hyperparathyroidism except for 25-OH vitamin D: 17.4 ± 10 versus 33.2 ± 2.6 ng/ml, p \ 0.001 (Table 1). There was a high percentage of women in both groups with low 25-OH vitamin levels: 72.6 % (61/84) in normal PTH group versus 57.2 % in women with secondary hyperparathyroidism (9/15) (p = 0.32). Women with secondary hyperparathyroidism and normocalcemic hyperparathyroidism have normal values of renal function, bone turnover markers and bone mass measured by QUS. In the group consisting of secondary and normocalcemic hyperparathyroidism, PTH showed a negative correlation with QUS parameters: QUI: r = -0.621, p = 0.013; BMD r = -0.554, p = 0.032; Tscore r = -0.571, p = 0.026. No correlation was observed between PTH and bone mass in the group with normal PTH levels. After one-year of follow-up, PTH remained high in 86.7 % (13/15) of women and in 13.3 % (2/15) PTH has dropped to normal values. In women with secondary hyperparathyroidism there were no significant changes in biochemical and clinical variables (Table 1). The six women with baseline criteria of normocalcemic hyperparathyroidism remained in this category after 1 year. No episodes of hypercalcemia or other relevant clinical events were observed in this group. To our knowledge, no previous studies have evaluated the frequency of normocalcemic hyperparathyroidism in postmenopausal Spanish women. In the Canadian Multicentre Osteoporosis normocalcemic hyperparathyroidism was diagnosed in 16.7 % of subjects, but they considered 25-OH vitamin D \20 ng/ml as vitamin D deficiency which may have contributed to the higher prevalence observed. The evaluation of well known causes of secondary hyperparathyroidism in our sample (low vitamin D, renal disease, malnutrition) allowed us to exclude women A. Garcia-Martin (&) R. Reyes-Garcia M. Munoz-Torres Bone Metabolic Unit, Endocrinology Division, University Hospital San Cecilio, Avenida Doctor Oloriz 16, 18012 Granada, Spain e-mail: garciamartin_t@hotmail.com

Feasibility of Rapid Parathormone Assay for Enabling Minimally Invasive Parathyroid Excision

There is no doubt that the success of minimally invasive parathyroidectomy (MIP) has changed the whole treatment of patients with primary hyperparathyroidism, especially the approach towards traditional bilateral neck exploration. A single adenoma is the most common cause of primary hyperparathyroidism and its removal results in cure. Hence, it is worth the effort to localise and excise the single adenoma using modern technologies such as high-quality sestamibi scans and to confirm complete excision using rapid intra operative parathormone (IOPTH) assays. The objective of the study was to evaluate the feasibility of rapid IOPTH assay in successfully facilitating minimally invasive parathyroid excision. This research involved the retrospective study of seven patients, who underwent MIP at Sagar Hospital in Bengaluru, India, for parathyroid adenoma. All patients with evidence of unifocal disease on sestamibi scanning and cervical ultrasonography, underwent MIP via 2-3cm lateral incision. Blood samples for measurement of IOPTH were taken at the time of induction of anaesthesia and 10min after the adenoma excision. Reduction of parathormone (PTH) levels of more than 50% in the postexcision sample was taken as evidence for complete extirpation of parathyroid adenoma. A solitary adenoma was identified in all the seven patients. After MIP, IOPTH levels fell in six of the seven patients. Following the surgery, all the cases were followed up for a period of 1month. During this time, except for one patient, six patients remained asymptomatic and blood tests revealed normal serum calcium levels. A histopathological examination confirmed the diagnosis of parathyroid adenoma in six of the seven patients. After accurate preoperative localisation of the adenoma in patients with primary hyperparathyroidism, MIP with IOPTH measurement offers a safe and successful outcome.

Exacerbation of idiopathic paroxysmal kinesigenic dyskinesia in remission state caused by secondary hypoparathyroidism with hypocalcemia after thyroidectomy: Evidence for ion channelopathy

Most reported cases of paroxysmal kinesigenic dyskinesia (PKD) are idiopathic or familial; however, hypoparathyroidism is another unusual cause of secondary PKD. The pathomechanism of PKD remains poorly understood, and the association between idiopathic and secondary PKD remains an enigma, and has yet to be clearly elucidated. We recently encountered a patient with idiopathic PKD whose symptoms were aggravated by secondary hypoparathyroidism with hypocalcemia after having undergone a thyroidectomy. The patient’s paroxysms were ameliorated by the normalization of serum calcium levels. The results discussed herein may provide support for the hypothesis that PKD is associated with neuronal ion regulation.

Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism

While derangements in glucose metabolism in patients with primary hyperparathyroidism are well-defined, this issue is not investigated in patients with normocalcemic primary hyperparathyroidism (NPHPT). The aim of this study was to investigate the presence of insulin resistance in patients with NPHPT. Eighteen patients with NPHPT (two males and 16 females) and 18 healthy volunteers were enrolled into the study. Secondary causes of parathyroid hormone elevations were excluded in all patients. Blood samples were obtained for the measurement of serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, and serum lipid levels. Glucose and insulin responses to oral glucose tolerance test (OGTT) were obtained. Homeostasis model assessment (HOMA-IR) was also used as an indice of insulin resistance. Patients and control subjects had similar age, body mass index, and sex distribution. Although within normal limits, serum calcium and ALP levels were higher in patients than in the control subjects. None of the patients and the control subjects had diabetes mellitus, while eight patients and six control subjects had impaired glucose tolerance. Insulin responses to OGTT and HOMA-IR were not significantly different among the patient and control subjects. In addition, both groups have similar serum lipid levels. Patients with NPHPT do not exhibit insulin resistance and glucose intolerance. Since so little is known about this form of disease, subjects should be monitored regularly for the metabolic aspects of the disease as well as the progression of their disease.

Surgical Management of Normocalcemic Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT), typically defined as elevated serum calcium levels associated with inappropriately elevated parathyroid hormone (PTH) levels, can occur also in patients with normal serum calcium levels. This study investigated the characteristics, workup, and surgical management of patients with normocalcemic pHPT. A retrospective chart review of a prospectively collected, single-institution parathyroid database was performed on patients with sporadic pHPT who underwent parathyroidectomy between 12/99 and 12/08. In all, 93 of 771 (12%) pHPT patients had normal serum calcium levels 3 months prior to surgery. Ionized calcium (iCa) levels were available for 58 patients and were elevated in 50 (86%). Among those with elevated iCa levels 90% had single-gland disease (SGD), whereas 63% with normal iCa levels had SGD (p = 0.07). Preoperative imaging identified SGD in 60% of patients with normal iCa and in 66% with elevated iCa levels. Intraoperative PTH (IOPTH) monitoring identified cure in 51 of 58 (88%) patients including 6 (75%) with normal iCa. At a median follow-up of 358 days, postoperative calcium and PTH levels were similar in the groups. One (1%) patient had recurrent disease. Most patients with apparent normocalcemic pHPT have elevated ionized calcium levels. For patients with normocalcemic pHPT, we recommend measuring iCa levels preoperatively, performing localization studies, and utilizing IOPTH monitoring to guide a successful operation.

Calcium Metabolism and Hyper and Hypoparathyroidism

Calcium balance refers to the state of calcium body stores which are primarily in bone, determined largely as a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium concentrations by parathyroid hormone (PTH), the release and effect of which is dependent on the availability of 1,25-dihydroxyvitamin D, and levels of serum ionized calcium, which together regulate calcium absorption and transport in the tissues of the gut, kidney, and bone. Primary hyperparathyroidism is diagnosed on the basis of a raised PTH level in the presence of hypercalcemia. Hypoparathyroidism refers to the failure of the body to produce levels of PTH sufficient to maintain a normal level of serum calcium. Pseudoparathyroidismis characterized by end-organ resistance to PTH which presents as hypocalcemia and hyperphosphatemias under high PTH levels.

Normocalcemic versus Hypercalcemic Primary Hyperparathyroidism: More Stone than Bone?

Introduction. Normocalcemic primary hyperparathyroidism (NPHPT) is considered a variant of the more frequent form of the disease characterized by normal serum calcium levels with high PTH. The higher prevalence of renal stones in patients with HPTP and the well established association with bone disorders show the importance of studies on how to manage asymptomatic patients. Objective. To compare the clinical and laboratory data between the normocalcemic and mild hypercalcemic forms of PHPT. Methods. We retrospectively evaluated 70 patients with PHPT, 33 normocalcemic and 37 mild hypercalcemic. Results. The frequency of nephrolithiasis was 18.2% in normocalcemic patients and 18.9% in the hypercalcemic ones (P = 0.937). Fifteen percent of normocalcemic patients had a previous history of fractures compared to 10.8% of hypercalcemic patients, although there was no statistically significant difference (P = 0.726). Conclusion. Our data confirms a high prevalence of urolithiasis in normocalcemic primary hyperparathyroidism, but with the preservation of cortical bone. This finding supports the hypothesis that this disease is not an idle condition and needs treatment.

Cinacalcet in the management of primary hyperparathyroidism

Parathyroidectomy is currently the only curative treatment for primary hyperparathyroidism (PHPT). There are few alternative treatment options in patients who are ineligible for, or unwilling to undergo, surgery and those in whom parathyroidectomy has failed. Current options include the recently approved drug cinacalcet. Cinacalcet is an allosteric modulator of the calcium-sensing receptor, acting to sensitize this receptor to extracellular calcium. Cinacalcet has been found to be effective in reducing or normalizing serum calcium levels in several groups of PHPT patients, including those with mild-to-moderate PHPT, intractable disease, parathyroid carcinoma and multiple endocrine neoplasia Type 1. Cinacalcet slightly reduces parathyroid hormone levels and has no effect on bone mineral density. Cinacalcet is well tolerated when used at low doses, but side effects are not uncommon when relatively high doses are needed to control hypercalcemia. The current evidence indicates that cinacalcet may be of benefit in a wide spectrum of PHPT severities, offering a novel therapeutic option for the control of hypercalcemia in PHPT patients who are not able to undergo parathyroidectomy. It is presently unknown how much of the biochemical benefit of cinacalcet treatment translates into a clinical benefit, particularly in patients with mild-to-moderate hypercalcemia. Moreover, there are no data as to whether long-term treatment with cinacalcet can prevent the complications of PHPT.

Thallium 201 scanning can diagnose multiple recurrences in forearm implanted parathyroid tissue post total parathyroidectomy:

We report a case of a 48 years old male known to have chronic renal failure for more than 17 years. Patient was on regular haemodialysis for the last eleven years post failure of renal transplant due to graft rejection. Patient developed secondary hyperparathyroidism .He underwent total parathyroidectomy (surgical removal of the four parathyroid glands) with reimplantation of parathyroid tissue in the proximal right forearm in July 2009. Three months later, In November 2009, serum parathormone level (PTH) was elevated reaching up to 766pg/ml (N: 15-65 pg/ml) .Patient was operated upon for removal of the implanted tissue in the right forearm (no available preoperative diagnostic imaging modalities). Gross description in histopathology was two pieces of tissue representing two nodules each2X1 cm. Microscopically, the picture was consistent with chief cell hyperplasia .Post operatively both serum calcium and parathormone levels were normalized (Jan.2010). First presentation to king Abdulla Medical city was in August 2010, patient presented with mildly tender small swelling in proximal right forearm associated with intermittent generalized bony pains. Laboratory data revealed hypercalcemia (serum calcium level: 3.4 mmol/L -N:2.1-2.5 mmol/L)with markedly elevated serum PTH level (2184pg/ml) . CT scan of right forearm revealed presence of a nodular enhancing lesion of 29X11.6X7.7 mm with well defined margin in the site of implantation at lateral (radial) aspect of proximal right forearm just underlying the skin. Thallium201(TL201) scan revealed a well defined TL201 avid lesion located at lateral aspect of proximal right forearm just below the scar (Fig1). Besides, it revealed absence of any TL201 uptake that may represent overfunctioning parathyroid tissue neither in the neck nor in the mediastinum.(Fig 2) Patient was operated upon by removal of the lesion in the forearm for the second time (September2010). Histopathology proved to be parathyroid hyperplasia (Fig3). Post operative serum PTH level was still elevated (416.2 pg/ml) with persistent hypercalcemia (2.83 mmol/L). TL201 scan was repeated in January 2011. It revealed presence of small linear TL201 avid lesion in proximal right forearm (Fig4). Again, no TL201 avid lesions depicted in the neck or in mediastinum that may represent overfunctioning parathyroid tissue at normal anatomical sites of parathyroid glands nor at any expected ectopic site. The patient was reoperated upon with re-excision of the lesion in the right forearm for the third time. Again, Histopathology proved to be parathyroid hyperplasia. Serum partarthormone level at 2 months post surgery (March 2011) was 20.2pg/ml(N:15-65),with normal serum calcium level 2.2mmol/L. Patient is under regular follow up with normal serum calcium and parathormone levels till September 2011.

Normocalcemic parathormone elevation after successful parathyroidectomy: Long-term analysis of parathormone variations over 10 years

The long-term significance of normocalcemic parathormone elevation (NPE) after successful parathyroidectomy for sporadic primary hyperparathyroidism remains unclear. Of 239 consecutive patients who underwent targeted parathyroidectomy with intraoperative parathormone monitoring, 96 were followed for ≥ 10 years. NPE was defined as a normal serum calcium level and parathormone (PTH) above the normal reference range ≥ 6 months after successful parathyroidectomy. Recurrence was defined as elevated serum calcium and PTH levels ≥ 6 months after parathyroidectomy. Risk factors for NPE, patterns of postoperative PTH variation, and 10-year outcomes were analyzed. Of 96 patients followed ≥ 10 years, 42 had postoperative NPE. Only male gender (P = .008) was a risk factor for NPE, and NPE did not predict recurrence. Three patterns of postoperative NPE were identified in patients with ≥ 3 PTH measurements over this 10-year period. Group 1 (n = 11): 1 to 2 consecutive PTH elevations; none recurred, and most were explained by physiologic variation. Group 2 (n = 23): multiple PTH fluctuations; 3 recurred, and almost all had physiologic variations. Group 3 (n = 4): PTH always elevated; 2 recurred. Postoperative NPE may be a dynamic, reversible, and transient clinical entity that does not predict recurrence. Nevertheless, patients with postoperative NPE should be monitored and an attempt made to correct any obvious potential causes of PTH elevation.

Update on the use of cinacalcet in the management of primary hyperparathyroidism.

Cinacalcet is an allosteric modulator of the calcium sensing receptor acting to sensitize this receptor to the extracellular calcium. Cinacalcet has been shown to be effective in reducing or normalizing serum calcium levels in several groups of patients with primary hyperparathyroidism (PHPT), including patients with mild to moderate PHPT, intractable PHPT, and parathyroid carcinoma, and in PHPT as a part of multiple endocrine neoplasia type 1. Cinacalcet slightly reduces PTH levels and has no effects on bone mineral density. Cinacalcet at low doses is well tolerated, but side effects are more frequent and severe when relatively high doses are needed to control hypercalcemia. Cinacalcet may be of benefit in a wide spectrum of PHPT severity, offering a novel therapeutic option for the control of hypercalcemia in PHPT patients who are not able to undergo parathyroidectomy. To what extent the reduction of serum calcium particularly in patients with mild to moderate hypercalcemia, translates into a clinical benefit is currently unknown. Moreover, there are no data as to whether long-term treatment with cinacalcet can prevent the complications of PHPT. Finally, more data are needed on the long-term safety of cinacalcet, particularly at the renal level.

Contrast-enhanced ultrasonography for localization of pathologic glands in patients with primary hyperparathyroidism

The localization of enlarged parathyroid glands might, depending on size, histology, and concomitant goiter, be difficult in some patients. In the presented study, contrast-enhanced ultrasonography (CEUS) was applied as a new diagnostic tool to detect the site of parathyroid lesions. Thirty patients underwent operation for primary hyperparathyroidism (pHPT) between 8/2009 and 6/2010. Contrast-enhanced ultrasonography (CEUS) using a linear probe (6-9 MHz, LOGIQE9/GE), fundamental B scan, and Doppler ultrasonography, (99m)Technetium-sestamibi scintigraphy and magnetic resonance imaging (MRI) were performed in all patients preoperatively. The diagnostic sensitivity of the procedures, time requirements, and overall costs were analyzed. Using CEUS, all 31 pathologic glands could be detected, compared with 23 using conventional ultrasonography, 25 using (99m)Technetium-sestamibi scintigraphy and 22 using MRI (P = .015). Costs and time requirement were less using CEUS as compared with (99m)Technetium-scintigraphy and MRI examinations (P = .002). Minimally invasive, video-assisted parathyroidectomy could be performed successfully based on CEUS findings in all but 7 patients who required concomitant thyroid surgery or had underwent previous thyroid operations. All patients showed normal serum levels of calcium and parathyroid hormone serum levels 3 months after parathyroidectomy. CEUS represents a highly sensitive and cost-efficient method for localization of pathologic parathyroid glands in patients with pHPT. Future studies should confirm these findings in order to establish CEUS as a standard diagnostic procedure.

Sunitinib‐induced hyperparathyroidism

Sunitinib malate is an orally bioavailable tyrosine kinase inhibitor that is active against many tyrosine kinase receptors involving crucial pathways in both healthy tissues and malignant tissues. Because its use in clinical practice is quite recent, many of its possible side effects remain unknown. In this report, the authors describe the incidence of new-onset hyperparathyroidism in a cohort of patients with metastatic renal cell carcinoma who received treatment with sunitinib. Twenty-six patients who received first-line sunitinib for metastatic renal cell carcinoma were enrolled in this study for a mineral and parathyroid function assessment. Plasma levels of intact parathyroid hormone; serum levels of calcium, phosphorus, 25-hydroxyvitamin D(3), and 1,25-dihydrovitamin D(3); and urinary 24-hour calcium and phosphorus excretion all were measured in each patient. Biochemical evaluations were performed before the beginning of treatment and at the end of each sunitinib treatment period. Eighteen of 26 patients (69.2%) developed hyperparathyroidism with normal serum calcium levels, and 6 of them developed hypophosphatemia. Patients presented with a mean elevation of parathyroid hormone after 2.2 cycles of sunitinib. The levels of 25-OH vitamin D(3) were stable over the course of treatment, whereas 1,25-OH vitamin D(3) levels were increased in 5 hyperparathyroid patients. Those who presenting with elevated parathyroid hormone levels had low or undetectable urinary calcium levels. Parathyroid hormone elevation usually persisted but did not progress during long-term therapy with sunitinib. Permanent treatment interruption resulted in a resolution of hyperparathyroidism. Hyperparathyroidism developed in an high percentage of patients on sunitinib. Therefore, the authors concluded that sunitinib may affect parathyroid function and bone mineral homeostasis, possibly resulting in abnormal bone remodeling.

Calcium insufficiency accelerates type 1 diabetes in vitamin D receptor-deficient nonobese diabetic (NOD) mice.

Vitamin D exerts important regulatory effects on the endocrine and immune systems. Autoimmune type 1 diabetes (T1D) development in the inbred NOD mouse strain can be accelerated by vitamin D insufficiency or suppressed by chronic treatment with high levels of 1α,25-dihydroxyvitamin D(3). Consequently, a report that T1D development was unaffected in NOD mice genetically lacking the vitamin D receptor (VDR) was unexpected. To further assess this result, the mutant stock was imported to The Jackson Laboratory, backcrossed once to NOD/ShiLtJ, and progeny rederived through embryo transfer. VDR-deficient NOD mice of both sexes showed significant acceleration of T1D. This acceleration was not associated with alterations in immune cells targeting pancreatic β-cells. Rather, the capacity of β-cells to produce and/or secrete insulin was severely impaired by the hypocalcaemia developing in VDR-deficient NOD mice fed a standard rodent chow diet. Feeding a high-lactose calcium rescue diet that circumvents a VDR requirement for calcium absorption from the intestine normalized serum calcium levels, restored β-cell insulin secretion, corrected glucose intolerance, and eliminated accelerated T1D in VDR-deficient NOD mice. These findings suggest that calcium and/or vitamin D supplementation may improve disease outcomes in some T1D-prone individuals that are calcium deficient.

Pseudohypercalcaemia in patients with heat cramps: implications on clinical practice

Hypercalcaemia is often thought to provide important clues to the presence of unsuspected illness. A presumptive diagnosis of hypercalcaemia may often be made on an elevated total serum calcium concentration although it should, strictly speaking, refer to an elevation in the physiologically important ionized (free) calcium concentration. Pseudohypercalcaemia is rare, but should be excluded before pursuing unnecessary investigation for hypercalcaemia. Pseudohypercalcaemia refers to an increased serum total calcium concentration but in the presence of a normal ionized serum calcium level.1 Heat-related illness, although not widely reported, is an important cause of pseudohypercalcaemia. We describe three patients with heat cramps who were initially suspected to have hypercalcaemia. A 46-year-old Chinese male construction site worker was referred to the hospital because of severe bilateral leg cramps after working under hot weather for >8 h. He did not have constipation, abdominal pain, bone pain, weight loss, depression, peptic ulcer or pancreatitis. Upon admission, his oral mucosa was dry and his body temperature was 37.4°C. Radiograph of the chest and urinalysis were normal. Other laboratory results are shown in …

Familial tumoral calcinosis in two Chinese patients: a case series

IntroductionTumoral calcinosis is a rare and benign condition characterized by massive subcutaneous soft tissue deposits of calcium phosphate predominantly around large joints.Case presentationFamilial tumoral calcinosis was present in two members of a Han Chinese family, namely, the son and daughter. The 14-year-old son had the first operation on his right sole of the foot at the age of six, and then experienced subsequent surgeries at a lesion in his right sole of the foot and left hip, respectively. The 16-year-old daughter underwent her first operation at the age of six in her left gluteal region, and subsequent surgeries were performed due to recurrence at the same lesion. Pathologic diagnoses of surgical specimens in both of the patients were reported as tumoral calcinosis. The laboratory results showed hyperphosphatemia with normal levels of serum calcium and alkaline phosphatase. Only surgical treatment was performed in both patients with satisfactory prognosis.ConclusionThis is the first report of Chinese familial tumoral calcinosis. The etiopathogenisis and treatment are discussed.

Total Knee Arthroplasty in a Patient With Pseudopseudohypoparathyroidism

Pseudopseudohypoparathyroidism (PPH) is a rare genetic disorder characterized by multiple musculoskeletal anomalies and normal serum calcium, phosphate, and parathyroid hormone levels. Although the musculoskeletal manifestations of PPH are well known, little has been reported on the management of orthopedic problems. We report a case of total knee arthroplasty (TKA) performed in a patient with PPH. To our knowledge, this case is not only unique to the arthroplasty literature but is the first report of its kind. This report illustrates the unique pathoanatomy of PPH, the medical and surgical management required, and a previously unreported musculoskeletal abnormality associated with PPH: synovial osteochondromatosis of the knee. Common musculoskeletal anomalies associated with PPH include shortening/bowing of long bones; shortening of metacarpals, metatarsals, and/or phalanges; exostoses; calcification/ossification of subcutaneous and/or periarticular soft tissues; a thickened calvarium; microcephaly; bony coalitions of the hand; vertebral column abnormalities; cubitus valgus; radius/ulna curvus; coxa vara; coxa valga; and genu valgum. This case is the first to report an association of synovial osteochondromatosis with PPH. Because synovial osteochondromatosis and PPH share a common disorder of soft tissue calcification/ossification, as well as abnormal bone formation, this clinical finding does not seem merely coincidental.

Calcinosis Cutis: Report of 4 Cases

Calcinosis cutis is a condition of accumulation of calcium salts within the dermis. We are presenting four cases of calcinosis cutis, with different clinical presentations, occurring in healthy individuals, with normal serum calcium and phosphorus levels. Histologically, all cases showed similar morphology, the lesions were composed of large and small deposits of calcium. Foreign-body giant cell reaction was seen in one case. Another case had intact and ruptured epidermal cysts and calcification within the cyst.

An open-label randomized phase II trial of oral vitamin D3 supplementation in combination with standard chemotherapy or best supportive care compared with standard chemotherapy and best supportive care in patients with advanced solid tumors.

e19566 Background: The majority of patients with newly diagnosed stage IV cancer are vitamin D deficient at the time of diagnosis. We conducted a phase II trial to evaluate the efficacy and safety of oral supplementation with 25-hydroxyvitamin D3 [25(OH)D] in chemotherapy-naive patients. Methods: Eligibility critera included ECOG PS 0-3, low serum 25-hydroxyvitamin D3 [25(OH)D] at the time of diagnosis (using cutoff value of 32 nmol/L) and normal serum calcium level. Patients were randomized to receive oral supplementation with 2,000 IU of Vitamin D3 daily for 6 months with standard therapy or to continue standard treatment without vit D supplementation. Results: Sixty-seven patients were accrued, 42 were males and 25 females. The most common primary cancer sites were lung (36, 54%), colorectum (14, 21%), pancreas (7, 10%), breast (7, 10%) and kidney (3, 5%). The median 25 (OH) D level for all patients was 20,69 nmol/L. Response is evaluated by RECIST criteria at 8 weeks and toxicity was graded by the NCI CTCAE. No patient had a complete response, but ORR were significantly better in experimental arm (18% versus 6%, p=0.036). Vit D was well tolerated; the most common toxicities were neutropenia, diarrhoea, fatigue, nausea and constipation. Four patients had grade 1-2 of hypercalcemia (Table). Conclusions: The safety profile of vitamin D in combination with chemotherapy or BSC was acceptable and ORR was significantly greater for patients receiving oral vit D supplementation. However, there was no significant difference between the two arms in terms of 6 months survival rates. These data suggest that adding vit D to an already-effective treatment may result in clinical benefit beyond that associated with combination chemotherapy or BSC alone. Experimental arm (n=33) Control arm (n=34) P Vitamin D median nmol/L 19.64 21.72 0.40 Age median years 66 65 0.62 Male gender 22 20 0.15 Date of diagnosis 0.49 Winter-Spring 15 16 Summer-Autumn 17 17 Treatment 0.86 Chemotherapy 22 22 BSC 11 12 ORR 6 (18%) 2 (6%) 0.036 AE gr 3 or 4 8 8 0.95 Hypercalcemia 1 3 0.32