| 2020 | Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes. | Endocr Connect | Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two CYP24A1 missense variants.The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine.The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted calcium of 3.27 (upper reference limit (URL: 2.30) mmol/L), suppressed iPTH (<6 ng/L), elevated 25(OH)D (264 (URL: 55) nmol/L) and elevated 1,25(OH)D (293 (URL: <280) pmol/L). Ionized calcium was 1.55 (URL: 1.28) mmol/L. Sanger sequencing revealed two heterozygous missense variants in the CYP24A1: p.(Arg439Cys), R439C and p.(Trp275Arg), W275R. The proband's brother and sister had the same genotype. The brother had intermittent hypercalcaemia and hypervitaminosis D. Only the sister had a history of nephrolithiasis. The proband's daughter and two nephews were heterozygous for the R439C variant. The proband and her brother frequently had elevated 25(OH)D:24,25(OH)2D ratios (>50) during follow-up.W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family. |
| 2019 | Acute and long-term effects of zoledronate in adult patients with osteogenesis imperfecta. An observational Spanish study with five years of follow-up. | Endocrinol Diabetes Nutr (Engl Ed) | Osteogenesis imperfecta (OI) is an inherited disorder that causes low mineral density and bone fragility. Previous studies have shown the efficacy of bisphosphonates to increase bone mineral density (BMD). This study assessed changes over time in BMD and biochemical markers of bone metabolism in adult patients with osteogenesis imperfecta treated with intravenous zoledronic acid and the safety of this treatment.A prospective, observational study in patients with OI, osteoporosis or osteopenia (T score <-2) who were administered zoledronic acid infusions (4mg IV) every 6 months for three years and annually thereafter. Densitometry was performed annually. Acute changes in complete blood count and calcium, phosphate, and creatinine levels, as well as side effects of the infusion, were recorded 24 and 48h after treatment. Calcium, phosphate, parathyroid hormone (iPTH), 25OH-vitamin D and bone turnover markers (bone alkaline phosphatase, ß-crosslaps and urinary deoxypyridinoline) were measured at baseline and every 12 months. Adverse events and new fractures were recorded.Twenty patients (6 men and 14 women) were treated. Median follow-up time was five years. Calcium levels and platelet counts significantly decreased 24 and 48hours after the first infusion, and the red blood cell count decreased at 24hours. These changes were not clinically relevant. Seven patients experienced a flu-like episode after the first dose. Treatment induced significant increases in BMD in the lumbar spine (6.7%) after 12 months of follow-up (0.791±0.178 vs. 0.791±0.140g/cm, p=.003) and at three (5.7%) and five years (9%) of follow-up. Femoral neck BMD significantly increased after 3 years (11.1%): 0.648±0.148 vs. 0.720±0.138g/cm; p=.01. In total hip, increase in BMD (10.1%) was significant after three years of treatment (0.706±0.118 vs. 0.720±0.138, p=.01). There were no significant differences in calcium and 25OH-vitamin D levels during follow-up, phosphorus significantly decreased after one year, and iPTH increased at three years. ß-crosslaps decreased after one year of treatment. Only one patient sustained new fractures.Zoledronic acid is a convenient, safe, and effective treatment that increases BMD in adult patients with OI. |
| 2018 | ACUTE PHASE REACTIONS AFTER ZOLEDRONIC ACID INFUSION: PROTECTIVE ROLE OF 25-HYDROXYVITAMIN D AND PREVIOUS ORAL BISPHOSPHONATE THERAPY. | Endocr Pract | The most common adverse reaction to zoledronic acid (ZOL) infusion is the acute phase reaction (APR), characterized by transient, usually mild, flu-like symptoms. Previous treatment with oral amino-bisphosphonates (BPs) was reported as an independent protective factor for APR, and an association between APR and 25-hydroxyvitamin D (25(OH)D) levels in BP-naïve patients treated with ZOL was identified. The aims of our study were to confirm this association and to see if it was different in patients previously treated with oral BPs compared with BP-naïve patients and to investigate the role of 25(OH)D for the time of APR onset.We included 153 consecutive patients with postmenopausal osteoporosis undergoing their first ZOL infusion. Sixty-eight had been previously treated with oral BPs. Clinical, demographic, and serologic data were recorded.25(OH)D levels were significantly lower in patients experiencing APR compared to patients without APR (26.3 ± 12.7 vs. 37.0 ± 13.5 ng/mL, respectively; P<.0001). Patients with 25(OH)D <30 ng/mL had a significantly higher risk of APR (odds ratio [OR] 4.2 [95% confidence interval [CI] 2.1-8.2]) occurring in 65%. APR was significantly less frequent in patients previously treated with oral BPs than in BP-naïve subjects (33.8% [23/68] vs 52.9% [45/85], P = .018), but only a weak association remained after correction for 25(OH)D (OR 0.5, 95% CI 0.3-1.1, P = .08).Higher baseline 25(OH)D levels appear to be protective for APR post-ZOL infusion. The role of previous treatment with oral BPs as an independent protective factor for APR should be evaluated in a larger cohort.APR = acute phase reaction; BPs = amino-bisphosphonates; CI = confidence interval; 25(OH)D = 25-hydroxyvitamin D; OP = osteoporosis; OR = odds ratio; PTH = parathyroid hormone; ROC = receiver operating characteristic; ZOL = zoledronic acid. |
| 2013 | A rare cause of hypocalcemia. | Am J Case Rep | Many factors influence serum calcium concentration, but the major determinants of calcium homeostatsis are parathyroid hormone (PTH), vitamin D, the ionized calcium, and phosphate [1]. Therefore, deranged calcium metabolism is often seen in the presence of disordered parathyroid hormone (PTH) and/or vitamin D actions. Among these causes is end-organ resistance to the biological effect of parathyroid hormone.In this paper, we report a case of a patient who presented with flu like symptoms and incidental finding of hypocalcemia that is consistent with parathyroid hormone resistance.Familial causes of hypocalcemia, although rare, should be thought about after ruling out the other common causes of hypocalcemia. |
| 2009 | [The efficacy and safety of intravenous bisphosphonates in the treatment of primary hyperparathyroidism complicated by hypercalcemia crisis]. | Zhonghua Nei Ke Za Zhi | To study the efficacy and adverse events of intravenous bisphosphonates in the treatment of patients of primary hyperparathyroidism (PHPT) complicated by hypercalcemia crisis.From October 2003 to December 2007, 14 patients admitted into our hospital were diagnosed as PHPT complicated by hypercalcemia crisis, which was defined as a serum calcium concentration greater than 3.50 mmol/L. Of them, 6 cases had parathyroid adenoma, 1 had hyperplasia and 7 had parathyroid carcinoma. One of the intravenous bisphosphonates including pamidronate, ibandronate and zoledronic acid was given for 29 times in all the 14 cases. Serum calcium, parathyroid hormone, hematology, and other biochemical markers were monitored. Adverse events were recorded.After intravenous bisphosphonates, the serum total calcium (Ca) levels decreased from (3.85 +/- 0.50) mmol/L to (2.86 +/- 0.39) mmol/L in (1.4 +/- 0.6) days, and were kept below 3.50 mmol/L for (10.14 +/- 8.54) days. There was no significant difference of the magnitude of decrease in serum Ca levels among the patients using pamidronate, ibandronate or zoledronic acid. The change of serum Ca level was associated with the serum Ca level before treatment. The response to intravenous bisphosphonates evaluated by the decrease of serum total calcium levels was more significant in patients with parathyroid adenoma or hyperplasia than those with parathyroid carcinoma. The most common adverse event was pyrexia, which occurred 15 times (51.7%) and 75% of the pyrexia events occurred after the first infusion. Other manifestations included fatigue, flu-like symptom, myalgia, arthralgia and diarrhea with an incidence of 3.4% each (one event in the 29 times of treatment). There were 2 events (6.7%) with mild increase of serum creatinine concentration.Bisphosphonates can decrease serum total calcium levels in hypercalcemia crisis caused by PHPT effectively with mild adverse events. |
| 1991 | Clinical efficacy of recombinant human erythropoietin in the treatment of anemia in hemodialysis patients: influence of dosing regimen, iron status, and serum aluminum. | Gaoxiong Yi Xue Ke Xue Za Zhi | To evaluate the clinical efficacy of recombinant human erythropoietin (EPO) and its influencing factors in the treatment of anemia in hemodialysis (HD) patients, 17 chronic stable HD patients (10 males, 7 females; mean age: 46.0 +/- 2.6 years) with severe anemia were enrolled in this study. The study period (ranging from 5 to 11 months) was divided into the initial 12 weeks of correction phase and the subsequent maintenance phase. EPO, 1500 U initially, was administered intravenously twice weekly (BIW group, n = 10) or thrice weekly (TIW group, n = 7) at the end of each HD. Dose was doubled every 4 weeks until up to a maximum dose of 6000 U if increment of hematocrit (Hct) was less than 3%. At the end of correction phase, anemia was markedly improved. Hct and hemoglobin (Hb) increased from 19.3 +/- 0.8 to 28.7 +/- 1.1% and from 6.5 +/- 0.3 to 9.6 +/- 0.4 g/dl, respectively. Fifteen patients (88%) reached to the target Hct of 30% at 13.7 +/- 1.2 weeks. At the end of study, Hct and Hb was maintained at 29.1 +/- 0.7% and 9.6 +/- 0.3 g/dl, respectively. Requirement of EPO dose to reach the target and maintain the stable Hct (greater than or equal to 28%) was 99 +/- 14 and 62 +/- 11 U/kg/week, respectively. Laboratory parameters showed that serum iron, transferrin saturation, sugar and triglyceride decreased significantly and uric acid and aluminum (Al) increased significantly. There was no significant change in predialysis blood pressure, body weight, cardiac ratio, and ECG. Quality of life was markedly improved with the better subjective feelings, physical activity and Karnorfsky index. Common adverse effects included exacerbated hypertension (23%), hyperphosphatemia (18%), hyperkalemia (18%), and flu-like syndrome (12%). All of them could be managed by medical and dialysis treatment. Investigation of influencing factors on response to EPO suggests that 1) TIW group had a better response than BIW group 2) Response was better in patients with more adequate iron status and less severe Al burden. 3) Time to target Hct correlated approximately with basal serum Al levels but did not correlate with basal serum parathyroid hormone levels. In conclusion, low dose of EPO therapy corrects anemia effectively with minimal adverse effects in HD patients. Dosing regimen, iron status, and serum Al will influence the response to EPO. |