Normal Serum Calcium Concentrations Research Articles

Low Serum Calcium Concentration in Patients With Systemic Lupus Erythematosus Accompanied by the Enhanced Peripheral Cellular Immunity

ObjectiveThis study aims to explore the relationship between serum calcium concentration and peripheral lymphocyte status/Th1/Th2 cytokine levels in SLE patients, and the effect of glucocorticoids (GCs) on the calcium concentration and immune cell activation.MethodsThe peripheral blood TBNK lymphocyte subsets and Th1/Th2 cytokines in SLE patients with low or normal serum calcium concentration and healthy people were analyzed and compared retrospectively. Peripheral white blood cells (PWBCs) from SLE patients or healthy people were stimulated with PMA or GCs in vitro to test their extracellular calcium concentration and CD8+ T cell activation.ResultsThe percentages of CD8+ T in SLE patients increased, but the increase of the number of CD8+ T cells only occurred in the SLE patients with low serum calcium concentration, and the number of CD45hiCD8+ T cells also increased, suggesting that SLE patients with hypocalcemia tend to possess an enhanced cellular immunity. The results of Th1/Th2 cytokines in peripheral blood showed that the levels of serum IL-2, IL-10, IL-6 and IFN-γ in SLE patients with hypocalcemia were significantly increased. Although the serum levels of TNF-α in SLE patients were –similar to that in healthy people, it was significantly higher than that in SLE patients with normal serum calcium. When comparing the results of Th1/Th2 cytokines in two times of one patient, the serum levels of TNF-α in SLE patients increased while serum calcium levels decreased. The in vitro experiments showed that the decrease of serum calcium concentration in SLE patients was affected by the immune cell activation and the application of GCs, but GCs did not promote the immune cell activation.ConclusionsLow serum calcium may make SLE patients in an enhanced cellular immune status and GCs aggravates the decrease of serum calcium levels but has no role on the immune cell activation. It suggests that hypocalcemia possibly promotes the disease activity of SLE patient, which should be paid attention to clinically.

Occult Renal Calcifications in Patients with Normocalcemic Primary Hyperparathyroidism and Their Association with the Parathyroid Hormone-Vitamin D Axis.

Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated serum levels of parathyroid hormone (PTH) with persistently normal serum calcium concentrations after excluding secondary causes of hyperparathyroidism. Urolithiasis and/or nephrocalcinosis may occur in hypercalcemic PHPT, but little is known about these complications in NPHPT. Objectives. To identify occult urolithiasis and nephrocalcinosis in asymptomatic patients with NPHPT and evaluate biochemical markers as risk predictors for the development of renal calcification (RC). Methods. Cross-sectional analysis of 34 patients with no history of urolithiasis and/or nephrocalcinosis. The diagnosis of NPHPT was as follows: elevated serum PTH (reference range: 15–65 pg/mL), normal albumin-corrected serum calcium, normal urinary calcium excretion, serum 25(OH)D >30 ng/mL, eGFR (CKD-EPI) > 60 mL/min/1.73 m2, without intestinal disease, and not on medications such as thiazide diuretics, lithium, bisphosphonates, or denosumab. Patients were categorized according to the presence or absence of RC identified by renal imaging. Their clinical and biochemical characteristics were then compared. Results. The patients had a mean age of 67.97 ± 10.45 years, predominantly postmenopausal women (88.2%); serum PTH, 119.67 ± 64.44 pg/mL; 25(OH)D, 39.00 ± 8.88 ng/dL; 1.25(OH))2D, 74.53 ± 26.37 pg/mL; corrected serum calcium, 9.34 ± 0.62 mg/dL; and 24-hour urinary calcium, 134.87 ± 79.68 mg/day. RC was identified in 26.5% of the patients. There was no difference in anthropometric and clinical parameters, renal function, 25(OH)D, and urinary pH in patients with or without RC. Patients with RC had higher PTH values (176.22 vs. 99.32 pg/mL, P = 0.001), 1.25(OH) 2D (96.83 vs. 62.36 pg/mL, P = 0.005), and 24-hour urinary calcium (181.9 vs. 117.94 mg/day, P = 0.037). Conclusion. Occult renal calcifications are common in NPHPT and are associated with increased serum PTH, 1.25(OH))2D, and 24 h urinary calcium.

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

BackgroundNormocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients.MethodsA total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122).ResultsNPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions.ConclusionWe found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Chronic hypoparathyroidism and treatment with teriparatide

PurposeChronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term complications. The use of hormone replacement therapy with PTH peptides [teriparatide and rhPTH (1–84)] has therefore been proposed. The main purpose of this study was to investigate the efficacy of teriparatide dose at 20 µg once or twice daily, in order to maintain normocalcemia reducing standard treatment, in adult patients with chronic hypoparathyroidism not well controlled with conventional treatment.MethodsThe study was a Phase III, open-label, non-comparative, clinical investigation (study period: 3 months), at a tertiary care clinical research center. Thirty patients with chronic hypoparathyroidism were screened, and 12 started teriparatide. After the optimization phase (0–4 weeks), calcium and calcitriol supplements were progressively reduced, while teriparatide 20 µg once daily was administered (5–7 weeks), and then could be titrated up to 20 µg twice daily (7–17 weeks). The main outcome measures included serum and urinary biochemical exams and Rand 36-Item Short Form Health Survey.ResultsThis study showed that teriparatide 20 µg once daily was insufficient to discontinue calcium and calcitriol supplements to maintain normal serum calcium concentrations. Conversely, for more than half of patients treated with teriparatide 20 µg twice daily, calcium and calcitriol administration was avoidable, but in some cases at the expense of serum calcium and phosphate oscillations.ConclusionsSince intervention trials evaluating the efficacy and safety of teriparatide in hypoparathyroid patients are not yet available, the routine use of this molecule poses some doubts.

How should normocalcemic primary hyperparathyroidism be managed? Comparison with classical hypercalcemic form

Aim: Normocalcemic primary hyperparathyroidism (N-PHPT) is a different variant of primary hyperparathyroidism characterized by normal serum calcium (Ca) concentrations and elevated parathormone (PTH) levels in the absence of secondary causes of hyperparathyroidism. However, the clinical course and therapeutic approaches of this entity have been not fully demonstrated. We aimed to determine the clinicopathological characteristics and surgical outcomes of patients with N-PHPT, comparing with patients who had hypercalcemic PHPT (H-PHPT). Materials and Methods: A total of 185 patients who underwent parathyroidectomy for PHPT were included in the study. The patients were classified as N-PHPT and H-PHPT. The two groups were then compared between each other in terms of all demographic, clinical, and surgical features. Results: One hundred and fifty-one (81.6%) patients had a diagnosis of H-PHPT while 34 (18.4%) patients were normocalcemic. Both groups were similar in age, preoperative vitamin D level, preoperative PTH level, and type of surgery (p > 0.05). Preoperative Ca level was significantly different between the groups (p 0.05). Conclusion: N-PHPT patients had similar demographic and clinical features in comparison to those with H-PHPT, indicating that the surgical decision in patients with N-PHPT should be similar with H-PHPT cases.

Effect of dietary supplementation with yeast Saccharomyces cerevisiae on skin, serum and liver of gilthead seabream (Sparus aurata L).

The effect of dietary supplementation with Saccharomyces cerevisiae on gilthead seabream (Sparus aurata L.) was studied. Four replicates of fish (n = 6) were fed with a commercial diet containing 0 (control, no yeast added) or 10 mg per kilogram of heat-killed (30 min, 60°C) S. cerevisiae. After 4 weeks, half of the fish (two replicates) were injured and continued with the same diet. At 3 and 7 days post-wounding, samples of blood, skin mucus, skin and liver were obtained from each fish. The results showed that calcium concentrations were significantly higher (with respect to control fish) in the serum from fish sampled at 3 days post-wounding, whereas antioxidant enzymes in the skin mucus were altered after wounding (at both 3 and 7 days). Histological analyses revealed oedema, signs of inflammation and white cell recruitment together with a reduction in the epidermis layer in the wounded regions of fish fed control diet. Yeast supplementation did not change growth performance and helped maintain the normal serum calcium concentrations in wounded fish. Furthermore, a reduction in inflammation around wounds in the animals fed yeast with respect to that fed control diet was evident in the histological study. Furthermore, increased levels of stress-related gene expression in liver and skin from wounded fish were obtained. Overall, yeast supplementation seemed to be a functional and appropriate dietary additive to improve skin recovery reducing the stress resulting from wounds.

Chronic Kidney Disease –Mineral Bone Disorder (CKD- MBD) – Further Insight at the Indian patients.

The kidneys play an important role in maintaining normal serum calcium (Ca) and phosphorous (P) concentrations. Chronic kidney disease (CKD) is associated with significant disturbances in bone and mineral metabolism, leading to altered serum concentrations of Ca, P, vitamin D and parathyroid hormone (PTH)1,2,3. These changes are initially detected when the glomerular filtration rate (GFR) falls to ≤60 mL/min and are nearly uniform as GFR drops to &lt;30ml/min2,3. This leads to a number of bone abnormalities previously called “renal osteodystrophy”, renamed as CKD-Mineral Bone Disorder (CKD-MBD) by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) consensus group4 . CKD-MBD is a systemic disorder manifested by either one or a combination of a) abnormalities of Ca, P, PTH or vitamin D metabolism, b) abnormalities in bone turnover, mineralization, volume, linear growth or strength c) vascular or soft tissue calcification. This has over time been expanded to include left ventricular hypertrophy, hypertension, immune dysfunction and inflammation5,6.

High Rate of Occult Urolithiasis in Normocalcemic Primary Hyperparathyroidism

Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevations in serum parathyroid hormone levels in the presence of normal serum calcium concentrations after exclusion of secondary hyperparathyroidism. We have previously demonstrated no differences in the prevalence of clinically active urolithiasis between NPHPT and hypercalcemic asymptomatic PHPT, and that it is significantly higher in postmenopausal osteoporotic women with NPHPT in comparison to women with normal serum PTH and calcium concentrations. Few studies have addressed the occurrence of silent or occult kidney stones in asymptomatic hypercalcemic PHPT, but no data are available for NPHPT. Objective: To determine the presence of occult urolithiasis in NPHPT patients using routine abdominal ultrasonography. Methods and Results: We studied 35 patients with NPHPT (mean age 63.2 ± 10.7 years, 96% women; serum PTH 116.5 ± 39.2 pg/mL, 25OHD 38.5 ± 6.82 ng/mL, total calcium 9.1 ± 0.56 mg/dL; albumin 4.02 ± 0.37 g/dL; BUN 34.35 ±10.23 mg/dL; p = 3.51 ± 0.60 mg/dL; estimated glomerular filtration rate 88.44 ± 32.45 mL/min/1.73 m2, and 24-h urinary calcium excretion 140.6 ± 94.3 mg/24 h). The criteria for the diagnosis of NPHPT were as follows: serum PTH above the reference range (11–65 pg/mL), normal albumin-corrected serum calcium concentrations, normal 24-h urinary calcium excretion, serum 25OHD above 30 ng/mL, estimated GFR (MDRD) above 60 mL/min/1.73 m2 (with the exclusion of medications such as thiazide diuretics, lithium, bisphosphonates, and denosumab), a history of clinical symptoms of urolithiasis, and a family history of kidney stones. Thirty-five patients were evaluated and 25 of them met the inclusion criteria. Five patients presented nephrolithiasis corresponding to 20% of the study population. There were no statistically significant differences in any of the clinical or laboratory variables studied between patients with or without urolithiasis, although mean serum PTH levels were higher in patients with stones (180.06 ± 126.48 vs. 100.72 ± 25.28 pg/mL, p = 0.1). The size of the stones ranged from 0.6 to 0.9 cm and all of the stones were located in the renal pelvis. Conclusion: We found a high prevalence of occult kidney stones in NPHPT patients, similar to what is observed in clinically manifested urolithiasis, in hypercalcemic PHPT.

Tumor-induced osteomalacia

Tumor-induced osteomalacia is a rare paraneoplastic syndrome with approximately 500 cases reported. It presents with a variety of nonspecific symptoms including weakness, muscle and bone pain, and fracture. Characteristic laboratory findings are hypophosphatemia, an elevated alkaline phosphatase, normal parathyroid hormone, normal serum calcium concentration, and an inappropriately low 1,25(OH)2-vitamin D3 concentration. Initially, tumor-induced osteomalacia is misdiagnosed in over 95% of cases. Hypophosphatemia results from renal phosphate wasting occurring as a consequence of FGF-23 production by the tumor. FGF-23 reduces expression and stimulates endocytosis of two sodium-phosphate cotransporters found in the luminal membrane of the proximal tubule resulting in renal phosphate wasting. FGF-23 also inhibits the formation and stimulates the degradation of 1,25(OH)2 vitamin D3. The most common tumor causing tumor-induced osteomalacia is a mixed connective tissue tumor known as a “phosphaturic mesenchymal tumor.” Due to its rarity, it is often misdiagnosed. Molecular studies have shed light on the mechanisms of tumorigenesis with the identification of a fibronectin and fibroblast growth factor receptor 1 fusion protein expressed in about half of cases and a fibronectin and fibroblast growth factor 1 fusion protein in a small subset of tumors. Often small and slow growing, the tumors may be found in unusual locations, such as the extremities and nasal sinuses and are difficult to localize. Definitive treatment involves identification and removal of the tumor. Absent tumor removal, therapeutic goals include improvement of symptoms, raising the serum phosphorus concentration to the lower limit of normal, and maintenance or achievement of normal parathyroid hormone and alkaline phosphatase concentration. Two recent drugs that target pathways involved in the molecular pathogenesis of tumor-induced osteomalacia have recently been developed and are in early-phase clinical trials: the humanized anti-FGF-23 monoclonal antibody burosumab (KRN23) and the FGFR-1,2,3 inhibitor NVP-BGJ398.

Peripherally inserted central catheters for calcium requirements after successful parathyroidectomy: a comparison with centrally inserted catheters.

BACKGROUND Intravenous calcium supplements are often required following parathyroidectomy to avoid postoperative hypocalcaemia. The aim of this study was to compare application effect of a femoral central venous catheter (CVC) and peripherally inserted central catheter (PICC) on intravenous calcium supplements after parathyroidectomy. METHODS We retrospectively reviewed the hospital records of 73 patients with secondary hyperparathyroidism who underwent a successful parathyroidectomy at the Huashan Hospital attached to Fudan University between 1 April 2011 and 1 February 2016. RESULTS Of the 73 study participants, 39 (53.4%) had a PICC and 34 (46.6%) had a CVC, respectively. Patients in the CVC group needed 6-7 days of intravenous calcium supplements, while patients in PICC group needed only 2-3 days to achieve normal serum calcium concentration (2.2-2.6mmol/L). Furthermore, the duration of calcium supplementation was 71.62±4.48 hours in PICC group and 100.4±5.43 hours in CVC group (P<0.05). Of the patients in PICC group, the incidence of catheter occlusion, operation failure and hypocalcaemia was 0%, which was significantly lower than those in CVC group (2.56%, 7.69% and 7.69%, respectively). CONCLUSIONS PICC is a safe and efficient alternative in contrast to CVC for providing venous access for calcium supplementation in surgical patients after parathyroidectomy.

Efficacy of microwave ablation for severe secondary hyperparathyroidism in subjects undergoing hemodialysis

Severe secondary hyperparathyroidism (SHPT) is a serious problem in patients undergoing hemodialysis. The efficacy and safety of microwave ablation (MWA), a minimally invasive treatment, for severe SHPT are as yet unclear. To clarify the role of MWA, we administered it to patients with severe SHPT and assessed its efficacy and safety. This was a prospective, single-center, single-arm, clinical trial. We enrolled patients with severe SHPT attending our hemodialysis center who met the inclusion and exclusion criteria. We then assessed primary outcome measures (serum concentrations of intact parathyroid hormone) and secondary outcome measures (serum concentrations of calcium and phosphorus). Twenty-six patients were enrolled in this study, 10 of whom (38.46%) were responsive to MWA and 16 (61.54%) of whom were not. The main complication was hypocalcemia (10 cases, 38.46%), which had occurred in all cases by one week after administration of MWA. Responding patients with hypocalcemia all achieved normal serum calcium concentrations within seven months and non-responding patients within three months. There were no changes in serum phosphorus concentrations after MWA in either responders or non-responders. Microwave ablation is relatively ineffective in patients with severe SHPT undergoing maintaining hemodialysis and should not be the initial therapy in such cases.

Acute and chronic oxalate toxicity in Miniature Horses associated with soursob (Oxalis pes‐caprae) ingestion

SummaryOver the period of 11 years (2004–2015) 14 miniature horses in six separate outbreaks presented with clinical signs consistent with acute or chronic oxalate toxicity. All animals had access to Oxalis pes‐caprae or soursob. Miniature horses with acute oxalate toxicity and hypocalcaemia had muscle fasciculations, tremors and synchronous diaphragmatic flutter; these horses responded to treatment with intravenous and oral calcium. Chronic oxalate toxicity was associated with ill‐thrift, stiffness, enlarged heads, kyphosis and neurological signs. These animals had normal serum calcium concentrations, but increased serum alkaline phosphatase activity. Radiographs indicated that affected animals had bones that were osteopenic, often with pathological fractures. Bones that were examined histologically showed increased osteoclastic and osteoblastic activity, consistent with nutritional secondary hyperparathyroidism and fibrous osteodystrophy. These animals were treated, with mixed success, with oral calcium supplementation. A palatability trial showed that horses will readily eat soursobs, and measured total oxalate concentrations in soursobs collected from five different properties ranged from 13.5 to 18.5%. The presentation of affected animals with either acute hypocalcaemia or nutritional secondary hyperparathyroidism, together with a history of grazing soursobs, suggest that acute and chronic oxalate toxicity are the cause of the clinical signs seen in affected miniature horses.

ULTRASOUND TREATMENT AS INTERVENTION IN INTRAUTERINE HYPERPARATHYROIDISM

Hypocalcemia during pregnancy reduced the normal foetal growth, skeletal mineralization and serum calcium concentration. Untreated maternal hyperparathyroidism associated hypocalcemia predisposed the foetal to intrauterine hyperparathyroidism resulting in adverse effect to skeletal mineralization. In vivo study has discovered that prenatal ultrasound exposure has the ability to reduce the foetal PTH level. Ten-month-old nulliparous New Zealand White (NZW) does were assigned to three different groups; Control (C), healthy NZW does and free from ultrasound exposure; hypoparathyroidism (HyPT), negative control groups having hypocalcemia condition established through external parathyroidectomy surgery and free from prenatal abdominal ultrasound exposure; treatment (T), experimental groups having hypocalcemia condition and receiving prenatal abdominal ultrasound exposure during pregnancy as intervention to hypoparathyroidism. In the treatment group, rabbits were exposed for 30, 60 and 90 minutes to parathyroid ultrasound on the 1st, 2nd and 3rd gestational stage accordingly. Following birth, foetal serum calcium (SCa), body weight (BW), crown-to-rump length (CRL), total body length (TBL), bi-parietal diameter (BPD) and femur length (FL) of the foetal were measured. Maternal hypocalcemia during pregnancy gave birth to litters with small to gestational age (SGA) and the reduction of BW, CRL, TBL, BPD, FL and SCa were also noted. Meanwhile, the outcome of ultrasound exposure given during the middle of 2nd gestational stage resulted in significant increase in progeny mean average BW, CRL, TBL, BPD FL and SCa compared to the HyPT group. Prenatal abdominal ultrasound helps to control the level of foetal parathyroid hormone and while still in the womb limits the postnatal complication.

ULTRASOUND LOCAL HEATING IMPROVE FOETAL PHYSIOLOGICAL DEVELOPMENT IN MATERNAL HYPERPARATHYROIDISM

Parathyroid disorder associated with hypercalcemia during pregnancy reduces the normal foetal growth, skeletal mineralization and serum calcium concentration. Hypercalcemia increases the risk of birth loss and foetal postpartum complications which includes intrauterine growth retardation, low birth weight, preterm delivery, neonatal hypocalcaemia, tetany and still-birth. Human and animal study exhibit benefits from local hyperthermia induced by ultrasound exposure. Ten-month-old primiparous New Zealand White (NZW) does were assigned into three different groups; control (C), healthy NZW does and free from ultrasound insonation; hyperparathyroidism (HPT), a positive control group having hypercalcemia conditions established through administering phosphate intravenously for 5 months and free from parathyroid ultrasound insonation; treatment (T), an experimental group experiencing hypercalcemia condition and receiving parathyroid ultrasound insonation during pregnancy as intervention to hyperparathyroidism. In treatment group rabbit were exposed for 30, 60 and 90 minutes of parathyroid ultrasound exposure on 1st, 2nd and 3rd gestational stage accordingly. Following birth, foetal serum calcium (SCa), body weight (BW), crown-to-rump length (CRL), total body length (TBL), bi-parietal diameter (BPD) and femur length (FL) of the foetal were measured. Maternal hypercalcemia during pregnancy produced small to gestational age (SGA) progeny with significant reduction of BW, CRL, TBL, BPD, FL and SCa compared to normal. While the outcome of ultrasound exposure given during middle 2nd gestational stage resulted in significantly increase in progeny mean average BW, CRL, TBL, BPD FL and SCa compared to HPT group. Ultrasound induced local heating demonstrated an improved in the physiological development of progeny in the cases of maternal hypercalcemia condition.

Effect of calcium ions on the nanostiffness of articular cartilage

Calcium is one of the major elements in human body, and critical in the biological and physiological functions. Soft tissue hardening due to calcification has been reported in various diseases. However, the quantitative relationship between the mechanical properties of soft tissues and calcification has not yet been fully understood. In this study, using human articular cartilage as prototype material, the relationship between the ex vivo calcium concentration and the nanostiffness of soft tissues was investigated by indentation-type atomic force microscopy. It is found that the nanostiffness of tissue shows a significant dependence on concentration of calcium ions, when it is higher than the normal serum calcium concentration. Structural observation of collagen fibrils indicated that the increase of nanostiffness should be the result of the increase of crosslinking with the introduction of calcium among collagen molecules.

Investigation of glucose intolerance in patients with normocalcemic primary hyperparathyroidism: 4-year follow-up

Normocalcemic primary hyperparathyroidism (NPHPT) is a clinical phenomenon in which elevated serum PTH levels are observed with normal serum calcium concentrations in lack of secondary causes such as vitamin D deficiency, renal or liver disease or malabsorption [1, 2]. While derangements in glucose and lipid metabolism in primary hyperparathyroid patients are well-defined, only a few reports exist regarding metabolic abnormalities in patients with NPHPT. Recently, we have shown in 18 patients with NPHPT that those patients do not exhibit increased rates of insulin resistance and glucose intolerance [3]. Similarly, Tassone et al. [4] also showed that patients with NPHPT have similar insulin sensitivity and glucose tolerance with age and sexmatched control subjects. Since there is no prospective study in patients with NPHPT, we have evaluated the changes regarding insulin resistance and glucose intolerance in the same patient group after 4 years of follow-up. Sixteen patients (2 males and 14 females) out of 18 with NPHPT were admitted to regular visits during the 4 years after their first diagnosis as NPHPT. Two patients did not come to visits. The whole data of the patients were described previously [3]. All subjects underwent a physical examination and biochemical data including serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, serum lipids, 25 (OH) D levels were determined regularly after an overnight fast. Standart oral glucose tolerance test (OGTT) with 75 g glucose were started between 08:00 and 09:00 h. Blood samples were taken just before (0 min) and 30, 60, 90 and 120 min after administration of glucose with 300 ml water orally for the measurement of serum glucose and insulin concentrations. Area under the curves (AUC) of glucose and insulin during OGTT were calculated according to trapezoid rule. Glucose tolerance was evaluated by using the criteria of the American Diabetes Association, and impaired glucose tolerance (IGT) was defined as a 2-h post-load glucose of C140 and \200 mg/dl. Statistical analysis was performed using the SPSS 15.0 program. All data were subjected to a Kolmogorov–Smirnov test for normality and data was presented as mean ± SEM. Paired t test was used to compare differences at the beginning and at the end of the study. P \ 0.05 was accepted as significancy. Four years of data after initial diagnosis for each patient were evaluated. One (6.25 %) patient developed hypercalcemic hyperparathyroidism. The data of this patient was not used in the analysis. Serum PTH level was significantly higher (103.8 ± 12.5 pg/ml) than normal limits (5–65 pg/ml) at the end of the 4 years. None of the patients had vitamin D deficiency [mean serum 25 (OH) D level was 54.6 ± 5.9 ng/ml]. Three out of five patients with IGT had diabetes mellitus and the two others remained as IGT at the end of the 4 years. None of the patients with normal glucose tolerance developed glucose intolerance during follow-up. The patient who developed hypercalcemia and three patients with diabetes mellitus were excluded from the analysis and we found that insulin responses to OGTT were not significantly different before (AUCinsulin 5059 ± 765 mg/dl 9 120 min) and after 4 years (AUCinsulin 4293 ± 537 mg/dl 9 120 min) of follow-up. Serum lipid levels, kidney and liver function tests were also normal during 4 years follow-up. Several previous data demonstrated close relationship between primary hyperparathroidism (PHPT) and impaired H. Diri K. Unluhizarci (&) F. Kelestimur Department of Endocrinology, Erciyes University Medical School, 38039 Kayseri, Turkey e-mail: kursad@erciyes.edu.tr

Report on a case of fibrogenesis imperfecta ossium and a possible new treatment option

Fibrogenesis imperfecta is an extremely rare acquired progressive bone disorder of unknown etiology. In its course, normal bone architecture is replaced at sites by structurally unsound collagen-deficient tissue resulting in a disorganized bone structure and a skeleton that is radically susceptible to deformity and fracture. Herein, we report the case of a patient who had experienced constant bone pain and several spontaneous fractures since 1997. In 10years' time with the sole exception of his skull, the disease affected the entire skeleton causing a significant decrease in height and progressive disablement. Laboratory findings included elevation of serum alkaline phosphatase and C-terminal telopeptide of type 1 collagen, with normal serum calcium, phosphate, 25-hydroxy-vitamin-D, and parathyroid hormone concentrations. Monoclonal gammopathy was present with no pathological plasma cells in bone marrow. Radiological and histological results were inconclusive suggesting either osteoporosis, osteomalacia, or Paget's disease and later on osteosclerosis. Treatment administered for the abovementioned conditions has proven to be of no effect. The findings eventually raised the possibility of fibrogenesis imperfecta ossium, which was confirmed by polarized light microscopy as well as transmission electron microscopy. The suggested therapy for the disease is melphalan that could not be initiated due to legal restrictions. Steroid monotherapy also reported to be moderately successful in one case resulted in no improvement. Paraproteinemia had been suggested not only to be a characteristic feature but also a possible etiological factor in this condition. In 2012, plasmapheresis was initiated monthly at the beginning, later on biweekly. In response, the patient's symptoms improved dramatically supporting the abovementioned theory.

Multiple organ dysfunction caused by parathyroid adenoma-induced primary hyperparathyroidism

We present a 27-year-old male with multiple organ dysfunction caused by parathyroid adenoma-induced primary hyperparathyroidism (PHPT). Initially, the patient experienced a sudden onset of gastrointestinal symptoms, polyuria, polydipsia, bone pain, renal dysfunction, nephrolithiasis, and acute pancreatitis, symptoms associated with hypercalcemia. Biochemical findings suggested PHPT. Renal biopsy showed an acute tubular injury and massive calcium deposits in the tubular epithelial cells and tubular lumina. Moreover, neck ultrasonography suggested the possibility of a parathyroid tumor. We excised his right parathyroid gland. Histopathological analysis revealed features of a parathyroid adenoma. Post-operatively this patient had normal serum calcium concentration, but was renally insufficient. A recent repeat biopsy showed chronic renal tubular injury. Our findings illustrate the complications of various systems that can occur in patients with PHPT caused by a parathyroid adenoma.

The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients

Recent publications show that elevation of FGF23 is independently associated with progression or renal disease, left ventricular hypertrophy and cardiovascular mortality. Dietary restriction of phosphate and phosphate binders are used for control phosphate balance and elevation of serum FGF23 levels. The aim of this study is to compare the effectiveness of calcium carbonate vs. lanthanum carbonate in reducing serum FGF23 levels in Chronic Kidney Disease (CKD) patients. 32 patients from the Nephrology outpatient clinic with CKD 4 - 5 non-dialysis were included. Patients receive a 4-month treatment period of calcium carbonate or lanthanum carbonate. Patients had normal serum calcium concentration, 25 (OH) levels >30 ng/ml and they were not on VDR activators or cinacalcet. As compared with calcium carbonate, patients on lanthanum carbonate had lower serum levels of FGF23 (226 ± 11 vs. 158 ± 9 pg/ml) and less urinary excretion of phosphate. No significant changes in serum calcium and PTH levels were observed in both groups. In conclusion, in CKD 4 - 5 patients lanthanum carbonate is effective in reducing phosphate load and FGF23 levels; this effect was not observed with calcium carbonate.

PTH inhibition rate is useful in the detection of early-stage primary hyperparathyroidism

Objective This study was to establish biochemical thresholds for the intravenous calcium suppression test in the early diagnosis of primary hyperparathyroidism (PHPT). Design and methods One hundred and thirty-three patients were divided into three groups: Group 1: surgically proven hypercalcemic PHPT, Group 2 surgically proven mild PHPT, and Group 3: normocalcemia with elevated serum PTH levels. Intravenous calcium suppression tests were performed in Groups 2 and 3 as well as in 20 controls with normal serum calcium and PTH concentrations. Results The serum PTH inhibition rate (PTH-IR) was less pronounced in Group 2 compared with Group 3 (P < 0.001) and the controls (P < 0.001). Receiver operating characteristic curve analysis suggests that a serum calcium level higher than 2.43 mmol/L and a PTH-IR less than 73% may differentiate Group 2 from normal controls. Conclusion It is quite useful to combine serum calcium levels with the PTH-IR to identify patients at early stage of PHPT, even in the presence of vitamin D deficiency.