Calcitriol pulse therapy is not more effective than daily calcitriol therapy in controlling secondary hyperparathyroidism in children with chronic renal failure

Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism, but its efficacy and safety are still under discussion. The present randomized multicenter study compares the effect of an 8-week course of daily versus intermittent (twice weekly) calcitriol therapy on parathyroid hormone (PTH) suppression in 59 children (mean age 8.4±4.7 years) with chronic renal insufficiency (mean C_cr 22.4±11.6 ml/min per 1.73 m²) and secondary hyperparathyroidism. After a 3-week washout period, the patients were randomly assigned to treatment with daily oral calcitriol (10 ng/kg per day) or intermittent oral calcitriol (35 ng/kg given twice a week). The calcitriol dose was not changed throughout the study period of 8 weeks. At start of the study, the median intact PTH (iPTH) level was 485 pg/ml (range 83–2032) in the daily group (n=29) and 315 pg/ml (range 93–1638) in the intermittent group (n=30). After 8 weeks, the respective median iPTH concentrations were 232 pg/ml (range 63–1614) and 218 pg/ml (range 2–1785) (ns). The mean iPTH decrease from baseline was 19.2±57.8% and 13.7±46.7% respectively (not significant). Calcitriol reduced the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group. One episode of hypercalcemia (>11.5 mg/dl) was observed in both groups and a single episode of hyperphosphatemia (>7.5 mg/dl) was observed in the daily group. It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively than the daily administration of calcitriol in children with chronic renal failure prior to dialysis. Received: 29 September 1999 / Revised: 2 February 2000 / Accepted: 9 February 2000     

Intraoperative Monitoring of Intact PTH in Surgery for Renal Hyperparathyroidism as an Indicator of Complete Parathyroid Removal

In the setting of total parathyroidectomy and autotransplantation surgery (TPT × AS) as treatment for secondary hyperparathyroidism (SHPT), we evaluated whether intraoperative parathyroid hormone (iPTH) monitoring is useful as a reference for total parathyroid removal. We conducted a prospective, open, single value measurement efficacy study of the intraoperative (i.o.) diagnostic monitoring of iPTH in a cohort of surgical patients. All patients (n = 25) underwent TPT × AS at the Department of Surgery, Donostia Hospital from January 2002 to October 2004. The primary outcome measures were kinetics of serum levels of iPTH during surgery and prediction time of the of descent of PTH levels (measured in the clinic on the day of admission and intraoperatively during induction of anesthesia, every 5 and 10 minutes after removal of the adenoma, and again 24 hours thereafter). iPTH levels returned to normal in all 25 patients, decreasing from pathological levels at the beginning of the operation (1302.24 + 424.9 pg/ml) to half (50%) values at the third intraoperative determination, minute 10 (614.8 ± 196.62), becoming undetectable at 24 hours. Frozen sections were conclusive for parathyroid tissue (20.56 + 10.3 minutes after removal). Intraoperative measurement of iPTH is useful in the prediction complete removal of all parathyroid tissue prior to autotransplantation, thus avoiding persistence of disease because of incomplete surgery.     

Parathyroid graft function after presternal subcutaneous autotransplantation for renal hyperparathyroidism

HYPOTHESIS: Presternal subcutaneous autotransplantation of parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism could be at least as effective as intramuscular grafting, without its complications. DESIGN: Prospective study of a postoperative diagnostic method of monitoring intact parathyroid hormone (iPTH) levels among a cohort of surgical patients, without loss to follow-up. SETTING: Hemodialysis unit in a university hospital. PATIENTS: Twenty-five patients (17 women and 8 men) underwent total parathyroidectomy and presternal subcutaneous autotransplantation for renal hyperparathyroidism at Donostia Hospital, San Sebastián, Spain, between January 1, 2002, and June 30, 2004. MAIN OUTCOME MEASURES: Evaluation of parathyroid graft function by measurement of serum iPTH levels at admission and 24 hours and 1, 3, 5, 15, 30, and 60 weeks after surgery. RESULTS: The mean +/- SD preoperative serum iPTH level was 1302 +/- 425 pg/mL; the iPTH level was undetectable in all patients 24 hours after surgery. Subsequent mean +/- SD iPTH levels obtained were 14 +/- 10 pg/mL after 1 week, 54 +/- 1 pg/mL after 5 weeks, 64 +/- 9 pg/mL after 15 weeks, 77 +/- 8 pg/mL after 30 weeks, and 106 +/- 21 pg/mL after 60 weeks. Autotransplanted parathyroid tissue appears to be adequately functional at week 5 (criterion level of adequate functioning, 50 pg/mL). CONCLUSIONS: Presternal subcutaneous autotransplantation after total parathyroidectomy for renal hyperparathyroidism may be an alternative to avoid musculus brachialis grafting and its complications. Our functional results compare favorably with the published data on other surgical techniques for the treatment of renal hyperparathyroidism. Long-term follow-up of this series is planned.     

Vitamin D Status During Puberty in French Healthy Male Adolescents

The vitamin D status was determined on one to four occasions either after summer (September–October) or after winter (March–April) in 175 male adolescents (13–17 years), resulting in 394 measurements of serum 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH). The subjects lived in a rural area to the north of Paris (49° N). After summer the 25(OH)D concentration was 58.5 ± 18.0 nmol/l (mean ± SD), while after winter it had fallen to 20.6 ±6.0 nmol/l (p= 0.0001). Meanwhile the iPTH concentration was 2.76 ± 0.97 pmol/l (mean ± SD) after summer and increased to 4.20 ± 1.21 pmol/l after winter (p= 0.0001). All the results were pooled and a nonlinear population model with random parameters was used to describe the relationship between serum iPTH and 25(OH)D. When the concentration of 25(OH)D was higher than 83 nmol/l, an iPTH mean ‘plateau’ level at 2.48 pmol/l was reached. When 25(OH)D concentrations fell below 83 nmol/l, the increase in iPTH concentration accelerates, and when the mean 25(OH)D concentration was equal to or lower than 10 nmol/l the mean iPTH level (4.97 pmol/l) was twice as high as the ‘plateau’ value. Received: 26 November 1998 / Accepted: 15 February 1999     

Calcidiol and PTH Levels in Women Attending an Osteoporosis Program

We performed a retrospective study of 237 patients attending a specialty osteoporosis practice. Secondary causes for reduced bone mineral density (BMD) were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age was 56 ± 13.8 years (mean ± SD). BMD was measured by dual-energy X-ray absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour urinary calcium were measured, and serum and urine protein (SPEP and UPEP) electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in iPTH levels. Among the osteoporotic patients (T score <−2.5 SD), 17% had 25(OH)D levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (−2.5 < T < −1.0 SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score ≤−1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D levels were inversely related to high iPTH values (r = 0.30, P < 0.0001). Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65 pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in 4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of 25(OH)D levels is recommended in the evaluation of secondary causes for reduced BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25 ng/ml, the level required to prevent increments in iPTH levels. Received: 9 February 1998 / Accepted: 1 October 1998     

Parathyroidectomy for Renal Hyperparathyroidism in Children and Adolescents

Background Renal hyperparathyroidism (rHPT) almost inevitably develops in pediatric patients with end-stage chronic kidney disease (CKD) and may require parathyroidectomy (PTX) despite intensified conservative therapy. Long-term duration of uncontrolled rHPT may result in disabling osteodystrophy and vascular calcifications. Only a few reports on children undergoing PTX for rHPT are available and mainly consist of case reports with short follow-up periods. To study this entity, we analyzed the course of 23 pediatic patients who underwent PTX for rHPT. Methods Twenty-three patients with a mean age of 15 years and who underwent PTX for rHPT between 1986 and 2006 were evaluated. Surgical indications and techniques, specific postoperative management, and follow-up courses are described. Results Preoperative mean serum (s-) calcium was 2.7 ± 0.05 mmol/L (normal range = 2.2–2.7 mmol/L); s-phosphate was 1.8 ± 0.1 mmol/L (normal range = 0.8–1.6 mmol/L), and mean intact parathyroid hormone (PTH) level was 1240.1 ± 160.1 pg/ml (normal range = 11–65 pg/ml). Twenty-one patients underwent initial PTX and two patients underwent reoperative PTX. Total PTX with parathyroid autotransplantation (AT) was performed in 18 patients. In three patients less than four parathyroid glands were identified and no AT was performed consecutively. Postoperatively, no complications with respect to bleeding or vocal cord damage were recorded. The postoperative values of s-calcium, s-phosphate, and PTH decreased to or below normal range (s-calcium = 2.0 ± 0.1 mmol/L, s-phosphate = 1.2 ± 0.1 mmol/L, PTH = 50.1 ± 11.2 pg/ml). All 15 children below the age of 15 years required calcium intravenously. Follow-up was obtained in all patients 69.6 ± 11.4 months after PTX. Bone pain resolved in all previously symptomatic patients. S-calcium was 2.2 ± 0.2 mmol/L, s-phosphate was 1.4 ± 0.3 mmol/L, and PTH was 90.2 ± 21.5 pg/ml. No patient required repeated parathyroid autografting, and only one underwent an explantation of his AT six years after initial PTX. Conclusion Total PTX with AT in pediatric patients with rHPT is a safe and effective procedure. It should be considered if rHPT is refractory to conservative treatment, in view of the risk of potentially lethal vascular calcifications developing in the majority of adults with childhood onset of CKD. K. Schlosser and C. P. Schmitt contributed equally to this work.     

Evidence that factors other than 1,25 dihydroxyvitamin D may play a role in augmenting intestinal calcium absorption in patients with primary hyperparathyroidism

Summary We examined 17 patients with primary hyperparathyroidism for their serum 1,25 dihydroxyvitamin D levels and for their fractional intestinal calcium absorption rates using a whole body counter and calcium-47. As controls, 10 normal volunteers were examined both before and after administration of 1α-hydroxyvitamin D to increase serum 1,25 dihydroxyvitamin D. Values of serum 1,25 dihydroxyvitamin D were 71.6±37.6 pg/ml (mean ±SD) in patients with primary hyperparathyroidism and 75.3±27.7 pg/ml (mean ±SD) in normal volunteers after administration of 1α-hydroxyvitamin D, while values of intestinal calcium absorption rate were 61.5±16.5% (mean ±SD) in patients with primary hyperparathyroidism and 34.1±5.1% (mean ±SD) in normal controls, respectively. There was a positive correlation between values of serum 1,25 dihydroxyvitamin D and intestinal calcium absorption in both groups. However, in patients with primary hyperparathyroidism, intestinal calcium absorption was more increased than that in normal volunteers when compared to their serum values of 1,25 dihydroxyvitamin D. This suggests that another factor than 1,25 dihydroxyvitamin D plays an important role in the intestinal calcium absorption in patients with primary hyperparathyroidism.     

Serum markers of bone turnover in dialyzed patients separated according to age

Background Bone metabolism changes with aging in healthy population. Our aim was to determine serum markers of bone turnover in dialysis patients separated according to age. Methods Peritoneal dialysis (PD) or hemodialysis (HD) patients were divided into two groups. Group I (n = 30) consisted of patients older than 65 years. Patients at the age less or equal 65 years were included in group II (n = 37). In all patients we determined serum concentration of intact parathyroid hormone (iPTH), cyclase activating parathyroid hormone (CAP), osteoprotegrin (OPG) and osteoprotegrin ligand (OPGL). Cyclase inactive parathyroid hormone (CIP) was calculated. Healthy volunteers (n = 13) at the age of 42.1 years (range 23.5–70.9 years) served as controls. Results When results of dialysis patients were adjusted to gender, dialysis modality and duration, group I revealed significantly lower iPTH (113.0, 10.3–606.3 pg/ml), CAP (70.0, 6.5–442.6 pg/ml) and CIP (53.3, 3.3–214.4 pg/ml) than group II (310.6, 13.7–1266.9 pg/ml for iPTH; 205.0, 9.3–887.9 pg/ml for CAP; 76.0, 2.4–399.0 pg/ml for CIP), but this group showed significantly higher serum OPG (7.39, 1.52–15.84 pg/ml) than group II (5.45, 0.95–16.47 pg/ml) and controls (2.17, 1.05–3.95 pg/ml). Only patients of group II showed significantly higher iPTH, CAP and CIP than controls (34.9, 18.9–76.9 pg/ml; 24.3, 11.2–42.6 pg/ml, 12.0, 1.0–34.2 pg/ml, respectively for iPTH, CAP and CIP). Conclusion Our results suggest that age over 65 years is a risk factor for low bone turnover in dialyzed patients. An increase in serum OPG probably reflects a paracrine mechanism of bone cells to compensate for age dependent bone loss.     

术中甲状旁腺素监测在腔镜辅助甲状旁腺切除术中的应用

目的:探讨术中甲状旁腺素监测在腔镜辅助甲状旁腺切除术中的作用及效果。方法:回顾分析2006年10月至2012年12月有完整资料的10例腔镜辅助甲状旁腺切除患者的临床资料,其中男3例,女7例。患者术前血钙2.76～3.82 mmol/L,平均(2.87±0.69)mmol/L。术前甲状旁腺激素(parathyroid hormone,PTH)268.0～1390.8 pg/ml,平均(627.58±156.30)pg/ml。患者均通过B超、核素99mTc-MIBI(99锝m-甲氧基异丁基异腈)和/或CT定位。结果:10例均成功完成手术,无一例中转开放及再次探查手术。术中出血量平均(7.5±3.5)ml,手术时间平均(38.3±12.6)min。腺瘤切除后5 min,PTH平均(306.3±59.38)pg/ml;腺瘤切除后20 min,PTH平均(51.7±13.20)pg/ml,多降至正常。术后石蜡病理证实为甲状旁腺腺瘤,术后均无声嘶、呛咳、出血发生,2例发生短暂性低钙血症,术后随访9例患者2～73个月,美容效果满意,未见复发。结论:临床上内镜辅助甲状旁腺手术安全、可行,术后患者康复快,颈部美容效果好,术中结合甲状旁腺监测可有效保证手术的彻底性,避免盲目探查。     

Parathormone levels after subtotal and total (autotransplantation): Parathyroidectomy for secondary hyperparathyroidism

To compare results of subtotal versus total parathyroidectomy with autotransplantation in dialysis patients with secondary hyperparathyroidism, pre- and postoperative calcium, phosphorus, alkaline phosphatase, and immunoreactive parathormone (iPTH) were measured. In eight patients with subtotal parathyroidectomy, the mean preoperative iPTH of 903 ± 139 μl-eq/ml decreased to a mean of 26.6 ± 9 μl-eq/ml, 6 to 29 months postoperatively. In six patients with total parathyroidectomy and autotransplantation the mean preoperative iPTH of 1289 ± 248 μl-eq/ml decreased to a mean peripheral iPTH of 32 ± 7 μl-eq/ml, 4 to 18 months postoperatively. Both groups were similar in (1) pre- and postoperative iPTH levels, (2) the absence of postoperative clinical or chemical hyperparathyroidism, (3) improvement in symptoms, and (4) demonstrable functioning parathyroid tissue. None of the patients required reexploration for persistent hyperparathyroidism. Subtotal parathyroidectomy and total parathyroidectomy with autotransplantation appear to be equally effective modalities for treatment of secondary hyperparathyroidism in patients with end-stage renal disease.     

Implications of intermittent calcitriol therapy on growth and secondary hyperparathyroidism

Secondary hyperparathyroidism is the most common skeletal lesion in pediatric patients undergoing maintenance dialysis. The present review summarizes a prospective randomized study that evaluated the biochemical and skeletal responses to intermittent calcitriol therapy in 33 pediatric patients on peritoneal dialysis with secondary hyperparathyroidism. Also, the effect of intermittent calcitriol therapy on linear growth was evaluated in 16 of 33 patients who had completed the clinical trial. Serum parathyroid hormone levels decreased by 62% from 648±125 pg/ml in patients treated with intermittent intraperitoneal (IP) calcitriol, and values remained unchanged from pre-treatment levels of 670±97 pg/ml with oral calcitriol therapy. Overall serum total and ionized calcium levels were higher in patients treated with IP calcitriol during the study. In contrast to these biochemical findings, the skeletal lesions of secondary hyperparathyroidism improved after 12 months of treatment in both groups and adynamic bone occurred in 33% of the patients. Z-scores for height decreased from –1.80±0.3 to –2.00±0.3, P<0.01, after 12 months of intermittent calcitriol therapy. Such findings suggest that an intermittent schedule of calcitriol administration adversely affects chondrocyte activity within epiphyseal cartilage in pre-pubertal children with end-stage renal disease. Received: 20 August 1999 / Revised: 2 February 2000 / Accepted: 9 February 2000     

Hyperparathyroidism in chronic kidney disease: a retrospective cohort study of costs and outcomes

Hyperparathyroidism may play a role in the excess morbidity and mortality in chronic kidney disease. This study examined utilization and outcomes of patients with hyperparathyroidism and chronic kidney disease. In a US health maintenance organization (HMO), patients with chronic kidney disease were identified from the electronic medical record. Patients included in the study had at least one intact parathyroid hormone (iPTH) measurement ordered by a nephrologist and were at least 20 years of age with no history of renal replacement therapy (RRT, n = 455). Cohorts were determined by index iPTH level and were followed for 1 year. Rates of health care utilization were compared between cohorts using Poisson regression; costs comparisons were made using linear regression; mortality and RRT were evaluated using Cox regression. Increasing levels of iPTH were associated with a significantly elevated risk of mortality and RRT, even after adjustment for potential confounders such as stage of chronic kidney disease. Compared to iPTH of <110 pg/ml, we found a 66% increase combined mortality-RRT risk (HR 1.66, 95% CI 1.41–1.97) for those with iPTH 110–199 pg/ml, and a HR of 4.57 (95% CI 3.86–5.43) for iPTH ≥300 pg/ml. We did not find a convincing association between iPTH level and utilization. While this study provides no evidence that treating patients with higher levels of iPTH will ameliorate poor outcomes, it suggests that iPTH levels beyond the targets suggested by clinical guidelines are associated with increased harm in patients with chronic kidney disease. This work was presented in part at the National Kidney Foundation 2006 annual meeting and at the 2006 International Society for Pharmacoeconomics and Outcomes Research meeting.     

Limited role for intraoperative intact PTH measurement in parathyroid surgery.

Primary hyperparathyroidism may be cured surgically by complete excision of abnormal parathyroid tissue. Reoperation for persistent hypercalcaemia due to residual abnormal parathyroid tissue may be associated with a high complication rate. It is possible to assay intact parathormone (iPTH) intraoperatively and as iPTH has a relatively short half-life, its measurement intraoperatively may be used to predict successful parathyroidectomy. We have studied intraoperative iPTH levels in a consecutive series of 33 patients undergoing surgery for primary hyperparathyroidism. We found that iPTH levels fell significantly (P < 0.05) from a median pre-excision level of 122 pg/ml to a median level of 36 pg/ml 20 min after excision. However, in 3/31 successful parathyroidectomies, the intraoperative iPTH levels either remained unchanged or had risen. Reliance on intraoperative iPTH levels in these patients may have resulted in unnecessary re-exploration. We conclude that intraoperative iPTH measurement has limited usefulness as a predictor of successful parathyroidectomy for primary hyperparathyroidism.     

Efficacy and safety of cinacalcet for the treatment of secondary hyperparathyroidism in patients with advanced chronic kidney disease before initiation of regular dialysis

Aim: To evaluate the compassionate use of cinacalcet for the management of secondary hyperparathyroidism in patients who are not on dialysis. Methods: Patients with stage 4–5 chronic kidney disease (CKD) who were not on dialysis, had an intact parathyroid hormone (iPTH) level greater than 300 pg/mL, and had not responded satisfactorily to treatment with phosphate binders and vitamin D were prospectively studied. Patients received 6 months of compassionate treatment with cinacalcet, which was initiated at a dose of 30 mg/day orally and flexibly dosed thereafter based on iPTH levels. Results: Twenty‐six patients with a mean age ± standard deviation (SD) of 58.8 ± 16.1 years were enrolled in the study and included in the statistical analysis. The mean percentage change in iPTH levels from baseline after 6 months of treatment was ?67.9 ± 17.0%, with 92.3% (95% confidence interval (CI), 75.9–97.9) of patients showing an iPTH level within the limits recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. The mean serum calcium concentrations had decreased significantly at the end of the study (?8.0 ± 6.9%), while the mean serum phosphorus concentration had significantly increased (+8.3 ± 17.0%). Conclusion: Our results suggest that cinacalcet may be a useful alternative for the treatment of secondary hyperparathyroidism in pre‐dialysis patients who are unresponsive to other treatments. The hypocalcemia and hyperphosphatemia reported in previous studies may not occur if a moderate dose of calcimimetics is used in patients with marginal glomerular filtration rates, especially if combined with vitamin D analogues and calcium‐based phosphate binders.     

Bone Metabolism and Gonad Function in Male Patients Undergoing Liver Transplantation: A Two-Year Longitudinal Study

Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48 ± 13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2–L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score <–2.5 SD and the mean BMD was 0.806 ± 0.11 g/cm² (range 0.470–1.045 g/cm²). The BMD was lower 3 months after OLTx and significantly higher 12 and 24 months after OLTx. A significant increase in serum BGP was observed at 6, 12 (p<0.05) and 24 months (p<0.005) after OLTx. The mean serum PTH level was 26.6 ± 3.1 pg/ml at baseline and increased significantly at 12 and 24 months (to 49.4 ± 9.9 and 61.2 ± 10.1 pg/ml, respectively; p<0.05). 25OHD serum levels were low at baseline and returned to the normal range after 12 and 24 months (baseline, 8.73 ± 1.54 ng/ml; 12 months, 16.4 ± 2.6 ng/ml; 24 months, 17.67 ± 3.1 ng/ml; p<0.05). FT was significantly lower at baseline than in a group of 10 healthy controls (5.09 ± 10.99, vs 10.3 ± 1.1 pg/ml; p<0.0001). After OLTx a significant increase in FT was recorded at 6, 12 (p<0.05) and 24 months (p<0.005). FT was not correlated with BMD, however. After OLTx an increase in FSH and LH was observed (but failed to reach statistical significance) at 3 and 6 months, followed by a slight reduction at 12 and 24 months. Thus a high proportion of men with end-stage liver disease do have osteoporosis. After OLTx, an early recovery of gonad function is observed, followed by an increase in bone mass, which occurs from the sixth month onward. Received: 3 October 2000 / Accepted: 21 March 2001     

Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid hormone levels

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values. METHODS: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals. RESULTS: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values. CONCLUSIONS: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.     

Subtotal Parathyroidectomy in Renal Failure: Still Needed after All These Years

There are scant data on the frequency of parathyroidectomy (PTX) for end-stage renal disease (ESRD). Medical therapy for ESRD and secondary hyperparathyroidism has evolved to include better dialytic urea removal and the use of calcitriol. The aim of this study was to determine whether medical therapy has changed the frequency or indications for PTX in the management of renal failure. Hospital and clinic records were analyzed to gather information on all patients undergoing PTX for secondary hyperparathyroidism (2HPT) (n= 48) and tertiary hyperparathyroidism (3HPT) (n= 26) from 1986 through 1998 at our institution. Prospective computer databases were queried for information concerning both chronic dialysis and renal transplant patients at our center. The patients were divided based on date of operation before or after 1991, a divider that separated the patients into groups before or after the widespread adoption of intravenous calcitriol treatment during hemodialysis at our institution. Over the 12 year period, the proportion of our chronic dialysis patients undergoing PTX did not change significantly, ranging from 0% to 2.5% per year. Comparing all patients undergoing PTX for 2HPT during 1986–1991 versus 1992–1998, there was no significant difference in time on dialysis [7.0 ± 4.2 (n= 11) vs. 7.5 ± 4.6 (n= 36) years, mean ± SD]. The later group had higher intact parathyroid hormone (iPTH) levels [765 ± 415 (n= 6) vs. 1377 ± 636 (n= 28) pg/ml; p= 0.03], lower serum calcium [11.2 ± 1.0 (n= 12) vs. 9.9 ± 1.5 (n= 34) mg/dl; p= 0.006], and higher serum phosphate [5.7 ± 1.6 (n= 12) vs. 7.2 ± 2.3 (n= 31) mg/dl; p= 0.042]. Among the population of patients with transplants undergoing PTX for 3HPT, the average percent per year undergoing PTX ranged from 0% to 4.2% and did not change during the study period. Comparing the 1986–1991 group to the 1992–1998 group, the time from transplantation to PTX did not change during the study period (3.3 ± 2.3 vs. 2.9 ± 3.0 years; p= 0.391), and there were no significant differences between preoperative calcium levels or iPTH levels. Despite advances in dialysis technique and pharmacologic therapy, there has been no change in the proportion of dialysis patients requiring PTX for 2HPT or 3HPT. There was also no change in the time on dialysis for patients with 2HPT or the time from transplant to PTX for patients with 3HPT. Analysis of preoperative biochemical markers as evidence of disease severity suggests there was no change in indications for PTX during our study. From this information we conclude that parathyroid pathophysiology is incompletely understood and medical therapy is not optimal, resulting in a continuing need for PTX in some patients.     

Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.     

Acute Responses of Parathyroid Hormone and 1,25 Dihydroxyvitamin D3 to Unilateral Nephrectomy in Healthy Donors

Plasma immunoreactive parathyroid hormone (iPTH), 1,25(OH)₂D3calcium and phosphate and urinary creatinine, calcium and phosphatewere measured before and following unilateral nephrectomy insix kidney donors. Unexpectedly, plasma calcium rose, from 2.27±0.02mmol/l (mean±SEM) to 2.41±0.03 mmol/l on day 7and to 2.37±0.02 mmol/l on day 30 (P<0.02). A parallelrise in iPTH occurred, from 0.61±0.16 ng/ml initially,to 1.83±0.54 ng/ml on day 7 (P<0.05) and to 1.18±0.18on day 30 (P<0.01). The ratio of maximal tubular reabsorptionof phosphate to GFR (TmP/GFR) fell by day 2 (P<0.001), remainingreduced on day 30 (P<0.05). The significance of elevated iPTH in renal insufficiency wasfurther assessed by determining the time course of the disappearanceof iPTH after parathyroidectomy in three haemodialysis subjects.Fifty per cent baseline iPTH level occurred after an averageof 104.7 min, suggesting that the assay did not predominantlyrecognize C-terminal PTH fragments. By day 2, plasma 1,25(OH)₂D3had fallen from 34.3±4.5 pg/ml to 22.8±3.8 pg/ml(P<0.001), but by day 4 had regained its pre-nephrectomyvalue. Our results suggest that hypocalcaemia may not be thesole stimulus to parathyroid hormone secretion. It is speculatedthat reduction in circulating 1,25(OH)₂D3 may be involved.     

Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients

Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5±5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228±496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26±8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (−60.4±34% versus −65.4±28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium × phosphorus product (Ca×P)≥70 mg²/dl² occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.