Parathyroid hormone and bone histology: response to hypocalcemia in osteitis fibrosa

The parathyroid hormone (PTH) response to hypocalcemia was studied in 18 hemodialysis patients with osteitis fibrosa, and the relationship with PTH and bone histology in 26 hemodialysis patients. Hypocalcemia was produced during hemodialysis by the use of a dialysate devoid of calcium. Both amino (N) (P less than 0.05) and carboxy (C) (P less than 0.005) terminal PTH attained maximum levels by 15 min despite only a minimal decline in plasma calcium. Throughout the remainder of the study, C and N-PTH levels remained elevated but did not increase despite a further decline in plasma calcium. Five patients increased both C and N-PTH to maximum or near maximum levels by the first sampling, although plasma calcium remained above 9 mg/dl. Basal C and N-PTH correlated with the maximum levels of each induced by hypocalcemia (P less than 0.005). Both basal N-PTH and the maximum change in C-PTH produced by hypocalcemia correlated with osteoblastic osteoid, active resorption, osteoclasts/mm2, and endosteal fibrosis (P less than 0.005). In conclusion, (1) a minimal decline in plasma calcium produces a maximum C and N-PTH response; (2) an altered PTH set point may be present in some hemodialysis patients; (3) the correlation between basal and maximally stimulated PTH levels suggests that basal PTH levels may reflect parathyroid gland mass; and (4) a correlation with basal and stimulated PTH and bone histology is present.     

Effect of calcitriol in the control of plasma calcium after parathyroidectomy. A placebo-controlled, double-blind study in chronic hemodialysis patients

Severe, prolonged hypocalcemia in observed in some, but not all, hemodialysis patients after parathyroidectomy performed because of uncontrolled hyperparathyroidism. The aim of the present study was to investigate whether calcitriol and calcium supplementation in the immediate period after parathyroidectomy (days 1-14) was of more help in the control of plasma calcium than calcium supplementation alone. Fourteen hemodialysis patients were enrolled in a prospective, randomized, double-blind and placebo-controlled study. From the day after parathyroidectomy, 7 patients received calcitriol and the remaining 7 a placebo using incremental doses adjusted to the degree of hypocalcemia (up to 4 micrograms/day for calcitriol). Plasma calcium, phosphorus, alkaline phosphatase and immunoreactive parathyroid hormone levels before parathyroidectomy were comparable in both patients groups, as was the lowest plasma calcium achieved after parathyroidectomy. The decrease in plasma calcium after parathyroidectomy was related to plasma alkaline phosphatase and to the number of osteoclasts and osteoblasts on bone biopsy surface before parathyroidectomy. The mean decrement of plasma calcium (days 3-9) as compared to that before parathyroidectomy was less pronounced in calcitriol-treated than in placebo-treated patients (0.25 +/- 0.06 versus 0.45 +/- 0.05 mM, mean +/- SEM, p less than 0.025). Treatment with placebo was interrupted before day 14 because of persistent severe hypocalcemia in 4 of 7 patients, whereas calcitriol treatment was continued in all 7 patients up to 14 days. Patients on calcitriol treatment required less mean calcium supplements (days 1-9) than patients receiving placebo (37.4 +/- 3.2 versus 49.4 +/- 3.7 g, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hysteresis of the parathyroid hormone response to hypocalcemia in hemodialysis patients with low turnover aluminum bone disease.

During the study of parathyroid function in 19 hemodialysis patients with low turnover aluminum bone disease, it was observed that serum parathyroid hormone (PTH) levels were higher during the induction of hypocalcemia than during the recovery from hypocalcemia. This type of PTH response has been termed hysteresis. Hypocalcemia was induced during hemodialysis with a calcium-free dialysate. When the total serum calcium level decreased to 7 mg/dL, the dialysate calcium concentration was changed to 3.5 mEq/L and the dialysis session was completed. One week later, hypercalcemia was induced during hemodialysis with a high-calcium dialysate. The mean basal PTH level was 132 +/- 37 pg/mL (normal, 10 to 65 pg/mL; immunoradiometric (IRMA), Nichols Institute, San Juan Capistrano, CA) and increased to a maximal PTH level of 387 +/- 91 pg/mL during hypocalcemia. For the same ionized calcium concentration, the PTH level was higher during the induction of hypocalcemia than during the recovery from hypocalcemia. Conversely, for the same ionized calcium concentration, the PTH level was greater when hypercalcemia was induced from the nadir of hypocalcemia than when hypercalcemia was induced from basal serum calcium. The set point of calcium (defined as the serum calcium concentration required to reduce maximal PTH by 50%) was greater during the induction of hypocalcemia than during the recovery from hypocalcemia (4.44 +/- 0.10 versus 4.25 +/- 0.09 mg/dL; P = 0.03). The mean basal ionized calcium concentration and the mean ionized calcium concentration at the intersection of the two PTH-calcium curves were the same (4.61 +/- 0.13 versus 4.61 +/- 0.12 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis

The effect of intravenous calcitriol on parathyroid function was evaluated in nine chronic hemodialysis patients with secondary hyperparathyroidism. Two micrograms of calcitriol were administered intravenously after dialysis thrice weekly for ten weeks. Parathyroid function was assessed by inducing hypo- and hypercalcemia with low calcium (1.0 mEq/liter) and high calcium (4.0 mEq/liter) dialyses before and after ten weeks of intravenous calcitriol therapy. To avoid hypercalcemia during calcitriol administration, the dialysate calcium was reduced to 2.5 mEq/liter. Parathyroid hormone (PTH) values (pg/ml) from dialysis-induced hypo- and hypercalcemia were plotted against serum ionized calcium, and the sigmoidal relationship between PTH and calcium was evaluated. Basal PTH levels fell from 902 +/- 126 pg/ml to 466 +/- 152 pg/ml (P less than 0.01) after therapy without a significant change in the serum total calcium concentration. The ionized calcium-PTH sigmoidal curve shifted to the left and downward after calcitriol therapy. The maximal PTH response during hypocalcemia decreased after calcitriol from 1661 +/- 485 pg/ml before calcitriol to 1031 +/- 280 pg/ml afterward (P less than 0.05). The PTH level at maximal inhibition due to hypercalcemia decreased from 281 +/- 76 pg/ml before calcitriol to 192 +/- 48 pg/ml afterward (P less than 0.05). The slope of the sigmoidal curve changed from -2125 +/- 487 to -1563 +/- 385 (P less than 0.05). The set point of ionized calcium (4.60 +/- .11 mg/dl before vs. 4.44 +/- .07 mg/dl after) did not change significantly with calcitriol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of long-term intravenous calcitriol administration on parathyroid function in hemodialysis patients.

Secondary hyperparathyroidism is common in dialysis patients. Intravenous calcitriol has proven to be an effective therapy for the reduction of parathyroid hormone (PTH) levels. However, the effect of i.v. calcitriol on parathyroid function, defined as the sigmoidal PTH-calcium curve developed during hypocalcemia and hypercalcemia, has not been evaluated during the prolonged administration of i.v. calcitriol. Six hemodialysis patients with marked secondary hyperparathyroidism, PTH levels greater than 500 pg/mL (normal, 10 to 65 pg/mL), were treated for 42 wk with 2 micrograms of i.v. calcitriol after each hemodialysis. Parathyroid function was evaluated before and after 10 and 42 wk of calcitriol therapy. Between baseline and 42 wk, the basal PTH level decreased from 890 +/- 107 to 346 +/- 119 pg/mL (P less than 0.02) and the maximally stimulated PTH level decreased from 1293 +/- 188 to 600 +/- 140 pg/mL (P less than 0.01). In addition, calcitriol administration significantly decreased PTH levels throughout the hypocalcemic range of the PTH-calcium curve. Although the slope of the PTH-calcium curve (with maximal PTH as 100%) decreased between baseline and 42 wk (P less than 0.05), the set point of calcium did not change. Two patients with a decrease in both basal and maximally stimulated PTH levels after 10 wk of calcitriol, developed marked hyperphosphatemia between 10 and 42 wk; this resulted in an exacerbation of hyperparathyroidism despite continued calcitriol therapy. In conclusion, prolonged i.v. calcitriol administration is an effective treatment for secondary hyperparathyroidism in hemodialysis patients provided that reasonable control of the serum phosphate is achieved. In addition, the slope of the PTH-calcium curve may be a better indicator of parathyroid cell sensitivity than the set point of calcium.     

Utility of rapid intraoperative parathyroid hormone assay to predict severe postoperative hypocalcemia after reoperation for hyperparathyroidism

BACKGROUND: Patients undergoing reoperative parathyroidectomy may develop severe transient or permanent hypoparathyroidism. This study's purpose was to determine the utility of intraoperative parathyroid hormone (IO-PTH) values in predicting the development of severe hypocalcemia for patients undergoing reoperation for primary hyperparathyroidism. METHODS: Between March 1999 and October 2001, 68 patients with persistent or recurrent hyperparathyroidism underwent reoperation using IO-PTH measurements. The maximum percent decrease and lowest actual PTH value obtained at surgery were compared to determine any correlation with the development of postoperative hypocalcemia requiring supplementation. RESULTS: Of 68 patients, 25 required calcium and calcitriol postoperatively and 43 did not. There was a significant difference between the 2 groups with respect to lowest IO-PTH value (18.4 +/- 2.6 vs 28.0 +/- 3.9 pg/mL; P =.02), percent decrease in IO-PTH (89% +/- 1% vs 80% +/- 3%; P =.03), and lowest postoperative ionized calcium (1.06 +/- 0.01 vs 1.19 +/- 0.01 mmol/L; P <.001). A percent decrease in IO-PTH of 84% or greater was found to be predictive of patients experiencing hypocalcemia requiring supplementation with a positive predictive value of 46% and a negative predictive value of 82%. CONCLUSIONS: Although a maximum percent decrease in IO-PTH of 84% or greater was associated with an increased incidence of postoperative hypocalcemia requiring supplementation in the 68-patient cohort, on further analysis the association was significant only for patients with multiglandular disease and not those with single adenomas. This value may be useful for identifying patients who will need closer postoperative monitoring or prophylactic supplementation.     

Intraoperative parathyroid hormone assay: an accurate predictor of symptomatic hypocalcemia following thyroidectomy

HYPOTHESIS: Intraoperative parathyroid hormone (IOPTH) assay is useful for predicting symptomatic hypocalcemia following total thyroidectomy. DESIGN: A prospective study of 30 patients undergoing total thyroidectomy with IOPTH levels obtained following skin closure and ionized calcium (Ca2+) levels obtained 6 hours postoperatively and on postoperative day 1. All patients were evaluated for symptoms of hypocalcemia. SETTING: University teaching hospital. MAIN OUTCOME MEASURES: Patients who developed symptomatic hypocalcemia were compared with asymptomatic patients in regard to age, diagnosis, thyroid weight, thyrotropin level, Ca2+ level, parathyroid status, and IOPTH level. RESULTS: The onset of symptomatic hypocalcemia ranged from 8 to 48 hours postoperatively (n = 10). One patient required readmission. Of 10 patients with symptoms, 5 developed tetany. There were no significant differences in age, diagnosis, thyroid weight, thyrotropin level, or the number of parathyroid glands preserved in patients with or without symptomatic hypocalcemia. All patients with an IOPTH level of less than 10 pg/mL (1.1 pmol/L) had symptoms (n = 8). The mean +/- SD IOPTH level (7.6 +/- 12.0 pg/mL [0.8 +/- 1.3 pmol/L]) in patients who developed symptomatic hypocalcemia was significantly lower than the mean IOPTH level (55.7 +/- 31.8 pg/mL [5.9 +/- 3.3 pmol/L]) in patients without symptoms (P =.001). The 6-hour and postoperative day 1 Ca2+ levels were significantly lower in patients with symptomatic hypocalcemia (P =.19 and P =.13, respectively). An IOPTH level of less than 10 pg/mL is 80% sensitive and 100% specific for the development of symptomatic hypocalcemia. CONCLUSION: The incorporation of the IOPTH assay in the management of thyroid disease is recommended to prevent and prospectively treat symptomatic hypocalcemia, thereby reducing readmissions following thyroidectomy.     

Post-parathyroidectomy hypocalcemia: incidence, risk factors, and management

The purpose of this study was to evaluate the incidence and severity of hypocalcemia after parathyroidectomy and delineate its risk factors. Data was retrieved from a prospective database. Patients with postoperative hypocalcemia were identified and risk factors were investigated including primary versus renal hyperparathyroidism (HPT), preoperative calcium, parathyroid hormone (PTH) and alkaline phosphatase levels, gland weight, pathology, extent of surgery, and reoperative surgery. Of the 162 patients who underwent parathyroidectomy, 84 (52%) were hypocalcemic postoperatively: 55 (42%) of 132 patients with primary and 29 (97%) of 30 patients with renal HPT (P = 0.0001). Patients with renal HPT had more profound hypocalcemia with a mean +/- SD calcium of 7.34 mg/dL +/- 1.07 versus 7.76 mg/dL +/- 0.59 for patients with primary HPT (P < 0.05). Symptoms were present in 28 (51%) of 55 patients with primary and 13 (45%) of 29 patients with renal HPT. Only three (2%) patients with primary compared to 29 (97%) with renal HPT were treated with intravenous calcium. The average length of stay for hypocalcemic patients was 0.7 days for primary HPT versus 4.7 days for renal HPT (P < 0.0005). Patients with primary HPT who underwent subtotal parathyroidectomy had significantly lower postoperative calcium levels (7.95 mg/dL +/- 0.64) than patients who had a single or double adenoma removed (8.49 mg/dL +/- 0.79) (P = 0.036). No other factor was predictive of postoperative hypocalcemia. Patients with renal HPT develop profound postoperative hypocalcemia requiring intravenous calcium and vitamin D therapy. Hypocalcemia in patients with primary HPT develop less severe hypocalcemia that is amenable to outpatient oral calcium therapy and should be routinely initiated following subtotal parathyroidectomy.     

Acute effects of calcium carbonate and citrate on secondary hyperparathyroidism in chronic renal failure.

Two grams of elemental calcium as carbonate or citrate were given after an overnight fast to 14 patients with advanced renal failure (serum creatinine 759 +/- 365 mumol/l, mean +/- SD). The suppressibility of their hyperparathyroidism was confirmed with a calcium infusion test. Both calcium citrate and carbonate increased significantly plasma ionized calcium (6.8 and 4.5%, respectively) and total calcium (9.3 and 6.0%), p less than 0.001. In the majority of the patients, calcium citrate but not carbonate increased plasma calcium sufficiently to induce the suppression of hyperparathyroidism. The decrease of plasma intact parathyroid hormone was 35.9 +/- 24.8% (mean +/- SD); p less than 0.001) after calcium citrate and 9.2 +/- 18.9% (mean +/- SD; NS) after calcium carbonate.     

Urine calcium excretion, nephrogenous cyclic-adenosine monophosphate and serum parathyroid hormone levels in patients with essential hypertension.

To evaluate the role of calcium and the parathyroid gland in the pathophysiology of essential hypertension, creatinine clearance, urinary excretion of sodium, calcium and nephrogenous cyclic adenosine monophosphate (NcAMP) and serum parathyroid hormone (PTH) levels were measured in 25 newly diagnosed essentially hypertensive patients before institution of any treatment and in 25 age- and sex-matched normal volunteers. While no significant differences in creatinine clearance, serum total calcium levels or 24-hour sodium excretion existed between the two groups, hypertensives had a higher mean (+/- SD) 24-hour calcium excretion rate (199.0 +/- 44.7 vs. 152.8 +/- 33.6 mg, p less than 0.001), a higher mean NcAMP excretion rate (2.54 +/- 0.8 vs. 1.87 +/- 0.5 nmol/100 ml glomerular filtrate, p less than 0.001) and a higher mean serum PTH concentration (1.87 +/- 0.6 vs. 1.53 +/- 0.4 ng/ml, p less than 0.001) than the normotensives. A significant positive correlation existed between calcium and sodium excretion in both hypertensives (r = 0.66, p less than 0.001)) and normotensives (r = 0.67, p less than 0.001), but given the same levels of creatinine clearance and sodium excretion, hypertensives excreted more calcium than normotensives (p less than 0.001)). In both hypertensives and normotensives, serum PTH levels were positively correlated with NcAMP excretion (r = 0.42, p less than 0.05, and r = 0.41, p less than 0.05, respectively) and the ratio of urinary sodium to urinary calcium excretion (r = 0.59, p less than 0.001, and r = 0.75, p less than 0.001), respectively). The above results suggest that in essential hypertension, increased activity of parathyroid glands may occur as a consequence of increased urinary calcium losses which are presumably due to an intrinsic defect in renal calcium handling.     

Applicability of intraoperative parathyroid hormone assay during thyroidectomy

OBJECTIVE: To evaluate the applicability of intraoperative parathyroid hormone (quick PTH) assay to monitor parathyroid function and to identify clinically significant hypocalcemia compared with postoperative serum calcium monitoring. SUMMARY BACKGROUND DATA: Close monitoring of serum calcium levels is a standard of care to identify post-thyroidectomy hypocalcemia due to parathyroid insufficiency. METHODS: Quick PTH assay was performed before and after thyroidectomy for 100 patients at risk of postoperative hypocalcemia and 20 control patients who underwent unilateral lobectomy. Postoperative serum calcium levels were closely monitored. RESULTS: Control patients had a normal but 38.9 +/- 5.9% (mean +/- SEM) decline in quick PTH after thyroidectomy. Eleven of 100 at-risk patients (11%) developed postoperative hypocalcemia. Hypocalcemic patients had significantly lower quick PTH values after thyroidectomy compared with that of normocalcemic patients. Serum calcium was significantly lower in hypocalcemic patients the morning after operation but not early after the operation (within 6 hours). A normal or less than 75% decline in quick PTH after thyroidectomy can accurately identify normocalcemic patients during surgery as compared to more than 24 hours by serum calcium monitoring. CONCLUSIONS: The quick PTH assay can monitor parathyroid function during thyroidectomy and identify patients at risk of clinically significant hypocalcemia much earlier than serum calcium monitoring. It may facilitate early discharge and the use of parathyroid autotransplantation during thyroidectomy.     

Effect of aluminum and parathyroid hormone on osteoblasts and bone mineralization in chronic renal failure

Bone aluminum, quantitative bone histology, and plasma parathyroid hormone (PTH) were compared in 29 patients undergoing chronic hemodialysis. Histologic techniques included double tetracycline labeling and histochemical identification of osteoclasts and osteoblasts. Bone aluminum was measured chemically by flameless atomic absorption spectrophotometry, and histochemically. When measured chemically, the bone aluminum was 67 +/- 46 (SD) mg/kg dry weight (normal 2.4 +/- 1.2 mg/kg); histochemically, aluminum was present at 2.9 +/- 4.4% of trabecular surface. The biochemical and histochemical results agreed well (r = 0.80, P less than 0.001). No double tetracycline labels were seen at the mineralization front where aluminum was deposited, indicating cessation of mineralization at these sites. The osteoblast surface correlated positively with plasma PTH (r = 0.67, P less than 0.001) and negatively with bone aluminum level (r = -0.42, P less than 0.05). Multiple linear regression showed a correlation of aluminum with osteoblasts additional to that of PTH, consistent with a direct effect of aluminum in depressing osteoblast numbers. Though a relationship between PTH and chemically determined bone aluminum level could not be demonstrated, there was a negative correlation between osteoclast count and aluminum, and the nine patients with severe hyperparathyroid bone disease had lower chemically determined aluminum levels than the other patients. These results suggest that aluminum (a) directly inhibits mineralization, (b) is associated with decreased PTH activity and hence osteoblast numbers, and (c) directly reduces osteoblast numbers. In addition to inducing severe, resistant osteomalacia, aluminum appears to contribute to the mild osteomalacia commonly seen in renal failure, characterized by extensive thin osteoid and low tetracycline and osteoblast surfaces.     

甲状旁腺全切＋自体移植术治疗继发性甲状旁腺功能亢进症疗效分析

目的探讨甲状旁腺全切＋自体移植术(tPTX＋AT)治疗维持性血液透析患者继发性甲状旁腺功能亢进症(SHPT)的有效性、安全性以及术后低钙的危险因素。 方法纳入我院2013年1月至2016年11月因SHPT行tPTX＋AT手术的维持性血液透析患者93例,收集术前术后症状、血钙、磷、碱性磷酸酶(ALP)、全段甲状旁腺激素(iPTH)、病理类型、并发症等临床资料。依据术后24 h血钙水平分为正常血钙组(Ca≥2.11 mmol/L)及低钙血症组(Ca<2.11 mmol/L),应用单因素分析及逐步Logistic回归分析术后早期低钙血症的危险因素。 结果手术成功率92.5%。切除360枚甲状旁腺腺体,异位甲状旁腺10枚。病理结果多为腺瘤样增生(96.4%)。同术前相比,术后血清iPTH、磷、ALP明显下降(P<0.05)。低钙血症是术后最常见并发症,发生率82.8%,血钙水平与术前血钙、年龄正相关(r＝0.300, P<0.01;r＝0.265, P<0.01),与术前iPTH、ALP水平负相关(r＝－0.461, P<0.01;r＝－0.477, P<0.01)。术前低血钙(OR＝0.113, P＝0.045)、高ALP水平(OR＝1.050, P<0.001)、高iPTH水平(OR＝1.002, P＝0.004)是术后早期低钙血症发生的独立危险因素。 结论tPTX＋AT可以安全、有效、快速的降低维持性血液透析患者血清iPTH水平,改善机体的钙磷代谢紊乱,但需重视并积极纠正术后低钙血症。针对存在术前低血钙、高iPTH及高ALP水平等高危因素的患者,术前积极纠正低钙血症可能是预防术后低钙的有效干预方式。     

High deposition rate of aluminum in tissues in diabetic hemodialysis patients

Aluminum (Al) accumulation in bone is a serious problem in patients on hemodialysis. We studied deferoxamine infusion test (DFO test) in 14 diabetic patients on hemodialysis (HDDM) and 23 hemodialysis patients originated from glomerulo nephritis (HDCGN) to determine whether Al accumulation is different between the two groups or not. There was no difference in hemodialysis duration and total oral intake of Al containing drugs between two groups. Serum C-terminal parathyroid hormone (C-PTH) in HDDM was lower than that in HDCGN group (1.82 +/- 1.30 vs. 3.80 +/- 1.82 ng/ml; P less than 0.01). However serum Al (s-Al) levels were comparable (61.9 +/- 53.0 vs, 45.0 +/- 32.3 micrograms/l). A significant correlation was observed between duration of dialysis period and s-Al in HDDM (r = 0.806, p less than 0.01), but in HDCGN, the relation was not significant. The patients in HDDM whose cumulative aluminum intake was less than 2.0 kg showed the higher serum A1 concentrations before DFO and greater increases in s-Al after DFO test, as compared with those in HDCGN with matched aluminum intake (93.8 +/- 67.6 vs. 35.9 +/- 23.6 micrograms/l; p less than 0.001 and 141.2 +/- 81.8 vs. 70.3 +/- 41.1 micrograms/l; p = 0.035). These results indicate that in uremic diabetic patients with lower intake of Al containing drugs, an early accumulation of Al in the whole body occurs possibly because of the enhanced absorption rate of Al at an intestine and/or the low PTH level.     

Acute effects of repetitive hemodialysis on circulating immunoreactive parathyroid hormone levels in uremic patients undergoing vitamin D (calcitriol) therapy

The acute effects on parathyroid gland activity of repetitive hemodialysis with a dialysate calcium concentration of between 3.5 and 4 mEq/l were evaluated in 21 hemodialysis patients on calcitriol therapy for 1 year or more. In this study circulating immunoreactive parathyroid hormone (iPTH) levels were measured using radioimmunoassay specific for C-terminal iPTH (C-PTH), middle molecule iPTH (MM-PTH) and intact iPTH (I-PTH), before the dialysis session at the end of the week (I), after 4 h regular hemodialysis (II) and after a further 72 h (III). C-PTH was abnormally high (202 +/- 64 pmol/l) (I) in 18 patients with no documented parathyroid hyperplasia and showed no significant difference in subsequent controls. MM-PTH was also high (379 +/- 125.5 pmol/l) (I), but decreased to 348 +/- 136.7 (II) (p less than 0.05) and returned to predialysis levels (III). I-PTH (I) was 8.2 +/- 5.3 pmol/l (normal levels in 8 patients), fell to 3.4 +/- 2.6 pmol/l (II) (p less than 0.01), and increased (p less than 0.01) with respect to the basal levels of 11.1 +/- 7.5 pmol/l (III). Three patients presented echographically documentable parathyroid hyperplasia and, despite constantly high iPTH levels, showed a similar I-PTH behavior while MM-PTH and C-PTH revealed no constant pattern. The decrease in iPTH levels was accompanied by a significant increase in total calcium and ionized calcium during the hemodialysis session. No significant changes in iCa and Ca together with I-PTH levels were found in 4 volunteers before and after the hemodialysis session with dialysate calcium 2.75 mEq/l. We conclude that I-PTH assay has been shown to capture acute changes in parathyroid gland activity in hemodialyzed patients for both low and high iPTH levels. High calcium dialysate hemodialysis inhibits acutely intradialytic PTH secretion but the effect is just temporary and the 72-hour interdialytic period, despite vitamin D therapy, stimulates parathyroid secretion significantly. Nevertheless, I-PTH fluctuations occur in some patients within the normal range, and high dialysate and calcitriol therapy seem to be capable of controlling parathyroid activity; as regards the remaining population, we suggest that a personalized therapeutic approach should be studied with a view to achieving a better control of interdialytic calcium homeostasis.     

Management of calcium and bone abnormalities in hemodialysis patients

In chronic renal failure, hyperphosphatemia, hypocalcemia, hyperparathyroidism, reduced activation of vitamin D, decreased level of calcium-sensing receptor, osteitis fibrosa, and osteomalacia are features related to calcium abnormalities. Hyperparathyroidism is a risk factor for survival of hemodialysis patients as well as hypoparathyroidism, which is another feature in hemodialysis patients. Treatment of these abnormalities includes control of parathyroid hormone (PTH) secretion, counteracting hyperphosphatemia, correction of hypocalcemia, and others. Various kinds of vitamin D analogs have been introduced recently in addition to calcitriol and alfacalcidol, which have a rather long history (eg, maxacalcitol and falecalcitriol). Sevelamer is a newly developed phosphate binder to treat soft-tissue calcification.     

Suppression of serum parathyroid hormone levels by intravenous alphacalcidol in uremic patients on maintenance hemodialysis. A pilot study

Seven patients on chronic hemodialysis were given alphacalcidol (1 alpha-OH-vitamin D3) intravenously in a pilot study during 3 months. Before treatment all patients had serum calcium values within the normal range, but elevated levels of parathyroid hormone (PTH). When serum calcium was raised above the normal range by treatment with alphacalcidol, all patients displayed marked suppression of PTH levels with a mean reduction of 40 +/- 20% (SD; p less than 0.01). When the dose of alphacalcidol was reduced so that the serum calcium values were kept at the upper limit of the normal range, a partial return towards pretreatment values of PTH was seen but the levels were still lowered (p less than 0.05). Thus, intravenous administration of the vitamin D compound appeared to be useful for the management of secondary hyperparathyroidism in patients on dialysis. A direct effect of alphacalcidol on the parathyroid glands could, however, not be distinguished from the calcemic action.     

Controlled trial of calcitriol in hemodialysis patients

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.     

Low parathyroid hormone levels after thyroid surgery: a feasible predictor of hypocalcemia

BACKGROUND: Selecting patients with a low risk of hypocalcemia is mandatory if patients are to be discharged on the first day after bilateral thyroidectomy. This study investigated the predictive value of intraoperative parathyroid hormone (PTH). METHODS: Thirty-eight patients underwent total or near-total thyroidectomy. Patients with or without biochemical and symptomatic hypocalcemia were compared regarding intraoperative PTH levels and previously suggested risk factors. The accuracy of intraoperative PTH to predict patients at risk for postoperative hypocalcemia was compared with a calcium concentration of less than 2.00 mmol/L (8.0 mg/dL) on the first postoperative day. RESULTS: PTH levels after resection of the second lobe, age, and number of parathyroid glands identified intraoperatively were independently associated with the reduction in serum calcium concentration measured at nadir on the first or second postoperative day. PTH levels after resection of the second lobe were lower among patients who developed biochemical (P <.001) and symptomatic hypocalcemia (P <.01) compared with those who did not. Low levels of intraoperative PTH identified the 3 patients who required intravenous calcium during the first 24 postoperative hours. An intraoperative PTH level below reference range and a calcium concentration of less than 2.00 mmol/L measured 1 day postoperatively both predicted biochemical hypocalcemia with a similar sensitivity (90% vs 90%) and specificity (75% vs 82%). Intraoperative PTH was slightly better than a serum calcium concentration of less than 2.00 mmol/L on postoperative day 1 to predict symptomatic hypocalcemia, with a sensitivity of 71% vs 52% and a specificity of 81% vs 76%, respectively. CONCLUSIONS: Parathyroid gland insufficiency is the main determinant of transient hypocalcemia after bilateral thyroid surgery. Low intraoperative PTH levels during thyroid surgery are therefore a feasible predictor of postoperative hypocalcemia.