Results of systematic subtotal parathyroidectomy with thymectomy for tertiary hyperparathyroidism after renal transplantation - 70 patients

BACKGROUND: Due to the relatively small number of patients involved, there is currently no consensus on what operation should be performed in patients with tertiary hyperparathyroidism after renal transplantation. METHOD: Retrospective analysis of the 70 patients with tertiary hyperparathyroidism who all underwent subtotal parathyroidectomy with transcervical thymectomy in the same institution between 1978 and 2003. RESULTS: The delay between transplantation and parathyroidectomy was 4,1+/-4,3 years. Follow up was available for all patients. Mean follow-up was 5,6+/-5 years. Glomerular filtration rate (GFR) was 53+/-21 ml/min at parathyroidectomy and 42+/-29 ml/min at follow-up [<30 ml/min in 26 patients (37%), 30 - 60 ml/min in 25 patients (36%) et>60 ml/min in 19 patients (27%)]. One patient was successfully reoperated for persistent tertiary hyperparathyroidism during follow-up. No patient was hypercalcemic at follow-up. Four patients with a GFR<30 ml/min had a PTH level>fourfold normal values (6%) without signs or symptoms of hyperparathyroidism. One patient was hypocalcemic (1,5%) and two patients were normocalcemic with undetectable or infranormal PTH level (3%) under oral vitamin D and calcium medication. CONCLUSION: This approach permits not only to cure the majority of patients with tertiary hyperparathyroidism but also to avoid recurrence when the renal function declines. When medical management has failed, we recommend systematic subtotal parathyroidectomy with thymectomy for patients with tertiary hyperparathyroidism and this should usually be performed during the second year after transplantation.     

Less-than-subtotal parathyroidectomy increases the risk of persistent/recurrent hyperparathyroidism after parathyroidectomy in tertiary hyperparathyroidism after renal transplantation

BACKGROUND: The optimal surgical approach for tertiary hyperparathyroidism (HPT) after kidney transplantation is unknown. Existing studies are limited by small sample size, lack of adjustment for kidney function, and no long-term follow-up. METHODS: We retrospectively analyzed 74 patients with tertiary HPT who underwent parathyroidectomy at two centers since 1978. Persistent HPT was defined as parathyroid hormone (PTH) concentrations in excess of the K/DOQI target range for the corresponding estimated creatinine clearance (eCrCl). RESULTS: Seventy-four patients had 83 operations (72 subtotal and 11 less-than-subtotal parathyroidectomies). Mean follow-up time was 5.4 +/- 4.7 years. Calcium concentrations decreased significantly after parathyroidectomy (2.83 vs 2.28 mmol/L, P < 0.001), as did eCrCl (54.5 vs 44.9 mL/min, P < 0.001) and PTH (382 vs 132 pg/mL, P < 0.001). In the multivariable regression analysis, only the type of operation and postoperative eCrCl were significantly correlated with PTH at follow-up. A limited parathyroidectomy was associated with a fivefold increase in risk of persistent or recurrent hyperparathyroidism. CONCLUSIONS: The use of limited parathyroidectomy for tertiary HPT after kidney transplantation has a higher risk of persistent/recurrent HPT. Subtotal parathyroidectomy is recommended for patients with tertiary HPT.     

Accuracy of intra-operative PTH measurement during subtotal parathyroidectomy for tertiary hyperparathyroidism after renal transplantation

Background and aims Intra-operative parathyroid hormone (IOPTH) results are not known in the setting of tertiary hyperparathyroidism (HPT) after renal transplantation.Materials and methods A retrospective analysis of 35 tertiary HPT patients who all underwent subtotal parathyroidectomy and IOPTH monitoring was conducted.Results The mean follow-up time was 2.2±1.4 years. Thirty-four patients were cured; one patient (2.8%) had a persistent disease and was cured after reoperation. Median parathyroid hormone (PTH) (median percent decrease from highest) at baseline and at 5, 10, 20, and 30 min were 244, 78 (69%), 63 (75%), 53 (79%), and 49 pg/ml (83%), respectively. Four patients who were cured had a decrease of <50% at 5 min and two of them had a decrease of <50% at 10 min. The patient with persistent disease had a decrease of >50% at 10 min. The sensitivity of the test was 94% at 10 min using the Miami criteria.Conclusion This study shows that IOPTH in tertiary hyperparathyroidism has a high sensitivity. However, because of the low risk of persistent hyperparathyroidism when a subtotal parathyroidectomy is performed, its potential impact on the overall success rate is very small. We therefore do not recommend the routine use of IOPTH in tertiary hyperparathyroidism.This paper was presented at the 24th Arbeitstagung der Chirurgischen Arbeitsgemeinschaft für Endokrinologie (CAEK), 25–26 November 2005, Hamburg.     

The role of intraoperative parathyroid hormone testing in patients with tertiary hyperparathyroidism after renal transplantation

BACKGROUND: Intraoperative parathyroid hormone (PTH) testing has been shown to accurately define adequacy of parathyroid resection in patients with primary hyperparathyroidism (HPT) and alters the operative management in 10% to 15% of cases. However, the benefit of this technique in patients with tertiary HPT after renal transplantation undergoing parathyroidectomy is unclear. METHODS: Intraoperative PTH was measured in 32 consecutive patients undergoing parathyroidectomy for tertiary HPT after renal transplantation between March 2001 and November 2004 by using the Elecsys assay at baseline and, subsequently, 5, 10, and 15 minutes after curative resection. The outcomes of these patients were evaluated. RESULTS: All patients were cured after surgery. Of the 32 patients, 29 were found to have parathyroid hyperplasia, while 1 had a single adenoma and 2 had double adenomas. The average drop in intraoperative PTH levels after curative resection was 69 +/- 3.5% at 5 min., 77 +/- 2.3% at 10 minutes, and 83 +/- 3.4% at 15 minutes. PTH testing changed the intraoperative management in 5 (16%) patients. One patient with a single adenoma and 2 patients with double adenomas had a >50% drop at 10 minutes. after excision; therefore, the operation was terminated without further resection. Two patients did not have a >50% drop at 10 minutes after 3.5 gland resection. These patients were explored further, and additional supernumerary parathyroid glands were identified and resected. After resection of these additional glands, the PTH fell by >50%, indicating cure. CONCLUSIONS: In patients undergoing parathyroidectomy for tertiary HPT after renal transplantation, a decrease in intraoperative PTH levels >50% at 10 minutes after completion of the operation indicated adequate resection. Furthermore, intraoperative PTH testing altered the operative management in 16% of patients. Therefore, similar to its role in patients with primary HPT, intraoperative PTH testing appears to play an equally important role in the management of patients with tertiary HPT undergoing parathyroidectomy.     

A successful application of the intraoperative parathyroid hormone assay in tertiary hyperparathyroidism

The role of the intraoperative parathyroid hormone (IOPTH) assay in patients with tertiary hyperparathyroidism (3HPT) is not well defined. To evaluate the utility of the IOPTH in 3HPT, we compared its use in 72 patients with primary hyperparathyroidism (1HPT) and 3HPT undergoing parathyroidectomy. Sixty-three patients with 1HPT and nine patients with 3HPT were identified. There were 30 men and 42 women (mean age, 58 years). The mean serum calcium and preoperative intact PTH levels in 1HPT were 11.1 mg/dL and 214 pg/mL compared with 11.2 mg/dL and 849 pg/mL in 3HPT (Ca, non significant; PTH, P < 0.05). Intraoperatively, a solitary abnormal gland was found in 62 of 72 (86%) patients. Seven patients with 3HPT had three- or four-gland hyperplasia. The two groups were compared to determine if a 10-minute postexcision IOPTH decline > 50 per cent would have similar success rates. Seventy-one of 72 (98.6%) patients had a > 50 per cent decline from the baseline IOPTH at the end of the operation. The average reduction from baseline was 85.3 per cent in 1HPT and 88.6 per cent in 3HPT (not significant). Average follow-up was 9.8 months for 1HPT and 11.1 months in 3HPT. Three of 63 patients (4.8%) with 1HPT and five of nine patients (55.6%) with 3HPT had inappropriate elevations in PTH (P < 0.05). All patients with 3HPT were normocalcemic compared with 62 of 64 (97%) patients with 1HPT (not significant). The IOPTH assay can be used in 3HPT in an identical fashion with an equivalent rate of normocalcemia compared with its applications in 1HPT.     

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.     

Study of intact (1-84) parathyroid hormone secretion in patients undergoing parathyroidectomy

Patterns of intact (1-84) parathyroid hormone (intact PTH) elimination and subsequent recovery of parathyroid function were studied in 12 patients undergoing parathyroidectomy. Nine patients had primary hyperparathyroidism (HPT), with single gland disease in 6 and multiple gland disease in 3. Two patients had subtotal parathyroidectomy for HPT secondary to chronic renal failure and 1 underwent excision of a hyperfunctioning parathyroid autograft. Using a sensitive 2-site immunochemiluminometric assay, serum intact PTH levels were measured preoperatively, intraoperatively, and postoperatively. A dual phase pattern of hormone clearance was found in 10 of the 12 patients, including the patient undergoing autograft excision. A monoexponential clearance pattern was seen in the remaining 2 patients, both of whom had subtotal parathyroidectomies for multiple gland disease. In the patients with primary HPT due to single gland disease, the early phase of intact PTH clearance had a half-life (T1/2) of 3.3 (+/- standard deviation 0.9) minutes and a late T1/2 of 96.4 (+/- standard deviation 92.7) minutes. Calculation of decay curves and half-lives for the patients undergoing subtotal parathyroidectomy was more difficult because of the inherent uncertainty in determining time zero. Nevertheless, in all but 2 patients, the clearance pattern was biexponential and the T1/2 measurements were very similar to those encountered in patients with single-gland disease. In the 2 patients with monoexponential clearance, the T1/2 figures were 86.7 minutes and 26.7 minutes, respectively. In the patients undergoing parathyroidectomy for primary HPT, levels of intact PTH were lowest at 1-3 hours after surgery, recovering to normal in the majority of patients by 18-40 hours.     

Significance of monitoring Bio-Intact PTH (1-84) during parathyroidectomy for secondary hyperparathyroidism

BACKGROUND: The Bio-Intact PTH (1-84) assay has recently been developed to specifically measure the intact PTH (1-84) molecule, and in this study we used it to investigate sequential changes in serum Bio-Intact PTH (1-84) levels during parathyroidectomy for secondary HPT. MATERIAL AND METHODS: The subjects of this study were 70 patients (41 women, 29 men) who underwent parathyroidectomy between April 2002 and March 2005. Ethylene diamine tetraacetic acid serum samples were drawn via a peripheral venous catheter after induction of anesthesia (basal), and at 5, 10, and 30 min after diseased glands excision. Serum active PTH (1-84) was measured by the Bio-Intact PTH (1-84) assay, which is a two-site chemiluminometric assay. RESULTS: When 4 or more diseased parathyroid glands were removed, the basal of Bio-Intact PTH (1-84) level in patients without persistent HPT (52 cases) was 539 +/- 355 pg/mL. The level of the Bio-Intact PTH (1-84) at 30 min after sufficient parathyroidectomy had decreased to less than 45 pg/mL, whereas the Bio-Intact PTH (1-84) level in patients with persistent HPT at 30 min was greater than 45 pg/mL (3 cases). After removal of three or fewer diseased parathyroid glands (15 cases), the Bio-Intact PTH (1-84) at 30 min in patients without persistent HPT (13 cases) was less than 45 pg/mL. The 2 patients whose the Bio-Intact PTH (1-84) at 30 min was greater than 45 pg/mL underwent reoperation, and residual enlarged parathyroid gland in the neck was removed. CONCLUSIONS: The Bio-Intact PTH (1-84) level at 30 min after parathyroidectomy seems to be useful for judging whether the parathyroidectomy is complete irrespective of the number of glands removed from patients with secondary HPT. When only three diseased parathyroid glands are removed, the surgeon can decide whether to continue or stop neck exploration according to the level of Bio-Intact PTH (1-84) at 30 min.     

Total Parathyroidectomy Without Autotransplantation for Renal Hyperparathyroidism: Experience with a qPTH-controlled Protocol

Background Controversy regarding the optimal surgical treatment for secondary hyperparathyroidism (sHPT) continues. Subtotal parathyroidectomy (PTX) with a small remnant and total parathyroidectomy with autotransplantation prevail, although impaired by considerable recurrence rates. Concerns about postoperative management and long-term supplementation prevent broader acceptance of total parathyroidectomy without autotransplantation. Materials and Methods The standardized surgical procedure with intraoperative PTH assessment (qPTH) included cervical thymectomy, histological proof of four parathyroid specimens and obligatory cryopreservation of parathyroid tissue in all 23 patients undergoing total PTX without autotransplantation. Whenever qPTH did not normalize, complete cervical exploration of ectopic sites was performed. Another 64 patients with subtotal PTX for sHPT served as comparison for the postoperative course. Results There were 13 primary and 10 completion (5 persistent, 5 recurrent sHPT) total PTX with 14 concurrent thyroid resections performed. Mean preoperative PTH was 1.351 pg/ml (12–72 pg/ml) and serum calcium was 2.5 mmol/l (2.25–2.5 mmol/l). PTH showed intraoperative normalization in 15 patients and a 50% PTH reduction from preoperative values in all. Postoperative course was not significantly different from the subtotal PTX group and showed PTH within the normal range for 5 patients (4 < 35 pg/ml), 7 with PTH < 12 pg/ml, and 4 without measurable PTH. In 4 patients PTH did not normalize postoperatively. Serum calcium levels were below normal in all patients: < 2.25 mmol/l in 9, < 2.00 mmol/l in 7, and <1.8 mmol/l in 6 patients. Only 1 patient required intermittent early postoperative i.v. calcium supplementation, 6 patients received oral calcium and vitamin D supplement for low calcium levels, but no severe hypocalcemic symptoms were encountered. Mean postoperative hospital stay was 5 days. No recurrent laryngeal nerve palsies were encountered. Complications were two cervical bleedings following postoperative hemodialysis requiring evacuation. Conclusions Total PTX without autotransplantation proves to be an equally safe and successful procedure for sHPT as subtotal PTX or total PTX with autotransplantation. Measurable PTH after total PTX as demonstrated in this study, supports the idea of uncontrollable isolated cell nests that are inevitably prone to stimulated growth with time. Therefore, total PTX is superior with regard to prevention of recurrence. Adequate supplementation with calcium and vitamin D, often necessary after subtotal PTX to suppress inadequate PTH and protect from recurrence, will prevent severe hypocalcemia and with the modern aluminium-diminishing dialysis regimen, development of adynamic bone disease appears less likely than feared. If necessary, cryopreserved parathyroid tissue can be autotransplanted on demand.     

Novel parathyroid hormone (1-84) assay as basis for parathyroid hormone monitoring in renal hyperparathyroidism

HYPOTHESIS: Cross-reactivity of parathyroid hormone (PTH) fragments with immunometric "intact" PTH assays limited the use of intraoperative PTH monitoring in renal hyperparathyroidism. A new assay generation measuring whole PTH (1-84) should be able to predict complete or incomplete resection of hyperfunctioning parathyroid tissue. DESIGN: Consecutive series for evaluation of intraoperative PTH monitoring using a second-generation assay. SETTING: University hospital section of endocrine surgery. PATIENTS: Twenty-two patients received hemodialysis; 9 patients showed good and 4 patients reduced graft function after kidney transplantation. INTERVENTIONS: Total parathyroidectomy, central neck dissection, bilateral thymectomy, and immediate autotransplantation was the standardized approach in 35 consecutive patients. Blood samples were drawn before incision and at 5-minute intervals after excision of the last gland. Stored samples were analyzed using a "second-generation" assay (Bio-Intact PTH [1-84]; Nichols Institute Diagnostics, San Clemente, Calif). Parathyroidectomy was classified as total, subtotal, or insufficient according to first-generation intact PTH values in the first postoperative week. MAIN OUTCOME MEASURES: Intraoperative ability to predict total, subtotal, or incomplete parathyroidectomy. RESULTS: Independent of renal function, Bio-Intact PTH dropped into the normal range in all patients with total and subtotal resections after a maximum of 20 minutes. It indicated insufficient parathyroidectomy in 4 (80%) of 5 patients. One failure was caused by devascularization of remaining parathyroid tissue. An intraoperative differentiation between total and subtotal resection was not possible. CONCLUSIONS: Intraoperative monitoring with quick, second-generation assays for PTH (1-84) seems to be a valuable new tool in surgery for renal hyperparathyroidism because a more accurate differentiation between sufficient and insufficient parathyroidectomy may be achieved. An intraoperative decision about the need for immediate or delayed autotransplantation seems impossible because a differentiation between total or subtotal parathyroidectomy cannot be made. Because of possible devascularization of parathyroid tissue, Bio-Intact PTH monitoring can only be interpreted in the context of the operative findings.     

The role of quick bio-intact PTH(1-84) assay during parathyroidectomy for secondary hyperparathyroidism

OBJECTIVE: The role of the quick PTH assay in surgery for secondary HPT is unclear because of overestimation of intact PTH(1-84) values due to the cross-reactivity of currently available first-generation PTH assays with non-PTH(1-84) fragments that accumulate in renal failure. In this study, we used a second-generation quick PTH immunometric assay that are claimed to detect the biologically active PTH(1-84) molecule with no cross-reactivity with PTH fragments to investigate the potential utility of the assay during parathyroidectomy for secondary HPT. MATERIAL AND METHODS: The study was performed on 18 patients (12 women, 6 men) between October 2004 and March 2005. EDTA serum samples were drawn via a peripheral venous catheter after induction of anesthesia (basal), and at 5, 10, and 30 min after excision of diseased parathyroid glands. Serum active PTH(1-84) was measured by the quick Bio-Intact PTH(1-84) assay, which is a two-site chemiluminometric assay. RESULTS: At 30 min the quick Bio-PTH(1-84) level of 16 patients was under 45 pg/mL. Four parathyroid glands were removed macroscopically from 12 of the 16 patients, and three glands were removed from the other four patients. All patients were cured of their HPT. Four enlarged parathyroid glands were removed from a patient whose Bio-Intact PTH(1-84) at 30 min had not fallen below 45 pg/mL, and no other glands were found by further exploration. At the 6 mo follow-up examination, the first-generation intact PTH level of this patient was over 45 pg/mL, but several diagnostic imaging methods did not reveal any enlarged parathyroid glands. Three enlarged parathyroid glands from the other patient, and exploration led to the identification of an ectopic parathyroid gland at the carotid bifurcation. CONCLUSIONS: The results of this prospective study show that quick Bio-Intact PTH(1-84) monitoring is a valuable new tool for use in the surgical treatment of secondary HPT. An intraoperative, quick Bio-Intact PTH(1-84) assay will be of value for the adequate prediction of surgical cure.     

Increased resting energy expenditure in hemodialysis patients with severe hyperparathyroidism

Several metabolic derangements, including enhanced protein catabolism, have been suggested to be associated with increased circulating parathyroid hormone (PTH) in patients with secondary hyperparathyroidism (HPT). Such conditions, therefore, might lead to an increase in energy expenditure. The present study examined by indirect calorimetry the resting energy expenditure (REE) of 15 hemodialysis patients who have severe HPT (PTH = 1457 +/- 676 pg/ml) and were pair-matched for age and gender to 15 hemodialysis patients with mild to moderate HPT (PTH = 247 +/- 196 pg/ml). Both groups were also pair-matched for age and gender to a group of 15 healthy adult subjects (control). In six patients from the severe HPT group submitted to total parathyroidectomy, REE was determined 6 mo after the surgery. The groups were not different regarding lean body mass (LBM) measured by bioelectric impedance, serum C-reactive protein, and bicarbonate. Thyroid-stimulating hormone was within the normal range in all groups. Nonadjusted REE was significantly higher in the severe HPT group (1674 +/- 337 kcal/d) compared with patients with mild to moderate HPT (1388 +/- 229 kcal/d; P < 0.05). Both groups did not differ from the control group (1468 +/- 323 kcal/d). When adjustment of REE for LBM was performed using the multiple regression analysis, patients with mild to moderate HPT and control subjects had significantly lower REE (-231 and -262 kcal, respectively) than that of the severe HPT group. Considering all patients together, nonadjusted REE correlated directly with LBM (r = 0.61; P < 0.01). PTH correlated strongly with LBM in the severe HPT group (r = -0.82; P < 0.01). In the multiple linear regression analysis, only LBM and PTH were independent determinants of REE (n = 30; R(2) = 0.47). REE decreased significantly in the six patients who were evaluated 6 mo after parathyroidectomy (from 1617 +/- 339 to 1226 +/- 253; P = 0.02). These results demonstrate that hemodialysis patients with severe HPT have increased REE that might be reduced after parathyroidectomy.     

PTH secretion in patients with chronic renal failure assessed by a modified CiCa clamp method: effects of 1-year calcitriol therapy

BACKGROUND: Secondary hyperparathyroidism (secondary HPT) in patients with chronic renal failure (CRF) is characterized by parathyroid gland hyperplasia and an intrinsic defect in the recognition of parathyroid hormone (PTH) secretion. Conflicting results have been reported regarding the set point for calcium-regulated PTH release and its modification by calcitriol therapy in hemodialysis patients. Additionally, the effect of calcitriol on the calcium/PTH relationship in predialysis CRF patients with early secondary HPT has not been investigated. Our objective in this controlled study was to investigate the calcium/PTH relationship and to determine the calcium set point in patients with early stages of CRF before and after a 1-year treatment with calcitriol and in normal volunteers. METHODS: Nine patients with an early stage of CRF (GFR between 20 and 50 ml/min x 1.73 m2 b.s.) aged 35-77 years and 13 healthy volunteers (HV) aged 26-60, years were included in the study. All participants were investigated by sequential lowering and raising of serum calcium levels comprising the following phases: blood-ionized calcium (Ca2+) was lowered by about 0.2 mmol/l (3 steps), steady-state hypocalcemia of Ca2+ 0.2 mmol/l below the baseline (step 4), stop of the infusion for 5 minutes (step 5), Ca2+ was raised to about 0.2 mmol/l above baseline (steps 6 and 7), and a steady state hypercalcemia of Ca2+ 0.2 mmol/l above baseline (step 8). Ionized calcium and intact PTH (iPTH) were measured at 30 time points during 240 minutes. The calcium set point was determined using the classical 4-parameter model. The CiCa clamp test was performed before and after a 1-year treatment with 0.5 microg of calcitriol thrice weekly. RESULTS: No differences in the set point were observed between HV and CRF patients with early secondary HPT. Four of 9 patients responded to calcitriol treatment with a decrease in basal serum iPTH levels ("responders"). There was no difference between renal function (GFR 18 +/- 6 vs. 17 +/- 8 ml/min x 1.73 m2 b.s.), set point (Ca2+ 1.07 +/- 0.13 vs. 1.07 +/- 0.06 mmol/l) and suppressibility of PTH secretion (PTHmin% 7.3 +/- 1.6 vs. 8.2 +/- 2.9) in responders vs non-responders, nor did these values change after treatment with calcitriol. PTHmin% decreased significantly in the whole group after treatment (10.4 +/- 8.5 vs. 7.8 +/- 2.4). CONCLUSIONS: Although the calcium set point was not different in predialysis CRF patients with early secondary HPT compared to HV, calcitriol treatment improved the calcium-related suppression of PTH secretion (PTHmin%).     

Surgical Treatment of Tertiary Hyperparathyroidism: The Choice of Procedure Matters!

Background Parathyroid surgery (PTX) in patients with tertiary hyperparathyroidism (tHPT) may endanger the long-term survival of transplanted renal grafts. The mechanism by which graft function deteriorates is unknown. We reviewed our experience in regard to the operative procedures and postoperative outcome. Methods Sixty-nine patients were operated on for tHPT between 1987 and 2006 at our institution. Serum (s) calcium, s-creatinine, and levels of intact parathyroid hormone (PTH) were measured before and after PTX. The Modification of Diet in Renal Disease (MDRD) equation was used to estimate glomerular filtration rate (GFR). Results The entire patient group developed a deterioration of kidney graft function after PTX. Nineteen of 69 patients developed a decrease in GFR of more than 20% during the hospital stay, persisting for more than one year after PTX. Ten of them had to restart dialysis during the first year after PTX. Mean preoperative s-creatinine was 4.4 ± 0.6 mg/dl in these patients. When divided according to the surgical procedure performed, only the subgroup who underwent total parathyroidectomy showed a significant worsening of graft function when compared to subtotal or reoperative PTX. Conclusions PTX is an efficient way to treat tHPT but represents a risk for impairing graft function, especially for patients that already demonstrate poor kidney function at the time of surgery. In the aim to prevent transient hypoparathyroidism, which may provoke reduced graft perfusion, as one possible cause of kidney graft deterioration associated with PTX, one should consider subtotal instead of total parathyroidectomy.     

The severity of secondary hyperparathyroidism in chronic renal insufficiency is GFR-dependent,race-dependent,and associated with cardiovascular disease

Secondary hyperparathyroidism (SHPT) is an important complication of end-stage renal disease. However, SHPT begins during earlier stages of chronic renal insufficiency (CRI), and little is known about risk factors for SHPT in this population. This study evaluated 218 patients in an ethnically diverse ambulatory nephrology practice at the University of California San Francisco during calendar years 1999 and 2000. Demographic data, comorbid diseases, medications, and laboratory parameters were collected, and independent correlates of intact parathyroid hormone (PTH) were identified by using multiple linear regression. The mean estimated GFR was 34 ml/min per 1.73 m(2) (10%-90% range, 13 to 61 ml/min per 1.73 m(2)); PTH was inversely related to GFR (P < 0.0001). The adjusted mean PTH was higher among African Americans and lower among Asian/Pacific Islanders compared with white patients (233 versus 95 versus 139 pg/ml; P < 0.0001). Moreover, among the 196 patients with GFR <60 ml/min per 1.73 m(2), the slope of GFR versus PTH was significantly steeper among African Americans than among white patients (10.6 versus 3.9 pg/ml per ml per min per 1.73 m(2); P = 0.01). After adjusting for age and diabetes, PTH was associated with a history of myocardial infarction (OR, 1.6; 95% CI, 1.1 to 2.3 per unit natural log PTH) and congestive heart failure (OR, 2.0; 95% CI, 1.3 to 2.9 per unit natural log PTH) and not associated with other co-morbid conditions. These factors should be considered when screening and managing SHPT in CRI.     

Parathyroid hormone and large related C-terminal fragments increase at different rates with worsening of renal function in chronic kidney disease patients. A possible indicator of bone turnover status?

BACKGROUND: The intact parathyroid hormone (PTH) serum value has been the non-invasive biomarker of choice for the early diagnosis of renal bone disease in the chronic kidney disease (CKD) patient population. It has now been known that the intact PTH assay value is the sum of 1-84 PTH (true hypercalcemic PTH) and large C-terminal PTH fragments, mainly 7-84 PTH, a fragment with hypocalcemic hormone actions. AIM: The aim of this study was to investigate the differences among the different functional stages of CKD in the following PTH parameters: intact PTH, 1-84 PTH, 7-84 PTH, and the ratio 1-84 PTH/7-84 PTH. GFR (clearance of 99mTc-DTPA) was measured in 164 (85 males and 79 females) adult CKD patients with different degrees of renal function impairment (serum creatinine 0.50 12.1 mg/dl, mean 2.00). PATIENTS AND METHODS: Plasma concentrations of calcium, phosphate, 1-84 PTH and intact PTH were also measured. The value of 7-84 PTH was calculated as the difference between intact PTH and 1-84 PTH. The reduction of, GFR was accompanied by an increase of intact PTH, with a prevalent increase of 7-84 PTH over 1-84 PTH, resulting in a decrease of the ratio 1-84 PTH/7-84 PTH. RESULTS: The values of 7-84 PTH showed a discrimination between Stages 1 and 2 (GFR > 60 ml/min ) and Stage 3 (GFR 30 60 ml/ min) CKD patient populations. In fact, 7-84 PTH was already significantly increased in patients at CKD Stage 3. The analysis of individual patients indicated that a low value (< 1.4) of the ratio 1-84 PTH/7-84 PTH, suggestive for low bone turnover, was already found in more than 20% of CKD Stage 3 patients. CONCLUSION: The results of the present study demonstrate that the reduction in GFR is accompanied by a higher increase in 7-84 PTH with respect to 1-84 PTH, which suggests the possibility that bone metabolism and calcemic status are already reduced in patients with moderate renal failure (CKD Stage 3).     

Major depression due to primary hyperparathyroidism: a frequent and correctable disorder

While primary hyperparathyroidism (primary HPT) is recognized as a correctable cause of nephrolithiasis and osteoporosis, its role as an organic cause of major depression is less clear. The rate of major depression in primary HPT, response of symptoms to parathyroidectomy, and potential cost benefits were reviewed. From August 1994 to September 2002, 360 patients underwent parathyroidectomy for primary HPT. Thirty-five patients met Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM IV-TR) criteria for major depression. Postoperatively, a modified form of the Outcomes Institutes Health Status Questionnaire 2.0 was used to evaluate patient mood and continued need for antidepressant medication (ADM). Cost analysis of ADM use was performed. Thirty-five of 360 patients (10%) with primary HPT met criteria for major depression. Thirteen of 35 (37%) required ADM preoperatively. Postoperatively, 29/35 (83%) patients responded to a phone survey: 90 per cent stated depression no longer impacted their ability to work or activities of daily living; 52 per cent reported an improved quality of life; 27 per cent discontinued preoperative ADM; and 27 per cent reduced their ADM dose. Reduction in ADM resulted in a savings of dollars 700 to dollars 3000 per patient per year. Major depression occurs in 10 per cent of patients undergoing parathyroidectomy for primary HPT. Parathyroidectomy reduces symptoms of major depression, improves quality of life, and can eliminate or reduce the need for antidepressant medication in up to 54 per cent of patients.     

Impact of Intraoperative Parathyroid Hormone Levels on Surgical Results in Patients with Renal Hyperparathyroidism

The aim of our study was to evaluate the impact of intraoperative parathyroid hormone (PTH) measurement on surgical results in patients with renal hyperparathyroidism (HPT). From December 1999 to February 2004, a series of 95 consecutive patients underwent total parathyroidectomy and intraoperative PTH measurement for renal HPT. Intraoperative PTH was measured before and 15 minutes after parathyroidectomy with the Immulite DPC assay for intact PTH. The median PTH levels before surgery were 133.0 pmol/L, which declined to 5.9 pmol/L at the end of the operation. At follow-up, 91 of 95 (96%) patients presented with normal calcium levels. Persistent renal HPT was seen in three patients, and recurrent HPT was diagnosed in another. In 99% of the patients the intraoperative PTH levels declined more than 50% and in 73% the PTH decay was more than 90%. In 64% of the patients PTH levels dropped into the normal range (< 7.6 pmol/L). Altogether, 97% of the patients with an intraoperative PTH decrease of more than 90% presented with normal PTH levels postoperatively (p = 0.0237), as did all of the patients whose intraoperative PTH dropped into the normal range (p = 0.0432). Intraoperative PTH measurement with a decrease in intraoperative PTH of at least 90% is highly predictive of successful parathyroidectomy and normalization of postoperative calcium and PTH levels.     

Increase in Bone Mineral Density after Successful Parathyroidectomy for Tertiary Hyperparathyroidism after Renal Transplantation

BACKGROUND: Few studies have reported changes of bone mineral density (BMD) after parathyroidectomy in patients with persistent hyperparathyroidism after renal transplantation (3 HPT). PATIENTS AND METHODS: We retrospectively analyzed 14 patients who underwent successful parathyroidectomy for 3 HPT and who had available BMD data before and after parathyroidectomy. RESULTS: Median follow-up time was 26 months (IQR: 16.8-40.2). Serum calcium levels decreased significantly after parathyroidectomy (2.32 +/- 0.09 versus 2.66 +/- 0.16 mmol/l; p < 0.01), as did PTH levels (5.1 +/- 3.0 versus 27.8 +/- 23.7 pmol/l; p < 0.01). Nine patients (64%) had a steroid-free immunosuppression at follow-up. Mean increase in BMD was 9.5 +/- 8.0% for the spine and 9.5 +/- 7.9% for the hip (p < 0.01 for both sites). Patients with osteoporosis (T-score 相似文献   

Comparison of parathyroid hormone levels from the intact and whole parathyroid hormone assays after parathyroidectomy for primary and secondary hyperparathyroidism

BACKGROUND: Most commercial intact parathyroid hormone (intact PTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH). Using a whole-molecule PTH (whole PTH) assay that specifically measured only 1-84 PTH, we compared the kinetics of whole PTH and intact PTH after parathyroidectomy in patients with primary hyperparathyroidism (HPT) and secondary HPT. METHODS: This study comprised 74 patients with primary HPT caused by a single adenoma and 18 patients with secondary HPT who underwent parathyroidectomy. Blood samples were drawn after anesthesia, just before excision of a single adenoma in primary HPT, and just before excision of the last parathyroid gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the whole PTH value from the intact PTH value. RESULTS: There was a difference between the percentage of 7-84 PTH/intact PTH in plasma samples from patients with primary HPT and secondary HPT (28%+/-12% vs 35%+/-9%; P<.05). Plasma whole PTH decreased more rapidly than intact PTH after parathyroidectomy in patients in both the primary HPT (P<.0001) and secondary HPT groups (P<.0001). Decline of intact PTH was slower in patients with secondary HPT than in patients with primary HPT; however, there was no significant difference in the decline of whole PTH between the 2 groups. CONCLUSIONS: The quick intact PTH assay is not used frequently during surgery in patients with secondary HPT; however, our results suggest that a quick whole PTH assay may be a more useful adjunct to parathyroidectomy in both secondary HPT and primary HPT.