Secondary hyperparathyroidism in chronic renal failure. Role of subtotal parathyroidectomy

Fourteen patients with chronic renal failure and secondary hyperparathyroidism were treated by subtotal parathyroidectomy. Bone pain and hypercalcemia were the main indications to surgery respectively in 13 and 1 patients. Bone pain disappeared or was significantly reduced in 12/14 patients. Two patients had a persistent hyperparathyroidism. Serum alkaline phosphatase returned to normal in 12 patients and PTH in 11 of 12 patients with pretreatment high levels.     

Low-Turnover Bone Disease in Hypercalcemic Hyperparathyroidism After Kidney Transplantation

Hypercalcemia in persistent secondary hyperparathyroidism after kidney transplantation is considered to result from increased bone resorption. Bone biopsies' studies, however, have never been performed in these patients. Bone biopsies after double tetracycline labeling were obtained from 17 patients with hypercalcemic hyperparathyroidism and an estimated glomerular filtration rate > 30 mL/min/1.73 m2. Serologic bone markers, calcitriol, intact fibroblast growth factor-23 (iFGF-23), and serum and 24h urine concentration of calcium and phosphate were measured in all patients. Tubular maximum for phosphate corrected for GFR (TmP/GFR), and the fractional excretion of calcium (FeCa) were calculated. High-turnover renal osteodystrophy (ROD) was present in nine and low-turnover ROD in eight patients. The bone formation rate was significantly associated with bone alkaline phosphatase, c-telopeptide and osteocalcin. In patients with high turnover ROD, osteocalcin was also significantly higher than in patients with decreased bone formation. The FeCa was normal or below normal in 14/17 patients. TmP/GFR was below normal in all patients. Neither intact PTH nor iFGF-23 was associated with TmP/GFR, FeCa or any histomorphometric bone parameter. We conclude that hypercalcemia of posttransplant hyperparathyroidism can be associated with high or low turnover bone disease. Decreased calcium excretion suggests an additive tubular effect on hypercalcemia.     

Recurrent disease after limited parathyroidectomy for sporadic primary hyperparathyroidism

BACKGROUND: Limited parathyroidectomy guided by intraoperative parathyroid hormone (PTH) assay (QPTH) is highly successful (97% to 99%) in predicting postoperative eucalcemia, usually with less extensive dissection when compared with bilateral neck exploration. Because fewer glands are excised when resection is guided by QPTH as opposed to resection guided by gland size, a higher recurrence rate may occur. Recurrence rate after bilateral neck exploration is 0.4% to 5%, but frequency of recurrence after limited parathyroidectomy is unknown. This study reports outcomes of this operative approach in sporadic primary hyperparathyroidism. STUDY DESIGN: Four-hundred twenty-three patients with sporadic primary hyperparathyroidism undergoing limited parathyroidectomy, followed 6 months or more or considered operative failures, were studied. In most patients, calcium and PTH levels were measured immediately after operation, and then at 2 and 6 months and yearly intervals. Operative failure is defined as hypercalcemia and high PTH within 6 months after operation, and recurrent hyperparathyroidism is hypercalcemia and elevated PTH occurring after a successful parathyroidectomy. Recurrence distributions were estimated using Kaplan-Meier analysis. RESULTS: The success rate of limited parathyroidectomy is 97% (412/423). Four-hundred six patients were eucalcemic over an average of 34 months (median 27, range 6 to 118 months) of followup and recurrent hyperparathyroidism developed in 6 of 412 (1.5%). Estimated 5 years recurrence-free rate was 97% (95% confidence interval, 91% to 99%). Earliest and latest recurrences were diagnosed at 24 and 83 months, respectively. QPTH results did not predict any recurrence. Overall success rate was achieved, with multiple gland resections performed in only 3% of patients. CONCLUSIONS: Recurrence rate after limited parathyroidectomy is similar to rates reported after bilateral neck exploration. Parathyroidectomy guided by QPTH is successful not only in resolving hypercalcemia in the short term, but also in providing longterm eucalcemia.     

A clinical study on active vitamin D pulse therapy in hemodialysis patients with secondary hyperparathyroidism

The oral active vitamin D pulse therapy was performed for 20 chronic hemodialysis patients with secondary hyperparathyroidism (2 degrees HPT). Before pulse therapy, all patients showed high-turnover bone diseases, elevated serum alkaline phosphatase (Alp) and elevated serum parathyroid hormone (PTH). They had at least one parathyroid gland detected by ultrasonography. In one patient, serum PTH level did not decrease during three months. In five patients, hypercalcemia was observed so that the pulse therapy was with drawn. Another patient was resistant to the second pulse therapy for recurrence of 2 degrees HPT. Total parathyroidectomy and autotransplantation was performed in these seven patients. The size of parathyroid gland in patients undergoing surgical treatment was significantly larger than those estimated by ultrasonography in patients successfully treated with pulse therapy (p < 0.005). In all patients with surgical treatment, the conventional oral active vitamin D therapy was performed with caution to hypercalcemia preoperatively. The preoperative Alp levels decreased compared with those of at the beginning of the pulse therapy. Postoperatively, the total amount of intravenous administered calcium decreased, and serum calcium levels were easily controlled.     

Prospective study on dialysis patients after total parathyroidectomy without autoimplant

Aim: Secondary hyperparathyroidism is common in chronic kidney disease. When medical treatment fails, subtotal or total parathyroidectomy with autoimplant is done but both are associated with a high recurrence rate. The third surgical strategy is total parathyroidectomy without autoimplant. We evaluate the outcomes of patients who had total parathyroidectomy with no autoimplant. Methods: Thirteen patients who had total parathyroidectomy without autoimplant were prospectively studied from 1998–2002. Intact parathyroid hormone, biochemistry and bone mineral densities were measured at baseline and serially. All patients had bone biopsies done preoperatively and seven had repeat bone biopsies at a mean of 37.7 months postoperatively. Histomorphometric studies were done for all bone biopsies. Patients were observed for fractures. Results: Five patients were on haemodialysis and eight on peritoneal dialysis. Mean duration of follow up was 68 months. Postoperatively, mean intact parathyroid hormone decreased precipitously and remained within or just above normal. Mean serum calcium phosphate product decreased and remained normal. Out of seven patients who had repeat bone biopsies, two showed reversal of hyperparathyroid bone disease to normal, two had mild hyperparathyroidism, while three had adynamic bone disease. One patient with adynamic bone disease subsequently developed biochemical recurrence of hyperparathyroidism. Serial bone densitometry showed remarkable improvement. There was no fracture. Conclusion: In the studied series of total parathyroidectomy without autoimplant, adynamic bone disease occurred in three out of seven repeat bone biopsies while improvement occurred in the rest. Bone mineral density was much improved and there was no fracture.     

Total parathyroidectomy with or without autoimplantion in the therapy of secondary hyperparathyroidism

BACKGROUND: Secondary hyperparathyroidism (HPTs) in patients with chronic renal failure is related to a reduction of absorption of calcium with hyperplasia of main cells and an increase of PTH levels: this often leads to complications in dialysis. METHODS: Data from 10 patients (mean age 55 years) with HPTs who underwent total parathyroidectomy from November 1999 to November 2001 were retrospectively collected. Surgical indications included: persistent hypercalcemia, bone fractures, fatigue, joint pain and itching. Median preoperative PTH level was 800 pg/ml. Presurgical work-up included: serum PTH, calcium and alkaline phospha-tases. Thyroid ultrasound and scintigraphy, 99Tc sestamibi scintigraphy, CBM, FNB were also performed. In 5 patients 2 hours prior to the operation 2 MCu of sestamibi 99Tc had been injected. Patients underwent cervical exploration radioguided in 5 cases under general anesthesia. The operation consisted in the removal of all glands with subcutaneous forearm implant in 4 cases. PTH dosage at starting time of operation (time 0) was performed; it was repeated after the removal of each parathyroid gland and postoperatively on days 1 and 3 and then every month for 6 months. RESULTS: Twenty-four hours postoperatively 9 patients showed a great reduction of PTH levels with improved symptoms already on day 1 postoperative. In the patient with persistent HPT an autoimplant had been performed. CONCLUSIONS: Secondary HPT still shows unclear aspects. Parathyroidectomy determines an immediate improvement in symptoms. In all observed patients PTH was significantly reduced, serum calcium returned to normal and in any case hypoparathyroidism was detected.     

Early and Severe Hyperparathyroidism Associated with Hypercalcemia After Renal Transplant Treated with Cinacalcet

Bone disease is a common clinical problem following renal transplantation. In renal transplant recipients, multiple underlying factors determine the extent of bone loss and the subsequent risk of fractures. In addition to the well-recognized risk to bone disease posed by steroids, calcineurin inhibitors and pre-existing bone disease, persistent hyperparathyroidism (HPT) contributes to post-transplant bone loss. HPT is usually treated with vitamin D supplements combined with calcium. Patients whose HPT is associated with hypercalcemia pose a difficult therapeutic dilemma which often requires parathyroidectomy. Cinacalcet, a calcium mimetic agent, offers a unique pharmacologic approach to the treatment of patients with post-transplant hypercalcemia and HPT. In this paper, we describe the clinical course and biochemical changes in 10 renal transplant recipients with hypercalcemia and severe HPT early after renal transplantation treated with cinacalcet. Cinacalcet therapy corrected hypercalcemia and decreased parathyroid hormone (PTH) levels in all cases. A transient rise in the level of alkaline phosphatase was noted following initiation of cinacalcet therapy. In this patient population, correction of HPT was not permanent as discontinuing cinacalcet therapy led to a rapid rise in PTH level.     

甲状旁腺激素测定在继发性甲状旁腺功能亢进手术中的临床应用

目的 探讨甲状旁腺激素测定在继发性甲状旁腺功能亢进手术中的应用和标准.方法 17例继发性甲状旁腺功能亢进患者行甲状旁腺次全切除术,分别测定麻醉后切开皮肤前PTH值(PTH0)及最后1个旁腺次全切除后10 min的PrrH值(PTH10).预测手术成功标准:(1)最后旁腺切除后10 min PTH10下降至≤150 pg/mL,(2)最后旁腺切除后10 rain PTH10与PTH0直接比≤30%.结果 15例符合预测成功标准,术后第7天,PTH＜15 pg/mL者4例,PrrH在15～65 pg/mL者6例,PTTH在65-185.2 pg/mL 5例.术后骨痛症状均消失.结论 术中甲状旁腺激素测定有助于继发性甲状旁腺功能亢进的旁腺切除,能极大提高手术成功率.     

Severe hypercalcemic hyperparathyroidism developing in a patient with hyperaldosteronism and renal resistance to parathyroid hormone

We evaluated an African American woman referred in 1986 at age 33 years because of renal potassium and calcium wasting and chronic hip pain. She presented normotensive, hypokalemic, hypocalcemic, normophosphatemic, and hypercalciuric. Marked hyperparathyroidism was evident. Urinary cyclic adenosine monophosphate (cAMP) excretion did not increase in response to parathyroid hormone (PTH) infusion, indicating renal resistance to PTH. X‐rays and bone biopsy revealed severe osteitis fibrosa cystica, confirming skeletal responsiveness to PTH. Renal potassium wasting, suppressed plasma renin activity, and elevated plasma and urinary aldosterone levels accompanied her hypokalemia, suggesting primary hyperaldosteronism. Hypokalemia resolved with spironolactone and, when combined with dietary sodium restriction, urinary calcium excretion fell and hypocalcemia improved, in accord with the known positive association between sodium intake and calcium excretion. Calcitriol and oral calcium supplements did not suppress the chronic hyperparathyroidism nor did they reduce aldosterone levels. Over time, hyperparathyroid bone disease progressed with pathologic fractures and persistent pain. In 2004, PTH levels increased further in association with worsening chronic kidney disease. Eventually hypercalcemia and hypertension developed. Localizing studies in 2005 suggested a left inferior parathyroid tumor. After having consistently declined, the patient finally agreed to neck exploration in January 2009. Four hyperplastic parathyroid glands were removed, followed immediately by severe hypocalcemia, attributed to “hungry bone syndrome” and hypoparathyroidism, which required prolonged hospitalization, calcium infusions, and oral calcitriol. Although her bone pain resolved, hyperaldosteronism persisted. © 2013 American Society for Bone and Mineral Research.     

Total parathyroidectomy without autotransplantation as a standard procedure in the treatment of secondary hyperparathyroidism

BACKGROUND: Total parathyroidectomy with autografting of parathyroid tissue and subtotal resection of the parathyroid glands are currently considered as standard surgical procedures for the treatment of severe secondary hyperparathyroidism. However, a considerable recurrence rate following these procedures ranges from 5% to 80%. We present a retrospective analysis of the results of parathyroidectomy with autotransplantation to the forearm versus parathyroidectomy alone. PATIENTS AND METHODS: We analyzed the clinical course of 11 consecutive patients who had undergone parathyroidectomy between 1995 and 1999, and who were not simultaneously autografted. Controls were 11 patients in whom autotransplantation of parathyroid tissue into the forearm had been routinely performed between 1993 and 1996 at our institution. Clinical symptoms and recurrence of hyperparathyroidism were assessed for comparison of the alternative treatment modalities. Recurrence of disease was defined by elevated parathormone (PTH) levels (>7.6 pmol/l) with clinical symptoms and/or need for reoperation. RESULTS: No recurrence of hyperparathyroidism was observed in patients without autotransplantation after a mean follow-up of 23 months (range 1-49). Measurement of intact serum PTH revealed residual PTH secretion even after removal of four glands (mean 2.02 pmol/l). Clinical symptoms improved substantially after surgery. In the historical control group 3 of the 11 autotransplanted patients (27%) required resection of transplanted tissue. Additionally, two patients (18%) presented with increased PTH secretion and clinical symptoms of recurrent hyperparathyroidism during follow-up. Thus, a total of five patients (45%) experienced relapsing hyperparathyroidism caused by the implanted tissue. CONCLUSIONS: Total parathyroidectomy without autotransplantation is a safe procedure with a low rate of recurrent hyperparathyroidism when compared to parathyroidectomy with autotransplantation to the forearm in a historical control. These preliminary results mandates further investigations including a randomized trial.     

Measurement of intraoperative parathyroid hormone predicts long-term operative success

HYPOTHESIS: A decrease in the intraoperative parathyroid hormone (PTH) level predicts long-term operative success. DESIGN: A case series of consecutive patients undergoing parathyroidectomy with intraoperative PTH measurement. SETTING: A university hospital. PATIENTS AND INTERVENTION: One hundred two patients with sporadic primary hyperparathyroidism underwent parathyroidectomy according to the principles of unilateral exploration with intraoperative PTH measurement. MAIN OUTCOME MEASURES: Longitudinal effects on levels of serum calcium and PTH. RESULTS: In 94 of 98 patients who underwent primary exploration because of a solitary adenoma, intraoperative PTH decreased at least 60% 15 minutes after gland excision. The 4 cases in which PTH fell to less than 60% were classified as false negatives. Patients examined for multiglandular disease (n = 4) were correctly predicted not to have an adenoma. Twenty-two patients (22%) were unavailable for 5-year follow-up. These patients were followed up for 2 months to 48 months (median, 24 months), and none developed recurrent primary hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4 mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels at least once during the postoperative study period, with normal or slightly decreased calcium concentrations. The prediction of late postoperative normocalcemia by means of intraoperative PTH measurement had an overall accuracy of 95%. CONCLUSIONS: The measurement of intraoperative PTH during surgery for primary hyperparathyroidism accurately differentiates between single- and multiple-gland disease and ensures good long-term results.     

A Comparison of Calcium to Zoledronic Acid for Improvement of Cortical Bone in an Animal Model of CKD

Patients with chronic kidney disease (CKD) have increased risk of fractures, yet the optimal treatment is unknown. In secondary analyses of large randomized trials, bisphosphonates have been shown to improve bone mineral density and reduce fractures. However, bisphosphonates are currently not recommended in patients with advanced kidney disease due to concern about oversuppressing bone remodeling, which may increase the risk of developing arterial calcification. In the present study we used a naturally occurring rat model of CKD with secondary hyperparathyroidism, the Cy/+ rat, and compared the efficacy of treatment with zoledronic acid, calcium given in water to simulate a phosphate binder, and the combination of calcium and zoledronic acid. Animals were treated beginning at 25 weeks of age (approximately 30% of normal renal function) and followed for 10 weeks. The results demonstrate that both zoledronic acid and calcium improved bone volume by micro–computed tomography (µCT) and both equally suppressed the mineral apposition rate, bone formation rate, and mineralizing surface of trabecular bone. In contrast, only calcium treatment with or without zoledronic acid improved cortical porosity and cortical biomechanical properties (ultimate load and stiffness) and lowered parathyroid hormone (PTH). However, only calcium treatment led to the adverse effects of increased arterial calcification and fibroblast growth factor 23 (FGF23). These results suggest zoledronic acid may improve trabecular bone volume in CKD in the presence of secondary hyperparathyroidism, but does not benefit extraskeletal calcification or cortical biomechanical properties. Calcium effectively reduces PTH and benefits both cortical and trabecular bone yet increases the degree of extra skeletal calcification. © 2014 American Society for Bone and Mineral Research.     

Parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors.

Parathyroid hormone-related protein (PTHrP) and PTH share the common PTH/PTHrP receptor. Although an elevated level of circulating PTHrP in patients with malignancies causes hypercalcemia as does PTH, chronic and systemic effects of PTHrP on bone metabolism in humans are not well understood because tumor-burden patients showing hypercalcemia usually have a poor prognosis. We investigated bone and calcium metabolism in a patient with malignant islet cell tumors showing hypercalcemia due to the elevated plasma PTHrP level for 7 years. Hypercalcemia and hypercalciuria continued throughout the clinical course in spite of frequent infusions of bisphosphonates. Bone resorption markers and a bone formation marker were consistently elevated as seen in primary hyperparathyroidism, a disease caused by an autonomous hypersecretion of PTH. Based on biochemical measurements including bone markers and serum 1,25-dihydroxyvitamin D, the clinical features of this case essentially are the same as those of primary hyperparathyroidism except for the elevated level of plasma PTHrP with suppressed intact PTH level. Therefore, it is suggested that chronic and systemic effects of PTHrP on bone as well as calcium metabolism are indistinguishable from those of PTH in human.     

Oral Paricalcitol Reduces the Prevalence of Posttransplant Hyperparathyroidism: Results of an Open Label Randomized Trial

Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 μg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24‐h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1‐year posttransplant. Eighty‐seven patients completed the trial. One‐year posttransplant, 29% of paricalcitol‐treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 μg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.     

Serial changes in bone mineral density and bone turnover after correction of secondary hyperparathyroidism in a patient with pseudohypoparathyroidism type Ib.

Pseudohypoparathyroidism (PHP) is a disorder characterized by hypocalcemia and secondary hyperparathyroidism caused by primarily renal resistance to the effects of parathyroid hormone (PTH). However, as an indication of normal PTH responsiveness in bone, some patients with PHP develop skeletal disease because of longstanding secondary hyperparathyroidism. A patient is described with hypocalcemia, hyperphosphatemia, marked secondary hyperparathyroidism, and an increased alkaline phosphatase level. Subsequent evaluation revealed a diagnosis of PHP type Ib. The patient had radiographic evidence of skeletal disease caused by secondary hyperparathyroidism. A urinary level of N-telopeptide cross-links of type I collagen (NTX) was elevated markedly. Bone mineral density (BMD) was in the normal range at all measured sites, with BMD at the spine being higher than at the femur and distal radius. Treatment was initiated with calcium and calcitriol. Seven months later, calcium and PTH levels had normalized. The level of urinary NTX fell by 83%. Spinal BMD improved by 15%, and BMD at the femoral neck improved by 11%. Radial BMD was unchanged. This case emphasizes the importance of evaluating patients with PHP for hyperparathyroid bone disease and shows that correction of secondary hyperparathyroidism in patients with PHP can result in a significant suppression of previously accelerated bone turnover and to substantial gains in BMD at sites containing a major percentage of cancellous bone. The case also implies that assessment of bone turnover with urinary NTX and measurement of BMD with dual-energy X-ray absorptiometry (DEXA) may be useful in following the response of the skeleton to therapy in these patients and suggests the need for more studies of both NTX and BMD in patients with PHP.     

Minimally invasive radioguided parathyroidectomy

BACKGROUND: Minimally invasive radioguided parathyroidectomy (MIRP) combines technetium sestamibi scan, intraoperative gamma probe, methylene blue dye, and measurement of circulating parathyroid hormone (PTH) levels. STUDY DESIGN: All patients presented with biochemically proved primary hyperparathyroidism. A technetium sestamibi scan was performed preoperatively. Technetium sestamibi and methylene blue dye (7.5 mg/kg) were administered IV on the day of operation. Operative dissection was directed by the gamma probe. Blood samples for PTH assay were obtained before and after excision of an abnormal gland. When an appropriate decrease in the PTH assay was obtained, the exploration was concluded. Persistent PTH elevation instigated further neck exploration. RESULTS: Thirty-six consecutive patients were explored for untreated primary hyperparathyroidism and three for recurrent hyperparathyroidism. Hypercalcemia was corrected in all 39 patients. A single adenoma was found in 32 of 36 patients with untreated primary hyperparathyroidism, and a single abnormal gland was identified in all of those with recurrent hyperparathyroidism. Persistently elevated PTH prompted further exploration in two patients, identifying a second abnormal gland in one and hyperplasia in the other. Minor local complications occurred in 8% (3 of 39) of the patients. Forty-four percent (16 of 36) of the patients were discharged on the day of operation and 83% (30 of 36) within 23 hours after the initial neck exploration for primary hyperparathyroidism. Comparison of charges for MIRP with charges for "standard" neck exploration revealed lower costs with MIRP because of decreased duration of the operation, anesthesia, and hospital stay, and elimination of intraoperative histologic analysis. CONCLUSIONS: MIRP is a safe and effective procedure, resulting in the correction of hypercalcemia in all patients. The combination of intraoperative gamma probe and methylene blue dye allows rapid identification of the abnormal gland with minimal dissection through a small incision. PTH assay after excision provides biochemical confirmation that the abnormal gland has been removed. Most patients undergoing MIRP can be treated on an outpatient basis. Low postoperative complications, a small incision, and rapid return to normal activities resulted in very high patient acceptance of the procedure.     

Is serum parathormone assay necessary in evaluating primary hyperparathyroidism?

Serum parathormone (PTH) values are believed useful in diagnosing hyperparathyroidism and in evaluating patients before parathyroid operation. From 1975 through 1983, 328 adults patients with persistent hypercalcemia and normal renal function underwent cervical exploration for presumed primary hyperparathyroidism. Preoperative serum PTH values were obtained in 137 patients. Eight had negative explorations (5.8%): serum PTH values were normal in three patients and elevated in five. Serum PTH values were normal or low in 31 of the other 129 patients (false-negative rate = 24%). Of 191 patients for whom neither serum PTH nor nephrogenic cyclic adenosine-3',5'-monophosphate values did not were obtained preoperatively serum PTH values did not reduce the incidence of negative cervical explorations and, when obtained, they were misleading in one fourth of patients who benefitted from parathyroid exploration.     

Long-term effects of parathyroid operation on serum calcium and parathyroid hormone values in sporadic primary hyperparathyroidism.

BACKGROUND. This study investigates 410 persons (median age, 67 years) who underwent parathyroid operation for sporadic primary hyperparathyroidism 6 to 32 years (mean, 14.2 years) before 1991. METHODS. Patient records and operative specimens were scrutinized, the patients answered a questionnaire, and fasting serum samples were analyzed for calcium, albumin, creatinine, and intact parathyroid hormone (PTH) values. RESULTS. After primary parathyroid operations were performed with a conservative surgical approach, persistent and recurrent hypercalcemia were noticed in 3.7% and 1.7% of patients, respectively, whereas 4.7% of patients required vitamin D substitution or had essentially mild hypocalcemia. The PTH values were generally increased in patients with postoperative hyperparathyroidism, low in those with vitamin D substitution, and normal to elevated in the patients with hypocalcemia and in those with postoperative normocalcemia. The mean serum creatinine concentration was just below the upper reference range and correlated strongly with serum PTH value. No significant differences in serum PTH values were present between the normocalcemic patients and matched control patients after operation (n = 107), but the patients who underwent operation exhibited greater variation in the PTH concentration. CONCLUSIONS. The results substantiate the efficacy of parathyroid operation in sporadic primary hyperparathyroidism. Biochemical derangements compatible with secondary hyperparathyroidism may evolve during long-term follow-up and contribute to decreases in serum calcium values and increases in serum PTH values of these patients.     

Experienced radio-guided surgery teams can successfully perform minimally invasive radio-guided parathyroidectomy without intraoperative parathyroid hormone assays

Minimally invasive parathyroidectomy is an accepted treatment option for primary hyperparathyroidism. The need for intraoperative parathyroid hormone assays (iPTH) to confirm adenoma removal remains controversial. We studied minimally invasive radio-guided parathyroidectomy (MIRP) performed using preoperative sestamibi localization studies, intraoperative gamma detection probe, and the selective use of frozen section pathology without the use of iPTH. This is a single institution review of patients with primary hyperparathyroidism treated with MIRP by surgeons experienced in radio-guided surgery between October 1, 1998 and July 15, 2005. Information was obtained by reviewing computer medical records as well as contacting primary care physicians. Factors evaluated included laboratory values, pathology results, and evidence of recurrence. One hundred forty patients were included with a median preoperative calcium level of 11.3 mg/dL (range, 9.6-17) and a PTH level of 147 pg/mL (range, 19-5042). The median postoperative calcium level was 9.3 mg/dL. All patients were initially eucalcemic postoperatively except for one who had normal parathyroid levels. However, five (4%) patients required re-exploration for various reasons. Of the failures, one was secondary to the development of secondary hyperparathyroidism, and therefore would not have benefited from iPTH, one had thyroid tissue removed at the first operation, and three developed evidence of a second adenoma. One of these three patients had a drop in PTH level from 1558 pg/mL preoperatively to 64 pg/mL on postoperative Day 1, indicating that iPTH would not have prevented this failure. Thus, only three (2.1%) patients could have potentially benefited from the use of iPTH. MIRP was successful in 96 per cent of patients using a combination of preoperative sestamibi scans, intraoperative localization with a gamma probe, and the selective use of frozen pathology. This correlates with reported success rates of 95 per cent to 100 per cent using iPTH. We conclude that minimally invasive parathyroidectomy can be successfully performed without using iPTH assays.     

The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease

Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH < or = 250 pg/ml compared with placebo patients (20%; P = 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH > or =30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism.