Operative treatment of tertiary hyperparathyroidism: a single-center experience.

OBJECTIVE: To review the experience with the operative treatment of tertiary hyperparathyroidism (TH) from a single renal transplant center. SUMMARY BACKGROUND DATA: Most patients with chronic renal failure show evidence of secondary hyperparathyroidism by the time maintenance hemodialysis begins. Persistent secondary hyperparathyroidism (i.e., TH) requiring surgical intervention is uncommon in the authors' experience. METHODS: Charts of patients who underwent parathyroidectomy for TH were reviewed retrospectively. Information obtained included demographics, laboratory data, symptoms, operative procedure (including morbidity and mortality rates), and pathology. Comparisons of demographic data and allograft survival were made between the transplant population as a whole and a matched cohort group of patients. RESULTS: Thirty-eight patients from 4344 renal transplant procedures during a 29-year period required parathyroidectomy for TH. All patients had hypercalcemia; 20 were asymptomatic and 18 had varying symptoms. Mean time from renal transplantation to parathyroidectomy was 997 +/- 184 days, with a mean preoperative calcium level of 12.2 +/- 0.14 mg/dl. Total parathyroidectomy with parathyroid autograft was performed in 26 of 34 primary procedures. There were no deaths. The operative morbidity rate was 6% (wound separation and vocal cord hemiparesis, one each). Pathology was reported in all patients and recently reviewed in 28 patients. Twenty-four had diffuse hyperplasia and nine had nodular hyperplasia; one had an adenoma. Parathyroid glands diagnosed as nodular hyperplasia were significantly larger by total mass than those with diffuse hyperplasia. Comparison of allograft survival between the study group and a matched cohort group of patients revealed no difference in long-term graft survival. CONCLUSIONS: Operative intervention is recommended in patients with an asymptomatic increase in serum calcium to >12.0 mg/dl persisting for >1 year after the transplant, acute hypercalcemia (calcium >12.5 mg/dl) in the immediate posttransplant period, and symptomatic hypercalcemia.     

Management of hypercalcemic hyperparathyroidism after renal transplantation

To determine the optimal management of posttransplant hypercalcemia, a chart analysis of 100 stable renal allograft recipients (longer than one year) was accomplished. The incidence of hypercalcemia ranged from 12% to 20% up to 30 months after transplantation. The mean serum alkaline phosphatase level, phosphate level, and duration of dialysis in hypercalcemic patients did not differ significantly from normocalcemic patients; however, serum creatinine levels were significantly lower at 12 and 24 months in patients with hypercalcemia. In patients with hypercalcemia at three and six months, greater than 50% underwent spontaneous resolution, whereas this occurred in 25% of the patients with hypercalcemia at 12 months. Seven patients underwent parathyroidectomy with prompt resolution of their hypercalcemia and ten patients with persistent hypercalcemia have been followed up from 14 to 66 months without sequelae of hyperparathyroidism. In conclusion, hypercalcemic hyperparathyroidism is a frequent occurrence after renal transplantation. Sequelae of this condition are rare, however, and parathyroidectomy should be reserved for progressive clinical and/or roentgenographic findings.     

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.     

Treatment of severe hypercalcemia due to refractory hyperparathyroidism in renal transplant patients with the calcimimetic agent cinacalcet

Calcimimetic agents increase the sensitivity of calcium sensing receptors of parathyroid glands and suppress both serum calcium levels and parathyroid hormone. There are still limited data on the treatment of renal transplant patients with severe hypercalcemia and hyperparathyroidism with calcimimetics (cinacalcet). We describe two such renal transplant patients with chronic kidney disease Stage 3 who presented with persistent hypercalcemia (serum calcium 11.5-12 mg/dl) and refractory hyperparathyroidism (iPTH 194-547 pg/ml). Control of hypercalcemia with cinacalcet (serum calcium <10 mg/dl) resulted also in an improvement of hyperparathyroidism, but with a slower rate than that of the lowering of serum calcium. Addition of a vitamin D analog together with the calcimimetic agent resulted in faster control of the resistant hyperparathyroidism in both patients (iPTH <145 pg/ml) with clinical improvement and without any side effect. It seems that this new agent will improve our clinical approach of renal bone disease permitting a more integrated and successful treatment of hyperparathyroidism and its consequences on patients with chronic kidney disease.     

Parathyroidectomy after successful kidney transplantation: a single centre study.

BACKGROUND: Successful kidney transplantation is believed to cure secondary hyperparathyroidism, but persistent disease has emerged in a significant number of allograft recipients. A parathyroidectomy is ultimately required in some of these patients. To gain insight into the incidence, risk factors and consequences of parathyroidectomy in patients with a functioning renal graft, we performed a retrospective case-controlled study. METHODS: Charts of 1743 recipients of a kidney allograft, transplanted between 1989 and 2004, were reviewed. Patients with a functioning graft subjected to parathyroidectomy were identified. Their charts were checked for various demographic, clinical and biochemical variables. The data were compared with those obtained from patients transplanted in the same period, but not subjected to parathyroidectomy (controls). RESULTS: Persistent hyperparathyroidism in patients with a functioning graft requiring parathyroidectomy developed in 90 patients, corresponding to an overall parathyroidectomy rate of 8.89 per 1000 person-years at risk. Female gender (OR 1.79, P < 0.05) and higher pre-transplant serum concentrations of PTH (OR per 1 ng/l increase, 1.003, P < 0.0001) and calcium (OR per 1 mg/dl increase, 2.58, P < 0.0001) were identified as independent predictors of post-transplant parathyroidectomy. A significant increase of the serum creatinine was observed after parathyroidectomy (1.91 +/- 0.72 vs 1.76 +/- 0.63 mg/dl, P < 0.01). Graft survival, however, was similar in cases and controls. CONCLUSION: Persistent hyperparathyroidism requiring parathyroidectomy after successful renal transplantation is a common clinical problem. Female patients with a high pre-transplant serum level of PTH and calcium are especially at risk. Although graft function deteriorates shortly after parathyroidectomy, graft survival, overall, is not different from controls.     

Clinical manifestations of hypercalcemia and hypophosphatemia after kidney transplantation

Introduction

Abnormalities of calcium and phosphorus metabolism in end-stage renal disease patients can persist after transplantation. We investigated their natural courses after transplantation, their risk factors for posttransplantation hypercalcemia and hypophosphatemia, and their impacts on allograft outcomes.

Methods

We retrospectively analyzed a total of 490 adult patients who underwent kidney transplantations between 2000 and 2009.

Results

The serum calcium continued to increase, and reaching a plateau at around 3 months after transplantation. Thereafter it decreased, reaching a stable level by 2 years. Forty-four patients (9.0%) displayed hypercalcemia within 1 year; it persisted longer than that in 23 subjects (4.7%). Both longer dialysis duration (odds ratio [OR] 1.423; 95% confidence interval [CI], 1.192-1.699) and high intact serum parathyroid hormone (iPTH) level before transplantation (OR 1.002; 95% CI, 1.000-1.003) increased the risk for posttransplantation hypercalcemia. After a significant decrease during the first week, the serum phosphorus level increased, becoming stable between 1 and 6 months after transplantation. Hypophsphatemia occurred in 379 patients (77.3%) with 336 patients displaying hypophosphatemia without hypercalcemia. However, neither hypercalcemia nor hypophosphatemia influenced graft outcomes. Eight patients underwent pretransplantation parathyroidectomy, whereas 4 patients underwent posttransplantation parathyroidectomy. Neither group of patients experienced posttransplantation hypercalcemia.

Conclusions

Both hypercalcemia and hypophosphatemia are common after renal transplantation, especially among patients with a long history of dialysis before transplantation. Strict control of hyperparathyroidism including parathyroidectomy before transplantation may be the appropriate approach to these abnormalities.     

A case report: primary hyperparathyroidism--comparison before and after parathyroidectomy by oral calcium tolerance test

To evaluate the cause of hypercalciuria, we carried out the oral calcium tolerance test before and after parathyroidectomy in a patient with primary hyperparathyroidism who had recurrent and multiple nephrolithiasis. Preoperative laboratory examination showed hypercalcemia, hypophosphetamia, hypercalciuria, decrease in % tubular reabsorption of phosphorus and strikingly elevated urinary cyclic AMP excretion. The oral calcium tolerance test indicated a significantly greater increase in serum calcium (delta serum calcium: 1.4 mg/dl vs 0.8 mg/dl) and a significantly greater suppression of urinary cyclic AMP excretion (delta U-cyclic AMP:-3.56 moles/gCre vs-1.17 moles/gCre) before parathyroidectomy than after. These results showed that hypercalciuria in this case was induced not only by the significant increase in the filtrated load of calcium but by the reduction in the resorption of calcium in the distal tubule caused by the significantly suppressed parathyroid hormone effect.     

A case of post-transplant hyperparathyroidism treated with ethanol injection

A 15-year-old boy with chronic renal failure secondary to Alport’s syndrome underwent living-related renal transplantation from his 48-year-old father. His primary immunosuppressive regimen was composed of tacrolimus, mizolibine, and methylprednisolone. The postoperative course was satisfactory with one episode of mild acute rejection, treated successfully with methylprednisolone pulse therapy. Two months later, hypercalcemia (11.8–13.2 mg/dl) and hypophosphatemia (2.5–3.0 mg/dl) were noted without any bone symptoms. The serum intact-parathyroid hormone (PTH) and serum alkaline phosphatase levels were 240 pg/ml and 2483 IU/l, respectively. Ultrasound studies revealed enlargement of the two parathyroid glands. Under the diagnosis of ter-tiary hyperparathyroidism, he underwent percutaneous ethanol injection (PEIT) into the left parathyroid gland. Although levels of serum calcium and phosphorus returned to normal ranges and the intact PTH level decreased to 95 pg/ml with the three injections, another injection was needed to normalize recurrent hypercalcemia 2 months later. The patient experienced only transient mild dysphonia and local pain after PEIT. Although PEIT is believed less effective than parathyroidectomy, it has some advantages such as applicability to high-risk patients, repeatability of treatment, low incidence and severity of side effects. Received: 26 June 2001 / Revised: 21 November 2001 / Accepted: 24 November 2001     

Cinacalcet improves bone density in post-kidney transplant hyperparathyroidism

The recent availability of cinacalcet has provided a possible alternative to parathyroidectomy in kidney transplant patients with persistent hyperparathyroidism, but its effect on bone mass density (BMD) is unknown. From our database containing 163 kidney transplants performed at our center from 1999 to 2007, we compared recipients who received cinacalcet for persistent hypercalcemia and hyperparathyroidism following renal transplantation (n = 8) with up to two other posttransplant patients matched for age, sex, race, and graft function (n = 15). The outcome of the study was BMD changes from baseline to 12, 24, and 36 months post-renal transplantation. Repeated-measures mixed model was used to assess the difference of BMD change between two groups. Cinacalcet therapy was started at a median of 9 (range = 1 to 24) months posttransplant with a mean dose 56 ± 29 mg/d (mean duration = 1.6; range = 1 to 2.1 years). Cinacalcet therapy was associated with significant reduction of serum calcium compared to control. Cinacalcet therapy was associated with greater BMD increase at the hip over the 36-month posttransplant period. Cinacalcet was well tolerated. Our results suggest that cinacalcet may have a small but favorable effect on bone density following kidney transplantation.     

Cinacalcet for the treatment of hypercalcemia in renal transplanted patients with secondary hyperparathyroidism

Persistent hyperparathyroidism is the most frequent cause of hypercalcemia after renal transplantation, namely, hypercalcemia is observed in about 10% of patients at 1 year. This prospective study evaluated the effect of cinacalcet, a second-generation calcimimetic, on serum calcium and parathyroid hormone (PTH) blood levels among recipients with hypercalcemia due to persistent hyperparathyroidism. Thirteen renal transplanted patients (10 women and 3 men) were included based upon: a total serum calcium >10.5 mg/dL; intact PTH (iPTH) blood levels >65 pg/mL; graft function >6 months, and stable maintenance immunosuppressive therapy. After inclusion, patients initially received 30 mg of cinacalcet once daily. The mean time of initiation was 64 +/- 7 months after transplantation. The follow-up was 6 months. The median dose of cinacalcet was 30 mg/d (5 patients received 60 mg/d). During the study period, renal function remained stable. Serum calcium levels decreased significantly from 11.7 +/- 0.39 to 10.35 +/- 0.8 mg/dL (P < .001). Serum phosphate levels increased from 2.82 +/- 0.34 mg/dL to 3.2 +/- 0.41 mg/dL (P < .05). The mean iPTH levels significantly decreased from 308 +/- 120 to 210 +/- 80 pg/mL (P < .05). There were no significant change in 25-hydroxyvitamin D3 blood levels (from 17.7 +/- 9 to 17.4 +/- 6 ng/mL), but the 1,25-dihydroxyvitamin D3 blood levels decreased from 53.8 +/- 18.2 to 32.6 +/- 9.2 pg/mL (P < .01). There were no significant changes in blood levels of alkaline phosphatase, magnesium, bicarbonate, calciuria, phosphaturia, and immunosuppressive drugs. Cinacalcet was well tolerated in all patients except one who had gastrointestinal discomfort. In summary, cinacalcet corrected hypercalcemia and improved phosphatemia in patients with persistent hyperparathyroidism after transplantation with no negative effects on renal function.     

Effect of Cinacalcet in Kidney Transplant Patients With Hyperparathyroidism

ObjectiveIn dialysis patients, cinacalcet could be an effective alternative to parathyroidectomy for treating hyperparathyroidism. In the present study, we aimed to determine the characteristics of subjects with persistent hyperparathyroidism who require parathyroidectomy despite the use of cinacalcet.MethodsNine kidney transplant patients (7 men, 2 women; mean age 53.2 [SD, 8.9] years) who had tertiary hyperparathyroidism were reviewed in a single center. Pre- and postcinacalcet levels of calcium, phosphorous, intact parathyroid hormone (iPTH), and renal function were analyzed to evaluate the effect of cinacalcet treatment in these patients. The baseline parameters before cinacalcet treatment were compared in patients who did and did not undergo parathyroidectomy.ResultsCinacalcet reduced serum calcium levels in all patients (11.48 [SD, 0.73] mg/dL to 10.20 [0.70] mg/dL; P = .008). Serum phosphorous levels significantly increased from 2.28 (SD, 0.77) mg/dL to 3.02 (SD, 0.65) mg/dL (P = .03). The iPTH levels in 7 patients decreased, while the mean level remained unchanged in total subjects. The iPTH levels increased even with cinacalcet treatment in 2 patients. In 3 patients, serum calcium levels abruptly increased after cinacalcet withdrawal. Five patients who showed persistent hypercalcemia due to hyperparathyroidism underwent parathyroidectomy. These 5 patients had significantly different characteristics compared with 4 patients who did not undergo parathyroidectomy: hypercalcemia (11.92 [SD, 0.68] mg/dL vs 10.93 [SD, 0.26] mg/dL; P = .02), hypophosphatemia (1.74 [SD, 0.36] mg/dL vs 2.95 [SD, 0.58] mg/dL; P = .03), and hyperparathyroidism (252.2 [SD, 131.4] pg/dL vs 101.5 [SD, 18.4] pg/dL; P = .02).ConclusionCinacalcet reduced hypercalcemia due to hyperparathyroidism in the transplant patients. However, patients who had pre-existing higher iPTH, hypercalcemia, and hypophosphatemia needed parathyroidectomy. Therefore, cinacalcet could be considered an alternative to parathyroidectomy in selected patients.     

The Outcome of Cervical Exploration for Asymptomatic and Symptomatic Patients with Primary Hyperparathyroidism

This study examined the success and safety of cervical exploration in patients with primary hyperparathyroidism (HPT). The presentation, pathologic findings, and outcome of patients with asymptomatic primary HPT were compared with those with symptomatic disease. Records of patients undergoing cervical exploration for primary HPT from January 1993 until December 31, 2003, were reviewed. Information collected consisted of preoperative symptoms, calcium and parathormone (PTH) levels, imaging studies, operative findings, pathology, and outcome of the patients. The groups with asymptomatic and symptomatic primary HPT were compared. In all, 139 patients were studied; 31 (22.3%) were asymptomatic (group I), and 108 (77.7%) had symptoms (group II). The two groups were also comparable regarding mean age, sex, and the yield of the imaging studies. The mean preoperative serum calcium level was comparable in the two groups (11.1mg/dl versus 11.3 mg/dl). However, PTH levels were significantly lower in group I than in group II (142 pg/dl versus 283 pg/dl, P = 0.01). The weight of the adenoma was also significantly less in group I than in group II (1082 mg versus 1679 mg P = 0.079). The outcome of the surgical exploration was comparable in the two groups with an immediate success rate close to 98% and a long-term success rate of 95.4%. Cervical exploration and parathyroidectomy in patients with primary HPT is a safe procedure with a high success rate and favorable outcome.     

Parathyroidectomy: new criteria for evaluating outcome

Following successful parathyroidectomy, subjective improvement in recognized symptoms and in the overall "well being" of asymptomatic primary hyperparathyroid patients has been well documented. Because quantitative methods for measuring parathyroid hormone (PTH) and normal reference ranges of serum calcium have changed in recent years, a revised biochemical criteria for evaluating postoperative outcome has become necessary. Two hundred seventy-one selected patients were followed for an average of 6.3 years after parathyroidectomy. Although 257 patients had serum calcium levels <10.6 mg/dL during the entire follow-up period, 15 per cent of them had elevated intact PTH (iPTH) levels. Fourteen patients had calcium levels > or =10.6 mg/dL at some point during follow-up, with nine patients (64%) showing high iPTH levels and eight (57%) of them developing recurrent hyperparathyroidism (calcium > or =11 mg/dL and iPTH > or =68 pg/mL). Of the 14 remaining patients, 5 had hypercalcemia with normal iPTH levels. In patients with successfully treated primary hyperparathyroidism, the recommended annual follow-up is: 1) monitor total serum calcium only if serum calcium level is <10.6 mg/dL, or if serum calcium level is > or =10.6 mg/dL; and 2) monitor serum calcium and PTH levels, because these patients have an increased incidence of hyperfunctioning parathyroid glands, which may point to late recurrence.     

Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation

Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 ± 74 mo vs 57 ± 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)², and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.     

Treatment With Cinacalcet of Secondary Hyperparathyroidism After Renal Transplantation

Background

The treatment of posttransplant secondary hyperparathyroidism (SHP) with vitamin D analogues is determined by their effectiveness to reverse hypercalcemia. Calcimimetics inhibit parathyroid hormone (PTH) secretion by modulating the calcium-sensing receptor in the parathyroid gland. Cinacalcet, a calcimimetic drug, has proven its effectiveness for the treatment of SHP among patients in phase V of chronic renal disease.

Patients and Methods

This retrospective analysis included 48 patients with SHP who were treated with cinacalcet. The initial dose of 30 mg/d could be increased to 180 mg, administering calcitriol also, depending on the serum calcium and PTH levels. The objectives were a PTH level between 75 and 125 pg/mL or a decrease >40%, and a serum calcium level below 10.5 mg/dL.

Results

The average PTH at baseline was 244 pg/mL, decreasing to 131 pg/mL at 1 year (P < .01). The average calcium at baseline was 10.1 mg/dL descending to 9.2 mg/dL at 1 year (P < .01). Among patients with hypercalcemia, the calcium decreased from 11 to 9.6 mg/dL at 1 year (P < .01). Seventy percent of patients without hypercalcemia reached the desired value of PTH, and 100% of those with hypercalcemia. Among patients with hypercalcemia, the desired calcium level was reached in 91% of cases. Ten patients developed hypocalcemia. In 3 cases we stopped the treatment with cinacalcet due to digestive intolerance.

Conclusions

Treatment with cinacalcet controlled hyperparathyroidism and hypercalcemia among patients with posttransplant SHP. It was a safe drug, with a low incidence of side effects.     

Rapid onset intratubular calcification following renal transplantation requiring urgent parathyroidectomy

BACKGROUND: Secondary hyperparathyroidism is a common complication of end-stage renal disease often requiring parathyroidectomy. Renal transplant with the restoration of normal renal function often allows resolution of hyperparathyroidism, avoiding the need for parathyroid surgery. However, a proportion of patients with hyperparathyroidism become overtly hypercalcemic after renal transplantation which poses management dilemmas between medical and surgical treatment. CASE: We present the case of a 48-yearold man with end-stage renal failure known to have secondary hyperparathyroidism who received a living related renal transplant. Postoperatively he developed prompt hypercalcemia, polyuria, polydipsia and rapid onset intratubular calcification, leading to acute tubular necrosis diagnosed on renal biopsy on Day 7 post transplantation. He underwent surgical parathyroidectomy with resolution of his hypercalcemia and improved renal transplant function. DISCUSSION: This case emphasizes the need for good management of secondary hyperparathyroidism together with close surveillance of PTH in patients awaiting renal transplantation. With good renal transplant function hyperparathyroidism usually resolves. Posttransplant surgical parathyroidectomy should be reserved for severe progressive end organ damage.     

Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia

The metabolic manifestations and operative findings in 10 patients with a diagnosis of parathyroid carcinoma were analyzed to determine whether they differ from those in patients with parathyroid adenomas and similar degrees of hypercalcemia. Two groups of patients with parathyroid adenomas were used for comparison. Group A consisted of eight patients with "atypical" benign adenomas (mean preoperative level of serum calcium: 13.4 mg/dl); group B consisted of 13 patients with benign typical adenomas--all with preoperative serum calcium levels greater than or equal to 13.0 mg/dl (mean: 14.2 mg/dl). The patients with carcinoma (mean preoperative level of serum calcium: 15.3 mg/dl) had a frequency of osteoporosis and osteitis fibrosa cystica (50%) comparable with that of group A (33%) and group B (62%). Seventy percent of the patients with carcinoma had renal disease (nephrolithiasis, nephrocalcinosis, or impaired renal function), whereas only 38% of group A and 15% of group B had similar disorders. The patients with carcinomas had the highest frequency of combined bone and renal disease (50% versus 14% in group A and 15% in group B). Anemia, peptic ulcer disease, and hypertension occurred with similar frequencies in the three groups. Three patients with recurrent parathyroid carcinoma died of profound hypercalcemia, renal failure, or cardiac arrhythmia. In general, although patients with parathyroid carcinomas have more profound metabolic abnormalities than do patients with primary hyperparathyroidism, the metabolic manifestations in patients with parathyroid carcinoma are comparable with those in patients with parathyroid adenomas and profound hypercalcemia. Furthermore atypical adenomas share many anatomic and histopathologic features with parathyroid carcinomas, and distinguishing between the two is sometimes possible only in cases of tumor recurrence.     

Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy

AIMS: The reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications. CASE HISTORY: A patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a "brown tumor". The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%). CONCLUSION: In this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.     

Hypercalcemia-induced upper gastrointestinal bleeding after renal transplantation

Hypercalcemia is common in patients after renal transplantation and may stimulate gastrin hypersecretion with associated peptic disease. We report on 2 patients with hypercalcemia and life-threatening gastrointestinal hemorrhage controlled by subtotal parathyroidectomy. Retrospective review of our last 10 patients with gastrointestinal hemorrhage revealed that all of those with normal renal function had elevated serum calcium levels. Because of the increased mortality associated with gastrointestinal hemorrhage in renal transplant patients (43%), patients prone to development of hypercalcemia may benefit from early subtotal parathyroidectomy.     

Secondary hyperparathyroidism. The role of surgery

A retrospective analysis was undertaken to better define the clinical presentation and therapy of patients with secondary hyperparathyroidism and the timing of surgical removal of the parathyroid glands in secondary hyperparathyroidism. Sixty-eight patients with end-stage renal disease (ESRD) underwent 74 parathyroid procedures over a 10-year period. There were 38 per cent women and 62 per cent men in this population--the same proportion of men and women with ESRD. These proportions are reversed when compared with patients with primary hyperparathyroidism. The mean time between initiation of dialytic therapy and parathyroidectomy was 5.4 years. Preoperative mean serum calcium and phosphorus levels were 10.1 +/- 0.2 and 6.1 +/- 0.2 mg/dl, respectively. All patients were symptomatic and 60 per cent of the patients had at least two symptoms before surgery. Renal osteodystrophy was the most common symptom (74%), whereas pruritus was noted in 65 per cent of this population. Patients underwent either subtotal (88%) or total (12%) parathyroidectomy with autotransplantation. Six patients required reoperation: five for recurrent disease (2 to 5 years after the initial surgery) and one for persistent disease. All patients were symptomatically improved after the surgery. Complications included the following: transient hoarseness (7%), hypocalcemia requiring calcium, and/or vitamin D therapy (32%) for 6 months after surgery. This analysis demonstrates that although the initial therapy of secondary hyperparathyroidism is medical, surgical therapy should be instituted before multiple symptoms develop in the ESRD population.