Persistent HPT Research Articles

A PROSPECTIVE STUDY OF POST RENAL TRANSPLANT MINERAL BONE DISORDER: A SINGLE CENTER EXPERIENCE

To evaluate sequential changes in biochemical bone parameters, parathyroid hormone (iPTH), and vitamin D levels over a period of 24 weeks after renal transplantation, we studied 52 patients (41 males, with a mean age of 31.98.) who underwent their first renal transplantation without a past history of parathyroid surgery or fractures. Serum calcium, phosphorus, albumin, Serum iPTH and vitamin D levels were measured before transplant, then at 2, 4, 12 and 24 weeks post transplantation. Serum calcium showed a significant increase from 2 to 12 weeks after transplantation, followed by a slight decline until 24 weeks. At the end of 12 and 24 weeks, 6 (11.53%) and 2 (3.8%) patients had hypercalcemia respectively. At the end of 12 weeks only 15.38% (8) patients had hypocalcemia and no patient had hypocalcemia at the end of 24 weeks. Serum phosphorus showed significant decline in the first 4 weeks post transplantation. At the end of 24 weeks 21.2% still had hypophosphatemia. iPTH levels declined rapidly in the first 4 weeks of post transplant period and there after decline slowly till the end of 24 weeks. Baseline iPTH and vitamin D3 levels did not correlate with persistent HPT. Hypovitaminosis D was seen in 16 (30.7%), 8 (15.3 %) and 11 (21.1%) patients at pretransplant, 12, and 24 weeks post transplant respectively. Unlike most studies in literature our patient population experienced lower prevalence of post transplant hypercalcemia, Hypovitaminosis D, and hyperparathyroidism which may have resulted from younger study population and shorter dialysis vintage.

Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data

There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia. to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy. This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured. Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018). The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

Persistent and Recurrent Primary Hyperparathyroidism: Etiological Factors and Pre-Operative Evaluation.

Primary hyperparathyroidism (pHPT) is the most common cause of hypercalcemia and currently the only definitive treatment is surgery. Although the success rate of parathyroidectomy is over 95% in experienced centers, surgical failure is the most common complication today. Persistent HPT (perHPT) is defined as persistence of hypercalcemia after parathyroidectomy or recurrence of hypercalcemia within the first 6 months, and recurrence of hypercalcemia after a normocalcemic period of more than 6 months is defined as recurrent HPT (recHPT). In the literature, perHPT is reported to be 2-22%, and the rate of recHPT is 1-15%. perHPT is often associated with misdiagnosed pathology or inadequate resection of hyperfunctioning parathyroid tissue, recHPT is associated with newly developing pathology from potentially pathologically natural tissue left in situ at the initial surgery. In the pre-operative evaluation, the initial diagnosis of pHPT and the diagnosis of perHPT or rec HPT should be confirmed in patients who are evaluated with a pre-diagnosis (suspect) of perHPT and recHPT. Surgery is recommended if it meets any of the recommendations in surgical guidelines, as in patients with pHPT, and there are no surgical contraindications. The first preoperative localization studies, surgical notes, operation drawings, if any, intraoperative PTH results, pathological results, and post-operative biochemical results of these patients should be examined. Localization studies with preoperative imaging methods should be performed in all patients with perHPT and recHPT with a confirmed diagnosis and surgical indication. The first-stage imaging methods are ultrasonography and Tc99m sestamibi single photon tomography Tc99mMIBI SPECT or hybrid imaging method, which is combined with both single-photon emission computed tomography and computed tomography (SPECT/CT). The combination of USG and sestamibi scintigraphy increases the localization of the pathological gland. In the secondary stage, Four-Dimensional computer tomography (4D-CT) or dynamic 4-dimensional Magnetic Resonance Imaging (4D-MRI) can be applied. It is focused on as a secondary stage imaging method, especially when the lesion cannot be detected by conventional methods. Positron Emission Tomography (PET) and PET/CT examinations with 11C-choline or 18F-fluorocholine are promising imaging modalities. Invasive examinations can rarely be performed in patients in whom suspicious, incompatible or pathological lesion cannot be detected in noninvasive imaging methods. Bilateral jugular vein sampling, selective venous sampling, parathyroid arteriography, imaging-guided fine-needle aspiration biopsy, and parathormone washout are invasive methods.

Parathyroidectomy versus cinacalcet for tertiary hyperparathyroidism; a retrospective analysis

IntroductionTertiary hyperparathyroidism (tHPT), i.e., persistent HPT after kidney transplantation, affects 17–50% of transplant recipients. Treatment of tHPT is mandatory since persistently elevated PTH concentrations after KTx increase the risk of renal allograft dysfunction and osteoporosis. The introduction of cinacalcet in 2004 seemed to offer a medical treatment alternative to parathyroidectomy (PTx). However, the optimal management of tHPT remains unclear.MethodsA retrospective analysis was performed on patients receiving a kidney transplantation (KT) in two academic centers in the Netherlands. Thirty patients undergoing PTx within 3 years of transplantation and 64 patients treated with cinacalcet 1 year after transplantation for tHPT were included. Primary outcomes were serum calcium and PTH concentrations 1 year after KT and after PTx.ResultsSerum calcium normalized in both the cinacalcet and the PTx patients. PTH concentrations remained above the upper limit of normal (median 22.0 pmol/L) 1 year after KT, but returned to within the normal range in the PTx group (median 3.7 pmol/L). Side effects of cinacalcet were difficult to assess; minor complications occurred in three patients. Re-exploration due to persistent tHPT was performed in three (10%) patients.ConclusionIn patients with tHPT, cinacalcet normalizes serum calcium, but does not lead to a normalization of serum PTH concentrations. In contrast, PTx leads to a normalization of both serum calcium and PTH concentrations. These findings suggest that PTx is the treatment of choice for tHPT.

Total parathyroidectomy without autotransplantation in the surgical treatment of secondary hyperparathyroidism of chronic kidney disease.

Subtotal parathyroidectomy (SP) and total parathyroidectomy (TP) with autotransplantation (TPai) are the most commonly adopted operations for the treatment of secondary hyperparathyroidism (2HPT). TP without autotransplantation had previously been confined to patients with advanced dialytic vintage, not eligible for kidney transplantation. Over the years, the procedure has gained more widespread use, but there is no precise knowledge on the immediate and long-term effects. The authors analyzed the immediate and long-term results of TP without autotransplantation, that is after the systematic removal of at least four glands in 20 patients operated for 2HPT, which were compared with results from TPai in an equal number of cases. An improvement of the typical clinical symptoms was found in every patient undergoing surgery, and a significant reduction in intact PTH (iPTH) serum levels was achieved. Immediate normalization of iPTH level was observed in 11/20 TP cases, hypoparathyroidism in 4/20 and persistent HPT in 5/20 cases. One year of follow-up showed a slight increase in hypoparathyroidism, with 1/20 (5%) recurrence of the disease. One-year TPai results showed a similar percentage of euparathyroidism, as well as a higher longterm recurrence rate (4/20, 20%), although values do not reach statistical significance. TP may still be considered the operation of choice in patients with aggressive forms of 2HPT or of advanced dialytic vintage, with no access to renal transplantation, because of its low recurrence rate (5%). Post-operative aparathyroidism is rare, while hypoparathyroidism and hypocalcemia can be well controled by medical treatment.

Surgery for patients with primary hyperparathyroidism and negative sestamibi scintigraphy—a feasibility study

We report the surgical treatment of a consecutive series of scan negative patients with the intention of unilateral parathyroid exploration with the aid of intraoperative quick PTH (qPTH). The study included 35 consecutive sestamibi scan negative patients (27 women, eight men) with sporadic pHPT subjected to first time surgery. Median age was 70 years and median preoperative calcium level 2.8 mmol/L. Thirty-three patients had a histological diagnosis of a parathyroid adenoma (median weight 0.48 g [range 0.12 g-2.5 g]). Nineteen patients were explored bilaterally and 16 patients (46%) were operated unilaterally. The median operation time was 40 min in the unilateral group and 95 min in the bilateral group (p < 0.001). Three patients were treated for postoperative hypocalcemia after bilateral exploration versus none in the unilateral group (p = 0.23). With a minimum of 12 months of follow-up, 33 patients (94.3%) were cured. One case of recurrent HPT presented after bilateral exploration with visualization of four glands. One case of persistent HPT was observed after unilateral exploration. qPTH was predictive of operative failure in both patients. Forty-six percent of the patients in our study could be operated unilaterally with a total cure rate of 94%. Patients in the unilateral group had a significant shorter operation time and a lower incidence of postoperative hypocalcemia. In conclusion our investigation shows that limited parathyroid exploration can safely be performed on patients with negative sestamibi scintigraphy by the aid of qPTH.

Significance of Monitoring Bio-Intact PTH (1–84) During Parathyroidectomy for Secondary Hyperparathyroidism

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. 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. 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. 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.

Parathyroidectomy in secondary hyperparathyroidism: Is there an optimal operative management?

Subtotal parathyroidectomy (SPTX) and total PTX with autotransplantation (TPTX + AT) are both accepted operations for secondary hyperparathyroidism (2HPT). Studies have shown the 2 procedures to have similar rates of recurrent or persistent HPT (0% to 10%). The majority of these reports are small case series and despite apparently similar outcomes; the optimal operative management for 2HPT remains controversial. The purpose of this study was to determine whether there were any clinical outcome differences between these apparently comparable operations. A meta-analysis of 53 publications on reoperative operation for 2HPT from 1983 to 2004 identified 501 patients who had undergone an operation for recurrent or persistent 2HPT. The data evaluated included the type of initial operation, the need for reoperative operation as it related to the type of initial operation, and the intraoperative findings. The initial operation had been a SPTX in 36% and a TPTX + AT in 64% of patients. Reoperative operation was for persistent 2HPT in 82 of 485 (17%) and for recurrent 2HPT in 403 of 485 (83%) patients. Findings at reoperation included: autograft hyperplasia (49%), supernumerary glands (20%), remnant hyperplasia (17%), a missed in situ gland (7%), and a negative exploration (5%). Supernumerary glands, missed in situ glands, and negative explorations occurred at equal rates for both operations. Reoperation determined that inadequate cervical explorations occurred in 42% of patients who had undergone a SPTX and in 34% of patients who had undergone a TPTX + AT. Operative failures occur because of the limitations in preoperative localization, inadequate exploration, and the natural history of hyperplastic parathyroid tissue. The initial operation should include an attempt to localize supernumerary glands both pre- and intra-operatively.

Re-operation is frequently required when parathyroid glands remain after initial parathyroidectomy for advanced secondary hyperparathyroidism in uraemic patients.

Parathyroidectomy (PTx) is the most successful treatment for advanced secondary hyperparathyroidism (2HPT) not responsive to medical treatment. However, persistent HPT remains problematic after PTx if some glands remain. The clinical course in patients with persistent 2HPT was evaluated to clarify the risk for re-operation after PTx. Between March 1981 and December 2001, initial total PTx with forearm autograft were performed in 1156 uraemic patients. Persistent HPT cases were defined as those in which the lowest post-operative intact parathyroid hormone (i-PTH) concentration was >60 pg/ml, and patients were classified into groups A, B and C, with i-PTH concentrations of >or=500, 300-500 and 60-300 pg/ml, respectively. These patients were followed for 7-234 months after PTx. Persistent HPT was identified in 49/1156 patients (4.2%), with nine cases in group A, 10 in group B and 30 in group C. Re-operation was required in 21/49 (42.8%) cases, and in seven of these the last i-PTH concentration was >or=500 pg/ml. All cases in group A required re-operation. In group C, 11/30 (36.7%) patients required re-operation. The missed glands removed at re-operation were supernumerary in 14 cases, and located in the mediastinum in 13 cases. The frequency of advanced HPT and re-operation was not negligible. To prevent persistent 2HPT, all parathyroid glands must be found and resected during the initial operation. Even if small parathyroid glands remain, there is a risk of progression. Complete PTx is the first treatment choice for advanced 2HPT.

Cases with fewer than four parathyroid glands in patients with renal hyperparathyroidism at initial parathyroidectomy.

In the surgical treatment of secondary hyperparathyroidism (2HPT) due to uremia, it is considered necessary to remove all parathyroid glands from the neck to prevent persistent and recurrent parathyroid hyperfunction. However, in some cases fewer than four parathyroid glands can be recognized at initial operation; in the present study, we evaluated the long-term prognosis and estimated surgical strategy in such cases. Between March 1981 and January 1999, 822 patients underwent total parathyroidectomy (PTx) with forearm autograft for advanced 2HPT at the Department of Transplant Surgery of Nagoya Second Red Cross Hospital. In 21 cases (2.6%) fewer than four parathyroid glands were macroscopically found at the initial operation. These cases were followed up and their parathyroid function was evaluated by measurement of intact parathyroid hormone (PTH). In 20 of the 21 cases three glands were found, in 1 patient only two glands. In 5 of these cases the fourth gland was identified first after postoperative histopathologic evaluation. In all these cases the intact PTH level was normalized. In 8 of the remaining 16 cases high PTH levels persisted after the initial operation, including 3 patients who underwent neck reexploration. However, in the other 7 patients PTH levels dropped within normal range immediately after PTx and a fourth gland has never been recognized. One patient was lost to follow-up. Thus, using our operative strategy, 12 of 822 cases (0.85%) did not develop persistent or recurrent HPT even though only three glands were identified at the operation. To avoid postoperative hypoparathyroidism, autotransplantation should be performed when fewer than four parathyroid glands are found at the initial operation.

Minimally invasive video-assisted parathyroidectomy: multiinstitutional study.

Unilateral and minimally invasive parathyroidectomies with endoscopic and video-assisted technique have been introduced. Most of these procedures utilize preoperative localization and intraoperative monitoring of parathyroid hormone. There are only a few reports on these procedures. The objective of this study was to evaluate video-assisted parathyroidectomy (MIVAP) for surgery in patients with primary hyperparathyroidism (pHPT). From February 1997 to June 1999 a series of 123 consecutive patients with pHPT at four surgical centers were evaluated. The patients' ages ranged from 18 to 77 years (median 50 years). Preoperatively, sestamibi scintigraphy and ultrasonography for localization were performed for all patients. Selection criteria for a MIVAP procedure excluded patients with negative localization, suspicion of multiglandular disease (MGD) or thyroid malignancy, a large thyroid mass, and prior surgery or irradiation to the neck. MIVAP was performed with a 1.5 cm suprasternal incision; the operation was then done through this incision with a 30 degree 5 mm endoscope and microsurgical instruments with brief CO2 insufflation for adenoma identification. We then proceeded with an open technique through the small incision under video-assistance. Intraoperative monitoring of intact parathyroid hormone (iPTH) assays was used in all patients. Among the 123 patients in whom MIVAP was attempted, the procedure was accomplished in 109 (89%). Conversion to conventional cervicotomy was required in 14 (11%) patients because of failed localization, failure of the iPTH level to fall appropriately, or technical problems. There was no persistent or recurrent HPT during the 3 to 12-month follow-up. Oral calcium replacement for symptomatic hypocalcemia postoperatively was given in 7 (6%) cases. A unilateral transient laryngeal nerve palsy, resolving within 6 months postoperatively, occurred in two (2%) patients. The median hospital stay was 1.5 days (range 0.5-5.0 days). This study showed the feasibility of MIVAP as an alternative surgical treatment for pHPT in a selected group of patients. Further studies are necessary to evaluate the efficacy and rationale of MIVAP compared to other techniques for parathyroidectomy in pHPT patients.

Surgical significance of supernumerary parathyroid glands in renal hyperparathyroidism.

In secondary hyperparathyroidism (2HPT) fundamentally all parathyroid glands, including supernumerary glands, become hyperplastic, and stimulation of parathyroid glands continues after parathyroidectomy (PTx). Therefore supernumerary glands have special significance during surgery for 2HPT, whether persistent or recurrent HPT. In the present study 570 patients underwent initial total PTx with a forearm autograft. The frequency, type, location, histopathology, and clinical significance of the supernumerary glands were evaluated. At the initial operation 90 supernumerary glands were removed from 82 to 570 patients (14.4%); 12 patients (2.1%) required extirpation of supernumerary glands for persistent/recurrent HPT. Altogether 104 supernumerary glands were identified at operation in 94 of the 570 patients (16.5%). Among these 104 glands, 25 (24.0%) were of the rudimentary, or split, type and 79 (76.0%) of the proper type. Supernumerary glands were most frequently identified in the thymic tongue (53/104, 51.0%); 32 (60.4%) of these 53 glands were identified only microscopically. In 6 of the 570 cases (1.1%), reoperation was required for persistent HPT due to supernumerary glands located in the mediastinum, and 6 patients underwent neck reexploration for recurrence. Histopathologically, 61 of 104 (58.7%) supernumerary glands, including 36 glands recognized only microscopically, showed diffuse hyperplasia, and 43 (41.3%) displayed nodular hyperplasia. Residual small supernumerary glands with diffuse hyperplasia have the potential to be transformed to nodular hyperplasia during long-term hemodialysis. Therefore all parathyroid glands including supernumerary glands should, if possible, be removed at the initial operation. Routine removal of the thymic tongue and careful examination of the regions surrounding the lower poles of the thyroid, especially on the left side, are important steps in the surgical treatment.

Results of reoperations for persistent or recurrent secondary hyperparathyroidism in hemodialysis patients

Among 258 patients operated on for secondary hyperparathyroidism (HPT II) from 1971 to 1988, a total of 33 had one or more reoperations for persistent or recurrent HPT II. These reoperations did not induce any mortality or significant morbidity. After inadequate parathyroidectomy (25 cases), 15 patients were reoperated. Twelve of these had undergone initial surgery at another institution. Three patients died of causes unrelated to their HPT II. The other 12 patients are disease-free. After successful subtotal parathyroidectomy (79 cases), 2 patients (2.5%) had a recurrence 5 and 6 years later, respectively. Currently, the 2 patients remain disease-free. After total parathyroidectomy with autotransplantation (152 cases), 16 patients (10.5%) had reoperations on the grafts. The mean time before reoperation was 2 1/2 years. Hypertrophy of grafted fragments was observed in 4 cases (2.6%), but only 2 of these 4 patients were cured by removal of the grafts. Residual parathyroid tissue or a supernumerary gland in the neck or the mediastinum was suspected in 5 patients, but this could not be confirmed because one had already been reoperated on in the neck without success, another still refuses reoperation, and 3 died. In 6 other patients, the recurrence was debatable and HPT II was not confirmed. In the last 3 patients, the diagnosis was incorrect and aluminum intoxication was proved later. Results of reoperations for persistent or recurrent HPT II depend, first, on a correct diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)