High serum levels of a non-(1–84) parathyroid hormone (PTH) fragment in pediatric haemodialysis patients

The measurement of serum intact parathyroid hormone (PTH) is routinely made in haemodialysed (HD) patients to diagnose and monitor secondary hyperparathyroidism. We measured pre- and post-dialysis serum ionized calcium (Ca²⁺) and PTH in 12 HD children (7 boys) aged 13.8±3.6 years. A group of 27 normal short-statured children served as controls. Serum PTH was assessed by a new assay (CAP) recognizing only the (1–84) molecule and an older one (Allegro) recognizing both the 1–84 and a non-(1–84) PTH equally. The concentrations obtained with the CAP assay were lower than those obtained with the Allegro assay both in controls and in HD patients. They were still lower in HD patients when expressed as multiples of the median of the control group. The Allegro/CAP ratio, was highly variable from one subject to another and was lower (P<0.0001) in controls (1.46±0.26) than in HD patients, both before (3.06±1.60) and after dialysis (2.94±0.65). During dialysis, Ca²⁺ increased significantly (P<0.0001) and PTH decreased significantly (P<0.0001) with both the CAP and the Allegro assays, but was more often normal or low with the CAP than with the Allegro assay. Although the two assays correlate well, they may provide different clinical information in some HD children which could lead to different therapeutic decisions. Received: 13 March 2001 / Revised: 12 July 2001 / Accepted: 12 July 2001     

Intraoperative parathyroid hormone levels measured by intact and whole parathyroid hormone assays in patients with Graves’ disease

Purpose To find out if the whole parathyroid hormone (wPTH) assay has practical advantages over the intact (iPTH) assay in patients with Graves’ disease. Methods We measured iPTH and wPTH levels before and after subtotal thyroidectomy in 111 consecutive patients (94 women and 17 men) with Graves’ disease. Blood samples for assays were obtained after the induction of anesthesia (basal) and following skin closure (postoperative). Results There was a significant correlation between wPTH and iPTH in both the basal and postoperative levels. Logistic regression analyses examining the relationship between the reduction in parathyroid hormone (PTH) levels and the incidence of tetany revealed that both the wPTH and iPTH assays were significantly equally predictive of postoperative tetany. Conclusion We found that both the wPTH and iPTH assays were useful for predicting postoperative tetany in patients with Graves’ disease, yielding similar results.     

Can the use of intraoperative intact parathyroid hormone monitoring be abandoned in patients with hyperparathyroidism?

Background

Ultrasound (US) and technetium-99m sestamibi scintigraphy (MIBI) are used to determine the localization of abnormal glands in cases of primary hyperparathyroidism (PHPT). Intraoperative intact parathyroid hormone (iPTH) monitoring is a reliable examination used to cure PHPT. The aim was to assess the necessity of intraoperative iPTH monitoring.

Methods

Sixty patients were examined using preoperative MIBI and US. iPTH was measured at 3 time points: (1) at the start of surgery; (2) 10 minutes after gland resection; and (3) more than 60 minutes after surgery. We defined a decreased iPTH level as an iPTH measured 10 minutes after resection that was less than 50% of the preoperative level.

Results

The iPTH of 55 patients with concordant lesions decreased to within the normal range more than 60 minutes after surgery.

Conclusions

It is not necessary to monitor intraoperative iPTH when single concordant lesions are preoperatively identified on both MIBI and US.     

The response of 0steoblasts to parathyroid hormone (PTH 1–34) in vitro

Morphological study of osteoblasts of the endocranial aspect of the rat calvarium showed that they responded to the 1–34 fragment of parathyroid hormone in exactly the same way as to parathyroid extract : thus, the osteoblasts become elongated and aligned parallel to one another and to the collagen in the most superficial layer of the bone matrix. Fluctuations in PTH levels may conceivably relate to the lamellar texture of mature bone.     

Significance of Bio-intact PTH(1–84) assay in hemodialysis patients

The aim of the present study was to examine whether the newly developed bio-intact parathyroid hormone (Bio-PTH) assay, which exclusively measures the intact PTH(1–84) molecule, provides a better assay for estimating parathyroid function in hemodialysis (HD) patients, and to evaluate the factors associated with serum PTH levels measured by Bio-PTH assay and by second-generation intact PTH (I-PTH) assay. The study also examined whether Bio-PTH/I-PTH ratio, an index of the active fraction of PTH, could provide information not obtainable from simple PTH results. Serum levels of PTH were measured in 177 male HD patients, together with the bone formation markers bone alkaline phosphatase (BAP), intact osteocalcin (iOC), N-midfragment osteocalcin (N-Mid OC), and N-terminal propeptide of type I collagen (PINP), and the bone resorption markers deoxypyridinoline (DPD), pyridinoline (PYD), and -CrossLaps (-CTx). Bone mineral density (BMD) was determined twice at distal radius one-third by dual-energy X-ray absorptiometry. Serum Bio-PTH was significantly elevated in HD patients compared to normal controls. Serum Bio-PTH and I-PTH correlated significantly in a positive manner with serum bone formation markers (BAP, iOC, N-Mid OC, PINP), and resorption markers (DPD, PYD, -CTx), and in a negative manner with BMD and annual change therein at distal radius one-third. The degree of correlation of Bio-PTH was not significantly different from that of I-PTH. The Bio-PTH/I-PTH ratio was significantly lower in HD patients than in normal individuals, due probably to accumulation of N-truncated PTH fragments in the former. The Bio-PTH/I-PTH ratio correlated significantly in a negative manner with serum calcium (Ca) (r=–0.251, P<0.001) and nutritional marker serum urea nitrogen, protein catabolic rate and serum creatinine. Multiple regression analysis further revealed that serum I-PTH, but not Bio-PTH, was significantly associated with each of these nutritional markers, and that the Bio-PTH/I-PTH ratio was negatively associated with serum Ca. It was also found that I-PTH, but not Bio-PTH, was influenced by nutritional state. It is concluded that serum Bio-PTH assay could be of similar value to I-PTH assay in evaluating parathyroid function in HD patients and that their combined use in the form of the Bio-PTH/I-PTH ratio could provide information not obtainable from simple PTH results.     

Is intraoperative parathyroid hormone assay mandatory for the success of targeted parathyroidectomy?

BACKGROUND: Minimally invasive parathyroidectomy has become the first surgical option for patients with primary hyperparathyroidism (HPT) in many places. Preoperative localization studies are mandatory, and the use of a quick parathyroid hormone (PTH) assay is highly recommended. The aim of this study was to analyze our initial series of targeted parathyroidectomies. STUDY DESIGN: In a 2-year period, 50 patients underwent unilateral neck exploration for HPT under local anesthesia and light sedation. After biochemical diagnosis, a technetium 99m sestamibi scan was performed on all patients, and cervical ultrasonography was obtained in some patients. Frozen section analysis was used to confirm parathyroid tissue in all patients. There was no biochemical intraoperative evaluation of PTH. Demographics, surgical details, results, and complications were analyzed. RESULTS: There were 35 women and 15 men, with a mean age of 56 years (range 23 to 85 years). Mean preoperative calcium was 11.4 mg/dL (range 10.0 to 14.8 mg/dL), and PTH was 342 pg/mL (range 105 to 2,231 pg/mL). Mean surgical time was 52 minutes (range 30 to 100 minutes), and mean hospital stay was 2 days (range 1 to 7 days). Mean parathyroid weight was 1,000 mg (range 117 to 17,000 mg). Sestamibi scan correctly localized the abnormal gland in 47 patients (94%). There was one postoperative complication (bleeding); two patients required contralateral exploration, and persistent hypercalcemia developed in one that required surgical reintervention. After a mean followup of 12 months (range 3 to 25 months), all patients were normocalcemic. CONCLUSIONS: Targeted parathyroidectomy is safe and effective. Despite the fact that quick intraoperative PTH assay was not used, the cure rate was 98%.     

Triweekly administration of parathyroid hormone (1–34) accelerates bone healing in a rat refractory fracture model

Background

Some reports have shown that intermittent parathyroid hormone (PTH) (1–34) treatment for patients with delayed union or nonunion have led to successful healing. In this study, we investigated whether systemic intermittent administration of PTH (1–34) has a beneficial effect on bone healing in a rat refractory fracture model.

Methods

We created a refractory femoral fracture model in 32 rats with periosteal cauterization that leads to atrophic nonunion at 8 weeks after surgery. Half the rats received subcutaneous intermittent human PTH (1–34) injections at a dosage of 100 μg/kg, thrice a week for 8 weeks. The other half received the vehicle only. At 8 weeks after fracture, radiographic, histological and mechanical assessments were performed.

Results

Radiographic assessments showed that the union rate was significantly higher in the PTH group than in the control group (P?<?0.05). The degree of fracture repair as scored using the Allen grading system in histological assessment was significantly greater in the PTH group than in the control group (P?<?0.05). The ultimate stress and stiffness measurements were significantly greater in the PTH group than in the control group (p?<?0.05).

Conclusions

We demonstrated that triweekly administration of PTH (1–34) increased union rate and accelerated bone healing in a rat refractory fracture model, suggesting that systemic administration of PTH (1–34) could become a novel and useful therapy for accelerating fracture healing in patients at high risk of delayed union or nonunion.

     

Intermittent weekly administration of human parathyroid hormone (1–34) improves bone-hydroxyapatite block bonding in ovariectomized rats

Hydroxyapatite (HA) blocks have been widely used for the reconstruction of bone defects and as a bone substitute. Bone-implant bonding depends on both implant-related factors and patient variables. Intermittent human parathyroid hormone (h-PTH) has a strong anabolic effect on bone formation. The purpose of the present study is to evaluate whether intermittent h-PTH administration enhances bone-HA block bonding in normal versus ovariectomized (OVX) rats. Cancellous bone osteotomy and HA-block implantation were performed on the proximal left tibia in both OVX and sham-operated 7-month-old female Sprague-Dawley rats. Newly formed cancellous bone around the HA block and bone-HA block bonding were evaluated by bone histomorphometry at 8 weeks after the administration of h-PTH (100 μg/kg/week) or its vehicle. The administration of h-PTH significantly increased cancellous bone volume by stimulating bone formation in OVX rats (p < 0.01). Although bone-HA block bonding was significantly decreased in OVX rats compared to that of sham-operated rats (p < 0.01), h-PTH improved the bone-HA block bonding in OVX rats (p < 0.01). These results suggest that intermittent h-PTH treatment may improve bone-HA bonding in osteoporosis by restoring cancellous bone volume and enhancing cancellous bone formation around the HA block.     

An intact parathyroid hormone–based protocol for the prevention and treatment of symptomatic hypocalcemia after thyroidectomy

Background

Symptomatic (SX) hypocalcemia after thyroidectomy is a barrier to same day surgery and the cause of emergency room visits. A standard protocol of calcium and vitamin D supplementation, dependent on intact parathyroid hormone (iPTH) levels, can address this issue. How effective is it? When does it fail?

Methods

We performed a retrospective review of the prospective Thyroid database from January 2006 to December 2010. Six hundred twenty patients underwent completion thyroidectomy or total thyroidectomy and followed our postoperative protocol of calcium carbonate administration for iPTH levels ≥10 pg/mL and calcium carbonate and 0.25 μg calcitriol twice a day for iPTH <10 pg/mL. Calcium and iPTH values, pathology, and medication were compared to evaluate protocol efficacy. A P value <0.05 was considered statistically significant.

Results

Using the protocol, sixty-one (10.2%) patients were chemically hypocalcemic but never developed symptoms and 24 (3.9%) patients developed breakthrough SX hypocalcemia. The SX and asymptomatic groups were similar with regard to gender, cancer diagnosis, and preoperative calcium and iPTH. The SX group was significantly younger (39.6 ± 2.8 versus 49 ± 0.6 y, P = 0.01), with lower postoperative iPTH levels. Thirty-three percent (n = 8) of SX patients had an iPTH ≤5 pg/mL versus only 6% (n = 37) of ASX patients. Although the majority of patients with a iPTH ≤5 pg/mL were asymptomatic, 62.5% (n = 5) of SX patients with iPTH levels ≤5 pg/mL required an increase in calcitriol dose to achieve both biochemical correction and symptom relief.

Conclusions

Prophylactic calcium and vitamin D supplementation based on postoperative iPTH levels can minimize SX hypocalcemia after thyroidectomy. An iPTH ≤5 pg/mL may warrant higher initial doses of calcitriol to prevent symptoms.     

Amino terminal cleavage of PTH(1–84) to PTH(7–84) is regulated by serum calcium concentration via calcium-sensing receptor in hemodialysis patients

Background  

Secondary hyperparathyroidism is one of the critical complications of end-stage renal disease patients. Conventionally intact parathyroid hormone (iPTH) was used to assess secondary hyperparathyroidism, but this assay measures both PTH(1–84) (full-length parathyroid hormone) and PTH(7–84) (amino (N)-terminal-cleaved parathyroid hormone). PTH(7–84) is biologically inactive or antagonistic for PTH. In this study, we examined the relationship between serum calcium concentration and PTH(7–84)/PTH(1–84) ratio and the effect of calcimimetics on the ratio in hemodialysis (HD) patients.     

Postmenopausal women treated with combination parathyroid hormone (1–84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS)

Summary

In postmenopausal women receiving combination parathyroid hormone (PTH) (1–84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia.

Introduction

PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1–84) and ibandronate.

Methods

Postmenopausal women with low bone mass (n?=?43) were treated with 6 months of PTH(1–84) (100 μg/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy.

Results

Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p?<?0.01 for each). Cortical thickness and BMD decreased at the radius (p?<?0.01), consistent with changes in dual-energy X-ray absorptiometry, while these parameters did not change at the tibia (p?≤?0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p?<?0.01) but not radius. Stiffness and failure load decreased at the radius (p?<?0.0001) but did not change at the tibia.

Conclusions

Cortical and trabecular changes in response to the PTH/ibandronate treatment combinations utilized in this study were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy.     

Effects of 1α-hydroxyvitamin D3 on serum calcium and immunoreactive parathyroid hormone in patients with chronic renal insufficiency

Six patients with chronic renal failure on regular dialysis treatment were given low doses (0.5–1.0 g/day) of 1-hydroxyvitamin D₃, monitoring the serum calcium, inorganic phosphate, immunoreactive parathyroid hormone concentration (IPTH) and alkaline phosphatase activity. The serum calcium rose in all patients after 7 days' treatment, in some subjects to hypercalcemic range; this effect persisted 6–14 days after withdrawal of 1-hydroxyvitamin D₃. The elevated serum IPTH rose in the first days of treatment, but later decreased to normal values. It is suggested that active vitamin D metabolites are necessary for normal response of parathyroid glands to variation in serum calcium. Low-dose 1-hydroxyvitamin D₃ treatment appears to be a promising method of correcting hypocalcemia and secondary hyperparathyroidism in chronic renal failure. Careful control of serum calcium is necessary, as hypercalcemia may occur even after minute doses of 1-hydroxyvitamin D₃.     

Effect of human parathyroid hormone hPTH (1–34) applied at different regimes on fracture healing and muscle in ovariectomized and healthy rats

Three experiments were conducted to investigate the effect of intermittent administration of parathyroid hormone (PTH) (1–34) applied at different regimes on fracture healing and muscle in healthy and ovariectomized (Ovx at 3 months of age) rats. Five-month old rats underwent bilateral transverse metaphyseal osteotomy of tibia and were divided into groups (12 rats each). In Exp 1, Ovx rats were either treated with PTH (7×/w, 1–35d), with oral estradiol-17β-benzoate (0.4 mg/kg BW, 1–35d) or untreated. In Exp. 2, there were 3 groups: healthy untreated or treated with PTH (5×/w, 1–35d or 7–35d). In Exp. 3, there were 7 groups: healthy, Ovx, “healthy PTH 5×/w 7–35d”, “Ovx PTH 5×/w 7–35d, 14–35d or 14–28d”, “Ovx PTH every other day 7–35d”. Single dosage of PTH was 40 μg/kg BW. After 35 days of healing one tibia was analyzed by computed tomographical, biomechanical, histological analyses. The other tibia was used in analyses of Alp, Oc, Trap 1, Igf-1, Rankl, Opg genes (Exp.2, 3). Serum Oc and Alp were measured. Body, uterus weight was recorded. M. gastrocnemius was analyzed for weight (Exp. 2), fiber size and mitochondrial respiratory activity (MRA) (Exp.3). Estrogen enhanced uterus weight, prevented body increase, however, did not improve bone healing in Ovx rats (Exp. 1). PTH administration from days 1 and 7 improved bone parameters in all rats regardless of the application frequency (7, 5×/w or every other day) (Exp. 1, stiffness Ovx: 118 + 13 N/mm, Ovx PTH: 250 ± 20 N/mm) being more effective in healthy rats (Exp. 3, stiffness improvement Healthy: 59 to 174 N/mm, Ovx: 52 to 98 N/mm). Serum Oc level was elevated in PTH treated rats. Application from day 14 proved to be less effective (Exp. 3). PTH had no effect (P > 0.05) on body, uterus and muscle weight, muscle fiber size, MRA and expression of bone markers. PTH promoted bone healing in Ovx and healthy rats, when it is applied during early stage of healing without having any adverse systemic effect. In perspective, PTH may represent a treatment for enhancement of fracture healing. The findings need to be confirmed by follow-up studies on other animals.     

Effect of sequential treatments with alendronate,parathyroid hormone (1–34) and raloxifene on cortical bone mass and strength in ovariectomized rats

Anti-resorptive and anabolic agents are often prescribed for the treatment of osteoporosis continuously or sequentially for many years. However their impact on cortical bone quality and bone strength is not clear.MethodsSix-month old female rats were either sham operated or ovariectomized (OVX). OVX rats were left untreated for two months and then were treated with vehicle (Veh), hPTH (1–34) (PTH), alendronate (Aln), or raloxifene (Ral) sequentially for three month intervals, for a total of three periods. Mid-tibial cortical bone architecture, mass, mineralization, and strength were measured on necropsy samples obtained after each period. Bone indentation properties were measured on proximal femur necropsy samples.ResultsEight or more months of estrogen deficiency in rats resulted in decreased cortical bone area and thickness. Treatment with PTH for 3 months caused the deposition of endocortical lamellar bone that increased cortical bone area, thickness, and strength. These improvements were lost when PTH was withdrawn without followup treatment, but were maintained for the maximum times tested, six months with Ral and three months with Aln. Pre-treatment with anti-resorptives was also somewhat successful in ultimately preserving the additional endocortical lamellar bone formed under PTH treatment. These treatments did not affect bone indentation properties.SummarySequential therapy that involved both PTH and anti-resorptive agents was required to achieve lasting improvements in cortical area, thickness, and strength in OVX rats. Anti-resorptive therapy, either prior to or following PTH, was required to preserve gains attributable to an anabolic agent.     

Intraoperative parathyroid hormone measurement during parathyroidectomy for treatment of primary hyperparathyroidism: When should you end the operation?

IntroductionThe study objective was to evaluate the intraoperative 50% decrease in PTH level ± PTH normalization for its accuracy and efficiency in predicting cure during parathyroidectomy (PTx) for the treatment of primary hyperparathyroidism (PHP).MethodsA retrospective review of patients undergoing PTx was conducted. The timepoints at which the 50% PTH decrease was reached were recorded. The accuracy of intraoperative PTH for predicting cure, defined as normocalcemia at 6 months postoperatively, was evaluated.ResultsThe study population was made up of 248 PHP patients, with 247 patients achieving normocalcemia at 6 months postoperatively. If a 50% PTH decrease was used to indicate operation conclusion, 1 patient would not be cured. Persistent PTH elevation above normal range at T10 had a PPV of 77%, NPV of 99.5%, sensitivity of 95.2% and specificity of 97.3% for predicting the presence of a contralateral pathological parathyroid gland. For the study cohort, 24.5 h of cumulative operating time would be saved if the 50% PTH decrease triggered operation conclusion.DiscussionA decrease in the pre-excision PTH level to 50% of the baseline level, or a decrease in the higher of the baseline or pre-excision PTH levels by 50% at 5 or 10 min post pathological parathyroid gland removal, regardless of whether the PTH level normalizes, reliably predicts cure from PHP and should be used to guide the surgeon during parathyroidectomy.     

Intermittently administered parathyroid hormone 1–34 reverses bone loss and structural impairment in orchiectomized adult rats

Male osteoporosis is emerging as a central theme in bone research. As in females, hypogonadism appears as a principal risk factor in men that leads to bone loss and increased fracture incidence. Intermittently administered parathyroid hormone (PTH) reverses bone loss in sex hormone-deprived women and female animals and increases bone mass in elderly men and normal male animals. This study was carried out to assess whether the PTH anabolic activity is also effective in adult castrated males and to gain insight into the underlying tissue processes. Bilateral orchiectomy (ORX) or sham-ORX was performed in 13-week old rats. Five weeks later, the ORX rats were treated intermittently with human PTH(1–34), 80 g/kg/day or vehicle for 6 weeks. Femora were evaluated by quantitative micro-computed tomography followed by dynamic histomorphometry. The trabecular bone volume density showed 40% and 56% ORX-induced loss in the distal metaphysis at 6 weeks and 12 weeks post-ORX, respectively. PTH(1–34) induced supraphysiologic recovery of this bone loss (155% recovery) consequent to a vast increase in trabecular thickness (174% over sham-ORX controls) and a partial reversal (62%) of the decrease in trabecular number. As compared with the results in 12-week, orchiectomized vehicle-administered rats, the PTH(1–34) treatment induced a significant decrease in osteoclast number (20%) and twofold increase in bone formation rate. While ORX did not affect the femoral diaphysis, PTH(1–34) induced marked cortical thickening via the stimulation of endosteal mineral appositional rate (154% over ORX rats). These data portray PTH(1–34) as a highly potent bone anabolic agent in adult ORX rats, mainly by increasing both the trabecular and cortical thicknesses through its effect on osteoblasts and osteoclasts. The adult ORX rat is useful for investigating the processes involved in bone anabolic activity in castrated osteoporotic males and for the development of bone anabolic agents for treating this condition.     

Utility of intraoperative bilateral internal jugular venous sampling with rapid parathyroid hormone testing in guiding patients with a negative sestamibi scan for minimally invasive parathyroidectomy—a randomized controlled trial

Background and aims  The purpose of this study was to determine the utility of bilateral internal jugular venous sampling with rapid parathyroid hormone assay (BIJV–IOPTH) in comparison to endocrine surgeon-performed ultrasonography of the neck as an alternative localizing modality in guiding patients with primary hyperparathyroidism (pHPT) and negative sestamibi scans for minimally invasive parathyroidectomy (MIP). Patients and methods  Seventy eight consenting patients with a negative subtraction sestamibi scan planned for parathyroidectomy underwent additional ultrasound parathyroid imaging and were randomized to undergo surgery without vs. with additional BIJV–IOPTH; n = 39 in each group. The patients with a positive alternative imaging test were qualified for video-assisted MIP, whereas the others underwent open neck explorations. The primary outcome measure was the number of patients with true-positive results of alternative imaging tests. Results  Of the 78 patients, 50 (64%) had a single adenoma, eight (10.3%) had double adenomas, and 20 (25.7%) demonstrated four-gland hyperplasia. Ultrasonography alone vs. combined with BIJV–IOPTH was true positive in detecting a solitary parathyroid adenoma in 8/24 (33.3%) vs. 17/26 (65.4%) patients, respectively (p = 0.023). Curative video-assisted MIP was successfully performed in all the patients with true-positive results. The remaining individuals were cured by more extensive open neck explorations (unilateral—4/39 vs. 4/39, respectively; p = 1.0 or bilateral—27/39 vs. 18/39, respectively; p = 0.039). Conclusions  Most patients with pHPT and a negative subtraction sestamibi scan (64%) have a single adenoma. BIJV–IOPTH as an addition to a surgeon-performed ultrasound of the neck allows for more accurate guiding for MIP in patients with a solitary parathyroid adenoma and negative subtraction sestamibi scans. Presented at the 3rd Workshop of the European Society of Endocrine Surgeons (ESES), “Modern techniques in primary hyperparathyroidism surgery: An evidence based perspective”, 19-21 of March 2009, Lund, Sweden. “Best of Endocrine Surgery in Europe 2009”     

Changes in Skeletal Microstructure Through Four Continuous Years of rhPTH(1–84) Therapy in Hypoparathyroidism

Bone remodeling is reduced in hypoparathyroidism, resulting in increased areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and abnormal skeletal indices by transiliac bone biopsy. We have now studied skeletal microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT) through 4 years of treatment with recombinant human PTH(1–84) (rhPTH[1–84]) in 33 patients with hypoparathyroidism (19 with postsurgical disease, 14 idiopathic). We calculated Z-scores for our cohort compared with previously published normative values. We report results at baseline and 1, 2, and 4 years of continuous therapy with rhPTH(1–84). The majority of patients (62%) took rhPTH(1–84) 100 μg every other day for the majority of the 4 years. At 48 months, areal bone density increased at the lumbar spine (+4.9% ± 0.9%) and femoral neck (+2.4% ± 0.9%), with declines at the total hip (−2.3% ± 0.8%) and ultradistal radius (−2.1% ± 0.7%) (p < .05 for all). By HR-pQCT, at the radius site, very similar to the ultradistal DXA site, total volumetric BMD declined from baseline but remained above normative values at 48 months (Z-score + 0.56). Cortical volumetric BMD was lower than normative controls at baseline at the radius and tibia (Z-scores −1.28 and − 1.69, respectively) and further declined at 48 months (−2.13 and − 2.56, respectively). Cortical porosity was higher than normative controls at baseline at the tibia (Z-score + 0.72) and increased through 48 months of therapy at both sites (Z-scores +1.80 and + 1.40, respectively). Failure load declined from baseline at both the radius and tibia, although remained higher than normative controls at 48 months (Z-scores +1.71 and + 1.17, respectively). This is the first report of noninvasive high-resolution imaging in a cohort of hypoparathyroid patients treated with any PTH therapy for this length of time. The results give insights into the effects of long-term rhPTH(1–84) in hypoparathyroidism. © 2020 American Society for Bone and Mineral Research.