Does the number of autotransplanted parathyroid glands affect postoperative hypoparathyroidism and serum parathyroid hormone levels?

BackgroundTo investigate how number of autotransplanted parathyroid glands (PGs) affects the incidence of postoperative hypoparathyroidism and the recovery of parathyroid function.MethodsA systematic search was performed in the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. The evaluated indices included the incidence of postoperative transient and permanent hypoparathyroidism and parathyroid hormone (PTH) levels during follow-up.ResultsTwenty articles with 7291 patients were included. A higher incidence of transient hypoparathyroidism was found in the PG autotransplantation group than in the preservation group (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.90, 2.96). However, there was no significant difference between the two groups regarding permanent hypoparathyroidism (OR: 1.17; 95% CI: 0.71, 1.91). Parathyroid hormone (PTH) levels in the PG autotransplantation group changed significantly more than the preservation group at postoperative 1-day and 1-month, but became similar at the 6-month, 1-year and 2-year follow-up. Autotransplantation of 2 and 3 PGs demonstrated a higher incidence of transient hypoparathyroidism than 1 PG (OR: 2.09; 95% CI: 1.41, 3.11 and OR: 9.70; 95% CI: 2.11, 44.39, respectively), but no significant difference was observed between the autotransplantation of 3 and 2 PGs (OR: 0.99; 95% CI: 0.03, 29.06). Additionally, the incidence of permanent hypoparathyroidism was not significantly different when different number of PGs was autotransplanted.ConclusionsPG autotransplantation is an effective mid- and long-term strategy for the preservation of parathyroid function. Although transient hypoparathyroidism was positively correlated with the number of autotransplanted PGs, no remarkable correlation was observed for permanent hypoparathyroidism.     

Discharging a Patient Treated With Parathyroid Allotransplantation After Having Been Hospitalized for 3.5 Years With Permanent Hypoparathyroidism: A Case Report

IntroductionParathyroid allotransplantation is one of the methods used in the treatment of permanent hypoparathyroidism. We present a patient who underwent continuous intravenous (IV) calcium replacement therapy because of permanent hypoparathyroidism after total thyroidectomy.Case PresentationA 47-year-old woman who underwent a total thyroidectomy with a multinodular goiter developed hypoparathyroidism and hypocalcemia 1 week after discharge. The patient was started on daily oral calcitriol, magnesium effervescent, vitamin D, and IV calcium gluconate and was unable to be discharged because the IV calcium could not be stopped. After 3.5 years, 50×10⁶ parathyroid cells were transplanted by injecting the cells into the left deltoid muscle of the patient. The immunosuppression of the patient, who used 20-mg methylprednisolone for the first month, was completely discontinued.ResultsNo complications were observed in the patient after transplantation. The parenteral calcium replacement of the patient was progressively interrupted after transplantation. The patient’s serum calcium level was 7.8 mg/dL and the PTH level was 6.9 pg/mL without IV calcium replacement at 12 weeks after transplantation, and the patient was discharged using oral ionized calcium. In the 10-week follow-up after discharge, the need for IV calcium was not observed in the patient.ConclusionParathyroid allotransplantation is a simple, fast, and cost-effective method that should be tried in patients with persistent hypoparathyroidism, especially those who have to take IV calcium replacement, because its cost is much cheaper than standard medical care, its morbidity is much more limited, and it increases the patient’s quality of life.     

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.     

Therapy of hypoparathyroidism with intact parathyroid hormone

Summary  

Hypoparathyroidism, a disorder characterized by low parathyroid hormone (PTH), is generally treated with oral calcium and vitamin D supplementation. We investigated the effects of PTH(1–84) treatment in 30 hypoparathyroid subjects for 24 months. PTH(1–84) treatment in hypoparathyroidism significantly reduced supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels.     

PTH 1-34 Replacement Therapy Has Minimal Effect on Quality of Life in Patients With Hypoparathyroidism

In addition to hypocalcemia, patients with hypoparathyroidism report poor quality of life (QOL), complaining of fatigue and “brain fog.” Parathyroid hormone (PTH) therapy can effectively manage hypocalcemia; however, the effects of PTH treatment on QOL are unclear. Thirty-one patients with hypoparathyroidism were treated in an open-label study with full replacement subcutaneous PTH 1-34 twice daily for up to 5.3 years, with individualized fine-dosing titration. Prior to initiation of PTH 1-34, conventional therapy was optimized. The 36-Item Short Form (SF-36) Health Survey, Fatigue Symptom Inventory (FSI), and 6-minute walk test (6MWT) were assessed at PTH start (baseline), every 6 months on PTH, and after PTH discontinuation. The SF-36 assesses physical function (PF), physical role limitations (RP), bodily pain (BP), general health (GH), vitality (VT), emotional role limitations (RE), social function (SF), and mental health (MH). Compared to population norms, patients at baseline had lower scores in RP, GH, VT, and MH (p < 0.05), consistent with impaired QOL. With PTH therapy, only GH at 6 months and VT at 12 months improved (p < 0.05). At the last treatment time point, RP, VT, and SF improved compared to baseline (p < 0.05). However, follow-up scores were unchanged from baseline or last PTH treatment, except for SF, which had decreased at follow-up compared to on-PTH (p < 0.05). On the FSI, there were no changes in fatigue frequency; perceived interference was improved at 12 and 18 months and composite severity was improved only at 60 months (p < 0.05). The 6MWT measures did not change. In conclusion, hypoparathyroidism is associated with decreased QOL. Despite the bias in open-label studies to predict improvements in QOL, PTH therapy had limited and non-sustained effects on QOL, inconclusive changes in fatigue experience, and no change in the 6MWT. Although PTH 1-34 can adequately manage the hypocalcemia in hypoparathyroidism, its effects on QOL appear to be minimal. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

What is the experience of our patients with transient hypoparathyroidism after total thyroidectomy?

BackgroundWe sought to better understand the experience of patients with transient hypoparathyroidism using patient interviews and quality of life surveys.MethodsThis is a prospective analysis of 62 patients after total thyroidectomy at a high-volume institution. Semistructured patient interviews and quality of life surveys were conducted preoperatively and postoperatively at 2 weeks, 6 weeks, 6 months, and 1 year and compared based on postoperative parathyroid hormone levels.ResultsPostoperative parathyroid hormone levels were <10 pg/mL in 32% of patients (n = 20), 10 to 20 pg/mL in 19% (n = 12), and >20 pg/mL in 48% (n = 30). Hypocalcemic symptoms at 2 weeks were reported in 28 of 55 patients (51%), but patients felt “well prepared” and reported it “wasn’t a big deal.” If symptoms persisted at 6 weeks, they became more bothersome. At 6 months and 1 year, patients reported calcium supplementation prevented most symptoms and did not interfere with daily activities. Quality of life as measured by the European Organization for Research and Treatment of Cancer and the 12-Item Short Form Survey demonstrated a slight improvement at 1 year postoperatively regardless of parathyroid hormone level.ConclusionEarly postoperative transient hypoparathyroidism is common but when appropriately managed did not have a substantial negative impact on the overall quality of life.     

Utility of Intraoperative Parathyroid Hormone Monitoring in Patients with Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism Undergoing Initial Parathyroidectomy

Background

Intraoperative parathyroid hormone monitoring (IOPTH) is a widely used adjunct for primary hyperparathyroidism (pHPT). However, the benefit of IOPTH in familial pHPT, such as in multiple endocrine neoplasia type I (MEN1), remains unclear.

Methods

We performed a retrospective analysis of 52 patients with MEN1-associated pHPT undergoing initial parathyroidectomy with IOPTH monitoring at our institution. Parathyroid hormone (PTH) levels were measured before skin incision and 10 min after resection of the last parathyroid gland. Variables analyzed included percent drop of PTH from baseline and the final PTH level compared to the normal reference range (RR).

Results

A total of 52 patients underwent initial subtotal parathyroidectomy with IOPTH. An IOPTH decrease cutoff of ≥75 % from baseline had the highest biochemical cure rate (87 %). In the remaining 13 % who met this cutoff, all had persistent pHPT, with ≥90 % drop of PTH from baseline. The remaining patients, who did not meet the ≥75 % cutoff, were cured. Follow-up was available for three of four patients with final IOPTH levels above the RR: one had persistent pHPT, two had hypoparathyroidism (50 %). When a postresection PTH level was within the RR, 88 % of patients were cured. While considered cured from pHPT, 7 % of patients in this group developed permanent hypoparathyroidism. When the final PTH level dropped below the RR, 28 % developed permanent hypoparathyroidism.

Conclusions

A cutoff in IOPTH decrease of ≥75 % from baseline has the highest biochemically cure rate in patients with pHPT associated with MEN1. However, a 75 % cutoff in IOPTH decrease does not exclude persistent pHPT. The absolute IOPTH value does not accurately predict postoperative hypoparathyroidism.     

Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 μg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3–10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Intraoperative parathyroid hormone measurement facilitates outpatient thyroidectomy in children

IntroductionWe hypothesize that intraoperative parathyroid hormone (ioPTH) measurement after a total thyroidectomy predicts children at risk for hypoparathyroidism and allow for outpatient procedure.MethodsBetween 2015 and 2019, we reviewed all patients under the age of 21 undergoing a thyroidectomy (total or lobectomy). Based on the ioPTH concentration, the patients were treated by the following protocol: a) PTH ≥20 pg/mL: no treatment; b) PTH = 10–19 pg/mL: 1000 mg calcium orally TID; c) PTH = 5–9 pg/mL: calcitriol 250 μg orally BID plus 1000 mg calcium orally TID; or d) PTH <5 pg/mL calcitriol 500 μg orally BID plus 1000 mg calcium orally TID.ResultsFifty-two patients were included with a median age of 16 (range 6–21 years). Thirty-two patients (62%) had normal PTH (≥10 pg/mL) while 20 (38%) had low PTH levels (<10 pg/mL). Of those patients with low PTH, 60% had normalization of levels within 2 weeks of surgery.ConclusionsThyroid surgery in children can be performed as an outpatient procedure. The ioPTH measurements and a protocol to treat patients with low PTH assists in safe discharge.     

Cryopreservation of Parathyroid Tissue after Parathyroid Surgery for Renal Hyperparathyroidism: Does it Really Make Sense?

Background

Metachronous autotransplantation of cryopreserved parathyroid tissue is a technique for treating postoperative hypoparathyroidism after parathyroid surgery for renal hyperparathyroidism (rHPT). The aim of the present study was to evaluate our institution’s experience with metachronous autotransplantation to analyze the role of cryopreservation in the treatment of rHPT and to determine for whom and when cryopreservation of parathyroid tissue should be deemed necessary.

Methods

A prospective database of patients with rHPT who underwent surgery between 1976 and 2011 was screened for patients with hypoparathyroidism who received a metachronous autotransplantation. Data were analyzed regarding clinical data, histopathological findings of the cryopreserved parathyroid tissues, and patient outcome after metachronous replantation of parathyroid tissue.

Results

Fifteen of 883 patients with rHPT underwent a metachronous autotransplantation under local anesthesia at a mean time of 23?months following the last cervical surgery. Histopathology of the parathyroid tissue chosen for transplantation revealed a necrosis rate of 0?% in 14 and 70?% in one patient. Mean preoperative serum calcium and parathyroid hormone (PTH) levels were 2.0?mmol/l and 3.7?pg/ml, respectively. Autotransplantation raised mean serum calcium and PTH levels to 2.2?mmol/l and 97.5?pg/ml, respectively, after a mean follow-up of 78?months.

Conclusions

Metachronous autotransplantation following parathyroid surgery in patients with rHPT effectively normalizes PTH and calcium levels. The success rate is high if an adequate cryopreservation procedure is applied. However, it is rarely necessary, and therefore the cryopreservation of parathyroid tissue in all patients has to be questioned, at least from an economic point of view.     

Prediction of Permanent Hypoparathyroidism after Total Thyroidectomy

Background

Hypoparathyroidism is a common complication with thyroid surgery. The ability to predict a high risk of permanent hypoparathyroidism is important for individual prognosis and follow-up.

Methods

Permanent hypoparathyroidism, defined as continuing need for vitamin D medication at 1-year post-operatively, was investigated in patients after total thyroidectomy. Blood levels of calcium and parathyroid hormone (PTH) were measured intra-operatively, the day after surgery and at 1 month post-operatively. Logistic regression analysis was performed to investigate the risk of vitamin D treatment at last follow-up, calculated as odds ratios (ORs) with 95 % confidence intervals (CIs). Patients were followed until cessation of vitamin D and/or calcium medication, until death, loss to follow-up, or end of follow-up, whichever came first.

Results

A total of 519 patients were included. The median (range) follow-up in patients unable to cease vitamin D was 2.7 (1.2–10.3) years. The rate of permanent hypoparathyroidism was 10/519, 1.9 %. Parathyroid auto-transplantation was performed in 90/519 (17.3 %) patients. None of these developed permanent hypoparathyroidism, nor did any patient with normal PTH day 1 (>1.6 pmol/l or 15 pg/ml). The adjusted risk (OR, 95 % CI) for permanent hypoparathyroidism for log PTH on day 1 was 0.25 (0.13–0.50). In patients not auto-transplanted and with unmeasurable PTH day 1 (<0.7 pmol/l or 6.6 pg/ml), 8/42 (19.2 %) developed permanent hypoparathyroidism.

Conclusions

Auto-transplantation protects against permanent hypoparathyroidism, whereas low PTH day 1 is associated with high risk.     

Selective parathyroid venous sampling in reoperative parathyroid surgery: A key localization tool when noninvasive tests are unrevealing

BackgroundPreoperative localization studies are essential for parathyroid re-exploration. When noninvasive studies do not regionalize the abnormal parathyroid gland, selective parathyroid venous sampling may be employed. We studied the utility of parathyroid venous sampling in reoperative parathyroid surgery and the factors that may affect parathyroid venous sampling results.MethodsPatients with hyperparathyroidism and previous cervical surgery undergoing evaluation for reoperative parathyroidectomy over a 20-year period were identified. Patients with indeterminate or negative noninvasive studies underwent parathyroid venous sampling. Parathyroid hormone values were mapped with a ≥2-fold increase above peripheral signifying positive parathyroid venous sampling. These results were correlated with reoperative findings.ResultsParathyroid venous sampling was positive in 113 of 140 (81%). Re-exploration occurred in 75 (66%). Parathyroid venous sampling correctly detected the region of abnormal glands in 58 (77%). With 1 gradient, 1 abnormal gland was found in 81%. With multiple gradients, 1 abnormal gland was found in 78%, most often at the site with the largest gradient. Eighty percent of patients who underwent reoperative parathyroidectomy were biochemically cured.ConclusionParathyroid venous sampling can guide parathyroid re-exploration when noninvasive localizing studies are indeterminate. Expectation of 1 versus multiple remaining glands was key in interpreting the results.     

Persistent hypoparathyroidism following magnesium repletion in burn-injured children

Children suffering severe burns develop hypocalcemia, magnesium (Mg) depletion, hypoparathyroidism, and renal resistance to parathyroid hormone (PTH) infusion. We hypothesized that Mg depletion accounted for both the hypoparathyroidism and the renal resistance to PTH, and that Mg repletion would improve both. Due to a lack of PTH for infusion, we studied only the effect of Mg repletion on the relationship between ionized Ca (iCa) and PTH in the serum of 14 sequentially recruited children burned ≥40% total body surface area. All received a urinary Mg retention test a median of 20 days post burn (range 8–137 days). Seven (50%) of the children remained Mg depleted, which was not attributable to burn size or to time from burn to study. Combined enteral and parenteral Mg intakes were not different between the depleted and repleted groups, 12.2±4.4 (SD) mg/kg per day and 14.2±6.2 mg/kg per day, respectively. Both groups had low intact PTH levels in relation to serum iCa concentration, indicating persistent hypoparathyroidism. We conclude that Mg depletion is not the chief cause of hypoparathyroidism following thermal injury and we postulate that the persistent hypoparathyroidism is consistent with a reduced set-point for Ca suppression of PTH secretion. Received: 18 February 1999 / Revised: 14 June 1999 / Accepted: 25 June 1999     

Incremento de la densidad mineral ósea en pacientes con hiperparatiroidismo terciario tras paratiroidectomía total y autotrasplante de glándula paratiroides

IntroductionChanges in bone metabolism and bone mineral density are observed in renal transplant patients with tertiary hyperparathyroidism. The objective of this work was to analyse the increase in bone mineral density, as well the laboratory results, after total parathyroidectomy and autotransplantation in renal transplant patients with tertiary hyperparathyroidism.Material and methodsA retrospective study was conducted in which the bone mineral density values at femoral and lumbar level were analysed, together with the serum levels of calcium, phosphorous, parathyroid hormone (PTH), and alkaline phosphatase in 13 renal transplant patients with tertiary hyperparathyroidism before and after total parathyroidectomy and autotransplantation of the parathyroid glands.ResultsParathyroidectomy is associated with an increase in bone mineral density at femoral and lumbar level, with an increase of 8.6 ± 6.7% at lumbar level, and 4 ± 16.1% at femoral level. The decrease in calcium after the parathyroidectomy was 2.8 mg/dL (95% CI; 1.9-4). The decrease in PTH was 172 pg/mL (95% CI; 98-354) and the decrease in alkaline phosphatase was 229 U/L (95% CI; 70-371).ConclusionsTotal parathyroidectomy and autotransplantation of the parathyroid glands in renal transplant patients with tertiary hyperparathyroidism increases the bone mineral density. Furthermore, the calcium, PTH and alkaline phosphatase returned to normal in the long-term.     

Effects of 25-hydroxyvitamin D level and its change on parathyroid hormone in premenopausal Chinese women

Summary  

Optimal levels of 25-hydroxyvitamin D [25(OH)D] were investigated in premenopausal Chinese women. Parathyroid hormone (PTH) change at 3 months was associated with change in 25(OH)D but not with baseline levels, and PTH fell even when starting levels of 25(OH)D were >40 nmol/L, consistent with optimal values for 25(OH)D of ≥40 nmol/l.     

Hypercalcemia in renal transplant patients: prevalence and management in Canadian transplant practice

Hypercalcemia, occurring in up to 25% of patients within 12 months following renal transplantation, and persistent hyperparathyroidism were evaluated following renal transplantation, by retrospective chart review of 1000 adult patients transplanted between January 1, 2003 and January 31, 2008 with at least six months follow‐up. Serum calcium, parathyroid hormone, and phosphate levels were recorded at 12, 24, 36, and 48 months. Average follow‐up was 766 (535) d (mean (SD); median 668 d). Majority were first transplants (85%); deceased donor 57%. Point prevalence of hypercalcemia (serum Ca²⁺ > 2.6 mM) was 16.6% at month 12, 13.6% at month 24, 9.5% at month 36, and 10.1% at month 48. Point prevalence of serum parathyroid hormone (PTH) > 10 pM was 47.6% at month 12, 51.1% at month 24, 43.4% at month 36, and 39.3% at month 48. Estimated glomerular filtration rate (GFR) was maintained throughout and was not different between patients with or without hypercalcemia or elevated PTH. Cinacalcet was prescribed in 12% of patients with hypercalcemia and persistent hyperparathyroidism; parathyroidectomy was performed in 112/1000 patients, 15 post‐transplant. Persistent hyperparathyroidism, often accompanied by hypercalcemia, is common following successful renal transplantation, but the lack of clear management suggests the need for further study and development of evidence‐based guidelines.     

The Antiresorptive Effect of GIP,But Not GLP-2, Is Preserved in Patients With Hypoparathyroidism—A Randomized Crossover Study

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted postprandially. In healthy humans, both hormones decrease bone resorption accompanied by a rapid reduction in parathyroid hormone (PTH). The aim of this study was to investigate whether the changes in bone turnover after meal intake and after GIP- and GLP-2 injections, respectively, are mediated via a reduction in PTH secretion. This was tested in female patients with hypoparathyroidism given a standardized liquid mixed-meal test (n = 7) followed by a peptide injection test (n = 4) using a randomized crossover design. We observed that the meal- and GIP- but not the GLP-2-induced changes in bone turnover markers were preserved in the patients with hypoparathyroidism. To understand the underlying mechanisms, we examined the expression of the GIP receptor (GIPR) and the GLP-2 receptor (GLP-2R) in human osteoblasts and osteoclasts as well as in parathyroid tissue. The GIPR was expressed in both human osteoclasts and osteoblasts, whereas the GLP-2R was absent or only weakly expressed in osteoclasts. Furthermore, both GIPR and GLP-2R were expressed in parathyroid tissue. Our findings suggest that the GIP-induced effect on bone turnover may be mediated directly via GIPR expressed in osteoblasts and osteoclasts and that this may occur independent of PTH. In contrast, the effect of GLP-2 on bone turnover seems to depend on changes in PTH and may be mediated through GLP-2R in the parathyroid gland. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

人胚甲状旁腺细胞移植治疗甲状旁腺功能低下症

目的　探讨人胚甲状旁腺细胞移植治疗甲状旁腺功能减退症的临床意义。　方法　将培养的人胚甲状旁腺细胞在B超引导下移植到 6例甲状旁腺功能减退症患者的肾周围脂脂囊中。应用放射免疫方法测定患者术前、术后血中甲状旁腺激素 (PTH)及钙水平 ,并进行自身对照 ,对疗效进行评价。　结果　 6例患者在接受人胚甲状旁腺细胞移植前 ,血钙及PTH平均水平分别为 (1 6 3±0 12 )mmol/L及 (1 36± 0 2 1)ng/L ;接受移植 3d后分别为 (1 77± 0 2 2 )mmol/L及 (9 5 3± 2 2 1)ng/L ,两者差异有显著性意义 (P <0 0 1) ;6d后达正常水平 ,临床症状逐渐减轻至消失 ;术后观察 9～ 12个月病情保持稳定。　结论　培养的人胚甲状旁腺细胞肾周围脂肪囊内移植是治疗甲状旁腺功能减退症的一种较理想的新方法     

Long-term response of cultured rat parathyroid glands to calcium and calcitriol: the effect of cryopreservation

AIM: This study aimed to investigate the longest period in which parathyroid glands cultured in vitro maintained their viability and functionality in order to study the response of the glands to factors that exert their main action in the long term (1-7 days). METHODS: Rat parathyroid glands from 104 Wistar rats were used. Cell viability was measured by flow cytometry for 7 days. Parathyroid tissue functionality was determined by parathyroid hormone (PTH) secretion in basal conditions and in the response of the glands to calcium and calcitriol. Calcium sensing receptor (CaR) synthesis was determined measuring protein levels by immunohistochemistry. Parathyroid glands were cryopreserved to study them in the same way as fresh tissue. RESULTS: Intact parathyroid glands maintained their cell viability >80% until the 6th day in culture, while the functional capacity was limited to 4 days: PTH release was stable for 4 days, whilst from the 5th day onwards, PTH secretion reduced to undetectable levels. Parathyroid glands responded accurately when calcium was reduced in the culture medium; a mean increase >50% in PTH secretion was observed. No differences were observed in CaR levels before and after the culture period. PTH synthesis and secretion inhibition was observed when the parathyroid glands were cultured with calcitriol; this inhibition achieved 90% after 4 days in culture. Cryopreserved parathyroid glands maintained their viability, but partially lost their functionality, as they were unable to respond to calcium. CONCLUSIONS: Intact parathyroid glands cultured in vitro maintained their functionality and their capacity to respond to their effectors for longer periods than in previously developed studies. It seems that part of this capacity is lost after cryopreservation. Nevertheless, this long-term culture model can be useful to study the response of the parathyroid glands.     

Preoperative evaluation of microencapsulated human parathyroid tissue aids selection of the optimal bioartificial graft for human parathyroid allotransplantation

Allotransplantation of microencapsulated parathyroid tissue is a promising approach to the treatment of permanent hypoparathyroidism. Preoperative assessment of the quality of microencapsulated parathyroid tissue could facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation. Parathyroid tissue from patients with secondary hyperparathyroidism (n = 15) was processed mechanically or enzymatically (collagenase type II). Tissue particles and single cells/cell clusters were routinely microencapsulated with amitogenic Ba(2+) alginate. Parathyroid secretion dynamics in response to stimulation of nonencapsulated and microencapsulated parathyroid tissue with Ca(2+) were evaluated in a perifusion system. The stability of the different types of microcapsule was assessed using an osmotic pressure test. Mechanical cutting of parathyroid tissue led to peripheral necrosis of tissue particles and impaired their vitality. Collagenase digestion, in contrast, resulted in single cells and cell clusters without peripheral necrosis. The quality of microencapsulation of single cells/cell clusters was significantly better than that of tissue particles (deformed and imperfect capsules). Microencapsulation itself did not decrease cell vitality. Nonencapsulated and microencapsulated tissue particles and single cells/cell clusters from different donors maintained their own levels of response to stimulation with low Ca(2+). Microcapsules containing tissue particles showed poor stability compared with those containing single cells/cell clusters. Preoperative evaluation of microencapsulated parathyroid tissue can disclose differences in vitality and function and thus facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation.