Identification of risk factors on secondary hyperparathyroidism undergoing long-term haemodialysis with vitamin D3

In order to evaluate the clinical outcome as well as the effectof vitamin D3 treatment on secondary hyperparathyroidism (SHPT)in the patients undergoing long-term dialysis therapy, we conducteda long-term follow-up survey on the demographic characteristicsof 425 patients who were observed for more than 3 years. Allpatients were treated with daily 1(OH)D3 treatment after theinitiation of dialysis. Among them the percentage of patientsneeding parathyroidectomy was 4.9% aggravation of SHPT, 11.8%an increase of the parathyroid hormone (PTH) level without radiographicalabnormalities, 17.4% stable, 56.2% and a decrease of the PTHlevel, 9.7% at the final observation. The average PTH levelsincreased year by year irrespective of the difference of originalrenal disease. Gender, age at the start of dialysis, originalrenal disease, duration of dialysis treatment, the decade ofstarting dialysis, the degree of phosphate control, and thePTH level at starting dialysis were analysed as potential riskfactors for SHPT, and assessed by multivariate analysis. Multivariateanalysis revealed that only the terms of duration of dialysisand the PTH level at starting dialysis were the significantrisks for developing overt SHPT. Logistic regression analysisrevealed that the relative risk was significantly higher inthe patients with more than 10 years history of dialysis andin those with the carboxyterminal PTH levels at the start ofdialysis being more than 5 ng/ml. These results suggest thatthe treatment with daily low-dose vitamin D3 administrationafter dialysis initiation is imperfect; therefore some prophylactictherapy from the predialysis stage is necessary to prevent overtSHPT, which will occur after long-term haemodialysis.     

Usefulness of Trabecular Bone Score (TBS) to Identify Bone Fragility in Patients with Primary Hyperparathyroidism

Background: Patients with primary hyperparathyroidism usually show decreased bone strength that are often not well diagnosed by conventional Dual-energy X-ray absorptiometry (DXA). Trabecular Bone Score (TBS) is a new technique for assessing bone microarchitecture indirectly. This cross-sectional study evaluates the usefulness of TBS in patients with primary hyperparathyroidism in clinical practice. Methodology: Bone mineral density (BMD) by DXA and TBS values by TBS InSight® software were determined in 72 patients with primary hyperparathyroidism to analyze its relationship with fragility fractures. A receiver operating curve was performed to evaluate the usefulness of TBS as predictor of fragility fractures. FRAX index with and without adjustment by TBS was calculated. Additionally, longitudinal data of a subgroup of patients according to the therapeutic management were also evaluated. Results: A total of 51.4% of the patients showed degraded microarchitecture while only 37.5% of them were diagnosed of osteoporosis by DXA. No significant correlation was found between TBS values and BMD parameters. However, TBS values were lower in osteoporotic patients compared to those classified as normal by BMD (1.16 ± 0.12vs 1.26 ± 0.17; p?=?0.043) and in patients with fragility fractures compared to nonfractured patients (1.19 ± 0.03vs 1.24 ± 0.02, p < 0.001). The area under the curve for TBS performed better than the combination of femoral, hip and spine-BMD for prevalent fractures (0.714vs 0.679). TBS-adjusted FRAX was higher than nonadjusted model for both major osteoporotic and hip fracture (4.5% vs 3%; 0.9% vs 0.7%; p < 0.001). At follow-up, an improvement in TBS values was observed in treated patients (medical or surgical) vs nontreated close to significance (1.27 ± 0.10vs 1.24 ± 0.11, p?=?0.074). Conclusions: TBS could be a useful tool to identify increased fracture risk in patients with primary hyperparathyroidism underdiagnosed by BMD. Moreover, FRAX adjusted by TBS could be a more robust tool for predicting the risk of osteoporotic fracture to help in therapeutic decisions in this population.     

原发性甲状旁腺功能亢进症的诊断与治疗(附11例报告)

１９８９年６月～１９９８年３月，我院外科收治原发性甲状旁腺功能亢进症１１例。术前根据临床表现、实验室检查以及经Ｂ超、ＣＴ、彩色多普勒超声波及９９ｍＴｃＭＩＢＩ检查获定性定位诊断者９例。１１例均行手术治疗，手术成功１０例。病理检查结果：甲状旁腺腺瘤１０例，正常甲状旁腺１例。作者认为：①应提高对本病的认识以利早期诊断，术前联合应用无创性影像学检测手段以准确定位；②术者应熟悉局部解剖，尤其对异位甲状旁腺的充分认识，要有清晰的探查思路和高超的操作技巧，并结合术中常规冰冻切片检查以提高手术成功率；③术后加强内科治疗及随访，以全面提高甲状旁腺功能亢进症的诊治水平。     

Apoptosis in Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD), parathyroid adenoma (PA), or parathyroid carcinoma (PC). Although several studies have already been conducted, there is a lack of a definite diagnostic marker, which could unambiguously distinguish MGD from PA or PC. The accurate and prompt diagnosis has the key meaning for effective treatment and follow-up. This review paper presents the role of apoptosis in PHPT. The comparison of the expression of Fas, TRAIL, BCL-2 family members, p53 in MGD, PA, and PC, among others, was described. The expression of described factors varies among proliferative lesions of parathyroid gland; therefore, these could serve as additional markers to assist in the diagnosis.     

A prospective evaluation of novel methods to intraoperatively distinguish parathyroid tissue utilizing a parathyroid hormone assay

BACKGROUND: Frozen section analysis has traditionally been used to confirm the identity of parathyroid tissue intraoperatively; however, it is time-consuming and costly and requires the excision of a significant portion of tissue. An intraoperative biopsy and analysis with a parathyroid hormone (PTH) assay is a possible alternative; however, this technique has not been perfected. METHODS: Two hundred twenty-three tissue specimens were collected prospectively from patients undergoing neck exploration. Each specimen was sampled intraoperatively using three different biopsy techniques: a fine-needle aspiration (FNA) with 10 passes of a needle (FNA10), a FNA with 20 passes of a needle (FNA20), and a tissue biopsy of approximately 1.0 mm3 (BIOPSY). The PTH concentration of each sample was determined via the Elecsys 1010 PTH immunoassay. The final tissue diagnosis was determined by histology or operative data. RESULTS: Parathyroid samples from all techniques had higher median PTH concentrations than nonparathyroid samples. However, the accuracies for the detection of parathyroid tissue varied markedly (PTH cutoff of 1000 pg/ml): the accuracies of the FNA10 and FNA20 were 71 and 80%, respectively, while the BIOPSY was 99% accurate. CONCLUSIONS: This is the first prospective study evaluating multiple methods to diagnose parathyroid tissue intraoperatively using a rapid PTH assay. We conclusively show that the BIOPSY technique is 99% accurate for the diagnosis of parathyroid tissue, and therefore, should be the method of choice when the intraoperative confirmation of parathyroid tissue is needed.     

甲状旁腺腺瘤合并甲状腺结节34例临床分析

目的探讨甲状旁腺腺瘤合并甲状腺结节的诊断及外科治疗方法。方法回顾性分析我院收治的34例甲状旁腺腺瘤合并甲状腺结节的临床诊治经验。结果甲状旁腺腺瘤单侧单发多见(3l/34),单侧甲状旁腺腺瘤合并同侧甲状腺结节多见(25/31)。甲状腺结节病变性质主要为结节性甲状腺肿(27/34)。34例均行外科手术治疗。术后早期有8例患者出现短时的低钙血症,余无明显并发症。术后随访26例,全部患者甲状旁腺腺瘤均无明显复发迹象,结节性甲状腺肿患者有2例术后复查再次发现甲状腺结节,均予以动态观察,未行进一步手术切除,其余病例甲状腺结节均无复发。结论手术切除是治疗甲状旁腺腺瘤合并甲状腺结节的最有效的方法,最常用手术方式为单侧颈部探查术,术前定性及定位诊断结合术中诊断是手术成功的关键。     

Large goiter and multiple rib tumors

We report an interesting case of a 47-yr-old who had a large goiter and multiple rib tumors. The patient was initially suspected of having thyroid cancer, which had metastasized on the ribs, based on imaging studies. However, laboratory tests revealed a high level of ionized calcium and parathyroid hormone (PTH). The large goiter was diagnosed as having parathyroid tumors owing to the high level of PTH in the tissue fluid. The biopsy specimen from a rib tumor was diagnosed as containing brown tumors associated with primary hyperparathyroidism (PHP). The patient also had prolactinoma and pancreatic gastrinoma. Her daughter had both prolactinoma and PHP, and her brother and her father had PHP. Thus, the patient was diagnosed as having multiple endocrine neoplasia type 1.     

Calcium, phosphorus, cardiovascular events and all-cause mortality in hemodialysis patients: a single-center retrospective cohort study to reassess the validity of the Japanese Society for Dialysis Therapy guidelines

Mineral and bone disorders frequently cause cardiovascular complications and mortality in hemodialysis patients, but few observational studies of Japanese patients have investigated this matter. A retrospective cohort study of 99 patients (53 males, 46 females; mean age: 65 +/- 12 year; 38% with diabetes mellitus) on maintenance hemodialysis in our dialysis center was conducted. Mean serum Ca, P and intact parathyroid hormone (iPTH) levels were 9.2 +/- 0.9 mg/dL, 6.1 +/- 1.7 mg/dL, and 233 +/- 333 pg/mL, respectively. The cutoff values for each of these three parameter were defined according to the target ranges recommended by the Japanese Society for Dialysis Therapy (JSDT) guidelines (Ca: 8.4-10.0 mg/dL; P: 3.5-6.0 mg/dL; iPTH: 60-180 pg/mL). During a 45-month follow up, patients with all parameters outside the target ranges showed the highest incidence of cardiovascular events and all-cause deaths (16.6 and 29.2 per 1000 person-years, respectively). The relative risks of cardiovascular events and all-cause deaths were analyzed by multivariate Cox regression models. The hazard ratio (HR) for cardiovascular events was significantly lower for patients who achieved serum Ca and P objectives compared with others (HR: 2.12; 95% CI: 1.04-4.34; P < 0.05), and similar differences were observed for all-cause deaths (HR: 3.10; 95% CI: 1.13-8.53; P < 0.05). However, the relationship between iPTH levels and each of the endpoints was less pronounced. The results of this study provide support for the JSDT guidelines, which give priority to the control of serum Ca and P levels over the control of parathyroid function.     

Risk factors for hypocalcemia in dialysis patients with refractory secondary hyperparathyroidism after parathyroidectomy: a meta-analysis

ObjectiveHypocalcemia after parathyroidectomy (PTX) results in tetany, diarrhea, cardiac arrhythmia, and even sudden death. However, a meta-analysis or systematic evaluation of risk factors with the occurrence and development of hypocalcemia in patients with secondary hyperparathyroidism (SHPT) after PTX has never been performed.MethodsA thorough search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and EMBASE, was performed to retrieve relevant studies from database inception to June 2021. Quality of the included studies was assessed by two independent reviewers using the Newcastle–Ottawa Scale. Review Manager 5.3 and Stata 16.0 were used for meta-analysis. The random-effects model was adopted to calculate the 95% CIs (I²> 50% or p < 0.05) of the combined effect size and the corresponding homogeneous data. Otherwise, a fixed-effects model was used.ResultsThirteen studies including 2990 participants who met the inclusion criteria were enrolled in the present meta-analysis. The overall quality of the enrolled studies had a score of >7 points. Risk factors significantly related to hypocalcemia in patients with SHPT after PTX were preoperative serum calcium (OR 0.19, 95%CI 0.11–0.31), preoperative alkaline phosphatase (ALP) (OR 1.01, 95% CI 1.01–1.02), and preoperative intact parathyroid hormone (iPTH) (OR 1.38, 95%CI 1.20–1.58). Meanwhile, age (OR 0.97, 95%CI 0.87–1.10) was not significantly correlated with hypocalcemia after PTX.ConclusionsBased on the current evidence, preoperative serum calcium, preoperative ALP, and preoperative iPTH were significant predictors of hypocalcemia in patients with SHPT after PTX. More attention should be given to patients with these risk factors for the prevention of postoperative hypocalcemia.     

The effect of secondary hyperparathyroidism and hemodialysis therapy on alveolar bone and periodontium

BACKGROUND: Alveolar bone is particularly sensitive to increased levels of parathyroid hormone (PTH) from either primary or secondary hyperparathyroidism (HPT). The purpose of this study was to examine the effect of secondary HPT on the periodontium of patients on hemodialysis. METHODS: The experimental group consisted of 35 patients with secondary HPT, with chronic renal failure treated by hemodialysis (E group). A control group (C group) was formed from 35 healthy age- and gender-matched subjects attending the maxillofacial outpatient clinic for a variety of reasons. Blood samples were taken from the E group, and the biologically active intact parathormone molecule, PTH(1-84), was assayed using two-site immunoradiometric assay (IRMA). The time of onset and the duration since diagnosis of HPT was also recorded. In addition, for a subgroup of 25 matched pairs of patients, a clinical periodontal examination was performed, and the Ramfjord index teeth were recorded for: Plaque index (PI); Gingival index (GI); Probing depth (PD); and Clinical attachment level (CAL). A standardized panoramic X-ray was taken from all patients and computer-based linear measurements were used to assess alveolar bone loss (BL). Unpaired Student's t-test served to compare the two groups. Pearson's correlation coefficient test was used to study the association between PI, PTH level, disease duration and BL. RESULTS: Demographically, both groups were similar with no statistical difference. PI was also similar in the C and E group (2.03 +/- 0.13 and 1.76 +/- 0.17, respectively). GI, however, was slightly greater in the C group (1.28 +/- 0.09) compared to the E group (0.97 +/- 0.01). PD in the E group (2.92 +/- 0.14 mm) was almost identical to that of the C group (2.90 +/- 0.12 mm). Likewise, CAL in the E group (4.43 +/- 0.29 mm) did not differ from CAL in the C group (4.03 +/- 0.25 mm). Mean BL was also similar in the E and C groups (3.60 +/- 0.23 mm and 3.85 +/- 0.24 mm, respectively). PI showed a positive, significant correlation with BL (r = 0.457, P = 0.0008). CONCLUSION: From this study it can be concluded that secondary HPT does not have an appreciable effect on periodontal indices and radiographic bone height.