X-ray microanalysis of elemental changes in human parathyroid glands in primary and secondary hyperparathyroidism

The elemental composition of chief cells of parathyroid glands from patients with adenomatous primary hyperparathyroidism (HPT) and uremic secondary HPT was studied by X-ray microanalysis. Glands histologically deemed normal were used as controls. The analyses were also carried out on tissue specimens incubated in hypo-, normo- and hypercalcemic media (0.5, 1.25, and 3.0 mM calcium concentration). Analysis of chief cells from normal glands did not reveal any significant differences in ionic composition after exposure to the different calcium concentrations. In chief cells from adenomatous and uremic hyperplastic glands, elemental changes were noted. In comparison with specimens incubated in 1.25 mM calcium medium, cells in 0.5 mM calcium medium had a lower content of potassium and phosphorus. After stimulation with increasing extracellular concentration, an increase in the K/Na ratio was observed, due to a marked decrease of sodium and an increase of potassium: the calcium concentration was almost unchanged. Our findings indicate that in HPT an increase in serum calcium concentration might exert a stimulatory effect on the Na/K pump (sodium pump) and on the calcium-activated potassium channels. Either of these mechanisms might contribute to a lowering of cytoplasmic calcium. Our observations suggest that changes in ionic content of the parathyroid cells may be of importance for the stimulus secretion process in the cells.     

Values and limitations of the radioimmunological determination of plasma parathyroid hormone in the study of the functional activity of the parathyroid glands

Aim of the present study was to establish the limits and difficulties prevailing in RIA of PTH due to different specificity of antisera. Studies were carried out on normal volunteers and 36 patients with primary hyperparathyroidism (HPT) employing two different assay techniques a) 211/32 antiserum from Wellcome Lab. and b) Immuno Nuclear Corporation Kit. Plasma iPTH values were higher in most primary HPT patients than in normal subjects with both techniques. It is possible nevertheless to differentiate the primary HPT patients with normal plasma iPTH values from normal subjects by correlating plasma iPTH values with corresponding serum calcium values.     

Hyperparathyroidism in pregnancy: case report and review of the literature.

The apparent incidence of hyperparathyroidism (HPT) is low in pregnancy but will likely increase now that more asymptomatic HPT is being diagnosed. However, since the serum calcium levels are decreased in pregnant women, mild primary HPT may go unrecognized. In untreated cases of HPT, complications during pregnancy or during the neonatal period have included spontaneous abortion, stillbirth, neonatal death, neonatal tetany and hypercalcemia. A review of the literature indicates a substantial improvement in fetal outcome when parathyroidectomy is done during pregnancy, as in the case reported here. Therefore, parathyroidectomy is the treatment of choice when the diagnosis is made during pregnancy, although oral phosphate therapy may be an alternative if surgery is contraindicated.     

A new, vitamin D-based, multidimensional nomogram for the diagnosis of primary hyperparathyroidism

ObjectiveTo refine the diagnostic criteria for primary hyperparathyroidism (1°HPT) to identify atypical patients, in whom serum calcium, parathyroid hormone (PTH), or both are within the “normal” range.MethodsTotal serum calcium, intact PTH, and 25-hydroxyvitamin D [25(OH)D] levels were measured in patients with 1°HPT and healthy patient groups. Multivariate analysis of healthy patient data first identified factors that significantly affected PTH levels and defined a new PTH reference range with a mathematical model. That nomogram was then validated for prediction of atypical 1°HPT in patients with surgically confirmed disease.ResultsOn multivariate analysis, calcium (P = .0002), 25(OH)D (P < .0001), and age (P = .015) independently affected PTH. With these variables, we created a 4-dimensional nomogram that distinguished normal patients from those with hyperparathyroid states. Mathematically, this nomogram predicts 1°HPT when the measured serum PTH value is higher than PTH calculated by the following formula: PTH (pg/mL) = 120-[6 × calcium (mg/dL)]-[0.52 × 25(OH)D (ng/mL)] + [0.26 × patient age (years)]. When applied to our surgical group of patients, this nomogram successfully identified 100% of patients (238 of 238) with classic 1°HPT, 84% (64 of 76) with normocalcemic 1°HPT, and 54% (20 of 37) with 1°HPT and normal PTH.ConclusionThis study uniquely defines a patientspecific upper limit of normal for PTH based on the readily available variables of serum calcium, 25(OH)D, and patient age. Our nomogram may allow for more rapid definitive diagnosis and treatment of 1°HPT in patients with atypical presentations. (Endocr Pract. 2012;18:124-131)     

Selective inhibition of proteoglycan and hyaluronate synthesis in chondrocyte cultures by cyclofenil diphenol, a non-steroidal weak oestrogen.

Cyclofenil diphenol, a weak non-steroidal oestrogen, binds to albumin. In the presence of concentrations of albumin just sufficient to keep cyclofenil diphenol in solution, the compound inhibited the synthesis of [35S]proteoglycans, [3H]glycoproteins, [3H]hyaluronate and [3H]proteins in primary cultures of chondrocytes from the Swarm rat chondrosarcoma in a dose-dependent manner. When excess albumin was present, conditions were found (90 micrograms of cyclofenil diphenol and 4 mg of albumin per ml of culture medium) which completely inhibited [35S]proteoglycan and [3H]hyaluronate synthesis but had little effect on [3H]protein or [3H]glycoprotein synthesis. The time of onset of inhibition of [35S]proteoglycan synthesis by cyclofenil diphenol was very rapid (t1/2 less than 25 min) and incompatible with an action mediated through suppression of proteoglycan core protein synthesis. Cyclofenil diphenol inhibited the synthesis of [35S]chondroitin sulphate chains onto p-nitrophenyl beta-D-xyloside in the cultures. Cyclofenil diphenol had little effect on the secretion from chondrocytes of [35S]proteoglycans synthesized immediately prior to treatment. Chondrocyte cultures treated with cyclofenil diphenol recovered their biosynthetic activities almost completely within 3 h of removing the compound from the culture medium. Cyclofenil diphenol had a similar inhibitory action on the synthesis of [35S]proteoglycans in secondary cultures of human dermal fibroblasts from both normal subjects and patients with systemic sclerosis. It is proposed that cyclofenil diphenol inhibits the synthesis of [35S]proteoglycans by interfering with the formation of the glycosaminoglycan side chains of these molecules in the Golgi apparatus of cells. The action may be due to disturbance of Golgi membrane organization by the compound.     

Hypoparathyroidism after surgery on thyroid cancer: is there a delayed chance for recovery after a prolonged period of substitutive therapy?

INTRODUCTION: Transient and persistent hypoparathyroidism (HPT) belong to the well known complications of total thyroidectomy performed because of thyroid carcinoma. The true frequency of persistent hypoparathyroidism is often higher than estimated in the reports published by the specialized centers with low rate of complications. THE AIM OF THE STUDY: Investigation whether the repeated check-up, performed over 2 years post thyroidectomy, reveals some cases of recovery in patients diagnosed with persistent HPT post thyroid cancer surgery. MATERIAL AND METHODS: In total, 115 patients were included into the study, all of them treated with vitamin D derivatives and calcium supplementation. In 17 of them a diagnosis of transient hypoparathyroidism was made on the basis of evaluation performed 6 months after surgery, the remaining 98 were diagnosed with persistent HPT. Parathyroid (PTH) function was reevaluated after withdrawal of active vitamin D derivatives for 10 days and of calcium carbonate for two days during the hospital stay in patients admitted for radioiodine scan, thus after thyroxine withdrawal. The control group consisted of 123 DTC (differentiated thyroid carcinoma) patients without parathyroid dysfunction. On the basis of intact PTH serum level and calcium and phosphorus estimations HPT was unequivocally confirmed in 49 patients (50%). The remaining 49 patients exhibited normal PTH level and in 43 (86%) of them Ca(2+) level was also within normal range, thus delayed, recovery from HPT was stated. RESULTS: Our results indicate that reevaluation of hypoparathyroidism post total thyreoidectomy is necessary, as delayed recover of parathyroid dysfunction is a frequent phenomenon. We also propose criteria of reevaluation of HTP in patients on chronic substitutive therapy.     

Low serum reverse T3 levels in patients with primary hyperparathyroidism

Although patients with primary hyperparathyroidism (1 degree HPT) were euthyroid, we measured serum thyroid hormone levels in 16 patients with 1 degree HPT together with 17 patients with hypercalcemia due to malignant diseases (HCM). In patients with 1 degree HPT, serum levels of T3, T4 and T3U were within normal range, but serum rT3 (reverse T3) levels (205 +/- 37 pg/ml, mean +/- SD) were significantly decreased as compared with those in normal controls (276 +/- 44 pg/ml, P less than 0.01). A significant inverse correlation was observed between the serum levels of rT3 and parathyroid hormone (PTH) (r = 0.54, P less than 0.05). After parathyroidectomy, serum rT3 levels were significantly elevated (240 +/- 56 pg/ml) compared to preoperative levels (P less than 0.01). Low levels of serum rT3 seemed to be attributed to the high levels of serum PTH. On the other hand, serum levels of T3 and T4 were low and serum rT3 levels were high in patients with HCM. Low serum rT3 allows for the differentiation of patients with 1 degree HPT from those with HCM.     

Efficacy of Repetitive Transcranial Magnetic Stimulation in the Treatment of Patients with Chronic Primary Insomnia

This study assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of patients with chronic primary insomnia. Hundred and twenty patients with chronic primary insomnia were randomly assigned to three study groups (n = 40 per group): rTMS, medication, or psychotherapy treatment (both latter as controls). The treatments proceeded for 2 weeks, after which treatment efficacies were assessed in each study group based on changes in polysomnography parameters, Pittsburgh sleep quality index, and indices of HPA and HPT axes (serum cortisol, adrenocorticotropic hormone, highly sensitive thyrotropin, free T3, and free T4). Further, the relapse and recurrence rates within 3 months after respective treatments were also measured. rTMS treatment significantly better (p < 0.05) improved stage III sleep and REM sleep cycle compared with both control groups. Further, rTMS treatment group was more advantageous in improving the indices of HPA and HPT axes (p < 0.05 vs. both control groups). In addition, the relapse and recurrence rates were also the lowest in rTMS treatment group. In conclusion, rTMS treatment is more advantageous than both medication and psychotherapy treatments in improving the sleep architecture. Further, rTMS significantly decreases the body awakening level and provides a better long-term treatment effect.     

Drug treatment of primary hyperparathyroidism: use of clodronate disodium.

Clodronate disodium (dichloromethylene diphosphonate), a specific inhibitor of bone resorption, was given by mouth (1.0-3.2 g daily) to nine patients with primary hyperparathyroidism for two to 32 weeks so that its clinical and metabolic effects could be evaluated. Bone resorption decreased in all patients as judged by a fall in the fasting urinary calcium to creatinine and hydroxyproline to creatinine ratios. Serum calcium concentration was increased in all patients before treatment and fell in response to treatment to values near the upper end of the normal range. Hypercalcaemia and hypercalciuria recurred when treatment was stopped. In three patients treated for longer than 19 weeks clodronate failed to sustain the reduction in serum calcium concentration but the concentration remained below pretreatment values. These results suggest that clodronate may be of use in the medical management of primary hyperparathyroidism, particularly in patients in whom suppression of bone disease is desirable before surgery or in whom surgery is contraindicated.     

唑来膦酸治疗原发性骨质疏松症的效果观察

目的：研究唑来膦酸在治疗原发性骨质疏松症过程中患者骨密度及疼痛的变化。方法：设计为期两年的随机、前瞻性研究,通过Achilles定量超声（QUS）系统测量骨密度（BMD）,进行问卷调查、疼痛评估,共入选60例原发性骨质疏松症患者。随机分为唑来膦酸组和对照组,唑来膦酸组使用唑来膦酸及元素钙治疗;对照组使用元素钙治疗。治疗前后分别进行骨密度测定及疼痛评估,进行对比研究。结果：治疗两年后.与治疗前比较,唑来膦酸组BMD上升（P〈0.05）;对照组BMD无明显变化（P〉0.05）。两组临床获益率分别为73.33%和46.67%,无显著差别（P〉0.05）。结论：唑来膦酸治疗原发性骨质疏松症有良好作用,能提高骨密度,对骨质疏松的治疗及预防骨折具有重要的意义。     

Optimizing efficacy of quick parathyroid hormone determination in the operating theater

The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.     

Design, synthesis, and evaluation of cyclofenil derivatives for potential SPECT imaging agents

To develop technetium- and rhenium-labeled nonsteroidal estrogen imaging agents for estrogen receptor (ER) positive breast tumors, two groups of rhenium and technetium cyclofenil derivatives were synthesized and characterized. The binding affinities of the rhenium complexes for ERs were determined. The tricarbonyl rhenium complex showed the highest binding affinity for ERs (81.2 for ERβ, 16.5 for ERα). Tricarbonyl technetium cyclofenil complexes were obtained in high radiochemical purity and radiochemical yields. The results of studies of their octanol/water partition and in vitro stability are presented. These results demonstrate that these radiolabeled cyclofenil derivatives may be considered as potential breast cancer imaging agents.     

Action of an ovulation stimulator on the genital function of the female rat]

Effect of cyclofenil on genital function implied organs, is studied in cyclic female rats injected s. cut: 0.5, 5 or 50 mg/kg/day, during 12 days. The treatment increases pituitary, adrenal and uterine weights, decreases ovarian weight, adrenal and ovarien cholesterol. These data suggest that cyclofenil acts directly or undirectly at different levels of hypothalamo-pituitary-genital axis with central inhibition and light peripheral stimulation.     

Clinical usefulness of the (chloride-90)/phosphate ratio for distinguishing primary hyperparathyroidism from hypercalcemia due to other causes

In order to obtain a good separation line between patients with primary hyperparathyroidism (1 degree HPT) and those with non-parathyroidal hypercalcemia (NPHC), serum chloride (Cl) and phosphate (P) concentrations were analyzed. Ninety-nine per cent of the patients with 1 degree HPT had a Cl/P ratio greater than or equal to 33, but 29% of patients with NPHC were also included in this range. When the (Cl-90)/P ratio was used to separate into two groups, 98% of the patients with 1 degree HPT had a ratio greater than or equal to 5.0, and 94% of the patients with NPHC had a ratio less than 5.0. From these results, while high sensitivity was achieved both with the Cl/P and (Cl-90)/P ratios, the (Cl-90)/P ratio provided higher specificity. Therefore we conclude that the (Cl-90)/P ratio was excellent in distinguishing 1 degree HPT from other types of hypercalcemia.     

Current concepts in primary hyperparathyroidism

622 patients were operated on between 1966 and 1988. Urolithiasis was the most common presenting symptom (26%) but routine measurements of serum calcium led to detect 50% cases. At present, the disease is three times more frequent in women than in men. Estrogenic deprivation, neck irradiation (3.4%) and lithium therapy favor the occurrence of hyperparathyroidism (HPT); frequent association with goiter (19.8%), diabetes (8.3%) and multiple endocrine neoplasia (3.5%) has been noticed. Bone Gla protein concentrations correlate with calcium and HPT blood concentrations but do not reflect the severity of bone damage. Dual photon absorptiometry is now available for quantification and follow-up of bone demineralization, especially in asymptomatic forms of HPT.     

Design and synthesis of functionalized cyclopentadienyl tricarbonylmetal complexes for technetium-94m PET imaging of estrogen receptors

Cyclopentadienyl tricarbonylmetal (CpTM, M = Re, (94m)Tc) complexes, some based on a typical nonsteroidal estrogen, were prepared with the aim of developing technetium- and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors. CpT[(94m)Tc] compounds with simple cyclopentadienyl substituents were first synthesized using a modified double ligand transfer reaction. The in vivo biodistribution of one of these CpT[(94m)Tc] complexes was determined by tissue dissection and microPET imaging. Novel C-ring substituted analogues of cyclofenil, a nonsteroidal compound known to bind the ER, were also prepared, and their ER binding was measured. Because of their low ER affinity, however, labeling and imaging studies of these compounds were not pursued. It is notable that the highest ER binding analogue, a CpTRe cyclofenil derivative, could be synthesized from the corresponding ferrocenyl cyclofenil analogue by the double ligand transfer reaction. This further demonstrates the versatility of the double ligand transfer reaction and indicates that the synthesis of technetium and rhenium radiolabeled agents for breast tumor imaging and therapy is also likely to be successful.     

Trabecular Bone Score in Patients with Normocalcemic Hyperparathyroidism

Objective: The effects of normocalcemic hyperparathyroidism (NHPT) on bone remain unclear. The objective of this study was to evaluate differences in the trabecular bone score (TBS) of NHPT patients and asymptomatic hypercalcemic hyperparathyroidism (HHPT) patients.Methods: We performed a prospective study that enrolled consecutive patients with asymptomatic hyperparathyroidism (NHPT and HHPT) with a follow-up ≥1 year at the University Hospital of Valladolid, Spain. Metabolic phosphocalcium plasma and urine parameters were evaluated in ≥2 determinations during follow-up to classify patients as NHPT patients or asymptomatic HHPT patients. A control group was enrolled during the same period. TBS and bone mineral density (BMD) were evaluated.Results: Thirty-nine patients with asymptomatic HPT (24 with NHPT and 15 with HHPT) and 24 controls were recruited. NHPT patients and HHPT patients had a similar mean age, vitamin D level, TBS, and areal BMD (all sites). Compared to controls, symptomatic HPT patients had significantly higher parathyroid hormone (PTH) and calcium levels and significantly lower TBS and areal BMD at all sites (all P<.05). A significant negative relationship between TBS and PTH was found in asymptomatic HPT patients (r = -0.320, P = .043), which remained significant after adjustment for age, sex, and body mass index.Conclusion: There was no difference in the TBS between NHPT and HHPT patients. However, there was a reduction in the TBS of patients with asymptomatic HPT that was related to PTH levels but had no repercussion on bone mass. Higher levels of PTH seem to be responsible for this alteration in microarchitecture texture.Abbreviations:aBMD = areal bone mineral densityBMD = bone mineral densityBMI = body mass indexDXA = dual-energy X-ray absorptiometryHHPT = hypercalcemic hyperparathyroidismHPT = hyperparathyroidismHR-MRI = high-resolution magnetic resonanceHR-pQcT = high-resolution peripheral quantitative computed tomographyNHPT = normocalcemic hyper-parathyroidismPTH = parathyroid hormoneTBS = trabecular bone score25vitD = 25-hydroxyvitamin D     

Abnormal parathyroid cell proliferation precedes biochemical abnormalities in a mouse model of primary hyperparathyroidism

The properties of neoplastic proliferation and hormonal dysregulation are tightly linked in primary hyperparathyroidism (HPT). However, whether abnormal parathyroid proliferation is the cause or result of a shift in calcium-sensitive parathyroid hormonal regulation has been controversial. We addressed this issue by analyzing the temporal sequence of these fundamental abnormalities in a mouse model of primary HPT. These transgenic mice (PTH-D1) harbor a transgene that targets overexpression of the cyclin D1 oncogene to parathyroid cells, resulting in parathyroid hypercellularity with a phenotype of chronic biochemical HPT and, notably, an abnormal in vivo PTH-calcium set point. We examined parathyroid cell proliferation and biochemical alterations in PTH-D1 and control wild-type mice from ages 1-14 months. Strikingly, abnormal parathyroid proliferation regularly preceded dysregulation of the calcium-PTH axis, supporting the concept that disturbed parathyroid proliferation is the crucial primary initiator leading to the development of the biochemical phenotype of HPT. Furthermore, we observed that decreased expression of the calcium-sensing receptor in the parathyroid glands occurs several months before development of biochemical HPT, suggesting that decreased calcium-sensing receptor may not be sufficient to cause PTH dysregulation in this animal model of primary HPT.     

不同病情急性缺血性脑卒中患者血清过氧化还原蛋白1、钙调蛋白、触珠蛋白水平与预后的关系分析

摘要 目的：探讨不同病情急性缺血性脑卒中（AIS）患者血清过氧化还原蛋白1(PRDX1)、钙调蛋白(CAM)、触珠蛋白(HPT)水平与预后的关系。方法：收集2018年4月~2019年4月期间本院收治的127例AIS患者为研究对象,根据患者的病情分为轻度组(39例)、中度组(48例)、重度组(40例),根据患者的改良Rankin 量表( mRS)评分将患者分为预后良好组(73例)和预后不良组(54例),另选同期在我院进行健康检查的健康受试者50例为对照组。对比所有受试者PRDX1、CAM、HPT水平。对比不同预后患者的一般资料、PRDX1、CAM、HPT水平。分析PRDX1、CAM、HPT与NIHSS评分、mRS评分的关系。以多因素Logistic回归分析AIS患者预后的影响因素。结果：轻度组、中度组、中度组的PRDX1、CAM、HPT水平均高于对照组,且随着患者的病情加重,PRDX1、CAM、HPT水平依次升高,差异均有统计学意义(P<0.05)。预后不良组患者的年龄、PRDX1、CAM、HPT均高于预后良好组(P<0.05)。经Pearson检验,AIS患者的PRDX1、CAM、HPT与NIHSS、mRS评分均呈正相关(P<0.05)。经多因素Logistic回归分析可得,年龄较高、PRDX1水平升高、CAM水平升高、HPT水平升高是AIS患者预后不良的危险因素(P<0.05)。结论：AIS患者的PRDX1、CAM、HPT水平异常升高,且与其病情及预后呈现明显的相关性,年龄、PRDX1、CAM、HPT是患者预后的影响因素,对于病情的评估、预后的判断有一定的临床指导价值。