Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

Intermittent low-dose treatment with parathyroid hormone (PTH) analogues has become widely used in the treatment of severe osteoporosis. During normal physiological conditions, PTH stimulates both bone formation and resorption, and in patients with primary hyperparathyroidism, bone loss is frequent. However, development of the biochemical measurement of PTH in the 1980s led us to understand the regulation of PTH secretion and calcium metabolism which subsequently paved the way for the use of PTH as an anabolic treatment of osteoporosis as, when given intermittently, it has strong anabolic effects in bone. This could not have taken place without the basic understanding achieved by the biochemical measurements of PTH. The stimulatory effects of PTH on bone formation have been explained by the so-called 'anabolic window', which means that during PTH treatment, bone formation is in excess over bone resorption during the first 6-18 months. This is due to the following: (1) PTH up-regulates c-fos expression in bone cells, (2) IGF is essential for PTH's anabolic effect, (3) bone lining cells are driven to differentiate into osteoblasts, (4) mesenchymal stem cells adhesion to bone surface is enhanced, (5) PTH has a direct antiapoptotic effect on osteoblasts and (6) when PTH interferes with remodelling, the osteoblasts over-compensate, and (7) PTH also decreases sclerostin levels, thereby removing inhibition of Wnt signalling which is required for PTH's anabolic actions. Thus, the net formative effect of PTH given in intermittent treatment emerges through a complex network of pathways. In summary, the effects of PTH on bone turnover are dependent on the mode and dose of administration and studies investigating the mechanisms underlying this effect are reviewed in this article.     

Angiogenesis inhibitor attenuates parathyroid hormone-induced anabolic effect

In vivo osteogenic responses to anabolic stimuli are expected to be accompanied by angiogenesis as well as in the process of remodeling of bone. Consequently, angiogenesis might play an important role in mediating bone forming stimulating effect of parathyroid hormone (PTH). To investigate this relationship, we used actively growing young Sprague–Dawley rats and CKD-732, one of the angiogenesis inhibitor (AI) to reveal the relationship of angiogenesis in the effect of PTH. The groups were divided as (1) vehicle [VEH group], (2) PTH(1–84) [PTH group], (3) AI alone [AI group], (4) PTH(1–84) + AI concomitance [PTH-AI group] and were treated for 6 weeks. The bone mineral density (BMD) of PTH group was higher than VEH group and the gain of bone mass was attenuated in PTH-AI group. The maximal failure load in PTH group was higher than VEH group, but it was definitely attenuated by concurrent use of AI. Moreover, the toughness showed similar significant deterioration in PTH-AI group. General bone turnover was also significantly decreased in PTH-AI group as shown by the absence of increase in osteocalcin and β-crosslaps and by decrease in metaphyseal length. The BMD or the biomechanic data of AI only group were similar to the VEH group, suggesting the minimal effect of AI itself on the normal modeling phase of the growing rats. In conclusion, the angiogenesis seemed to contribute to completing the anabolic effect of PTH especially for bone strength.     

Development of a highly sensitive and specific two-site enzyme immunoassay for parathyroid hormone (1-34): Application to pharmacokinetic study on intranasal parathyroid hormone (1-34) in human

A highly sensitive and specific two-site enzyme immunoassay for parathyroid hormone (1-34) (PTH(1-34)) and its usability for the pharmacokinetic study are described. Plasma samples were incubated simultaneously with 2,4-dinitrophenylated anti-PTH(1-34) IgG and anti-PTH(1-34) Fab′- β-D -galactosidase conjugate. The immune complex formed of the three components was trapped onto (anti-2,4-dinitrophenyl group) IgG-coated polystyrene balls. β-D - Galactosidase activity bound to the polystyrene balls was assayed by fluorometry. The practical detection limit of PTH(1-34) was 50 fg (12 amol)/0.05 ml of sample and 1 pg/ml as the concentration and practically no interference occurred by PTH(1-84) and PTH-related protein (1-34) up to 300 pg/ml and 10 ng/ml, respectively. The application of this method has enabled us to directly estimate the bioavailability of PTH(1-34) dosed intranasaly at the prescribed level (0.090 mg). The pharmacokinetic parameters of the intranasal PTH(1-34) (n = 4) thus estimated were as follows: the area under the plasma concentration-time curve (AUC) = 20,500 ± 15,900(SD) pg·min/ml; the mean residence time (MRT) = 194 ± 16.3(SD) min; and the maximal concentration (Cmax) = 98 ± 51(SD) pg/ml with the maximal time (Tmax) = 35.0 ± 12.2(SD) min. J. Clin. Lab. Anal. 12:268–275, 1998. © 1998 Wiley-Liss, Inc.     

甲状旁腺激素基因多态性对广东地区老年人骨密度的影响

目的:探讨甲状旁腺素(PTH)基因多态性与中国广东地区部分老年人群骨密度的相关性.方法:随机筛选广东老年人549例,年龄65～87岁,平均(71.03±7.37)岁,采用双能X线吸收测定其腰椎侧位、股骨颈、粗隆间、大转子、ward's三角等部位的骨密度值.用聚合酶链反应及限制性片段长度多态性技术检测外周血白细胞基因组PTH基因型.结果:549例受试对象中,PTH基因BB型382例,69.6%;Bb型148例,27.0%;和bb型19例,3.4%.无论是整个受试群体,还是根据性别将其分为男性及女性群体,其等位基因及基因型分布均符合Hardy-Wenbeng平衡定律.分析基因型与骨密度的关系显示,不同的基因型之间的骨密度均无统计学意义变化(P>0.05).结论:PTH基因多态性与广东地区汉族老年人群骨密度关系不密切,不能作为筛查和预示骨质疏松症的遗传易感位点.     

肥胖糖尿病肾病患者血清甲状旁腺激素及骨密度的研究

目的探讨肥胖糖尿病肾病患者的血清甲状旁腺激素(PTH)及骨密度(BMD)的特点。方法回顾性分析乌鲁木齐市友谊医院2018年2月至2019年2月收治的90例2型糖尿病肾病患者,根据体质指数(BMI)将其分为A组非超重型(体重正常,BMI 18.5~22.5 kg/m^2)糖尿病肾病患者,B组肥胖型糖尿病肾病患者(BMI 22.6~25.5 kg/m^2),C组超重型糖尿病肾病患者(BMI>25.5 kg/m^2)。另选取30例非肥胖非肾病的2型糖尿病患者作为对照组。测定并比较每组患者血清PTH,血钙,血磷与Ward三角区值、股骨大转子区、股骨颈、桡骨全段、腰椎区的骨密度值,记录血清PTH所导致的不良反应,以及骨质疏松所导致的并发症的情况进行统计分析。结果A组血钙水平显著高于对照组,血钙水平与对照组比较差异统计学意义(P>0.05);B、C两组患者的血清PTH、血磷水平均显著高于对照组,血钙水平低于对照组(P<0.05),且随着BMI升高,血清PTH、血磷水平显著升高,血钙水平显著降低。A组股骨大转子区、股骨颈、腰椎区骨密度值低于对照组(P<0.05),B、C两组Ward三角区值、股骨大转子区、股骨颈、桡骨全段、腰椎区骨密度值均明显低于对照组,且随着BMI升高,各部位骨密度值明显降低。A组疲劳乏力、肾结石绞痛的发生率均高于对照组(P<0.05),B、C两组疲劳乏力、肾结石绞痛、恶心呕吐、血清PTH型高血压的发生率均明显高于对照组,且随着BMI升高,血清PTH所导致的不良反应发生率明显升高。A组颈椎腰椎病、致残数的发生率均高于对照组,B、C两组行动受阻、颈椎腰椎病、骨折史,致残数均明显高于对照组,差异均具有统计学意义(P<0.05),且随着BMI升高,骨质疏松所导致的并发症发生率明显升高。结论血清PTH与BMD的测定对于肥胖糖尿病肾病的早期诊断具有重要意义,且PTH值随着糖尿病肾病患者的肥胖程度逐步增高,BMD值随着糖尿病肾病患者的肥胖程度逐步降低,且不同区域的骨密度均有不同程度的变化。     

甲状旁腺激素对HAEC细胞EndMT诱导作用及机制探讨

目的 探讨甲状旁腺激素（parathyroid hormone,PTH）是否诱导血管内皮细胞上皮细胞-间充质转化（endothelial-mesenchymal transition,EndMT）及相关机制.方法 血管内皮细胞HAEC培养至对数期,分别加入不同剂量的全长重组PTH（10-12 mol/L、10-11 mol/L、10-10mol/L、10-9mol/L、10-8mol/L）作用48h;再在10-8mol/L PTH作用下,选择12、24、36、60h 4个时间点;分别收集总蛋白.Western blot分析Ve-Cadherin、CD31、α-SMA、TGF-β1和ILK的表达改变.结果 Western blot结果表明在PTH作用下,血管内皮细胞标志分子Ve-Cadherin和CD31表达降低;纤维细胞标志分子α-SMA表达则显著升高,且呈时间和剂量依赖性.Western blot分析发现TGF-β1和ILK表达同时升高.结论 PTH减弱内皮细胞特征、增强纤维化特征,诱导HAEC细胞发生EndMT,TGF-β1-ILK通路是其调控的可能通路之一.     

糖尿病与非糖尿病血液透析患者血清甲状旁腺激素水平分析

目的评估糖尿病与非糖尿病血液透析患者血清全段甲状旁腺激素(intact parathyroid hormone,iPTH)水平的差异及其在长期血液透析中的变化。方法维持性血液透析患者89例,检测血清PTH值。将患者分为糖尿病肾病(diabetic nephropthy,DN)组(20例)、非糖尿病肾病合并糖尿病组(6例)与非糖尿病组(63例);根据患者透析龄的长短将各组分为短期组(透析龄<5年)与长期组(透析龄≥5年);分析各组iPTH水平之间的差异。结果 DN组的iPTH水平低于其它2组,具有显著性差异(P<0.05和P<0.01);非糖尿病组的iPTH水平在长期透析龄组中明显升高,高于其他各组,具有显著性差异(P<0.05)。结论 DN非糖尿病肾病血液透析患者具有较低的血清iPTH水平,长期血液透析患者iPTH水平的升高在非糖尿病患者中表现更显著。     

Quality control in parathyroid hormone radioimmunoassays: a multicentre study performed by the European Parathyroid Hormone Study Group

This paper reports the results of the second collaborative study of radioimmunological parathyroid hormone (PTH) determination in twenty-two serum samples, performed by twenty-four laboratories in the European PTH Study Group (EPSG). It demonstrates that radioimmunoassay systems can yield results that are clinically relevant in the differential diagnosis of hypercalcaemia. However, it also emphasizes, that numerical values, generated by a spectrum of different immunoassay systems cannot be compared directly. Numerical values can be compared, if the same reagents and method, provided as a kit, are used. Using their 'in house' reagents, fourteen out of twenty laboratories discriminated between low and normal iPTH serum, eleven of them between normal and marginal hyperparathyroid sera, seventeen of them between normal and grossly hyperparathyroid sera. Four laboratories agreed to a ranking order of serum samples, which was expected to cover all ranges on an average standard calibration curve, six were mistaking once, and ten two or more times. Using the kit, all participants but one discriminated between sera with low, normal, marginal and grossly elevated PTH and all agreed to the above ranking order of these sera. As far as these criteria are concerned, there was no relation between the quality of results, obtained with 'in house' reagents, and differences in antisera (but one, which was an anti human 1-34 PTH antiserum), methods of tracer preparation, and peptides used for tracer preparation. But only few laboratories, using bovine PTH standards were able to satisfy the above described conditions, whereas all of the laboratories, using human PTH standard preparations, did so with minor exceptions.     

Short Anabolic Peptides for Bone Growth

Loss of bone occurs in the age‐related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone‐anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone‐anabolic drug is available in the market. The discovery of more novel, cost‐effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone‐anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone‐anabolic peptides, and their development for promoting bone growth.     

激素替代治疗对绝经后妇女骨代谢的影响

目的探讨绝经后骨质疏松有效的预防措施。方法采用激素替代治疗(HRT)中的连续联合治疗方案,每日服用倍美安1片,连续半年,测定服药前后的血碱性磷酸酶(ALP)、骨钙素(BGP)、空腹尿钙/肌酐(Ca/Cr)、骨矿含量(BMC)、雌酮(E1)、雌二醇(E2)、睾酮(T)。结果与服药前相比较,ALP、BGP、Ca/Cr有显著性下降,以Ca/Cr下降最为显著,BMC维持不变,对照组的BMC下降4.9%。结论HRT对骨形成和骨吸收均有抑制作用,但以抑制骨吸收为主,从而防止骨丢失,保持骨量,预防骨质疏松。     

血液透析患者甲状旁腺激素水平与营养的关系研究

目的探讨血液透析患者甲状旁腺素与营养状况的关系,为提高患者透析充分而改善患者营养状况提供临床依据。方法①选择中山大学附属第一医院肾内科112例血液透析患者,测定患者透析前血清甲状旁腺(PTH)、血清白蛋白(ALB)、血红蛋白(Hb)、C-反应蛋(CRP)、转铁蛋白(TF);②人体指数学测量:肱二头肌皮褶(BSF)、肱三头肌皮褶(TSF)、上臂中部周径(MAC)、握力(HGS);③使用改良整体主观评估法(modifiedquantitativesubjectiveglobalassessment,MQSGA)评估患者营养状况;④测定患者透析前血清IGF-1、IGFBP3;⑤根据相关公式计算上臂中部肌肉周径(MAMC)、上臂中部肌肉面积(AMA);⑥统计分析PTH与各营养指标之间的直线相关和回归关系。结果PTH与MQSGA呈正相关(P<0.01),与ALB、MAC、MAMC、AMA呈负相关(P<0.05),与Hb呈显著负相关(P<0.001);PTH与MQSGA、Hb、MAMC、AMA之间存在回归关系(P<0.05)。结论PTH是影响血液透析患者营养状况的重要尿毒症毒素。     

A probable case of oral bisphosphonate-associated osteonecrosis of the jaw and recovery with parathyroid hormone treatment

Introduction: Bisphosphonates are effective for treating osteoporosis, Paget's disease of bone, and malignancy-associated bone diseases. Bisphosphonate-associated osteonecrosis of the jaw (ONJ) is a rare but serious adverse effect of bisphosphonate therapy. Due to inhibitory actions on bone turnover, bisphosphonate therapy may result in the accumulation of microdamage.Case summary: A 74-year-old Korean woman (height, 150 cm; weight, 51 kg) was referred to the Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea, for evaluation of pain and persistent abnormal exposure of jaw bone after extraction of teeth. She had been receiving weekly oral alendronate treatment for osteoporosis for ~5 years. The patient had the clinical features of bisphosphonate-associated osteonecrosis of the mandible, which was precipitated by teeth extraction ~14 months prior to the outpatient referral visit. At her clinical baseline visit, serum hormone concentrations and bone turnover markers were as follows: thyroid-stimulating hormone, 0.88 μIU/mL (reference range, 0.25-5.00 μIU/mL); 25-hydroxyvitamin D₃, 20.9 (9.0-37.6) ng/mL; parathyroid hormone (PTH), 57 (11-62) pg/mL; serum osteocalcin, 8.7 (12.9-55.9) ng/mL; and urine N-telopeptide 21 (26-124) nM/mM creatinine. She had multiple systemic risk factors for ONJ, including older age, type 2 diabetes mellitus, and long duration of bisphosphonate therapy. There was no mandibular lesion improvement despite repeated surgical procedures performed within a 14-month period. Bisphosphonate therapy was discontinued and PTH therapy was started. After 2 months, exposed oral mucosa had healed. After 4 months of treatment, the pain had completely subsided, and after 6 months the patient's eating and drinking habits returned. The serum concentration of osteocalcin, a bone formation marker, which was initially suppressed (8.7 ng/mL), increased 174% (15.1 ng/mL) from baseline after 6 months of treatment with PTH.Conclusions: Here we report a probable case of oral bisphosphonate-associated ONJ featuring suppressed bone turnover. Treatment with the bone formation-stimulating agent PTH was beneficial.     

血液透析患者成纤维细胞生长因子23水平及相关性分析

目的观察维持性血液透析（maintenance hemodialysis,MHD）患者成纤维细胞生长因子23（fibroblast growth factor 23,FGF-23）的水平,分析其与全段甲状旁腺激素（intact parathyroid hormone,iPTH）等生化指标的关系,探讨FGF-23对MHD患者的临床意义。方法选取行MHD治疗的患者41例,健康志愿者12例为对照组,收集一般情况及化验指标,采集血清检测FGF-23,并进行相关性分析。结果①MHD各组与对照组年龄、性别无显著差异,但MHD患者FGF-23显著高于对照组[（1077.4±967.46）pg/ml比（73.99±19.58）pg/ml,P〈0.001];②依据甲状旁腺激素（iPTH）不同将MHD分为A组（低iPTH组）、B组（iPTH达标组）、C组（高iPTH组）;FGF-23在3组间有显著性差异,[分别为（477.44±2293.53）pg/ml、（176.57±402.39）pg/ml、（1433.1±1984.76）pg/ml,P=0.016];③将MHD患者依据血磷不同水平分组比较,观察到高血磷组与非高血磷组相比,iPTH显著升高[（1319.66±1015.96）pg/ml比（583.36±980.81）pg/ml（P=0.012）]、FGF-23也显著升高[（1506.83±957.97）pg/ml比（452.31±696.12）pg/ml（P〈0.001）];④相关性分析显示：血钙（r=0.381,P=0.005）、磷（r=0.593,P〈0.001）、钙磷乘积（r=0.656,P〈0.001）、碱性磷酸酶（ALP）（r=0.276,P=0.045）均与FGF-23呈正相关。而iPTH在B组及C组与FGF-23呈正相关（r=0.384,P=0.005）,在A组与FGF-23无相关性。结论 MHD患者中FGF-23与血清钙、磷、钙磷乘积、ALP、iPTH密切相关,在继发性甲状旁腺功能亢进症（secondary hyperparathyroidism,SHPT）的发生中起着重要作用。     

甲状旁腺素、维生素D受体、雌激素受体基因多态对糖尿病患者骨密度的影响

目的探讨甲状旁腺素(PTH)基因多态与中国北方汉族人糖尿病患者骨密度的关系。分析维生素D受体(VDR)、雌激素受体(ER)基因多态性对PTH基因多态性与骨密度、骨量减少及骨质疏松关系的影响。方法运用PCR-RFLP技术检测1型糖尿病(T1DM)组54例、2型糖尿病(T2DM)组104例、健康对照(CON)组102例的中国北方汉族人PTH基因多态性。结果甲状旁腺素基因型和等位基因分布频率在T1DM组、T2DM组与CON组间差异无统计学意义(P0.05);DM患者Bb/bb基因型者发生骨量减少/骨质疏松的相对危险度增加(OR=2.8684)。联合VDR基因多态分析,Bbaa基因型组糖尿病患者并发骨量减少/骨质疏松的相对危险度增高(OR=4.3125);联合ER基因多态分析,bPxx基因型骨量减少/骨质疏松的相对危险度也增高(OR=4.0);联合分析PTH、VDR、ER基因型,同时存在3个或4个易感基因型者伴有骨量减少或骨质疏松,相对危险度增加(OR=5.5385)。结论糖尿病患者PTH基因多态性(BST B1位点)可能是预测骨量减少、骨质疏松易感性的遗传标志。联合VDR、ER基因多态有助于识别DM患者发生骨质疏松的高危人群。     

高磷对大鼠甲状旁腺组织及原代培养细胞的刺激作用

目的观察高磷刺激下,离体的大鼠甲状旁腺（PTG）组织和培养的原代甲状旁腺细胞的PTH分泌变化规律。方法解剖显微镜下切取28只Wistar雌性大鼠的两侧甲状旁腺,分别行组织和原代细胞培养。应用组织学形态学、PTH检测对甲状旁腺组织及原代培养细胞进行鉴定,并观察PTH的分泌规律。甲状旁腺组织及原代培养细胞组各分为正常磷、正常钙组（TN,CN,Pi1.0mml/l,Ca 1.25mmol/L）,高磷、正常钙组（TH,CH,Pi3.5mmol/L,Ca 1.25mmol/L）。隔天换液,分别于培养0h、4h、12h、24h、48h、72h、5d、7d、9d留取培养上清液,检测iPTH。结果本实验切取的大鼠甲状旁腺组织和培养的甲状旁腺细胞经组织形态学及iPTH检测证实。在正常磷、正常钙的培养液中,甲状旁腺组织和培养的原代甲状旁腺细胞PTH分泌曲线相似,均在48h达到分泌高峰。在高磷、正常钙的培养液中甲状旁腺细胞PTH分泌与正常磷、正常钙组同一时间比较,差异无统计学意义（P〉0.05）。培养的甲状旁腺组织在高磷刺激下,PTH水平明显升高,最高达基础值的10倍以上（48h）,除H0外,高磷、正常钙组（TH组）PTH与正常磷、正常钙组（TN组）同一时间比较差异均具有统计学意义（P〈0.001）。结论体外研究显示：高磷可以刺激甲状旁腺组织PTH分泌增加,而对分散的细胞无作用。进行高磷对甲状旁腺功能调节的体外研究,以选择甲状旁腺组织为宜,且时间选择在48h内。     

甲状旁腺素对新生大鼠心室肌细胞活力的影响

目的 观察大鼠甲状旁腺素1-34(rat parathyroid hormone 1-34,rPTH1-34)对体外培养新生大鼠心室肌细胞活力的影响.方法 原代培养新生大鼠心室肌细胞,以0.1 μmol/LPTH1-34分别孵育0、12、24、48、72 h,噻唑蓝(MTT)比色法测定细胞活力.结果 心肌细胞活力在12 h时最大(P<0.01),24 h时开始下降,但仍高于正常水平(P<0.01),48 h时降至正常水平,到72 h降至正常水平以下(P<0.05).结论 0.1 ttmol/L PTH刺激12 h时心肌细胞活力最旺盛.     

基线甲状旁腺激素水平对腹膜透析患者预后影响的探讨

目的本研究旨在探讨新进入腹膜透析人群中甲状旁腺激素水平分布,影响因素,及其对腹膜透析患者长期生存的影响。方法新进入腹膜透析治疗的成人终末期肾病患者按患者全段甲状旁腺激素(intact parathyroid hormone,iPTH)水平分为A组iPTH<150pg/ml;B组iPTH 150~300pg/ml;C组iPTH 300~600pg/ml;D组iPTH≥600pg/ml。比较各组患者的临床及化验资料;使用多元线性回归筛选与基线iPTH相关的危险因素。应用COX回归模型分析影响生存率的因素。应用Kaplan-Meier生存分析、COX回归模型分析比较4组患者的生存情况。结果共222例腹膜透析患者入选。其中,基线iPTH<150pg/ml的患者占43.7%。这组患者的特点包括:年龄大(F=6.235,P<0.001),合并糖尿病比例高(F=16.277,P=0.001),合并症多(F=4.348,P=0.005),eGFR较高(F=5.699,P=0.001)。但经过元线性回归分析,仅年龄(β=-8.700,P<0.001)、是/否合并糖尿病(β=145.400,P=0.012)对基线iPTH有独立的影响。生存曲线显示不同基线iPTH组间总体生存率存在差异(P=0.002)。多因素COX回归分析发现,仅年龄(B=0.066,P<0.001)是预测死亡的独立危险因素,基线iPTH(B<0.001,P=0.507)不能独立预测死亡。结论初进入腹膜透析治疗的患者中,年龄大、合并糖尿病的患者,更容易出现低iPTH的情况。但是,基线iPTH并不能独立预测死亡。     

Two-site assay of intact parathyroid hormone in primary hyperparathyroidism: studies in basal conditions, following adenoma removal and during calcium and EDTA infusion

This study has been carried out in order to investigate parathyroid hormone secretion in patients with primary hyperparathyroidism in basal conditions, during stimulation and suppression tests and following successful surgery. Parathyroid gland secretory activity has been evaluated by a highly sensitive immunoradiometric assay (IRMA) which detects only the biologically intact active hormone and with a well established midmolecule (MM) PTH RIA. There was a good correlation between the two assays in basal state (r = 0.779); however the correlation found between serum PTH levels and total calcium values was better for the intact hormone (P < 0.001) than for the radioimmunoassay (P < 0.05). Twenty-four hours following surgery, serum intact PTH levels were in all patients < 10 pg/ml while midmolecule PTH was still detectable, thereafter remaining at a higher level during the next six days. Serum IRMA PTH levels fell rapidly in response to the increase in serum calcium, then there was a trend to reach a plateau; serum midregion PTH levels fell, although slower than those of intact hormone. The percent increase obtained for serum intact hormone levels was higher than that observed for MM RIA, following EDTA stimulation. The results obtained indicate that the assays of intact and midmolecule parathyroid hormone clearly reflect different aspects of hormone metabolism ‘in vivo’ and may prove therefore to be useful for its investigation in various calcium disorders.