Nephrogenous cyclic AMP and plasma parathyroid hormone in hypercalcaemia: the influence of renal function

Immunoreactive parathyroid hormone (PTH) levels and nephrogenous cyclic adenosine monophosphate (cAMP) have been reported to be useful parameters in the diagnosis of hyperparathyroidism. Measurements in hyperparathyroid patients usually give values above the normal range when PTH is measured with a carboxyterminal radioimmunoassay and when nephrogenous cAMP is related to glomerular filtration rate. We tested these two parameters in two groups of hypercalcaemic patients (twelve cases of primary hyperparathyroidism and fourteen cases of hypercalcaemia of non-parathyroid origin) and in two groups of normocalcaemic subjects (twenty-one young healthy volunteers and fourteen elderly subjects without parathyroid disease). Slight impairment of renal function caused elevated values of immunoreactive parathyroid hormone in a carboxyterminal radioimmunoassay and also of nephrogenous cAMP when related to glomerular filtration rate. We found that elevated nephrogenous cAMP without parathyroid disease could be attributed to renal insufficiency and to the mode of expression generally used for the nephrogenous cAMP.     

Intact parathyrin in postmenopausal women

To establish a reference range, we measured intact parathyrin (parathyroid hormone, PTH) in 245 healthy postmenopausal women, ages 42-75 years, with use of the Allegro Intact PTH Kit from Nichols Institute Diagnostics. We also assayed serum from a subset of 120 of the women with kits specific for mid-molecule PTH. The mean intact PTH concentration for the 245 women was 32 ng/L (95% confidence interval 14-60 ng/L). Intact PTH values in these subjects were not normally distributed, although calcium concentrations in the same samples were. There was positive, but not significant (r = 0.12, P = 0.06), correlation between intact PTH and age, and a significant negative correlation between serum calcium and intact PTH that was not observed between calcium and mid-molecule PTH. The improved sensitivity of the intact PTH assay makes it useful in studies of calcium homeostasis in the normal population.     

Effects of phosphate therapy on parathyroid gland reactivity]

The effects of a single oral dose of phosphate (780 mg of elemental phosphorus as 100 drops of Phosphoneurol 120 from DOMS-Adrian Laboratories) on parathyroid function and on calcium and phosphate metabolism were studied in 10 young adults. The parathyroid response was checked by measurement of PTH 1-84 and of nephrogenous cAMP before and after a 10 days therapy by phosphate (780 mg of elemental phosphorus twice daily). Before treatment a 16 per cent increase in PTH 1-84 (p less than 0.05) and a 34 per cent increase in nephrogenous cAMP (p less than 0.02) was obtained. After treatment the increases were respectively 34 per cent for PTH 1-84 (p less than 0.001) and 67 per cent for nephrogenous cAMP (p less than 0.001). The responses in PTH 1-84 and in nephrogenous cAMP were significantly (p less than 0.05 and p less than 0.01) higher after than before treatment by phosphate.     

Effects of parathroid hormone and calcitonin on plasma and nephrogenous cclic adenosine-3.,5 -monophosphate in normal subjects and in pathological conditions

Abstract. To evaluate the response of bone cells and kidne to parathroid hormone (PTH) and calcitonin (CT), the acute effects of these hormones given intravenousl on plasma cclic adenosine 3',5'-monophos-phate (cAMP), nephrogenous cAMP and clearance ratio (cAMPxreatinine), have been studied in normal subjects and in patients with Paget's disease, hpoparathroidism and osteopetrosis.
Twent-five subjects were given bovine snthetic PTH, thirt-eight calcitonin (sixteen salmon, eighteen human and four porcine CT).
A different relative potenc of calcitonins in increasing plasma cAMP has been observed in normal subjects, according to previous results on the plasma calcium lowering effect. Paget's disease patients showed a greater increase in plasma cAMP following infusion than normal subjects.
The measurement of nephrogenous cAMP and the clearance ratio (cAMP: creatinine) demonstrated a minor involvement of the kidne in the production of cAMP after CT infusion; the late increase observed in nephrogenous cAMP was probabl due to a parathroid rebound following the hpocalcaemic effect of CT.     

Characterization of the molecular forms of immunoreactive parathyroid hormone in primary hyperparathyroidism and in hyperparathyroidism due to renal failure

Radioimmunological determination of immunoreactive parathyroid hormone (iPTH) in sera of patients with primary and secondary hyperparathyroidism was carried out using antisera specific for the amino-terminal and the mid-region part of the hormone. In 58 patients with primary hyperparathyroidism and in 29 patients with the secondary form of the disease due to renal failure, there was a linear correlation between the concentration of serum iPTH determined with the two types of antiserum. In all cases the mid-region-specific antiserum measured the highest iPTH concentrations. The molecular forms of serum iPTH were examined after gel filtration of Sephadex G-75 followed by Bio-Gel P-60 in nine patients. Fractions which represented molecular forms equal to or smaller than intact PTH were collected. Using the mid-region-specific antiserum, the predominant immunoreactivity (50-80%) eluted corresponding to one or several large fragments in both forms of the disease. In contrast, iPTH activity co-eluting with the intact hormone represented 2-8% of the total. Similar elution profiles were observed when the amino-terminal-specific radioimmunoassay was used. However, this antiserum showed that in both disease states relatively higher concentrations of iPTH co-eluted with the intact hormone (about 20%). In conclusion, the higher serum iPTH concentrations measured with mid-region-specific antiserum are mainly due to quantitative differences due to the presence of large and intermediate sized fragments. The appearance of higher concentrations of iPTH in secondary hyperparathyroidism may be due to a reduced degradation and/or filtration by the kidney.     

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.     

有氧运动对中年女性心肺功能和血管内皮功能的影响及其与雌激素的关系

目的:明确有氧运动对中年女性心肺功能的提高是否与血管内皮功能的改善有关,以及心肺功能的提高程度是否受女性雌激素水平的影响。方法:前瞻性募集51名45~55岁健康女性,随机分为运动组(31名,其中15名已绝经)和对照组(20名),运动组进行12周中等强度有氧运动,对照组不进行运动干预。运动心肺功能测试以PVO2反映心肺功能,ELISA测量血浆ADMA和NOS水平评价内皮功能,同时观察血浆雌二醇水平等。结果:运动12周后,运动组PVO2及NOS均较运动前及对照组有显著提高(P0.05),ADMA较运动前及对照组明显下降(P0.05),而E2、体重指数在运动前后及对照组比较均差异无统计学意义;对照组运动干预前后各项指标比较差异无统计学意义。有氧运动组中绝经者与未绝经者上述指标测值均无明显差异。Pearson相关分析显示运动前后PVO2的提高程度与血管内皮功能的改善程度有显著相关性(r=0.339,P=0.023),与ADMA显著负相关(r=0.333,P=0.025),而PVO2和内皮功能的程度均与基线雌激素水平无相关性。结论:有氧运动训练可以显著提高健康中年女性的心肺功能和改善其血管内皮功能,推测心肺功能的提高可能与内皮功能的改善有关;而内皮功能的改善并不依赖于受试者的基础雌激素水平,提示绝经前及绝经后女性均能从运动中得到相同的获益。     

Potential clinical utility of a new IRMA for parathyroid hormone in postmenopausal patients with primary hyperparathyroidism

BACKGROUND: A new commercially available (so-called second-generation) IRMA for parathyroid hormone (PTH) separately detects intact PTH and its N-truncated fragments; however, no studies have compared the first- and second-generation IRMAs for PTH in patients with primary hyperparathyroidism (PHPT) to assess their respective diagnostic accuracies. METHODS: We concomitantly investigated 39 postmenopausal patients with PHPT and a control group of 70 healthy postmenopausal women matched for age, renal function, and vitamin D status. In all individuals, PTH was measured with a classic IRMA (PTH-S; DiaSorin Inc.), which uses antibodies directed against epitopes 1-34 and 39-84, and a new method (Scantibodies Laboratory. Inc.), which uses antibodies against epitopes 1-4 and 39-84 (PTH-W) and epitopes 7-34 and 39-84 (PTH-T). We also assayed serum PTH in 10 PHPT patients every 24 h for 5 days after successful surgery. RESULTS: The different assays gave serum PTH values that were >2 SD higher than values for the control population in 59% (PTH-S), 77% (PTH-W), and 82% (PTH-T) of patients with PHPT. However, ROC curve analysis showed no significant differences among the three PTH assays, demonstrating overlapping diagnostic sensitivities. In PHPT patients, the correlation among the assays was highly significant (r = 0.91-0.92; P <0.001). The ratio PTH-W:PTH-T x 100 showed a gaussian distribution in both PHPT patients and controls, whose mean (SD) values [63.4 (13.3)% vs 64.5 (9.5)%, respectively] did not differ significantly. After parathyroidectomy, the mean percentages of variation in PTH detected with all of the assays were quite similar. CONCLUSIONS: The distribution of the PTH-W:PTH-T ratio in patients and controls suggests that PHPT does not markedly influence the rate at which biologically inactive fragments are generated by central or peripheral cleavage of PTH. The similar postoperative curves seem to contradict the hypothesized effect of acute hypocalcemia in modulating the central secretion of hormonal fragments. Our results indicate that the three investigated assays have similar diagnostic sensitivities in PHPT.     

Effects of estrogen on patterns of brain activity at rest and during cognitive activity: a review of neuroimaging studies

Animal and human studies provide evidence of systematic effects of estrogen on cerebral activity and cognitive function. In this article, we review studies of the activational effects of estrogen on cerebral activity during rest and during the performance of cognitive tasks in pre- and postmenopausal women. The goal is twofold--to better understand evidence suggesting that estrogen influences brain functioning and argue for the importance of considering hormone effects when designing neuroimaging studies. Hormone-related increases in blood flow during the resting state have been documented in healthy elderly women, elderly women with cerebrovascular disease, and middle-aged postmenopausal women with early menopause. There is no reliable influence of estrogen on blood flow during the resting state in women with Alzheimer's disease. Hormone therapy has been associated with changes in brain activation patterns in middle-aged and elderly postmenopausal women during performance of verbal and figural memory tasks, providing critical biological support for the view that estrogen might protect against age-associated changes in cognition and lower the risk of Alzheimer's disease. There is a paucity of studies examining changes in brain activation patterns across the menstrual cycle and a need for randomized studies of hormone therapy in postmenopausal women to confirm findings from observational studies. General procedural guidelines for controlling and investigating hormone effects in neuroimaging studies are discussed.     

Efficacy of estradiol vaginal cream in postmenopausal women.

In a double-blind parallel study daily intravaginal administration of conjugated estrogen cream and estradiol cream for 14 days relieved vasomotor and vaginal postmenopausal symptoms in 29 postmenopausal women. By day 14, therapy with the estradiol vaginal cream resulted in plasma estrone and estradiol levels closer to those in premenopausal women than therapy with the conjugated estrogen cream. The extent of improvement and final estradiol plasma levels in the estradiol vaginal-cream group correlated. There was no correlation with severity of symptoms or estradiol plasma level at baseline. The metabolism of the conjugated estrogen cream might account for absence of correlation between improvement and final estradiol plasma levels in the conjugated vaginal-cream group.     

Serum parathyroid hormone is associated with carotid intima-media thickness in postmenopausal women

Objectives: To test whether parathyroid hormone (PTH) might be related to the development of atherosclerosis in postmenopausal women, we measured serum levels of PTH, the carotid intima‐media thickness (IMT), and other clinical and biochemical parameters. Methods: One hundred and seven postmenopausal women were recruited for this study. The serum level of PTH was measured by immunoradiometric assay, and carotid IMT was measured with high resolution B‐mode ultrasonography. Results: On the basis of bivariate correlation analyses or unpaired t‐tests, the body mass index (BMI), waist circumference, estimated glomerular filtration rate, and 25‐hydroxyvitamin D were not associated with carotid IMT. In contrast, age (r = 0.414, p < 0.001), serum level of PTH (r = 0.304, p = 0.001), hypertension (p < 0.001), and hypercholesterolaemia (p = 0.004) were related to carotid IMT. On the basis of multiple regression analysis, the serum level of PTH (β = 0.198, p = 0.029), as well as age (β = 0.309, p = 0.001) and hypertension (β = 0.262, p = 0.006), were independent predictors of carotid IMT. Conclusions: Our results have demonstrated that serum PTH is an independent determinant of carotid IMT in postmenopausal women. This result suggests that serum PTH, even in the reference range, might be associated with the development of atherosclerosis or cardiovascular diseases in postmenopausal women. Further study is necessary in males and premenopausal women to fully elucidate the clinical significance of this finding.     

Comparison between intact and bioactive parathyroid hormone assays in patients with severe heart failure

ObjectivesParathyroid hormone (PTH) is a major systemic calcium-regulating hormone. Recent evidence has suggested that measurement of PTH might provide complementary information for the diagnosis and risk stratification of patients with heart failure (HF). The aim of our study was to compare intact and bioactive PTH assays in patients with severe heart failure.Design and methodsThe following measurements were carried out in blood samples from 73 patients with severe heart failure: bioactive PTH (1–84) assay, intact PTH assay, non-PTH (1–84), 25-hydroxyvitamin D, B-type natriuretic peptide (BNP), N-terminal proBNP (Nt-proBNP), Galectin-3 and high sensitive troponin T (hsTnT).ResultsThe correlation between intact and bioactive PTH assays was very high in HF patients. However, the bioactive PTH concentrations were lower than those measured with the intact assay. Intact and bioactive PTH as well as non-PTH (1–84) was significantly and positively correlated to BNP, Nt-proBNP, and galectin-3 but not to hsTnT. The strongest relationships with these cardiac biomarkers and with cardiovascular death were observed with the bioactive PTH assay.ConclusionsThe PTH concentrations obtained with intact and bioactive assays are not comparable in patients with severe HF. The specificity of PTH assays might therefore impact on the potential diagnosis and prognosis values of PTH testing in patients with heart failure.     

雌激素替代治疗对绝经后妇女内皮功能的影响

目的观察雌激素替代治疗(ERT)对绝经后妇女内皮功能的影响。方法绝经组妇女32例每天口服结合雌二醇0.625mg,共两周;同期24名正常月经妇女为对照组。分别采集绝经组妇女服药前后和对照组妇女空腹静脉血标本测雌二醇(E2)、一氧化氮(NO)水平,并采用无创性高分辨超声法检测内皮依赖性血管舒张功能。结果绝经组ERT前血流介导的血管舒张(FMD)、NO及E2明显低于对照组(P<0.05),ERT后显著增加(P<0.05),而硝酸甘油介导的血管舒张(NMD)治疗前后差异无显著性意义;FMD与E2、NO相关(P<0.001),而NMD与NO、E2均无相关性(P>0.05)。结论女性绝经后存在显著的内皮依赖性血管舒张功能异常,进行雌激素替代治疗可明显改善甚至逆转上述变化,该作用可能是雌激素的心血管保护机制之一。     

绝经前与绝经后妇女血清硬化素水平的变化及其相关影响因素

目的:探究绝经前与绝经后妇女血清硬化素水平的变化及其相关影响因素。方法:纳入符合条件的绝经前和绝经后妇女各30例,检测其血清硬化素水平、相关血生化指标、性激素水平和骨转换生物标志物。采用双能X线进行股骨颈,腰椎和髋骨骨密度检测。结果:与绝经前比较,绝经后妇女雌二醇(P<0.01)、雌激素(P=0.01)、游离雌激素指数(P=0.01)和各部位骨密度均显著下降;绝经后妇女与绝经前妇女相比血清硬化素水平升高(P=0.02);由于绝经前妇女多口服避孕药,故后续数据分析仅限于绝经后妇女。绝经后妇女血清硬化素水平与游离雌激素指数(r=-0.57,P=0.01),甲状旁腺激素(r=-0.48,P=0.03)及股骨颈骨密度(r=-0.49,P=0.01)呈负相关;多元回归分析发现,游离雌激素指数(β=-0.63,P=0.01)和甲状旁腺激素(β=-0.56,P=0.01)是血清硬化素水平升高的独立危险因素。结论:绝经后妇女血清硬化素水平高于绝经前妇女。血清硬化素水平可能受到雌激素和甲状旁腺激素的调节作用。     

Activity or mass concentration of bone-specific alkaline phosphatase as a marker of bone formation.

BACKGROUND: Recently published data identified bone-specific alkaline phosphatase (BALP) as a good marker of bone formation in different bone diseases and osteoporosis. Two methods are available for BALP determination: one measures enzyme activity, the other its mass concentration. We compared results for BALP activity and its mass concentration in a group of 88 healthy pre- and postmenopausal women to identify which is a more useful marker for detecting early menopausal bone remodelling changes. METHODS: We measured BALP activity and BALP mass concentration in relation to femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and some other widely used bone markers: osteocalcin (OC), procollagen type I N-terminal propeptide (PINP) and serum C-terminal telopeptide cross-links of type I collagen (CTx) in serum samples from 50 premenopausal (age 45.9+/-4.6 years) and 38 postmenopausal (age 54.4+/-4.5 years) women. RESULTS: Healthy postmenopausal women exhibited 34.2% (p<0.01) and 27.3% (p=0.000) higher levels of BALP activity and mass concentration than premenopausal women, respectively. At the same time, FN and LS BMD were not significantly different between the groups. CTx values were significantly higher in postmenopausal women (p=0.018), while OC and PINP were not. We observed significant correlation between BALP activity and mass concentration (r=0.85, p<0.01). The correlation between BALP activity and FN BMD or LS BMD was insignificant. BALP mass correlated significantly with LS BMD (r=-0.370, p=0.033) but not with FN BMD. As expected, we proved a significant positive correlation for both BALP methods with the other bone markers measured in our study. CONCLUSIONS: Postmenopausal women have slightly higher bone turnover. Since LS and FN BMD were not significantly lower in our group of healthy postmenopausal women, but BALP and CTx were markedly higher, we suggest that measurements of BALP and CTx might be useful as early markers of higher bone turnover. Finally, our results did not show any differences between the clinical utility of BALP activity and BALP mass concentration measurements.     

绝经后血清FSH、LH和E_2水平与骨代谢指标的关系

目的分析绝经后妇女促卵泡激素(FSH)、促黄体生成素(LH)和雌二醇(E2)与骨代谢指标的关系,为骨质疏松诊断和治疗提供参考。方法选取中国医科大学附属盛京医院门诊和住院就诊绝经后患者220例。通过罗氏Cobas 8000对血钙(Ca)、碱性磷酸酶(ALP)、甲状旁腺素(PTH)、β-胶原降解产物(β-Crossl)、N-端骨钙素(N-Osteoc)、总Ⅰ型前胶原氨基末端前肽(TPINP)进行检测,利用美国Beckman DXI-800对FSH、LH、E2进行检测。结果绝经后妇女FSH、LH和FSH/LH与N-Osteoc、TPINP呈正相关(P0.05),且FSH/LH和E2也与β-Crossl呈正相关(P0.05)。其中FSH/LH与TPINP的相关系数最高(r=0.341)。经多元线性回归分析发现血清FSH和FSH/LH作为自变量可解释各种骨转换生化指标水平变化的百分比范围分别为0.5%~6.6%,1.1%~30.9%,FSH/LH作为自变量可解释各骨转换指标水平变化的百分比最大,而LH仅为0.4%~2.3%。经多元Logistic回归分析显示年龄、FSH、FSH/LH、TPINP为绝经后骨质疏松的独立危险因子。以FSH=46.36和FSH/LH=2.09为临界值能有效诊断绝经后骨质疏松。结论绝经后妇女血清FSH、LH和FSH/LH水平随骨转换指标升高而升高。联合应用FSH和FSH/LH诊断绝经后骨质疏松均高于单独应用FSH或FSH/LH的诊断效能。     

Measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx) in aging, menopause, and osteoporosis with fractures

We have evaluated the effect of aging, menopause, and osteoporosis on the measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx). In 18 children, 86 premenopausal healthy women, 144 postmenopausal healthy women, 74 patients with vertebral fractures and 61 patients with hip fractures, alpha-CTx excretions were measured by a RIA. The age-related changes of alpha-CTx in healthy females show that the values were extremely high before the age of 16 years and decreased between ages 16 and 29, and that after the age of 40 years, the values tended to increase and to vary widely with age. In menopause, alpha-CTx in postmenopausal subjects was significantly higher than those in premenopausal subjects. There was no significant correlation between alpha-CTx and years since menopause in 102 postmenopausal subjects. Alpha-CTx in the vertebral fracture group were higher than those in the postmenopause group, but not significantly. Alpha-CTx in the hip fracture group were significantly higher than those in postmenopause and vertebral fracture groups. In age-matched comparisons, the values of the patients with vertebral fracture and the patients with hip fracture were significantly higher than those of corresponded age-matched postmenopausal women. Alpha-CTx well reflects an increase of bone resorption associated with bone modeling at childhood and high bone resorption after the menopause and higher bone resorption in osteoporotic patients with fractures.     

Transvaginal color Doppler assessment of endometrial status in normal postmenopausal women: the effect of hormone replacement therapy.

We used transvaginal color Doppler sonography to study the effects of hormone replacement therapy on the endometrial structure and vascular flow of 345 normal postmenopausal women. We studied women taking estrogen replacement alone, continuous combined estrogen and progestogen, and estrogen followed sequentially by estrogen-progestogen combination. Endometrial measurements prior to the initiation of hormone replacement therapy were used as baseline values. An increase in endometrial thickness was seen soon after initiation of hormone replacement therapy (P < 0.0001). Hyperplasia or adenocarcinoma was found only when endometrial thickness was greater then 9 mm. No correlation was found between hormone replacement therapy and the occurrence of endometrial hyperplasia or adenocarcinoma.     

绝经前后妇女雌激素水平与颈动脉内膜中层厚度相关性研究

摘 要 目的：探讨绝经前后妇女雌激素水平、抗氧化能力与动脉粥样硬化斑块的关系。方法：选取绝经前后健康妇女各40名，分为两组，观察各组颈动脉内膜中层厚度（IMT）和雌二醇（E2）浓度,并测定了血脂、羟自由基、丙二醛（MDA）和超氧化物歧化酶（SOD）的水平。结果：绝经后组颈动脉内膜中层厚度增加, 雌激素水平降低,两者变化显著相关,同时绝经后组抗氧化能力下降，而低密度脂蛋白水平（LDL）升高。结论：女性低雌激素状态易引起颈动脉内膜增厚,这可能与低雌激素状态引起抗氧化能力下降和血脂升高有关。     

Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism

Parathyrin (parathyroid hormone; PTH) was measured with three immunoassays: a two-site immunochemiluminometric (ICMA) and a two-site immunoradiometric (IRMA) method for intact PTH, and a sensitive radioimmunoassay for mid-region or "total" PTH, measuring both intact hormone and inactive fragments. Single specimens from normal subjects and from individuals with primary hyperparathyroidism, hypercalcemia associated with malignancy, and hypoparathyroidism were analyzed with all three methods. All individuals with primary hyperparathyroidism showed absolutely above-normal concentrations with the mid-region RIA, 28 of 29 did with the ICMA, and 21 of 29 did with the IRMA. PTH concentrations in primary hyperparathyroidism were most increased relative to normal subjects with the mid-region assay (10.4 times), less so with the intact assays (ICMA 5.5 times; IRMA 5.3 times). Concentrations of intact PTH were suppressed below normal in nearly all patients with hypercalcemia associated with malignancy, as measured with the ICMA (26 of 30) and the IRMA (28 of 30) assays. In marked contrast, results for mid-region PTH were normal or slightly above normal, consistent with studies suggesting that the parathyroids secrete both intact hormone and inactive fragments, the former being more sensitive to suppression by hypercalcemia. In hypoparathyroidism PTH concentrations were detectable but below normal in all patients by the intact assays and in all but one patient by the mid-region assay. These low concentrations are probably due to a nonspecific serum effect that could be resolved with selection of a more appropriate standard matrix. Although all three assays are useful in the differential diagnosis of hypercalcemia, two-site intact assays are more convenient and more specific in patients with compromised renal function.