Diagnosis of primary aldosteronism: Comparison of post-captopril active renin concentration and plasma renin activity

BackgroundA common pharmacologic test for the diagnosis of primary aldosteronism (PA) is the administration of captopril to determine whether an abnormal plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio(ARR) persists, although active renin concentration (ARC) may offer advantages with regard to processing and standardization.MethodsA prospective, head-to-head study was conducted between Feb 2008 and Dec 2008. One hundred and fourteen patients enrolled and received captopril to aid in the diagnosis of PA in the TAIPAI intervention.ResultsFifty-one patients were diagnosed with PA. Post-captopril ARC was significantly correlated with PRA. The area under the receiver operating characteristic curve of the post-captopril ARR was not different in PRA vs ARC measurements. When post-captopril ARC-based ARR (ARR_ARC) > 35.5 as the cut-off value, we obtained sensitivity of 75.0% and specificity of 86.4% to differentiate PA from essential hypertension.ConclusionsThe correlation of individual PRA and ARC after administration of captopril was excellent; especially at the lower PRA levels. Post-captopril ARR_ARC values used to diagnose PA are not different from post-captopril PRA-based (ARR_PRA) values in patients without kidney, liver and heart failures. Primary aldosteronism can be diagnosed with a post-captopril cut-off value of ARR_ARC > 35.5 pmol/ng.     

Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays

BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma renin concentration (PRC). METHODS: We studied 76 healthy normotensive volunteers and 28 patients with confirmed PHA. PAC and PRC were measured immunochemically in EDTA plasma on the Nichols Advantage chemiluminescence analyzer, and PRA was determined by an activity assay. RESULTS: In volunteers, PAC varied from 33.3 to 1930 pmol/L, PRA from 1.13 to 19.7 ng.mL(-1).h(-1) (0.215 ng.mL(-1).h(-1) = 1 pmol.L(-1).s(-1)), and PRC from 5.70 to 116 mU/L. PAC/PRA ratios ranged from 4.35 to 494 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios from 0.69 to 71.0 pmol/mU. In PHA patients, PAC ranged from 158 to 5012 pmol/L, PRA from 0.40 to 1.70 ng.mL(-1).h(-1), and PRC from 0.80 to 11.7 mU/L. PAC/PRA ratios were between 298 and 6756 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios between 105 and 2328 pmol/mU. Whereas PAC or PRC showed broad overlap between PHA patients and volunteers, the PAC/PRC ratio indicated distinct discrimination of these two groups at a cutoff of 71 pmol/mU. CONCLUSION: The PAC/PRC ratio offers several practical advantages compared with the PAC/PRA screening method. The present study offers preliminary evidence that it may be a useful screening test for PHA. Further studies are required to validate these results, especially in hypertensive cohorts.     

液相色谱串联质谱法对原发性醛固酮增多症的诊断价值

目的： 探讨液相色谱串联质谱（LC-MS/MS）检测方法中的卡托普利试验（captopril test，CCT）和生理盐水输注试验（saline infusion test，SIT）对原发性醛固酮增多症（primary aldosteronism，PA）的诊断价值。方法： 选取2018年2月至2019年2月复旦大学附属中山医院内分泌科收治的高血压患者127例，其中111例患者行CCT试验，101例患者行SIT试验。通过LC-MS/MS方法检测患者试验前后血浆醛固酮浓度（PAC）、肾素活性及醛固酮/肾素活性比值（aldosterone/renin ratio，ARR）水平。以手术或螺内酯试验为诊断金标准，采用CCT和SIT的ROC曲线探讨2种试验的诊断指标和最佳诊断截断值。结果： PA患者57例，原发性高血压患者70例。CCT后醛固酮、ARR及醛固酮抑制率的AUC分别为0.876、0.902和0.751；ARR为6.5时，诊断PA的灵敏度为94.2%，特异度为78%；PAC为34.8 pg/mL时，诊断PA的灵敏度为75.5%，特异度为93.2%。SIT后醛固酮、ARR及醛固酮抑制率的AUC分别为0.881、0.823和0.652；PAC为24 pg/mL时，诊断PA的灵敏度为87.2%，特异度为78.8%。结论： CCT后ARR和PAC均可作为PA的诊断指标，诊断截断值为6.5和34.8 pg/mL；SIT试验后PAC为PA诊断指标，诊断截断值为24 pg/mL。     

Method specific second-trimester reference intervals for thyroid-stimulating hormone and free thyroxine

ObjectiveTo determine second trimester reference intervals for TSH and FT4.DesignSamples from 3102 subjects were tested for TPO and Tg antibodies.MethodsElecsys E170 reference intervals for TSH and FT4 were determined using antibody-negative samples.ResultsSecond trimester reference intervals for TSH and FT4 were 0.18–4.07 mIU/L and 9.5–15.8 pmol/L, respectively. The Elecsys E170 TSH results were positively biased compared to ARCHITECT i2000_SR results for these same samples.ConclusionsMethod-specific reference intervals are required for TSH and FT4.     

Re‐evaluation of the fludrocortisone test: duration,NaCl supplementation and cut‐off limits for aldosterone

Objective. Primary aldosteronism (PA) is the most common form of secondary hypertension. Thus, the aims of this study were: (1) to clarify whether the fludrocortisone suppression test (FST), which confirms autonomous aldosterone secretion, is reliable when carried out during a shorter period of time and (2) to confirm the importance of NaCl supplementation. The cut‐off limits already obtained for aldosterone in healthy subjects during the FST were applied in hypertensive patients with a high aldosterone to renin ratio (ARR). Material and methods. The healthy subjects were allocated to three groups. Fludrocortisone was administered 4 times daily over 4 days and sodium chloride was supplemented in 3 different doses. The result was applied in 24 hypertensive patients, in 24 healthy subjects (10 women (23–38 years old) and 14 men (23–58 years old)) and in 24 patients with hypertension and high ARR (16 women (45–74 years old) and 8 men (56–73 years old)). Blood pressure, aldosterone, renin, potassium and sodium were measured. Results. After three days of FST, there was a significant decrease in the serum level of aldosterone in the healthy subjects, regardless of high or low sodium chloride supplementation (p<0.001). The decrease in serum aldosterone was significantly less pronounced in patients with PA than in healthy subjects and hypertensive patients without PA (p<0.001). The 95th percentile of plasma aldosterone at the end of the test was 225?pmol/L. Conclusions. The FST can be shortened to 3 days and a daily 500?mg NaCl supplementation is sufficient. A cut‐off value for aldosterone of 225?pmol/L after 4 days with FST is appropriate.     

Establishment of reference intervals for thyroid hormones in premature infants beyond the first week of life using Beckman Coulter Unicel DxI 800

BackgroundThis 4-year retrospective cohort study aimed to establish reference intervals for free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in premature infants using the Beckman Coulter Unicel DxI 800 automated immunoassay system.MethodsStudy subjects included 605 preterm infants with a gestational age of 26–36 weeks (corrected: 29–38 weeks). Pearson correlation was used to evaluate the association between hormone levels and gestational and corrected gestational ages. A nonparametric method was used to establish reference intervals based on corrected gestational age.ResultsFT3 and FT4 levels were positively correlated with gestational and corrected gestational ages, respectively. TSH levels were slightly negatively correlated with gestational and corrected gestational ages. FT3 significantly differed according to corrected gestational age (29–33 weeks vs 34–38 weeks); however, the difference was smaller than the reference change value (RCV) for the FT3 test. Thus, we combined the FT3 reference intervals into a single reference interval: 2.65–4.93 pmol/L (29–38 weeks). The reference intervals of FT4 and TSH were 11.20–24.97 pmol/L (29–38 weeks) and 1.01–10.14 mIU/L (29–38 weeks), respectively.ConclusionsUnlike those of full-term infants or adults, the reference intervals established in this study are applicable in premature infants. These results highlight the importance and complexity of establishing instrument-specific thyroid hormone reference intervals for preterm infants.     

Gestational thyroid reference intervals in antibody-negative Chinese women

ObjectivesThe aim of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function assays in pregnant Chinese women with ARCHITECT and compare them to other GRI studies.Design and methodThyroid antibody negative pregnant Chinese women were enrolled and followed to establish GRIs for thyroid function by use of the Abbott ARCHITECT i2000_SR analyzer (N = 1409). Samples from 360 non-pregnant Chinese women served as controls.ResultsGRIs of thyroid-stimulating hormone, free thyroxine and free triiodothyronine for first trimester pregnancies were 0.16–3.78 mIU/L, 10.9–17.7 pmol/L and 2.9–5.0 pmol/L, respectively. GRIs for second trimester pregnancies were 0.34–3.51 mIU/L, 9.3–15.2 pmol/L and 2.9–4.6 pmol/L. GRIs for third trimester pregnancies were 0.34–4.32 mIU/L, 7.9–14.1 pmol/L and 2.9–4.5 pmol/L.ConclusionsOur thyroid GRIs were different from those in other Chinese studies generated on other analyzers, but were similar to a Swiss study using the same analyzer. These data should prove useful for the interpretation of thyroid function assays among pregnant women measured on the Abbott analyzer.     

Prevalence of primary hyperaldosteronism assessed by aldosterone/renin ratio and spironolactone testing

Recent studies have suggested that primary hyperaldosteronism may be present in more than 10% of patients with hypertension. We aimed to estimate the prevalence in unselected patients in primary care, and investigate the influence of current drug treatment upon the aldosterone/renin ratio (ARR) and its prediction of blood pressure response to spironolactone. We measured blood pressure, plasma electrolytes, renin activity and aldosterone in 846 patients with hypertension. Spironolactone 50 mg was prescribed for one month to patients with blood pressure > or = 130/85 mmHg and ARR > or = 400. The primary outcome measure was to discover the proportion of patients with plasma aldosterone > or = 400 pmol/l and ARR > or = 800 and either an adrenal adenoma on computed tomography scan or a systolic blood pressure response to spironolactone > or = 20 mmHg. Only one patient had an adenoma, and only 16 (1.8%) had both a plasma aldosterone > or = 400 pmol/l and ARR > or = 800. By contrast, 119 patients (14.1%) had an elevated ARR but normal plasma aldosterone. In 69 patients out of the 119 who received spironolactone, blood pressure fell by 26/11 mmHg. These patients were normokalaemic but had uncontrolled hypertension despite multiple drugs. The response to spironolactone was best predicted by a low plasma renin, < or = 0.5 pmol/ml/h (<10 mU/l), despite treatment with an ACE inhibitor. We concluded that adrenal adenomas are an uncommon cause of hypertension. In the absence of hypokalaemia, a low plasma renin is a sufficient and simple way of detecting spironolactone-responders among patients with resistant hypertension. Only patients with both hypokalaemia and low plasma renin, measured while the patient is off beta blockade, require measurement of aldosterone. A plasma aldosterone >400 pmol/l together with renin activity < or = 0.5 pmol/ml/h should trigger further investigations for an adrenal adenoma.     

Establishment of assay method‐ and trimester‐specific reference intervals for thyroid hormones during pregnancy in Chengdu,China

BackgroundThe reference intervals of thyroid hormone will change at different stages of pregnancy because of physiological alterations. On the other hand, the reference intervals of thyroid hormone will also change in different detection systems due to the manufacturer''s methodology as well as a different race. The objective of this study was to establish the assay method‐ and trimester‐specific reference intervals for thyroid‐stimulating hormone, free thyroxine and free triiodothyronine for pregnant women in Chengdu.MethodsA prospective, population‐based cohort study involved 23,701 reference samples of pregnant women during the three trimesters and 8646 non‐pregnant women with pre‐pregnancy clinical and laboratory tests. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid‐stimulating hormone, free thyroxine and free triiodothyronine at each trimester of pregnant women according to ATA Guidelines.ResultsThe reference interval of thyroid‐stimulating hormone in the 2.5th and 97.5th percentiles has a significant increasing trend from the first trimester, to second trimester and to third trimester, which was 0.08–3.79 mIU/L for the first trimester, and 0.12–3.95 mIU/L for the second trimester and 0.38–4.18 mIU/L for the third trimester, respectively (p < 0.001). However, the reference intervals of free thyroxine and free triiodothyronine in the 2.5th and 97.5th percentiles have significant decreasing trends from the first trimester, to second trimester and to third trimester, which were 11.87–18.83 pmol/L and 3.77–5.50 pmol/L for the first trimester, and 11.22–18.19 pmol/L and 3.60–5.41 pmol/L for the second trimester, and 10.19–17.42 pmol/L and 3.37–4.79 pmol/L for the third trimester, respectively (both p < 0.001).ConclusionIt is necessary to establish assay method‐ and trimester‐specific reference intervals for thyroid‐stimulating hormone, free thyroxine, and free triiodothyronine because the reference intervals of these thyroid hormones are significantly different at different stages of pregnancy.     

A precise,sensitive and stable LC-MSMS method for detection of picomolar levels of serum aldosterone

Abstract

Background: Accurate quantification of aldosterone is essential in the diagnosis of primary aldosteronism. Liquid chromatography-tandem mass spectrometry (LC-MSMS) analysis is increasingly being used to improve analytical sensitivity and specificity, since this technology reduces most of the interferences observed with immunological methods.

Methods: Serum samples with d₇-aldosterone as internal standard were extracted with methyl tert-butyl ether, using liquid-liquid extraction (LLE). Chromatographic separation was performed on a C18 reverse phase column with a methanol-water gradient containing ammonium fluoride. Aldosterone detection was performed on an Agilent 6490 triple quadrupole using electro spray ionisation in positive mode.

Results: Multiple reaction monitoring transitions were m/z 361.2–315.1 for aldosterone, and 368.5–323.3 for d₇-aldosterone. Chromatographic retention time was 2.7?min. The method’s total CVs at aldosterone concentrations of 45.4 and 1080?pmol/L were 7.0% and 4.8%, respectively. The intra-assay CVs at concentrations of 60.0 and 637?pmol/L were 4.0% and 2.6%, respectively. The method’s LOQ and LOD were 10 and 5?pmol/L, respectively, demonstrating an excellent analytical sensitivity. The upper limit of quantification was set to 5000?pmol/L, corresponding to the highest calibrator concentration. The long-term stability of the method was evident from repeated measurements of external control pools from UKNEQAS over a period of about 3?years, showing CVs between 2.0 and 7.0%.

Conclusions: We have described a precise, sensitive and stable LC-MSMS method for the measurement of serum aldosterone. In addition, due to the use of LLE and a short LC-column, the method is simple to perform, with a short chromatographic run time.     

Combining body mass index and serum potassium to urine potassium clearance ratio is an alternative method to predict primary aldosteronism

BackgroundThough aldosterone–renin ratio (ARR) is the current routine screening method for suspicious primary aldosteronism, we hypothesized that the simple formula combining body mass index (BMI) and serum potassium to urine potassium clearance (PUKC) ratio was comparable to ARR.MethodsRecords of patients who were referred to the National Taiwan University Hospital for investigation of primary aldosteronism from January 1995 through December 2007 were retrieved. Primary aldosteronism was diagnosed based on the modified 4-corners criteria, otherwise essential hypertension was diagnosed. In both groups, the PUKC/BMI ratio was determined as well as the ARR. Bland–Altman and mountain-plot analysis were used to validate the agreement between ARR and PUKC/BMI. Receiver operating characteristic (ROC) curves were used to compare the sensitivity and specificity of PUKC/BMI and ARR.ResultsThe records for urinary potassium were analyzed for 177 hypertensive patients (134 patients with primary aldosteronism). ROC curves showed comparable areas under the curves of both methods (95% CI: ? 0.029 to 0.183; p = 0.186). Bland–Altman analysis further supported the agreement between ARR and PUKC/BMI ratio.ConclusionsWe found that the screening power of PUKC/BMI was as good as that of conventional ARR. With the quick and extensive availability of the PUKC/BMI method and its equivalence to ARR, this screening strategy would be a good first-line tool for massive community-based primary aldosteronism surveys.     

First trimester serum levels of the soluble transcobalamin receptor,holo-transcobalamin,and total transcobalamin in relation to preeclampsia risk

Background: Human placenta expresses CD320, a receptor that ensures the uptake of holo-transcobalamin (holoTC). Soluble CD320 (sCD320) is present in the circulation and its concentration increases during pregnancy.

Aims: To investigate a possible association of sCD320, holoTC and total transcobalamin (TC) with the risk of subsequent preeclampsia using serum samples from asymptomatic first trimester pregnant women. Moreover, we aimed to establish reference intervals of the aforementioned biomarkers for first trimester pregnant women who remained healthy throughout pregnancy.

Study design: This study was a retrospective case-control study that we performed on biobank serum samples. Cases (n?=?50) and controls (n?=?198) (matched for gestational age and date of sample collection) were asymptomatic women in early pregnancy [median (range) gestational age?=?10 (8–12) weeks]. Cases developed preeclampsia while the controls remained normotensive throughout pregnancy. We measured the serum concentration of sCD320, holoTC, and total TC by using in-house ELISA methods.

Results: First trimester median concentrations of sCD320, holoTC and total TC were not significantly different between cases and controls. The odd ratio for developing preeclampsia based on exposure to low or high levels of sCD320, holoTC or total TC at first trimester was not significant. The reference intervals (2.5–97.5% percentiles (median)) derived from the controls were 50–170 (90) pmol\L for sCD320, 20–140 (70) pmol\L for holoTC and 560–1300 (810) pmol\L for total TC.

Conclusions: The risk of preeclampsia is not predicted by first trimester serum concentrations of sCD320, holoTC or total TC. The first trimester reference intervals for the three parameters is reported.     

CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension

ObjectivesAldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure. Polymorphisms in aldosterone-synthase gene (CYP11B2) may associate with heterogeneous aldosterone production and hypertension. Hence, we investigated ? 344T/C, Iw/Ic polymorphisms of CYP11B2, plasma renin activity (PRA) and aldosterone concentration (PAC).Design and methodsConsecutive ethnically-matched 450 hypertensive patients and 360 controls were screened by PCR-RFLP for genotypes and haplotypes; PRA and PAC were measured.ResultsThe Iw/Ic polymorphism distribution differed significantly between the two groups (LRT χ² = 15.8, df = 2, P = 0.000). The mutant allele-Ic and genotype-Ic/Ic were overrepresented in patients (35% versus 27% and 13% versus 7%). Overrepresentation of T-Ic haplotype in patients was identified as risk haplotype (P = 0.000). Patients had significantly higher PAC and aldosterone-to-renin ratio (ARR; P  = 0.000), which was Ic-allele dependent.ConclusionsThe haplotype T-Ic associated with hypertension susceptibility. Correlation between Ic-allele and raised ARR likely serve in hypertension management.     

Free thyroxine reference interval in each trimester of pregnancy determined with the Roche Modular E-170 electrochemiluminescent immunoassay

ObjectiveTo determine using a simplified study design trimester-specific FT4 reference intervals in pregnancy with the Roche Modular immunoassay in routine use.Design and methodsSurplus blood from 300 women in each trimester, drawn at documented times in the gestation, and from 40 age-matched nonpregnant women were assayed for FT4, thyroid stimulating hormone (TSH) and antithyroid peroxidase autoantibody (anti-TPO).ResultsAfter excluding women positive for anti-TPO and with abnormal TSH, reference intervals were calculated as 12.5–19.1 pmol/L (nonpregnant group), 11–19 pmol/L (first trimester), 9.7–17.5 pmol/L (second trimester) and 8.1–15.3 pmol/L (third trimester). 3rd trimester FT4 was significantly lower than that of the second trimester (p < 0.001) which, in turn, was lower than that of the first trimester (p < 0.001). FT4 reference intervals in pregnancy were significantly lower than in the nonpregnant women (p < 0.002).ConclusionsThe observed trimester-specific FT4 reference intervals progressively decline with advancing gestation and differ significantly from one another.     

Immunoassays of human trefoil factors 1 and 2: measured on serum from patients with inflammatory bowel disease

Background: The trefoil factors (TFF1–3) are cysteine‐rich peptides expressed in the gastrointestinal tract where they play a critical role in mucosal protection and repair. The expression is up‐regulated at sites of ulceration in various chronic inflammatory diseases. Recently, we presented an ELISA method for measurement of TFF3. The aims of the present study were to develop and evaluate ELISAs for the other two known human trefoil peptides, TFF1 and TFF2, and to carry out a cross‐sectional study on serum TFF levels in patients with inflammatory bowel disease (IBD). Methods: The TFF1‐ELISA was based on two polyclonal rabbit antibodies and the TFF2‐ELISA on a monoclonal mouse antibody and a polyclonal rabbit antibody. RhTFF1 and 2 were employed to prepare the calibrators. TFF1–3 were assayed in serum from IBD patients (n=41) and controls (n=13). Results: The TFF1‐ (TFF2‐) ELISA had a detection limit of 3?pmol/L (6?pmol/L) and an analytical imprecision (CV_A) of 7.0–8.8 for mean concentrations of 24–120?pmol/L (6.1–8.0 for mean concentrations of 17–77?pmol/L). The central reference intervals (n=300) were 140–1400?pmol/L (37–190?pmol/L). There was no variation with age and menstrual cycle. Food intake reduced concentrations of TFF1 by ～15%, but did not influence concentrations of TFF2. TFF1 and TFF3 were increased in serum from IBD patients. Conclusions: We have developed assays for measuring TFF1 and TFF2. Finding increased TFF concentrations in serum from IBD patients suggests that measurements of trefoil peptides may be of clinical relevance in IBD.     

陕西省铜川地区妊娠妇女血清甲状腺激素水平参考范围的建立及临床应用

目的　建立陕西省铜川地区妊娠妇女血清甲状腺激素水平参考范围,为铜川地区临床诊治妊娠妇女甲状腺疾病提供参考依据。方法　①回顾性分析2017 年6 月1 日～ 2020 年10 月31 日在铜川市人民医院进行甲状腺激素水平检查的健康妇女样本,按照标准筛选后纳入9 442 例,其中对照组（T0）3 169 例,早孕组（T1）2 642 例,中孕组（T2）1 895 例和晚孕组（T3）1 736 例。使用西门子ADVIA centaur XP 全自动化学发光免疫分析仪检测受试者血清中的促甲状腺激素（thyroid stimulating hormone,TSH）、总三碘甲状腺原氨酸（total triiodothyronine,TT3）、甲状腺素（total thyroxine hormone,TT4）、游离三碘甲状腺原氨酸（free triiodothyronine,FT3）和游离甲状腺素（free thyroxinehormone,FT4）水平。②使用该研究建立的参考范围和《妊娠及产后甲状腺疾病诊治指南》第二版提供的参考范围,对纳入人群进行筛查,比较不同孕期甲状腺疾病的检出率。结果　①妊娠三期血清甲状腺激素水平不同,早、中、晚期和对照组TSH 参考范围分别为1.64（0.06 ～ 6.74） mIU/L,1.94（0.06 ～ 5.80） mIU/L,2.35（0.74 ～ 4.71 ）mIU/L 和2.42（0.55 ～ 7.59） mIU/L;TT3 分别为2.01（1.30 ～ 3.24） nmol/L,2.51（1.62 ～ 3.71） nmol/L,2.44（1.48 ～ 3.53 ）nmol/L 和1.69（1.16 ～ 2.39） nmol/L;TT4 分别为131.30（77.83 ～ 230.80 ）nmol/L,159.40（96.60 ～ 246.20 ）nmol/L,155.30（92.10 ～ 247.00） nmol/L 和104.40（65.10 ～ 152.70） nmol/L;FT3 分别为4.89（4.00 ～ 6.12 ）pmol/L,4.59（3.65 ～5.79 ）pmol/L,4.02（3.22 ～ 4.96 ）pmol/L 和5.04（3.97 ～ 6.19 ）pmol/L;FT4 分别为14.33（11.16 ～ 19.23 ）pmol/L,13.64（10.22 ～ 18.55） pmol/L,12.84（10.05 ～ 20.09 ）pmol/L 和14.81（11.54 ～ 17.20） pmol/L。TSH 在妊娠期低于非妊娠期,早孕期最低,中晚孕期有逐渐回升趋势;TT3 和TT4 在整个妊娠期高于未妊娠期;FT3 和FT4 在整个妊娠期低于未妊娠期。四组间TSH,TT3,TT4,FT3 和FT4 比较,差异均有统计学意义(Z=457.225 ～ 2 927.436,均P ＜ 0.05)。②相较于《指南》中的通用参考范围,使用新建的参考范围时,妊娠期单纯低甲状腺素血症、妊娠期亚临床甲减和妊娠期临床甲减的检出率低于应用《指南》中通用参考范围的检出率（χ2=9.218 ～ 60.437,均P ＜ 0.01）,而妊娠期甲状腺毒症的检出率高于应用《指南》中通用参考范围的检出率（χ2=7.559 ～ 8.199,均P ＜ 0.01）,差异均有统计学意义。结论　使用非本地区参考范围可能导致甲状腺疾病的误诊和漏诊,建立区域和方法特异的妊娠妇女血清甲状腺激素水平参考范围很有必要。     

Circulating secretoneurin concentrations in patients with moderate to severe aortic stenosis

BackgroundSecretoneurin (SN) concentrations provide important prognostic information in patients with myocardial dysfunction. Whether preoperative SN concentrations improve risk assessment in patients with moderate to severe aortic stenosis (AS) is unknown.MethodsWe included 57 patients with moderate to severe AS referred for presurgical evaluation. All patients were examined with comprehensive echocardiography, electrocardiogram (ECG), and biochemical measurements and compared to 10 age- and sex-matched healthy subjects.ResultsMedian (quartile 1–3) SN concentrations were 141 (121–163) pmol/L in AS patients and 132 (106–148) pmol/L in control subjects (p = .17). Lower estimated creatinine clearance and use of diuretics, but not standard ECG or echocardiographic indices and cardiac biomarkers, were associated with increasing SN concentrations. Fifteen patients (26%) died during 3.5 years median follow-up. SN concentrations were higher in non-survivors than survivors: 156 (133–209) vs. 140 (116–155) pmol/L, p = .007. Higher SN concentrations were associated with increased risk of mortality also after adjustment for established risk indices, biomarkers, and status regarding valvular surgery: hazard ratio per _lnSN 15.13 (95% CI 1.05–219.00); p = .046. Receiver operating characteristics area under the curve for SN to predict mortality was 0.74 (95% CI 0.60–0.88) compared to 0.73 (0.59–0.87) for high-sensitivity cardiac troponin T and 0.67 (0.51–0.82) for N-terminal pro-B-type natriuretic peptide. The previously identified cut-off of SN >204 pmol/L in cardiac surgical patients predicted mortality also in this cohort.ConclusionsSN concentrations improve risk assessment in patients with moderate to severe AS by providing additional prognostic information to established risk indices such as echocardiography, ECG, and established cardiac biomarkers.     

Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin–angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study

BackgroundAntihypertensive and tissue-protective properties of vitamin D metabolites are increasingly attributed to the inhibition of renin synthesis by 1,25-dihydroxyvitamin D [1,25(OH)2D] in the kidney.MethodWe aimed to document a potential association between 25-hydroxyvitamin D [25(OH)D], 1,25(OH)2D and the circulating renin–angiotensin system (RAS) in a large cohort of patients referred (n = 3316) to coronary angiography.ResultsOf the 3316 subjects, 3296 (median age: 63.5 (56.3–70.6) years; 30.2% women) had a baseline measurement of 25(OH)D [median: 15.6(10.1–23.0) µg/L)], 1,25(OH)2D [median: 33.2(25.2–42.9) pg/mL], plasma renin concentration [PRC; median: 11.4(6.0–24.6) pg/mL] and angiotensin 2 [median: 20.0(12.0–35.0) ng/L]. Multivariate adjusted ANCOVA showed a steady increase of PRC values across declining deciles of 25(OH)D and 1,25(OH)2D values (P = 0.013 and P = 0.045), respectively. Additionally, mean angiotensin 2 values increased significantly across decreasing 25(OH)D and 1,25(OH)2D values (P = 0.020 and P = 0.024, respectively). In contrast, multivariate adjusted ANCOVA revealed no significant associations between aldosterone, aldosterone-to-renin ratio and 25(OH)D/1,25(OH)2D values. In multivariate stepwise regression analyses both, 25(OH)D and 1,25(OH)2D emerged as independent predictors of plasma renin and angiotensin 2 concentrations.ConclusionsOur data showed for the first time in humans that both, lower 25(OH)D and 1,25(OH)2D values are independently related to an upregulated circulating RAS.     

High frequency of primary hyperaldosteronism among hypertensive patients from a primary care area in Sweden

OBJECTIVE: To search for primary hyperaldosteronism (PHA) among previously known hypertensive patients in primary care, using the aldosterone/renin ratio (ARR), and to evaluate clinical and biochemical characteristics in patients with high or normal ratio. DESIGN: Patient survey study. SETTING AND SUBJECTS: The study population was recruited by written invitation among hypertensive patients in two primary care areas in Sweden. A total of 200 patients met the criteria and were included in the study. MAIN OUTCOME MEASURES: The ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was set to 100, as confirmed in 28 healthy subjects. Patients with increased ARR were considered for a confirmatory test, using the fludrocortisone suppression test. RESULTS: Of 200 patients, 50 patients had ARR > 100; 26 patients were further evaluated by fludrocortisone suppression test. Seventeen of these patients had an incomplete aldosterone inhibition. CONCLUSION: In total 17 of 200 evaluated patients (8.5%) had an incomplete suppression with fludrocortisone. This confirms previous reports on a high frequency of PHA. No significant biochemical or clinical differences were found among hypertensive patients with PHA compared with the whole sample.     

An audit of holotranscobalamin (“Active” B12) and methylmalonic acid assays for the assessment of vitamin B12 status: Application in a mixed patient population

BackgroundVitamin B₁₂ insufficiency/deficiency is common in mixed patient populations. However there is no single marker which can reliably diagnose B₁₂ insufficiency/deficiency. Elevated concentrations of methylmalonic acid (MMA) are considered the most representative marker of metabolic vitamin B₁₂ insufficiency, but poor assay availability limits clinical utility. Low concentrations of serum vitamin B₁₂ are often used to assess vitamin B₁₂ status but this approach generates a high rate of false negative results. Emerging evidence indicates that holotranscobalamin (holoTC) may be a more reliable indicator of vitamin B₁₂ status.Aims and methodsWe substituted serum vitamin B₁₂ measurement with holoTC, supported by MMA in patients referred for assessment of vitamin B₁₂ status. A service evaluation was undertaken of the pattern of MMA values obtained for patients with holoTC 25–50 pmol/L (an indeterminate result). MMA cut-offs of 280 and 360 nmol/L were applied for patients ≤ 65 or > 65 years respectively.ResultsA total of 4,175 consecutive patients were investigated and MMA was analysed for 19% of patients. The incidence of elevated MMA was 41% (holoTC, 25–29 pmol/L), 32% (30–34 pmol/L), 33% (35–39 pmol/L), 30% (40–44 pmol/L), and 26% (45–50 pmol/L).ConclusionsOur results indicate that in the clinical setting a holoTC between 25 and 50 pmol/L is a poor predictor for the concentration of MMA provided the goal is to identify patients with MMA values above the limits used in the present study. Further studies are needed to evaluate to what extent holoTC < 25 and > 50 pmol/L reflect circulatory MMA concentrations.