جمعه بیستم اسفند 1389
Elecsys Refrence range part 1
ElecsysÒ FT3
Establishing values in reference range studies is based primary on samples obtained from outpatient clinics, hospitals, an commercial laboratories in which TSH and fT4 levels are found to be in the euthyroid range.
These patients often have non-thyroid diseases which might influence the thyroid function in general, and especially the fT3 level.
This may explain the differences obvserved when comparing the reference range based on different population groups using the same fT3 method. Beside local differences in iodine intake the overall health status of the individials involved is decisive for the outcome of the reference intervals. The Elecsys® fT3 assay was used to determine reference ranges in the following groups of individuals from different locations in Germany.
Adults
3.1-6.8 pmol/l (2.0-4.4 pg/ml)
From a coastally-situated commercial laboratory in Germany, 5366 routine samples with TSH between 1 and 3 µIU/ml were evaluated by non-parametric calculation of the central 95% limits and corresponding 95% confidence intervals (CI) for fT3 concentration:
|
Median |
2.5th percentile |
95th CI of the 2.5th percentile |
97.5th percentile |
95th CI of the 97.5th percentile |
Unit |
|
4.6 |
3.1 |
3.07-3.19 |
6.8 |
6.65-6.87 |
pmol/l |
|
3.0 |
2.0 |
2.00-2.08 |
4.4 |
4.33-4.47 |
pg/ml |
3.9-6.7 pmol/l (2.5-4.3 pg/ml)
870 samples derived from apparently healthy blood donors aged 20 to 69 years from a central German site were evaluated by non-parametric calculation of the central 95% limits and corresponding 95% confidence intervals (CI) for fT3 concentration:
|
Median |
2.5th percentile |
95th CI of the 2.5th percentile |
97.5th percentile |
95th CI of the 97.5th percentile |
Unit |
|
4.6 |
3.9 |
3.67-3.99 |
6.7 |
6.54-7.00 |
pmol/l |
|
3.0 |
2.5 |
2.39-2.60 |
4.3 |
4.26-4.56 |
pg/ml |
The following parameters were recorded in these individuals: the concentration of TSH, fT4 and auto-antibodies to TG and TPO; the volume and density of the thyroid gland measured by ultrasound; their case history, family, and personal thyroid history; their gender, age and iodine intake; and whether or not they smoked or taking oral contraceptives.
For results based on a variety of different inclusion and exclusion criteria, please refer to the separate information given in the brochure „Reference Intervals for Elecsys Thyroid Assays“.
2.4-6.03 pmol/l (1.5-4.1 pg/ml)
211 samples from dialysis patients were measured with Elecsys® FT3 in a multicenter evaluation (pilot study). The data represent the 2.5th and the 97.5th percentile.
1.3-6.3 pmol/l (0.8-4.1 pg/ml), median 3.2 pmol/l or 2.7 pg/ml.
94 samples from patient suffering from severe non thyroid illnesses (NTI’s) were measured with Elecsys® FT3 in a multicenter evaluation (pilot study). The data represent the 2.5th and the 97.5th percentile.
Children and adolescence:
Samples from newborns, infants, and adolescents up to 19 years of age, charcterized as apparently healthy by experts from a medical center in central Germany:
|
Age |
N |
Median |
2.5th percentile |
95th CI of the 2.5th percentile |
97.5th percentile |
95th CI of the 97.5th percentile |
Unit |
|
4-30 days |
40 |
5.2 3.4 |
3.0 2.0 |
2.6-3.8 1.7-2.5 |
8.1 5.2 |
7.3-8.3 4.7-5.4 |
pmol/l pg/ml |
|
2-12 month |
35 |
5.8 3.8 |
2.4 1.5 |
2.4-3.1 1.5-2.0 |
9.8 6.4 |
8.8-9.8 5.7-6.4 |
pmol/l pg/ml |
|
2-6 years |
73 |
6.1 4.0 |
3.0 2.0 |
2.9-3.6 1.9-2.4 |
9.1 6.0 |
8.2-9.5 5.3-6.2 |
pmol/l pg/ml |
|
7-11 years |
127 |
6.1 4.0 |
4.1 2.7 |
2.5-4.9 1.6-3.2 |
7.9 5.2 |
7.6-9.2 5.0-6.0 |
pmol/l pg/ml |
|
12-19 years |
140 |
3.5 2.3 |
3.5 2.3 |
3.1-3.7 2.0-2.4 |
7.7 5.0 |
7.3-9.2 4.8-6.0 |
pmol/l pg/ml |
The following exclusion criteria were stipulated in these individuals (both outpatients and holspitalized): no previous or acute thyroid disease, no family history or thyroid diseases, no coronary disease, no intensive care, and not postoperative medical care.
Status: Adults: MCE pilot study and ß-site study Elecsys® FT3, Cat.no. 03051986, February 2004, and excerpt „MCE Reference Ranges Thyroid“, June 2004. Children and adolescence: Reference Range study for thyroid values in children, June 2004.
Reference ranges for population groups from other locations are available on request and indicated in the Elecsys® FT3 product information (not available in the US) and in the brochure „Reference intervals for Elecsys® Thyroid Assays“.
ElecsysÒ FT4 |
|
2.5th - 97.5th percentile | |
|
|
n |
pmol/l |
ng/dl |
|
Adults euthyroid |
801 |
12 - 22 |
0.93 - 1.7 |
Status: MCE Reference Ranges Thyroid, Status 1st quarter 1998.
ElecsysÒ FT4 |
|
2.5th - 97.5th percentile | |
|
|
n |
pmol/l |
ng/dl |
|
Children |
|
|
|
|
0 - 12 month 1 - 6 years 7 - 12 years 13 - 17 years |
64 54 52 35 |
13.9 - 26.1 12.1 - 22.0 13.9 - 22.1 13.6 - 23.2 |
1.1 - 2.0 0.9 - 1.7 1.1 - 1.7 1.1 - 1.8 |
ElecsysÒ T3 |
|
2.5th - 97.5th percentile | |
|
|
n |
nmol/l |
ng/ml |
|
Adults euthyroid |
514 |
1.3 - 3.1 |
0.8 - 2.0 |
Status: MCE Elecsys® 2010, status 1996, verified 1st quarter 1998.
Reference values for children have not been evaluated yet.
ElecsysÒ T4
Measurements with Elecsys® T4 on 2526 samples from euthyroid test subjects in Germany and Japan yielded the following values (2.5-97.5th percentile):
66-181 nmol/l or 5.1-14.1 µg/dl
FT4 Index (T4/TBI) calculated from 825 serum samples from euthyroid test subjects measured with Elecsys® T4 and Elecsys® T-uptake (2.5-97.5th percentile):
62-164 nmol/l or 4.8-12.7 µg/dl
Following values were determined for the 99% percentile range from 275 serum and plasma samples from healthy test subjects in USA:
59-154 nmol/l or 4.6-12.0 µg/dl
FT4 Index:
57-147 nmol/l or 4.4-11.4 µg/dl
Reference values for children have not been evaluated yet.
ElecsysÒ TSH |
|
2.5th - 97.5th percentile |
|
|
n |
µIU/ml |
|
Adults euthyroid |
516 |
0.27 - 4.2 |
|
Children |
|
|
|
0 - 12 month 1 - 6 years 7 - 12 years |
64 54 52 |
1.36 - 8.8 0.85 - 6.5 0.28 - 4.3 |
ElecsysÒ T-uptake
Elecsys® T-uptake results (TBI) calculated in 974 serum samples from euthyroid subjects in Japan, Belgium and Germany:
TBI: Median 1.0 (range: 2.5th-97.5th percentile): 0.8-1.3
FT4 Index:
Elecsys® T4/TBI results calculated in 825 serum samples from euthyroid subjects in Germany and Japan (range: 2.5th-97.5th percentile): 62-164 nmol/l or 4.8-12.7 µg/dl.
The following values were determined for the 99th percentile range of results in a total of 275 serum and plasma samples from healthy subjects in the USA:
57-147 nmol/l or 4.4-11.4 µg/dl.
Values < 0.8 are indicative of hyperthyroidism or low TBG concentrations while values > 1.3 are indicative of hypothyroidism or elevated TBG concentrations.
ElecsysÒ TG
Studies performed by clinical centers in Austria, Spain and the USA on samples from 130 healthy subjects showed the following values:
1.4 – 78 ng/ml (5th-95th percentile)
Status: MCE Elecsys® Tg with Elecsys® 1010/2010, study no. B99P001, 9/2000; values recalculated after restandardisation: 10/2001.
Tg should no longer be measureable following complete ablation of thyroid tissue by thyroidectomy and radioiodine therapy. More extensive diagnostic measures are indicated if in such patients there is a rise in the Tg concentration.
ElecsysÒ Anti-TG
Studies conducted with Elecsys® Anti-TG in 5 clinical centers covering a total of 392 healthy subjects (MCE Elecsys® Anti-TG, status October 2001) confirmed the currently used threshold value of 115 IU/ml; this values corresponds to the 94th percentile.
ElecsysÒ Anti-TPO
Extendet studies with Elecsys® Anti-TPO performed on samples from 208 healthy test subjects in 3 clinical centers in Austria and Germany showed a borderline value for 34 IU/ml for 95% of the results.
Each laboratory should investigate the transferablility of the expected values to its own patient population and if necessary determine its own reference ranges.
For diagnostic purposes, the results should always be assessed in conjunction with the patient´s medical history, clinical examination and other findings.
Used Documents:
|
Assay |
Package insert (or Product Information) |
|
FT3 |
0804/05 |
|
FT4 |
0304/09 |
|
T3 |
0304/13 |
|
T4 |
0304/10 |
|
TSH |
0704/11 |
|
T-uptake |
0304/12 |
|
TG |
0404/06 |
|
Anti-TG |
0204/06 |
|
Anti-TPO |
0503/08 |
Cardiac:
ElecsysÒ CK-MB STAT
In studies with ElecsysÒ CK-MB STAT the following results were obtained (ng/ml):
|
|
n |
Median |
97.5th percentile |
|
Women |
760 |
0.97 |
2.88 |
|
Men |
628 |
1.35 |
4.94 |
Data (status July 1999) combined from: FRISC II (Fragmin during instability in coronary artery disease) study, results from Upsala, January 1999 and International ElecsysÒ 1010 study, cardiac marker, March 1999.
ElecsysÒ Digoxin
The usual therapeutic range for digoxin is 0.9 to 2.0 ng/ml (1.2-2.6 nmol/l). Concentrations above 2.0 ng/ml (2.6 nmol/l) are generally considered toxic. Some overlap of toxic and non-toxic values have been reported. Therefore, clinical diagnosis should be based on clinical and laboratory data. Each laboratory should establish and acceptable reporting format and identify procedures for the reporting of abnormal results.
ElecsysÒ Digitoxin
In the literature, the mean therapeutic serum level for digitoxin is indicated as being 10-30 ng/ml or 13-39 nmol/l.
Since the therapeutic and the toxic serum levels can overlap, the monitoring of the glycoside levels as well as the clinical findings must be taken into consideration to clarify a possible digitalis intoxication. See also the „Limitations – interference“ section.
ElecsysÒ Myoglobin STAT
In studies with ElecsysÒ Myoglobin STAT on 2162 healthy test subjects the following data were obtained:
|
|
Number |
2.5th-97.5th Percentile |
|
Men |
1030 |
28-72 ng/ml |
|
Women |
1132 |
25-58 ng/ml |
Data (status: July 1999) combined from: Multicenter Evaluation of Myoglobin STAT, April 1999 and International ElecsysÒ 1010 Study, Cardiac markers, March 1999.
ElecsysÒ proBNP
Interpretation of NT-proBNP values
With increasing age atherosclerosis and aging processes of the heart (e.g. fibrosis) result in cardiac dysfunction. Development of cardiac dysfunction is individually different and clinically asymptomatic in is early stages. NT-proBNP levels reflect cardiac function or dysfunction respectively. Interpretation of NT-proBNP results needs to consider sex, accompanying disorders and treatment of effects.
Therefore NT-proBNP values need to be interpreted in conjunction with the medical history, clinical findings and other information (e.g. imaging, laboratory findings).
Clinical cutoff
Based on a number of studies NT-proBNP values below 125 pg/ml are considered normal. Although differences in NT-proBNP values in healthy males and females have been observed, a clinical cutoff of 125 pg/ml reveals sufficient diagnostic accuracy. NT-proBNP values below 125 pg/ml exclude cardiac dysfunction with a high level of certainty. This is also true for asymptomatic patients with dyspnea. NT-proBNP values above 125 pg/ml may indicate early cardiac dysfunction and are associated with an increased risk of cardiac complications (myocardial infaction, heart failure, death). In cases of gender specific cut points decisions 100 pg/ml for male and 150 pg/ml for female can be used for rule out testing.
Expected values for blood donors
|
Age group classified and gender specific NT-proBNP levels in blood donors | ||||||
|
Age (years) |
18-49 |
18-49 |
18-29 |
18-29 |
30-39 |
30-39 |
|
Gender |
male |
female |
male |
female |
male |
female |
|
N |
964 |
574 |
278 |
232 |
379 |
194 |
|
Median |
20.0 |
39.3 |
20.0 |
37.0 |
20.0 |
36.9 |
|
95th percentile |
63.9 |
125 |
48.8 |
114 |
70.7 |
119 |
|
97th percentile |
84.2 |
146 |
64.7 |
130 |
88.1 |
132 |
|
Age group classified and gender specific NT-proBNP levels in blood donors | ||||||
|
Age (years) |
40-49 |
40-49 |
50-59 |
50-59 |
>60 |
>60 |
|
Gender |
male |
female |
male |
female |
male |
female |
|
N |
307 |
148 |
211 |
94 |
110 |
28 |
|
Median |
20.0 |
49.8 |
27.4 |
65.8 |
42.0 |
61.4 |
|
95th percentile |
64.0 |
146 |
125 |
186 |
194 |
204 |
|
97th percentile |
94.6 |
231 |
179 |
270 |
278 |
262 |
Correlation of NT-proBNP with NYHA classification (CHF population – congestive heart failure)
|
NYHA functional class | ||||
|
NYHA classification |
NYHA I |
NYHA II |
NYHA III |
NYHA IV |
|
Mean |
1016 |
1666 |
3029 |
3465 |
|
SD |
1951 |
2035 |
4600 |
4453 |
|
Median |
342 |
951 |
1571 |
1707 |
|
5th percentile |
32.0 |
103 |
126 |
148 |
|
95th percentile |
3410 |
6567 |
10,449 |
12,188 |
|
% > cutoff |
76.4 |
93.2 |
94.4 |
97.1 |
|
Minimum |
20.0 |
20.0 |
20.0 |
97.4 |
|
Maximum |
13,108 |
10,883 |
40,339 |
20,629 |
|
N |
182 |
250 |
234 |
35 |
Values for exclusion of congestive heart failure
NT-proBNP was retrospectively analyzed in a study of Svenstrup-Nielsen, et al. The study proposes that NT-proBNP values of 93 pg/ml and 144 pg/ml for men and women respectively allow to reliably exclude heart failure in symptomatic patients with a negative predictive value (NVP) of 97%.
|
|
Men (N = 143) 93 pg/ml |
Women (N = 141) 144 pg/ml |
|
Sensitivity |
96% |
94% |
|
Specificity |
67% |
69% |
|
Positive predictive value |
57% |
48% |
|
Negative predictive value |
97% |
97% |
Sensitivity, specificity, positive and negative predictive values of NT-proBNP for detecting heart failure in patients with dyspnea at the age of 50 years or older.
