Factors Affecting the Concentrations of Ferritin in Serum in a Healthy Australian Population

7/29/2019 Factors Affecting the Concentrations of Ferritin in Serum in a Healthy Australian Population

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1350 CLINICAL CHEM IS TRY, V ol.3 6, N o. 7 , 19 90

although, as an interim measure, the methods used hereseem to provide a reasonable approxim ation.References1. Rodbard D . S ta ti st ic al q u al it y contro land routin edata process-in g fo r rad ioim mu no asaay s an d im mu norad iom etric assay s. C linCh em 1974 ;2 0 :1 2 55 -7 0 .2. E kin s R P. T he p rec isio n p ro file: its u se in assay desig n, assess-ment and quality control. In : Hunter WM , Come JET, eds.Immunoassays fo r c li n ica l c hem istr y, 2 nd e d. E d in bu rg h: C h ur ch -i ll L iv in g st on e, 1 9 83 :7 6 -1 05.3 . Sadler W A, Sm ith M H. Estim ation of imprecision in inunu-noassay quality a sse ssm en t p ro gra mm es. Ann Clin Biochem1987;24:98-102.4. S adler W A, S mith M H, L egge H M. A m ethod for direct estim a-

C L IN . CH EM . 3 6/7 , 1 35 0-1 35 5 (1 99 0)

tion of im precision profiles, w ith reference to im munoassay data.C li n C hem 1 98 8;3 4: 10 58 -6 1.5. R aab G M. V alidity tests in th e sta tis tica l a na ly sis o f imm u-n oa ss ay d ata . Op . c it. (ref. 2):614-23.6. Raab G M, M cKenzie 1G M. A m odular com puter program fo rprocessing im munoassay data. In: W ilson D W, G askell SJ, K em pKW , e ds . Q ua lity c on tro l in c lin ic al e nd oc rin olo gy . C ard if f: A lp haOmega , 1 9 79 :2 25 -36 .7 . B ax te r R C . S im plif ie d a pp ro ac h to c on fid en ce lim its in ra dio im -muno as sa y. C li n C h em 1 98 0; 26 :7 63 -5 .8. R aggatt PR . D uplicates or singletons-an analysis of the needfo r re plic atio n in immunoassay a nd a c om pu te r program to calcu-late th e d is tr ib utio n o f o utlie rs , e rro r r ate a nd th e p re cis io n profilef rom a ss ay duplicates. Ann Clin B io chem 1989 ;26 :26 -37 .9. Bard Y. Nonlinear p ara mete r e stim ation . N ew Y ork : A ca de micPress, 1974 :2 0 5 pp .

Factors A ffecting the C oncentrations of Ferritin in S erum in a H ealthy A ustra lian P opulationB . A . Leggett,1 N . N . Brown,2S.J. Bryant,2 L Duplock,1 L. W . Powe ll ,1 and J . W. Ha l ll day1 3We m ea sure d b y d iffere nt te chn iq ues th e fe rn tin con ce ntra -tion in serum in tw o large asym ptom atic Austra lian popula-tion samples: 1367 bank employees and 601 insurancec orp ora tio n emp lo ye es. E th an ol in ta ke , d ie t, th e fre qu en cy o fblood donation, sm oking a nd e xe rcise habits, and pastmedical history were documented. The med ia n c on cen tr ati onof ferritin in serum varied according to age and sex, but wasgenerally higher than in previously reported popula tionsunder age 65 years. Results for th e tw o p op ula tio n s am ple swere in close agreement. Apart from the blood donationstatus, the m ost im portant factors influencing the concentra-tion of ferritin in serum were ethanol in take in men and diet inw om en. H eavy ethanol in take was associated with increasedvalues, even among men without evidence of liver disease.W e conclude that the reference range for ferritin concentra-tion in serum in the Australian population should be signifi-cantly increased and should b e r el at edto age as well as sex.This study em phasizes the need to determ ine local referenceranges for ferritin concentrations in serum .AddI tIona l Keyphrases: variation, source of e thano lsex- a nd a ge -re la te d effects im munoradiom efric assayreference range hem ochrom atosis

The concentration of ferritin in serum is widely usedclin ically as an index of body iron stores, but correctin terpretation relies on the availability of an appropriatereference range and knowledge of the variables other thaniron status that affect this range. A lthough there is goodevidence that a ferritin concentration


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SANK POPULATION

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INSURANCE POPULATION

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CLINICAL CHEM IS TRY, V ol. 3 6, N o. 7, 1990 1351

MethodsW e measured the concentration of ferritin in serum by a

two-site immunoradiom etric assay , using either a commer-cial kit (C iba Corning, Corning, NY ) for the bank employ-ees or the method of Halliday et al. (10) for th e insu ra ncecompany population. A complete blood count was per-formed w ith a Coulter Counter (Coulter E lectronics, H i-aleah, FL) and multip le biochem ical analysis w ith a SMACII (Technicon Instrument Corp., Tarrytown, NY ). C -reac-tive protein was measured by immunoturbidimetry . S tatis-tical analysis was done w ith the Statistical Package for theSocial Sciences X . The significance of association betweentwo variables was assessed by a chi-square test, w ith P


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MEDIANSERUM

FERRITIN

(p510

Men, Occaicoal li/y.., 2o1y.., 35/yea; 131131Cr E,q,y Uo,I 1-2*1 Oec.S ,on.I N,.R,GC y dAYS week

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300

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50061 1(47)12(15)

38 8(30)22(29)396(30)

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1352 CLINICAL CHEM IS TRY, V ol. 3 6, N o. 7, 1990

MEDIAN 10 0SERUM

FEERITINCONCENTRATION

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FREQUENCYOF BLOOD DONAT ION FREOUENCY OF MEAT INTAKEF ig . 2 . E ffect of b lood donation (left) and m eat in tak e (right) o n m e dia n concentration of ferntin in serum in 1367 bank emp lo yee sBoth assoc iat ions are s ign if icantat P


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T ab le 2 . C on trib utIo n o f V ar io us F ac to rs to th eVa ria bility o f F e rr itin Concen tr atio n In Se ra f rom MenF-value df P ChangebIn r2

Ag e, y ea rsFrequency of b loodd on atio n, n o/yr

29.080 4


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cient. In other studies, however, more than 20% of thew om en w er e ir on -d ef ic ie nt (8 , 14 , 15).

A s p re vio us ly observed, we saw a w ide spread of valuesfor serum ferritin in the present study, even w ithin groupsof the same age and sex. Factors postulated to alter theconcentration of ferritin in serum include exercise (16),smoking (4 , 17), liv er d is ea se (3, 18 , 19), and diet. Therewas no evidence in this population that the variability wasdue to the influence of smoking, exercise , or recent illness.The m ajor factors identified apart from the frequency ofblood donation were the meat intake of women and theethanol in take of men. D iet may have had a detectableeffect only in the women because they m ust ordinarilyabsorb a greater proportion of the iron in their diet tomaintain iron balance (20). Therefore, a decrease in theamount of bioavailable iron in their die t by a reduction inmeat intake is more likely to diminish their ability tocompensate fo r iron losses b y in crea sed ab so rption .

Although th e ferritin concentration is known t o i nc re as ein serum for many patients w ith liver disease (2 , 18, 19), itis unclear whether moderate-to-heavy ethanol intake inasym ptom atic subjects w ith norma l l iver-function tests isalso associated with an increase of serum ferritin . S tudiesof patients w ith alcoholism have demonstrated that highconcentrations of GO T in serum are correlated with a highf er ri ti n c on ce nt ra ti on (21,22). The authors of those studiessuggest that a high concentration of ferritin in serum isvery unlikely to be related to ethanol intake if the GOTconcentration is normal. However, they studied only a fewpatients with normal concentrations of GOT and did notcom pare these patients w ith controls to determ ine if therewas some increase of ferritin in th is group also . An in-creased GOT was associated with an increased ferritinconcentration in the present study but an effect of ethanolin take was apparent even among men w ith normal concen-trations of GOT in serum . Ethanol may have a specificeffect on ferritin synthesis, or increases of the ferritinconcentration in serum may be a very sensitive indicator ofthe effect of ethanol on the liver. The apparent lack ofinfluence of ethanol in take on the concentration of ferritinin serum of women may be due to either a true sex-relateddifference or the considerably lower prevalence of heavydrinking among women. L iver disease a s m an ife ste d byincreased concentrations of G OT or aspartate am inotrans-ferase w as associated w ith high concentrations of ferritinin serum from women.Ethanol intake in the A ustralian population is generallyhigh, being approximately tw ice that of the Swedish popu-lation (12); moreover, only 9% of American s ub je cts d rin k20 g or more of ethanol daily, compared w ith 32% of theA ustralian population studied (23). Ethanol in take in theU nited Kingdom is sim ilar to that in the Australianpopulation (24) but its effect may be offset by the lowerconsumption of meat in the British population (12). Notsurprisingly, therefore, the effect of ethanol on the concen-tration of ferritin in serum is clearer in the present study ofthe Australian population than in studies of populationsw ith a much lower ethanol intake. It contributes to thehigher median ferritin concentrations observed in men, butis not the o nly f ac to r involved. Even in men drinking


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CLIN ICAL CHEMISTRY ,Vo l . 36, No. 7, 1990 1355

age. Influence of biologicalnd pathologicalfactorsin a largeelderly p op ulation. C lin C him A cts 1985;149:37-45.18. Prie to J, Barry M , S he rlo ck S . S er um f er ritin i n pa ti en t s withiron overload and acute and chronic liver d iseases. G astroentero l-og y 1975;68:525-33.19 . Valberg LS, Ghennt CN , Lloyd DA, Frei JV , Chamberlain M J.Diagno s ti c e ff ic ac y of tests for the detection of iron overload inchronic liver disease. C an M ed A ssoc J 1978;119:229-36.20 . Bothw ell TH , Charlton RW , Cooke JD , F inch CA . Iron m etab-olism in m an. Oxford : B lackwell Scientific Publications, 1979.21 . M eyer TE , K assian ides C , Bothwell TH , G reen A . Effects ofheavy alcohol consum ption on serum fe rr it in c on ce nt ra tio ns . S AfrMed J 1 98 4;6 6: 57 3- 5.

CLIN . CH EM . 36/7 , 1355-1360 (1990)

22 . Lundin L , H allgren R , B irgegard G , W ide L . S erum ferritin inalc oh olic s a nd th e re la tio n to liver dam age, iron state and eryth-ro po ie tic a ctiv ity . A cts M e d S ca nd 1981;209:327-31.23. The Surgeon GeneralsReport on N utrition and H ealth ,DHHS (PHS) Publication N o. 88-50210. W ashington D C: US Deptof Health and Human Services, 1988.24 . Cade JE, B arker DJP , M argetts B M, Morris JA. Diet andinequalities in health in three English towns. Br Med J1988;296:1359-62.25 . Worwood M . Serum ferritin . C lin Sci 1986;70:215-20.26 . Bassett ML, Halliday JW , B ryant 5 , Dent 0, Powel l LW .Screening fo r hemochromatosis. Ann NY Acad Sc i 1988;526:274-89 .

Tw o N ew Two-S tep lmmunoassays for Free T hyroxin E valuated: S olid-P haseRadio immunoas sa y and T ime -Re so lv ed F lu oro immunoas sa yP Ine Nuu t jl a, 1 Per tt l Kesk lnen ,2 Ker ttu I rj aI a, 2L lnnea L lnke ,2 I fanna -Leena Ka lho la ,2J . U . Eskola,4 Rlsto E rkko la ,3 Pen tt lSepp&a, and Jo rma V II ka rI 1We measured concentrations of free thyroxin (F T4 ) in s er umby using two ne w two-step FT 4 assays-a so lid-p ha se two-ste p rad ioimm uno assa y, S pe ctn a# {17 4},nd a time-resolved flu-oro im munoassay, D elfia#{174}-and com pared the results w iththose by a tw o-step FT4 a ss ay ( RIA -g no st# {1 74 }) , o ne -s te p F T4a na lo g a ss ay (Am erle x-M# {1 74 }),nd FT4 measured after equi-librium dialysis. The new FT4 assays c la ss ifie d 3 0 hypothy-roid and 43 hyperthyroid patients (untreated) w ell. In 138p at ie nt s w ith n on th yr oi da l illn ess (N TI) a nd in la te p re gn an cy(n = 36), fewer subnormal FT4 values were reported bySpectria (P < 0.0 01 ), D elfia (P

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Factors Affecting the Concentrations of Ferritin in Serum in a Healthy Australian Population