Iron deficiency is a very common and treatable disorder. Of all the tests available to diagnose iron deficiency, the serum ferritin is the most able to discriminate iron deficiency from other disorders. However, the reference range for ferritin in many laboratories will lead to underdiagnosis of iron deficiency in women. Studies have shown that 30%-50% of healthy women will have no marrow iron stores, so basing ferritin cutoffs on the lowest 2.5% of sampled ferritins is not appropriate. In addition, several lines of evidence suggest the body physiologic ferritin “cutoff” is 50  ng/mL. Work is needed to establish more realistic ferritin ranges to avoid underdiagnosing a readily treatable disorder.

1.
Pasricha
S-R
,
Tye-Din
J
,
Muckenthaler
M-U
,
Swinkels
D-W
.
Iron deficiency
.
Lancet
.
2021
;
397
(
10270
):
233
-
248
.
doi:10.1016/S0140-6736(20)32594-0
.
2.
Plays
M
,
Müller
S
,
Rodriguez
R.
Chemistry and biology of ferritin
.
Metallomics
.
2021
;
13
(
5
).
doi:10.1093/mtomcs/mfab021
.
3.
Eisenstein
RS
,
Blemings
KP
.
Iron regulatory proteins, iron responsive elements and iron homeostasis
.
J Nutr
.
1998
;
128
(
12
):
2295
-
2298
.
doi:10.1093/jn/128.12.2295
.
4.
Gelaw
Y
,
Woldu
B
,
Melku
M.
The role of reticulocyte hemoglobin content for diagnosis of iron deficiency and iron deficiency anemia, and monitoring of iron therapy: a literature review
.
Clin Lab
.
2019
;
65
(
12
).
doi:10.7754/Clin.Lab.2019.190315
.
5.
Walters
GO
,
Miller
FM
,
Worwood
M.
Serum ferritin concentration and iron stores in normal subjects
.
J Clin Pathol
.
1973
;
26
(
10
):
770
-
772
.
doi:10.1136/jcp.26.10.770
.
6.
Guyatt
GH
,
Oxman
AD
,
Ali
M
,
Willan
A
,
McIlroy
W
,
Patterson
C.
Laboratory diagnosis of iron-deficiency anemia: an overview
.
J Gen Intern Med
.
1992
;
7
(
2
):
145
-
153
.
doi:10.1007/bf02598003
.
7.
Harms
K
,
Kaiser
T.
Beyond soluble transferrin receptor: old challenges and new horizons
.
Best Pract Res Clin Endocrinol Metab
.
2015
;
29
(
5
):
799
-
810
.
doi:10.1016/j.beem.2015.09.003
.
8.
Mast
AE
,
Blinder
MA
,
Gronowski
AM
,
Chumley
C
,
Scott
MG
.
Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations
.
Clin Chem
.
1998
;
44
(
1
):
45
-
51
.
doi:10.1093/clinchem/44.1.45
.
9.
Beutler
E
,
Larsh
SE
,
Gurney
CW
.
Iron therapy in chronically fatigued, nonanemic women: a double-blind study
.
Ann Intern Med
.
1960
;
52
:
378
-
394
.
doi:10.7326/0003-4819-52-2-378
.
10.
Vaucher
P
,
Druais
P-L
,
Waldvogel
S
,
Favrat
B.
Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial
.
CMAJ
.
2012
;
184
(
11
):
1247
-
1254
.
doi:10.1503/cmaj.110950
.
11.
Verdon
F
,
Burnand
B
,
Stubi
C-L
, et al.
Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial
.
BMJ
.
2003
;
326
(
7399
):
1124
.
doi:10.1136/bmj.326.7399.1124
.
12.
Burden
RJ
,
Morton
K
,
Richards
T
,
Whyte
GP
,
Pedlar
CR
.
Is iron treatment beneficial in iron-deficient but non-anaemic (IDNA) endurance athletes? A systematic review and meta-analysis
.
Br J Sports Med
.
2015
;
49
(
21
):
1389
-
1397
.
doi:10.1136/bjsports-2014-093624
.
13.
Bruner
AB
,
Joffe
A
,
Duggan
AK
,
Casella
JF
,
Brandt
J.
Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls
.
Lancet
.
1996
;
348
(
9033
):
992
-
996
.
doi:10.1016/S0140-6736(96)02341-0
.
14.
Zhu
X-Y
,
Wu
T-T
,
Wang
H-M
, et al.
Correlates of nonanemic iron deficiency in restless legs syndrome
.
Front Neurol
.
2020
;
11
:
298
.
doi:10.3389/fneur.2020.00298
.
15.
Robach
P
,
Recalcati
S
,
Girelli
D
, et al.
Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin
.
Blood
.
2009
;
113
(
26
):
6707
-
6715
.
doi:10.1182/blood-2008-09-178095
.
16.
Iron Fact Sheet for Health Professionals
. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/. Accessed
October
12
,
2023
17.
Scott
DE
,
Pritchard
JA
.
Iron deficiency in healthy young college women
.
JAMA
.
1967
;
199
(
12
):
897
-
900
.
PMID: 6071557
.
18.
Puolakka
J.
Serum ferritin in the evaluation of iron status in young healthy women
.
Acta Obstet Gynecol Scand Suppl
.
1980
;
95
:
35
-
41
.
doi:10.3109/00016348009156378
.
19.
Hallberg
L
,
Bengtsson
C
,
Lapidus
L
,
Lindstedt
G
,
Lundberg
PA
,
Hultén
L.
Screening for iron deficiency: an analysis based on bone-marrow examinations and serum ferritin determinations in a population sample of women
.
Br J Haematol
.
1993
;
85
(
4
):
787
-
798
.
doi:10.1111/j.1365-2141.1993.tb03225.x
.
20.
Rushton
DH
,
Barth
JH
.
What is the evidence for gender differences in ferritin and haemoglobin?
Crit Rev Oncol Hematol
.
2010
;
73
(
1
):
1
-
9
.
doi:10.1016/j.critrevonc.2009.03.010
.
21.
Galetti
V
,
Stoffel
NU
,
Sieber
C
,
Zeder
C
,
Moretti
D
,
Zimmermann
MB
.
Threshold ferritin and hepcidin concentrations indicating early iron deficiency in young women based on upregulation of iron absorption
.
E Clin Med
.
2021
;
39
:
101052
.
doi:10.1016/j.eclinm.2021.101052
.
22.
Tarancon-Diez
L
,
Genebat
M
,
Roman-Enry
M
, et al.
Threshold ferritin concentrations reflecting early iron deficiency based on hepcidin and soluble transferrin receptor serum levels in patients with absolute iron deficiency
.
Nutrients
.
2022
;
14
(
22
).
doi:10.3390/nu14224739
.
23.
Nilsson-Ehle
H
,
Jagenburg
R
,
Landahl
S
,
Svanborg
A.
Blood haemoglobin declines in the elderly: implications for reference intervals from age 70 to 88
.
Eur J Haematol
.
2000
;
65
(
5
):
297
-
305
.
doi:10.1034/j.1600-0609.2000.065005297.x
.
24.
Widdowson
EM
,
McCance
RA
.
Iron in human nutrition
.
J Hyg (Lond)
.
1936
;
36
(
1
):
13
-
23
.
doi:10.1017/s0022172400043370
.
25.
Natvig
H
,
Vellar
OD
.
Studies on hemoglobin values in Norway. 8. Hemoglobin, hematocrit and MCHC values in adult men and women
.
Acta Med Scand
.
1967
;
182
(
2
):
193
-
205
.
26.
Merz
LE
,
Siad
FM
,
Creary
M
,
Sholzberg
M
,
Weyand
AC
.
Laboratory-based inequity in thrombosis and hemostasis: review of the evidence
.
Res Pract Thromb Haemost
.
2023
;
7
(
2
):
100117
.
doi:10.1016/j.rpth.2023.100117
.
You do not currently have access to this content.