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• The wider implications of non-anaemic iron deficiency
  oscar,m jolobe
  Published on: 22 March 2016

• Published on: 22 March 2016

  The wider implications of non-anaemic iron deficiency

  • oscar,m jolobe, retired geriatrician

  The highly commendable and detailed characterisation of non-anaemic iron deficiency(1) is timely and, perhaps, even overdue, given the fact that animal studies show that, even in the absence of anaemia, iron deficiency can ,in its own right, adversely affect both cerebral function(2), and thyroid function(3). In the animal model of non-anaemic iron deficiency it has been shown that iron uptake by a divalent metal ion tr...

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  The highly commendable and detailed characterisation of non-anaemic iron deficiency(1) is timely and, perhaps, even overdue, given the fact that animal studies show that, even in the absence of anaemia, iron deficiency can ,in its own right, adversely affect both cerebral function(2), and thyroid function(3). In the animal model of non-anaemic iron deficiency it has been shown that iron uptake by a divalent metal ion transporter(DMT-1) is essential for normal hippocampal neuronal development and normal spatial memory behaviour(2). Furthermore, in developing rats, there is a heterogenous loss of iron from the brain following dietary iron deficiency, and a heterogenous restoration of iron with iron therapy. What is more, early iron deficiency(and its correction by iron replacement) "altered brain iron...in many regions different from those observed in a later period"(4). Although there are no comparable human data, the corollary to the animal study(4)is that "there might be critical periods of infant development that absolutely require adequate iron nutriture for normal development"(5). It has also to be recognised that, in the human context, a causal relationship has not yet been clearly established between iron deficiency during development and deficits in cognitive and behavioural function(6). The relationship between iron deficiency and cognitive function is mirrored, to some extent, by the relationship between iron deficiency and thyroid function where, again, the most convincing data come from animal studies(3)(7). In the animal studies context, it has been shown that iron deficiency significantly(P < 0.05) reduces thyroid peroxidase activity, with the consequence that iron deficiency anaemia emerges as a significant and independent predictor of both reduced serum triiodothyronine(T3)(p< 0.001), and reduced serum thyroxine(T4)(p < 0.0005)(3). Also in the animal model, perinatal iron deficiency reduces serum total T3 by 43%, and serum total T4 by 67%, and whole brain T3 by 25%(7). The coexistence of iron deficiency and subclinical hypothyroidism mirrors the relationship between iron deficiency and thyroid function(8). When the two disorders coexist, patients randomised to combined iron and thyroid replacement therapy experience significantly(p < 0.0001) greater increase in blood haemoglobin and serum iron levels than patients randomised to the sole use of iron replacement therapy(8). The other side of the coin is that the use if iron replacement therapy in goitrous children(mean age 8.5 in one study; mean age 10 in another) with iron deficiency significantly)P < 0.001)improves the efficacy of iodised salt in reducing thyroid size(9)(10). A study which has relevance to much younger children is the one which showed that maternal iron deficiency predicted both higher thyroid stimulating hormone and lower total T4 concentrations during pregnancy in Switzerland, the latter an area of borderline iodine deficiency(11). Maternal hypothyroidism is, in turn, a recognised predictor of significantly(p=0.005) poorer suboptimal intellectual performance in their offspring(12). Comment In order to put non-anaemic iron deficiency in its proper context in relation to iron deficiency anaemia we have to consider the study which enrolled a sample of 504 consecutive children aged 1-3 in New York. Thirty five percent of those children had evidence of iron insufficiency; 7% with non-anaemic iron deficiency, and 10% with iron deficiency anaemia(13). Given the potential neurodevelopmental impact of non-anaemic iron deficiency(including its interaction with thyroid function), non-anaemic iron deficiency is an entity which deserves to be characterised as fully as possible so as to facilitate its identification and diagnosis. Accordingly, for the sake of completeness, I would suggest that the most decisive way to validate its diagnosis is to demonstrate a reduction in the magnitude of red cell distribution width, and also a reduction in the severity of hypochromia and/or microcytosis following iron replacement therapy. Furthermore, in patients with non-toxic goitre, the diagnostic trial of iron replacement therapy could be usefully accompanied by monitoring of thyroid size during co-administration of iodised salt. References (1) Hinchliffe RF., Bellamy GJ., Finn A et al Utility of red cell distribution width in screening for iron deficiency Arch Dis Child 2013;98:545-547 (2)Carlson ES., Tkac I., Magid R et al Iron is essential for neuron development and memory function in mouse hippocampus The Journal of Nutrition 2009;139:672-679 (3) Hess S., Zimmermann MB., Arnold M., Langhans W., Hurrell RF Iron deficiency anemia reduces thyroid peroxidase activity in rats J Nutr 2002;132:1951-1955 (4)Pinero DJ., Li N-Q., Connor JR., Beard JL Variations in dietary iron alter brain metabolism in developing rts J Nutr 2000;130:254-263 (5)Beard J Iron deficiency alters brain development and functioning J Nutr 2003;133:1468S-1472S (6) McCann JC., Ames BN An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioural function Am J Clin Nutr 2007;85:931-945 (7 Bastian TW., Prohaska JR., Georieff MK., Anderson GW Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations Endocrinology 2010;151:4055-4065 (8)Cinemre H., Bilir C., Gokosmanoglu F., Bahcebasi T Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: A randomised, double-blind, controlled study J Clin Endocrinol Metab 2009;94:151-156 (9)Hess SY., Zimmermann MB., Adou P., Torresani T., Hurrell RF Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Cor d'Iviore Am J Clin Nutr 2002;75:743-8 (10) Zimmermann MB., Zeder C., Chaouki N.,et al Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron deficicnt children: a randomized double-blind, controlled trial European Journal of Clinical Endocrinology 2002;147:747-753 (11)Zimmermann MB., Burgi H., Hurrell RF Iron deficiency predicts poor maternal thyroid status during pregnancy J Clin Endocrinol Metab 2007;92:3436-3440 (12)Mitchell ML., Klein RZ The sequelae of untreated maternal hypothyroidism European Journal of Endocrinology 2004;151:U45-U48 (13 Eden AN., Mir M Iron deficiency in 1-3 year old children. A pediatric failure? Arch Pediatr Adelosc Med 1997;151:986-988

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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