A 45-year-old women presents for evaluation of fatigue. She has been tired for the past 6 months. She has had no problems with sleep and no other new symptoms. Her physical exam is unremarkable. Her Patient Health Questionnaire–9 score is 4. Lab results are as follows: hemoglobin, 13 g/dL; hematocrit, 39%; mean corpuscular volume, 90 fL; blood urea nitrogen, 10 mg/dL; Cr, 1.0 mg/dL; AST, 20 IU/L; ALT, 15 IU/L; ferritin, 35 mcg/mL; thyroid-stimulating hormone, 3.5 mIU/L.
What would you recommend?
A. Sertraline
B. Sleep study
C. Iron supplementation
I would treat this patient with iron. Verdon and colleagues conducted a randomized, double-blind placebo-controlled trial of iron treatment in nonanemic women.1 The women who received iron had a much greater reduction in fatigue score, compared with the women who did not (P < .004). Only women with ferritin levels less than 50 mcg/L benefited. Houston and colleagues performed a systematic review of the literature of iron supplementation for fatigue and concluded that iron should be considered for treatment of fatigue in nonanemic women.2 The key number for benefit was a ferritin level less than 50 mcg/L.
Hair thinning is a common concern for many women. Does iron deficiency have a possible role in this problem? A number of studies have correlated low ferritin levels with hair loss.3 There is less clear evidence of iron treatment being effective. Hard studied 140 women with diffuse hair loss, and found 19% had iron deficiency without anemia.4 All patients with iron deficiency were treated with oral iron and in all patients hair loss ceased, and hair regrowth occurred. The target ferritin goal for treatment is greater than 40 mcg/L.5
Iron deficiency is an important trigger for restless leg syndrome (RLS). All patients who present with RLS should have ferritin checked, and appropriate evaluation for the cause of iron deficiency if ferritin levels are low. Allen and colleagues published clinical practice guidelines for iron treatment of RLS.6 The guidelines conclude that ferric carboxymaltose (1,000 mg) is effective for treating moderate to severe RLS in those with serum ferritin less than 300 mcg/L and could be used as first-line therapy for RLS in adults, with oral iron (65 mg) possibly effective in patients with ferritin levels less than 75 mcg/L.
Pearl: Think of iron as therapy for fatigue in nonanemic women with a ferritin level less than 50 mcg/L, consider a trial of iron for thinning hair in women with ferritin levels less than 50 mcg/L, and a trial of iron in those with RLS with ferritin levels less than 75 mcg/L.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Verdon F et al. BMJ. 2003 May 24;326(7399):1124. .
2. Houston BL et al. BMJ Open. 2018 Apr 5;8(4):e019240.
3. Almohanna HM et al. Dermatol Ther (Heidelb). 2019 Mar;9(1):51-70. .
4. Hard S. Acta Derm Venereol. 1963;43:562-9.
5. Kantor J et al. J Invest Dermatol. 2003 Nov;121(5):985-8. .
6. Allen RP et al. Sleep Med. 2018 Jan;41:27-44. .