Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study

J Clin Endocrinol Metab. 2009 Jan;94(1):151-6. doi: 10.1210/jc.2008-1440. Epub 2008 Nov 4.


Context: In patients with coexisting iron-deficiency anemia and subclinical hypothyroidism, anemia does not adequately respond to oral iron therapy.

Objective: We studied whether iron-deficiency anemia might indicate treatment of subclinical hypothyroidism.

Design: PATIENTS were assigned to a control or experimental group: 240 mg/d oral iron alone (iron group) or 240 mg/d oral iron plus 75 microg/d levothyroxine (iron/levothyroxine group). Levels of hemoglobin, hematocrit, red blood cell count, serum iron levels, ferritin, total iron-binding capacity, TSH, and free T(4) were measured before and after treatment.

Setting: The study was conducted at a university hospital outpatient clinic.

Patients: Fifty-one patients with coexisting iron-deficiency anemia and subclinical hypothyroidism participated in the study.

Intervention: PATIENTS were treated as described above in either the iron group or the iron/levothyroxine group.

Main outcome measure: A clinically satisfactory increase in hemoglobin was regarded as successful.

Results: Mean hemoglobin levels increased by 0.4 g/dl in the iron group [95% confidence interval (CI) 0.2-0.7, P = 0.001], whereas it increased by a mean of 1.9 g/dl in the iron/levothyroxine group (95% CI 1.5-2.3, P < 0.0001). The increase in serum iron was greater in the iron/levothyroxine group by a mean of 47.6 microg/dl (95% CI 34.5-60.6, P < 0.0001). Increases in hemoglobin, red blood cells, hematocrit, and serum ferritin levels after treatment were statistically significantly greater in the iron/levothyroxine group (P < 0.0001). Starting hemoglobin and increase in hemoglobin were negatively correlated in the iron/levothyroxine group (r = -0.531, P = 0.006).

Conclusions: Subclinical hypothyroidism should be treated in iron-deficiency anemia patients when both conditions coexist. This would provide a desired therapeutic response to oral iron replacement and prevent ineffective iron therapy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / drug therapy*
  • Double-Blind Method
  • Female
  • Hemoglobins
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / drug therapy*
  • Male
  • Middle Aged
  • Thyrotropin / blood
  • Thyroxine / therapeutic use*


  • Hemoglobins
  • Thyrotropin
  • Thyroxine