Can iron deficiency cause hypothyroidism?

Iron Deficiency and Thyroid Function: The Connection to Hypothyroidism

Iron deficiency primarily causes hypothyroidism through impairment of thyroid hormone metabolism, affecting both the synthesis of thyroid hormones and the conversion of T4 to the active T3 hormone. 1

Mechanisms of Iron Deficiency-Induced Hypothyroidism

Iron plays several critical roles in thyroid function:

1. Thyroid Peroxidase (TPO) Function:

   • Iron is a key component of thyroid peroxidase, a heme-containing enzyme essential for thyroid hormone production 1, 2
   • Iron deficiency reduces TPO activity, directly impairing T4 synthesis

2. T4 to T3 Conversion:

   • Iron deficiency impairs the hepatic conversion of T4 to the active metabolite T3 1
   • This conversion depends on Type 1 5'-deiodinase, which requires adequate iron levels

3. Thyroid Hormone Metabolism:

   • Iron deficiency alters overall thyroid metabolism, leading to decreased production of thyroid hormones 1
   • This can manifest as subclinical or overt hypothyroidism

Clinical Manifestations and Associations

• Iron deficiency is strongly associated with subclinical hypothyroidism 3

• The combination can lead to:

  • Reduced metabolic rate
  • Fatigue and decreased exercise tolerance
  • Exacerbation of hypothyroid symptoms
  • Intolerance to levothyroxine treatment in some cases 4

• During pregnancy, maternal hypothyroidism due to iron deficiency increases the risk of:

  • Preeclampsia
  • Low birth weight
  • Congenital cretinism (growth retardation, mental retardation, and neuropsychological defects) 5

Diagnostic Considerations

When evaluating patients with suspected hypothyroidism:

• Assess both thyroid function (TSH, free T4) and iron status (ferritin, hemoglobin)
• Consider that iron deficiency may be masked by hypothyroid symptoms
• Be aware that correction of iron deficiency may unmask subclinical thyroid dysfunction

Treatment Approach

1. Combined Treatment Strategy:

   • A combination of levothyroxine and iron supplementation is more effective than either treatment alone in patients with both conditions 3
   • However, separate administration times are crucial (at least 4 hours apart) to prevent interference with levothyroxine absorption

2. Sequence of Treatment:

   • In patients with both conditions who experience intolerance to levothyroxine:
     • Correct iron deficiency first (4-7 weeks of iron supplementation)
     • Then initiate or resume thyroid hormone replacement 4

3. Monitoring Response:

   • Follow both thyroid function tests and iron parameters
   • Be alert for changes in thyroid hormone requirements as iron status improves

Clinical Pitfalls and Considerations

• Levothyroxine Intolerance: Patients with iron deficiency anemia may experience palpitations, nervousness, and restlessness when started on thyroid hormone replacement due to a hyperadrenergic state 4

• Incomplete Response: Failure to recognize and treat concurrent iron deficiency may result in suboptimal response to thyroid hormone replacement

• Metabolic Effects: Iron deficiency can worsen the hypometabolic state of hypothyroidism by impairing T4 synthesis and T4 to T3 conversion 1

• Pregnancy Considerations: Both conditions require prompt recognition and treatment during pregnancy to prevent adverse maternal and fetal outcomes 5

Iron deficiency screening should be considered as part of the standard evaluation of patients with hypothyroidism, particularly in women of reproductive age, as early detection and treatment of both conditions can significantly improve clinical outcomes and quality of life.