What is the cause of siderophages in the thyroid gland?

Siderophages in the Thyroid Gland

Siderophages in the thyroid gland result from iron deposition secondary to chronic iron overload conditions, most commonly from repeated blood transfusions, hemochromatosis, or chronic hemodialysis with transfusion therapy.

Primary Causes of Thyroid Iron Deposition

Hemochromatosis (Primary and Secondary)

• Genetic hemochromatosis causes abnormally high intestinal iron absorption, leading to excessive iron storage in multiple organs including the thyroid gland 1
• Secondary hemochromatosis develops from massive blood transfusions, particularly in chronic hemodialysis patients 2
• Iron accumulates in thyroid follicular cells and interstitial macrophages (siderophages), which can be demonstrated histologically and by imaging studies 2

Chronic Transfusion Therapy

• Repeated blood transfusions in dialysis patients lead to progressive iron accumulation in the thyroid, liver, spleen, pancreas, and other organs 1, 2
• Each unit of transfused blood contains approximately 200-250 mg of iron, and without adequate iron excretion mechanisms (as in dialysis patients), this leads to tissue deposition 1
• Siderophages represent macrophages that have phagocytosed iron-laden cells or free iron 2

Hemodialysis-Associated Iron Overload

• Chronic hemodialysis patients receiving intravenous iron supplementation and blood transfusions are at particular risk 1
• Historical autopsy studies from the pre-erythropoietin era showed abundant iron deposits in thyroid tissue of dialysis patients who received IV iron products 1
• The thyroid is among the organs affected by systemic iron overload, though typically to a lesser degree than liver, spleen, and bone marrow 1

Clinical Significance and Thyroid Dysfunction

Development of Thyroid Disease

• Primary hypothyroidism can develop from iron deposition in the thyroid gland, though this is a relatively rare manifestation of hemochromatosis 2, 3
• Men with hemochromatosis show approximately 80 times higher incidence of thyroid disorders compared to the general male population, likely due to greater iron burden 3
• Iron-induced thyroid injury may trigger autoimmune thyroid disease, with development of anti-thyroid antibodies and subsequent hypothyroidism 4, 3

Pathophysiologic Mechanism

• Direct iron toxicity causes cellular damage to thyroid follicular cells 3
• This injury may precipitate autoimmune thyroiditis (particularly Hashimoto's thyroiditis) in genetically susceptible individuals 4, 3
• Histologic examination shows iron accumulation, fibrosis, and variable lymphocytic infiltration 3

Important Clinical Caveats

Monitoring Recommendations

• Thyroid function should be periodically assessed in all patients with chronic iron overload conditions, including hemochromatosis and transfusion-dependent patients 4
• Check serum TSH, free T4, and anti-thyroid antibodies (anti-TPO, anti-thyroglobulin) in at-risk populations 3
• Iron studies (serum iron, ferritin, TIBC) should be obtained alongside thyroid function tests 5

Sex Differences

• The typical female predominance of thyroid disease is reversed in hemochromatosis, with men showing higher rates of thyroid dysfunction due to greater iron accumulation 3
• Women with hemochromatosis generally have lower iron burden due to menstrual blood loss and therefore lower risk of iron-induced thyroid damage 3

Diagnostic Approach

• Computed tomography and magnetic resonance imaging can demonstrate iron deposition in the thyroid gland non-invasively 2
• Histological confirmation shows hemosiderin-laden macrophages (siderophages) within thyroid tissue 2, 3
• Elevated ferritin levels (typically >1000 ng/mL) suggest significant iron overload 1