Graves' Disease and Microcytic Anemia: A Forgotten Connection

Area of Science:

• Endocrinology
• Hematology

Background:

• Microcytic anemia is infrequently associated with thyrotoxicosis, with limited recent literature.
• The underlying mechanism for this association remains poorly understood.

Observation:

• A 56-year-old man with Graves' disease presented with hyperthyroidism and concurrent microcytic anemia.
• Anemia and microcytosis resolved following methimazole treatment for hyperthyroidism.
• Iron deficiency was absent, as indicated by normal/high serum ferritin levels, which decreased with treatment.

Findings:

• Supraphysiological triiodothyronine (T3) levels induced proteotoxic stress in non-iron-deficient red cell precursors.
• This stress activated the integrated stress response, phosphorylating eIF2 and inhibiting globin mRNA translation.
• Reduced globin synthesis led to microcytosis, mimicking thalassemia.

Implications:

• This study proposes a novel mechanism linking thyrotoxicosis to microcytic anemia via impaired globin synthesis.
• The findings highlight the importance of considering thyroid function in unexplained microcytic anemia.
• Understanding this mechanism may lead to new diagnostic or therapeutic strategies.