Abstract
Background/Objectives: Thyroid hormone regulates erythropoiesis, but most population studies have used thyrotropin (TSH) alone and could not ask whether the erythroid response depends on the marrow's capacity to respond. We examined this in a population where inherited microcytosis and iron deficiency are both common. Methods: We analyzed 3871 adults of both sexes with paired free triiodothyronine (FT3), free thyroxine, TSH, and complete blood count from three hospitals in Jazan, Saudi Arabia (3673 with FT3 within the reference interval formed the primary analysis). All three analytes were entered simultaneously in models adjusted for age and sex; mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were pre-specified negative controls; discriminant indices assigned red cell phenotypes, validated against linked ferritin and transferrin saturation. Results: FT3 was associated with erythrocyte count (standardized β 0.097, 95% confidence interval (CI) 0.066–0.128, p < 0.001) and hemoglobin (+2.7 g/L per pmol/L); TSH was not (p = 0.547). The erythrocyte count association was present in normocytic (β 0.101) and acquired microcytic records (β 0.099) but absent in the inherited-trait pattern (β −0.017; interaction p = 0.002) and remained absent under a stricter trait definition. FT3 was unrelated to iron status, and the association survived adjustment for ferritin. In an exploratory comparison, both the count and hemoglobin associations were strongest in iron-replete normocytic patients (hemoglobin +3.6 g/L per pmol/L, p < 0.001) and attenuated in measured iron deficiency. Conclusions: FT3, not TSH, was associated with the erythron, and the response was absent where erythrocyte number is constitutionally elevated and blunted where hemoglobinization is iron-limited. These hypothesis-generating findings require replication with confirmed hemoglobin genotype.