Iron Deficiency Without Anemia: A Neglected Clinical Syndrome in Internal Medicine Practice

Abstract

Iron deficiency without anemia was identified as an underestimated condition in clinical practice, despite its high prevalence and impact on quality of life. Although iron has historically been linked solely to hemoglobin production, multiple studies have shown that this mineral is essential for mitochondrial, muscular, immunological, and neurological functions. Thus, patients with normal hemoglobin levels but low iron stores presented symptoms such as chronic fatigue, mild dyspnea, headaches, restless legs syndrome, tachycardia, and mild cognitive disorders.
This condition was observed more frequently in young women, people with chronic inflammatory diseases, heart failure, or older adults. In these individuals, ferritin was found to be reduced or functionally inactive, making timely diagnosis difficult due to the absence of obvious anemia. The traditional approach in internal medicine, which focused only on hemoglobin, ignored this deficiency, limiting the use of effective treatments such as oral or intravenous iron supplementation.
In countries such as Cuba, the need to update clinical guidelines to consider this condition as a separate entity was recognized. It was proposed to routinely include ferritin and transferrin saturation measurements in patients with nonspecific symptoms, especially in women of childbearing age and people with inflammatory comorbidities. Recognizing this deficiency led to significant diagnostic improvement and an opportunity to alleviate the functional and emotional burden on patients, highlighting the importance of modern, comprehensive, and evidence-based internal medicine.