From the Guidelines
A low transferrin saturation (TSAT) of 16% with normal iron levels in a 27-year-old likely indicates functional iron deficiency or iron sequestration, and the patient should undergo further evaluation to determine the underlying cause, including testing for inflammatory markers and ferritin levels, as recommended by the most recent guidelines 1. This condition can occur in early iron deficiency before serum iron levels drop, or in conditions where inflammation affects iron utilization despite adequate stores.
- Common causes include:
- Chronic inflammation
- Infection
- Certain medications
- Early pregnancy If inflammation is present, treating the underlying inflammatory condition may normalize iron metabolism.
- If early iron deficiency is suspected, iron supplementation with 325 mg of ferrous sulfate daily or 150-300 mg of elemental iron daily in divided doses may be appropriate, as suggested by previous studies 1. The discrepancy between TSAT and iron levels occurs because transferrin saturation reflects the percentage of iron-binding sites on transferrin that contain iron, providing a more sensitive indicator of iron availability for erythropoiesis than serum iron alone.
- According to the most recent guidelines, a TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency, but a ferritin of <100 ng/mL has a low sensitivity of 35%–48% 1. It is essential to monitor the patient's response to treatment and adjust the therapy as needed to avoid iron overload, which can be toxic, as noted in previous studies 1.
- The goal ferritin level in the absence of inflammation is 50 ng/mL, regardless of sex at birth, as recommended by the latest expert consensus guidelines 1.
From the Research
Iron Levels and Transferrin Saturation
- A transferrin saturation (TSAT) of 16% with normal iron levels in a 27-year-old may indicate iron deficiency without anemia, as iron studies will usually show a low ferritin and low transferrin saturation with a normal haemoglobin concentration 2.
- The cause of the iron deficiency should be identified and managed, and most people can be given oral iron supplements, with iron studies repeated after 60-90 days of oral iron supplements 2.
Diagnostic Tests for Iron Status
- Transferrin saturation (TSAT) is a common diagnostic test for iron status, but it may not always be an accurate indicator of iron availability, especially in patients with chronic kidney disease (CKD) 3.
- Serum iron may provide more information to guide iron therapy than TSAT, and other markers such as reticulocyte hemoglobin content (CHr) may also be useful in diagnosing iron deficiency 4.
Association with Pre-Diabetes
- High ferritin and low TSAT have been associated with pre-diabetes in a national representative sample of U.S. adults, suggesting that iron metabolism may play a role in the development of pre-diabetes 5.
- Further research is needed to examine the underlying mechanism of these associations, especially TSAT, in the pathophysiology of pre-diabetes 5.
Clinical Implications
- The diagnosis and management of iron deficiency should take into account the patient's overall clinical context, including the presence of CKD or other underlying conditions that may affect iron metabolism 6, 3.
- Iron supplementation therapy should be guided by clinical markers such as TSAT, and other factors such as serum ferritin and CHr should also be considered 4.