More to the Story: When Oral Iron is not an Effective Therapy

Your patient needs more iron. What do you suggest? 

Physicians today have several options when selecting the best iron supplements for their patients. In the past, oral iron was considered the gold standard, but with new safer parenteral iron supplements on the market, it might be time to reconsider. 

First, let’s discuss non-adherance. Many physicians (including myself) fall into the habit of automatically attributing oral iron failure to the patient’s inability to stick to a regimen due to the side effects. However, there are reasons oral iron fails to correct the deficiency. 

For example, remember that stomach acid is crucial for the absorption of non-heme iron. Therefore, gastritis (H. pylori), gastric bypass procedures, and possibly proton pump inhibitors may decrease absorption. Celiac disease, especially with duodenal involvement, may also be a problem. This month’s Top Paper forced me to dig deeper into the topic and taught me once again that simple is better.¹ 

Hypothyroism and Anemia

Let’s begin with some basics. Patients with hypothyroidism experience anemia. But hypothyroid anemias are not always the result of a single, pathological mechanism. Hypothyroid anemias may be accompanied by other comorbidities and can be micro-, normo-, or macrocytic. Interestingly enough, there seems to be a higher incidence of iron deficiency anemia in persons with hypothroidism.² 

Additionally, thyroid hormone deficiency can also be associated with pernicious anemia (macrocytic), celiac disease, and bacterial overgrowth syndromes. Even without an associated disorder (eg, celiac disease), thyroid hormone plays a critical role in erythropoiesis.³ Hypo-proliferation of red cell precursors with sufficient erythropoietin have been implicated in the anemia of dialysis patients who are simultaneously hypothyroid.⁴ 

In addition, subclinical presentations of thyroid deficiency include heart disease (arteriosclerosis), LDL cholesterol elevations, neuropsychiatric symptoms, fatigue, slowness, and progression to clinical hypothyroidism.² 

Did you know that persons with subclinical hypothyroidism do not absorb iron without the help of a thyroid hormone supplementation? That’s what the data tells us.⁵ 

Thyroid Replacement + Iron

Let’s look first at why the combination of thyroid replacement and iron is important in primary care. The Top Paper¹ (n=40 with subclinical hypothyroidism, 20 received levothyroxine plus iron, 20 iron alone) demonstrated a superior rise with both thyroid replacement plus iron. Subclinical hypothyroidism should be diagnosed and treated in persons with iron deficiency, especially those who do not have an alternative reason for unresponsiveness to oral iron. The results substantiated an earlier study demonstrating the same exact pattern.² 

A jump to parenteral iron would not be appropriate in this clinical situation (in fact, in several other clinical situations as well).⁶ Using parenteral iron would be guilty of 2 mistakes: missing the diagnosis of thyroid disease and wasting a more expensive therapy. The fundamental problem is a lack of response to erythropoietin mediated by a lack of thyroid hormone, which would persist. 

After reading this Top Paper, I am making changes to the way I practice and my patients are sure to benefit. I will now measure TSH levels to prior to starting an oral iron replacement. It was demonstrated 20 years ago that menorrhagic women (with and without IUDs) have a greater incidence of occult hypothyroidism. Now we know that this may just be the tip of the hypothyroid iceberg. My advice: Be on the lookout for the combination of subclinical hypothyroidism and failure to respond to oral iron! ■

References

1.Ravanbod M, Asadipooya K, Kalantarhormozi M, et al. Treatment of iron-deficiency anemia in patients with subclinical hypothyroidism. Am J Med. 2013;126:420-424.

2.Cinemre H, Bilir C, Gokosmanoglu F, et al. Hematologic effects of Levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study. J Clin Endocrinol Metab. 2009;94:151-6.

3.Das KC, Mukherjee M, Sarkar TK, et al. Erythropoiesis and erythropoietin in hypo- and hyperthyroidism. J Clin Endocrinol Metab. 1975;45:211-220.

4.Ng YY, Lin HD, Wu SC, et al. Impact of thyroid dysfunction on erythropoietin dosage in hemodialysis patients. Thyroid. 2013;23:552-561.

5.Duntas LH, Papanastssiou L, Mantzou E, et al. Incidence of sideropenia and effects of iron repletion with subclinical hypothyroidism. Exp Clin Endocrinol Diabetes. 1999;107:356-360.

6.Rizvi S, Schoen RE. Supplementation with oral vs. intravenous iron for anemia with IBD or gastrointestinal bleeding: is oral iron getting a bad rap? Am J Gastroenterol. 2011;106:1872-1879. 

7.Blum M, Blum G. The possible relationship between menorrhagia and occult hypothyroidism in IUD-wearing women. Adv Contracept. 1992;8:313-317. 

Gregory W. Rutecki, MD, is a physician at the National Consult Service at the Cleveland Clinic. He is also a member of the editorial board of Consultant. Dr Rutecki reports that he has no relevant financial relationships to disclose.