Two Common Causes of Fatigue and Depression

Fatigue and Depression

As a doctor, one of the most common complaints that patients present with is fatigue and low mood. In these cases, it still surprises me how often the common causes of fatigue and depression are not fully evaluated. It is well known that iron deficiency and hypothyroidism can both cause fatigue and depression and should be standard rule-outs for anyone struggling with fatigue, especially when combined with mental health symptoms (Chen 2013, Duntas 2013). 

Iron deficiency

Iron is a nutrient necessary for the creation of hemoglobin, a metal containing protein. Hemoglobin carries oxygen in the bloodstream to tissues for effective energy production. Common symptoms of iron deficiency include fatigue, feeling winded when exercising, restless leg syndrome and pica, a desire to eat dirt or other inedible objects (Miller 2013).  

Iron deficiency is quite common. It’s estimated that more than 2 billion people are iron deficient in the world today (Viteri 1998). Although more common in developing countries, it’s still a significant problem in the United States with around 10% of women of childbearing age being deficient (Looker 1997).  

Iron deficiency appears to contribute to both fatigue and mental health issues. A recent analysis in Taiwan showed that children and adolescents with iron deficiency anemia were (Chen 2013):

  • 2.34 times more likely to have a mood disorder including depression
  • 5.78 times more likely to have bipolar disorder
  • 2.17 times more likely to have an anxiety disorder
  • 1.67 times more likely to have attention deficit problems

Testing for Iron Deficiency

For anyone feeling tired with or without mental emotional symptoms, iron levels should be fully evaluated. It’s not unusual that iron deficiency is missed due to inadequate testing. The most common test, a complete blood count, can still miss a large percentage of patients. Red blood cells can be normal in size in up to 40% of patients with iron deficiency (Johnson-Whimbley 2011). Testing should typically include a complete blood count, ferritin (iron stores) and iron panel to fully rule out iron deficiencies.

In women, testing has additional challenges. Ferritin levels under 50-75 in some cases can be considered iron deficient (Soppi 2018). Yet, in women, standard labs often report levels of ferritin down to 15 as normal (LabCorp 2020). This can lead to significant underdiagnosis.  


The thyroid gland is in the neck. It produces thyroid hormones which set the pace at which the body functions. If hormone levels are too low, a person is sluggish and slow. If levels are too high a person can feel wired and jittery. Thyroid problems are fairly common with a ten times higher prevalence in women than men (Vanderpump 2011). Around 1-2% of the population has hypothyroidism (low thyroid hormones) with incidence increasing significantly with age. 

In addition, low thyroid has been “irrefutably linked” to depression. Depressed patients have a higher incidence of hypothyroidism and vice versa. Often, depressive symptoms correlate to the degree of hypothyroidism (Duntas 2013).

Testing for Hypothyroidism

Testing for thyroid problems, like iron, also has challenges. The standard test, thyroid stimulating hormone or TSH is often labelled as normal from 0.35 to 4.5. And yet research seems to clearly indicate that levels above 2.5 are likely not normal (Wartofsky 2005). How to treat these patients with borderline test results is controversial. 

Testing for specific thyroid hormone levels and antibodies can also yield more information about the health of the thyroid gland. Although again, running these additional tests can be controversial.

Disregarding the challenges of testing, it is still vital that individuals with fatigue and/or fatigue-based depression should have a thyroid workup to rule out problems. Cases that are borderline may need a second opinion to better evaluate a person’s symptoms and treatment.


Fatigue and fatigue-related mental health problems are common in our society. Two of the most prevalent causes, iron deficiency and hypothyroidism are often missed in symptomatic patients. If you struggle with fatigue, it makes sense to make sure common causes are fully ruled out. It could make a big difference in how you feel. 

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