In a 32‑year‑old cisgender female presenting with fatigue, which of the following are appropriate differential diagnoses: hypothyroidism, sleep disorders, viral or bacterial infection, mood disorder (depression or anxiety)?

Differential Diagnosis of Fatigue in a 32-Year-Old Female

All four conditions listed—hypothyroidism, sleep disorders, viral or bacterial illness, and mood disorders (depression or anxiety)—are appropriate differential diagnoses for fatigue in this patient population.

Hypothyroidism

• Hypothyroidism produces symptoms nearly identical to fatigue presentations, including low energy, physical tiredness, poor concentration, disturbed sleep, and cognitive difficulties 1
• Thyroid dysfunction should be actively excluded in any patient presenting with fatigue, as it represents a treatable medical cause 2
• Thyroid screening is specifically recommended for patients presenting with fatigue, particularly when assessing for reversible contributing factors 2
• Overt hypothyroidism can manifest with fatigue as a primary symptom, and untreated diagnosed hypothyroidism is significantly associated with mood symptoms that compound the fatigue presentation 3

Sleep Disorders

• Sleep disturbances are among the most common and important contributors to fatigue, affecting 30-50% of patients in various populations 2
• Insomnia is diagnosed when patients have difficulty falling asleep and/or maintaining sleep at least 3 times per week for at least 4 weeks, accompanied by distress 2
• Feelings of fatigue (low energy, physical tiredness, weariness) are more common than actual sleepiness in patients with chronic insomnia 2
• Sleep disorders should be assessed and treated as they directly impact fatigue, and improvements in sleep lead to improvements in fatigue, mood, and quality of life 2
• Obstructive sleep apnea, restless legs syndrome, and excessive daytime somnolence all present with fatigue as a cardinal symptom 2

Viral or Bacterial Illness

• Acute infectious processes are well-established causes of fatigue and should be considered in the differential diagnosis 2
• When fatigue is accompanied by other symptoms such as unintentional weight loss or pulmonary complaints, a more extensive workup is warranted to screen for infectious etiologies 2
• The presence of acute illness should prompt evaluation for treatable infectious causes before attributing fatigue to other chronic conditions 2

Mood Disorders (Depression or Anxiety)

• Distress, depression, and anxiety should be routinely assessed in patients presenting with fatigue 2
• Complaints of irritability, loss of interest, mild depression and anxiety are common among patients with chronic fatigue 2
• Depression is rarely a primary factor in fatigue but can exacerbate it, and treatment may improve overall function 2
• Patients at higher risk of depression (young patients, those with history of prior psychiatric disease, and patients with low socioeconomic status) require more probing assessment 2
• Emotional distress should be screened as a common contributing factor regardless of fatigue onset 2

Clinical Approach

The evaluation should systematically address all four categories:

• Screen thyroid function with TSH measurement, and if elevated, measure free T4 and free T3 to distinguish subclinical from overt hypothyroidism 1
• Assess sleep patterns including bedtime, sleep latency, number of awakenings, total sleep time, and daytime dysfunction 2
• Evaluate for acute infectious symptoms and consider appropriate diagnostic testing if clinical suspicion exists 2
• Screen for mood disorders using validated tools and assess for distress, depression, and anxiety 2

Common Pitfalls to Avoid

• Do not attribute fatigue solely to one cause without excluding the others, as these conditions frequently coexist 2
• Avoid missing hypothyroidism by failing to order thyroid function tests in young women with fatigue 1, 4
• Do not overlook sleep disorders, as they are frequently underdiagnosed despite being highly prevalent and treatable 2
• Remember that even treated hypothyroidism (on levothyroxine) can be associated with persistent mood symptoms and fatigue, requiring reassessment of thyroid dosing and mood 5