Can fatigue occur with hypothyroidism and hyperthyroidism?

Fatigue in Hypothyroidism and Hyperthyroidism

Yes, fatigue is a well-recognized symptom of both hypothyroidism and hyperthyroidism, though it manifests through different pathophysiologic mechanisms in each condition.

Fatigue in Hypothyroidism

Fatigue is one of the cardinal symptoms of hypothyroidism and should prompt clinical suspicion for thyroid dysfunction. 1

• Unexplained fatigue, along with weight gain, hair loss, cold intolerance, constipation, and depression are recognized symptoms that should raise suspicion for hypothyroidism 1
• Signs and symptoms include fatigue, muscle cramps, constipation, cold intolerance, and hair loss, with progression leading to voice changes, weight gain, intellectual slowness, and insomnia 1
• Fatigue is consistently listed as a primary symptom in hypothyroidism across multiple clinical guidelines 2, 3

Evidence on Fatigue Severity and Treatment Response

• In treated hypothyroidism patients, 89% fulfill criteria for abnormal fatigue despite thyroid hormone replacement, with mean FACIT-F scores of 20.5—comparable to or worse than many other chronic conditions 4
• Levothyroxine replacement therapy significantly reduces fatigue severity (FSS scores decreased from 53 to 36) and frequency (from 45.7% to 26.1%) after 6 months of treatment 5
• Both before and after levothyroxine treatment, fatigue severity correlates positively with TSH levels and negatively with free T4 levels 5

Risk Factors for Persistent Fatigue

Important clinical caveat: Not all patients experience complete fatigue resolution with levothyroxine replacement 5, 4

• An FSS score >34 or >36 before treatment increases risk of persistent fatigue by 3-4 fold 5
• Diabetes is a significant risk factor for persistent fatigue (RR 5.7) in hypothyroid patients 5
• Common symptoms of overt hypothyroidism are non-specific, and many patients with subclinical hypothyroidism are asymptomatic, making it challenging to attribute symptoms to their underlying cause 6

Fatigue in Hyperthyroidism

Fatigue can also occur in hyperthyroidism, though it is less commonly emphasized than the hypermetabolic symptoms.

• Thyrotoxicosis may present with weight loss, palpitations, heat intolerance, tremors, anxiety, and diarrhea, though patients may be asymptomatic 1
• Hyperthyroidism symptoms include tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, and hypertension 1
• Fatigue is specifically listed as a clinical finding that should prompt evaluation for hypophysitis (which can cause secondary thyroid dysfunction) in patients on immune checkpoint inhibitors 1

Hyperthyroidism and Fatigue Mechanism

• Therapeutic overdosage of levothyroxine (iatrogenic hyperthyroidism) lists fatigue as an adverse reaction under "General" symptoms 7
• The fatigue in hyperthyroidism likely results from the hypermetabolic state causing increased energy expenditure and muscle weakness 1

Clinical Approach to Thyroid-Related Fatigue

Diagnostic Evaluation

When fatigue is present with suspected thyroid dysfunction, obtain TSH and free T4 levels 1

• For hypothyroidism: High TSH with low free T4 indicates biochemical hypothyroidism 1
• For hyperthyroidism: Low/normal TSH with high free T4 or T3 indicates thyrotoxicosis 1
• Consider thyroid peroxidase (TPO) antibody testing when hypothyroidism is confirmed 1

Treatment Considerations

For hypothyroidism with fatigue:

• Even subclinical hypothyroidism should be considered for treatment when fatigue or other complaints are present 1
• Levothyroxine is the standard treatment and improves fatigue in most patients 5, 2, 3
• Monitor for comorbidities (cardiac, pulmonary, renal, hepatic, neurologic, endocrine dysfunction including hypogonadism or adrenal insufficiency) that may contribute to persistent fatigue 1

For hyperthyroidism with fatigue:

• Beta-blockers (propranolol or atenolol) should be started for symptomatic patients 1
• Conservative management during thyrotoxic phase of thyroiditis is usually sufficient 1

Important Pitfall

Do not assume all fatigue in thyroid patients is thyroid-related. A large population-based study showed similar rates of thyroid disease-related symptoms in subclinical hypothyroidism compared with euthyroid subjects, with TSH concentration having no impact on symptom score 6. This highlights the difficulty in attributing symptoms to their underlying cause and the importance of considering alternative explanations for persistent fatigue despite adequate thyroid hormone replacement.