What is the relationship between anxiety and thyroid dysfunction?

Relationship Between Anxiety and Thyroid Dysfunction

Patients with anxiety disorders have a significantly increased likelihood of concomitant thyroid dysfunction, and this relationship is bidirectional, with routine thyroid screening recommended when treating anxiety disorders. 1

Key Findings on Comorbidity

The comorbidity between anxiety disorders and thyroid disorders is statistically significant across both population-based and clinical samples, indicating this is not simply due to selection bias in treatment-seeking individuals. 1 This finding has been consistent across studies using varied diagnostic criteria for thyroid dysfunction, including different cut-off values for TSH, T3, T4, and antibodies. 1

Temporal Relationship

• Age-of-onset data suggests that anxiety disorders typically precede the onset of thyroid disorders in the majority of cases, which may indicate that subtle hypothalamic-pituitary-thyroid (HPT) axis alterations in anxious patients progress over time into subclinical and/or overt thyroid disorders. 1
• The temporal order supports screening for thyroid dysfunction in patients presenting with anxiety disorders. 1

Mechanisms of Thyroid-Related Anxiety

Hyperthyroidism

Hyperthyroidism precipitates anxiety through direct thyroid hormone effects on brain neurotransmitter systems and widespread activation of peripheral adrenergic receptors, according to the American College of Endocrinology. 2

• Thyroid hormone receptors are widely expressed throughout the limbic system, directly modulating mood regulation centers. 2
• The central thyroid system cross-communicates with noradrenergic and serotonergic pathways, disrupting neurochemical balance essential for emotional stability. 2
• Excess thyroid hormones increase beta-adrenergic receptor sensitivity throughout the body, amplifying sympathetic nervous system activity. 2

Hypothyroidism and Subclinical Hypothyroidism

Both overt and subclinical hypothyroidism are associated with increased anxiety symptoms, with thyroid hormone receptors widely expressed in brain areas involved in mood regulation. 3

• A diminished TSH response to thyrotropin-releasing hormone (TRH) in subclinical hypothyroidism suggests pituitary dysfunction that may affect brain function. 3
• Studies demonstrate a negative association between self-reported anxiety levels and TSH in large population samples. 3
• Both subclinical hypothyroid and subclinical hyperthyroid patients have significantly higher anxiety scores than euthyroid controls. 4

Clinical Presentation Patterns

Resting Thyroid Parameters

• Patients with panic disorder (PD) and social anxiety disorder (SAD) do not differ from healthy controls in resting thyroid parameters (TSH, T3, T4 measured at single time points). 1
• This null finding was consistent across studies regardless of standardization of sampling schedules. 1

Stimulated TSH Response

• Half of studies found evidence for attenuated TSH responses upon stimulation with TRH in patients with anxiety disorders, suggesting subclinical thyroid dysfunction. 1
• This blunted TSH response indicates subtle HPT axis alterations even when resting parameters appear normal. 1

Anxiety-TSH Relationship

• There is a negative relationship between self-reported anxiety levels and TSH levels, meaning higher anxiety correlates with lower TSH. 1
• This relationship was significant even after controlling for smoking status. 1

Prevalence Data

Anxiety prevalence in thyroid disorder patients ranges from 50-63%, with depression prevalence at 42-60%. 5, 6

Risk Factors for Higher Anxiety in Thyroid Patients

• Female gender (54.9% vs 33.3% in males). 5
• Lower economic status (73.9% vs 35.5% in higher status). 5
• Hyperthyroid state (64.1% vs 44.4% in hypothyroid). 5
• Anxiety symptoms are more severe in overt hypo- and hyperthyroidism compared to subclinical forms. 7

Clinical Implications

Screening Recommendations

Routine screening for thyroid disorders is recommended when treating patients with anxiety disorders, as supported by multiple professional societies. 1

• Thyroid function testing should be considered in patients presenting with new or worsening anxiety, especially middle-aged patients with mood disturbances or cognitive complaints. 3
• When evaluating altered mental status with anxiety symptoms, clinicians should consider subclinical hypothyroidism in the differential diagnosis. 3

Treatment Outcomes

Restoration of euthyroidism is accompanied by improvement in quality of life and psychological symptoms in patients with overt hypothyroidism, subclinical hypothyroidism, and overt hyperthyroidism. 7

• The overt hyper- and hypothyroidism groups show more improvement than subclinical groups after treatment. 7
• Management of thyroid disorders should incorporate treatment of anxiety and depression, with routine psychiatric screening advisable. 5

Important Clinical Caveats

• The nature (hypothyroidism vs. hyperthyroidism) and severity (subclinical vs. overt) of comorbid thyroid disorders often remains unclear in clinical practice, as studies rarely report these details systematically. 1
• Part of the observed comorbidity may be due to simultaneous presence of mood disorders, which are highly co-occurring with generalized anxiety disorder. 1
• Overlap of symptoms common to both thyroid dysfunction and anxiety (palpitations, tremor, sweating, fatigue) is an important limitation when making clinical assessments. 4
• Stress-related long-term alterations in the hypothalamic-pituitary-adrenal (HPA) axis may foster autoimmunity and contribute to shared etiopathogenetic mechanisms between anxiety and thyroid dysfunction. 1