What is the differential diagnosis for a patient presenting with anxiety symptoms, considering potential underlying psychiatric and medical conditions?

Differential Diagnosis for Anxiety

When evaluating a patient presenting with anxiety symptoms, systematically rule out medical conditions first (hyperthyroidism, cardiac arrhythmias, hypoglycemia, pheochromocytoma), then assess for substance-related causes (caffeine, medications, withdrawal), followed by other psychiatric disorders (depression, panic disorder, PTSD, adjustment disorder), before diagnosing a primary anxiety disorder. 1

Medical Conditions That Mimic Anxiety ("Masqueraders")

The following medical conditions must be excluded as they can present with identical anxiety symptoms:

Endocrine Disorders

• Hyperthyroidism is a critical differential, presenting with tremor, palpitations, sweating, and restlessness that closely mimics generalized anxiety 1
• Hypoglycemic episodes in diabetic patients can cause acute anxiety symptoms with autonomic hyperactivity 1
• Pheochromocytoma, though rare, causes episodic anxiety with severe hypertension and should be considered with paroxysmal symptoms 1

Cardiovascular Conditions

• Cardiac arrhythmias present with palpitations, chest discomfort, and fear that overlap with panic attacks 1
• Cardiac valvular disease can cause dyspnea and palpitations mimicking anxiety 1

Neurological Conditions

• Central nervous system disorders including seizure disorders, particularly temporal lobe epilepsy, can present with episodic fear and autonomic symptoms 1
• Migraine is associated with anxiety symptoms and may be comorbid 1

Respiratory Conditions

• Asthma and hypoxia cause shortness of breath and air hunger that trigger secondary anxiety 1
• Chronic obstructive pulmonary disease with hypoxia presents with restlessness and fear 1

Other Medical Conditions

• Caffeinism from excessive caffeine intake causes tremor, restlessness, and insomnia identical to anxiety 1
• Chronic pain/illness frequently presents with or causes secondary anxiety 1
• Systemic lupus erythematosus and other autoimmune disorders can have neuropsychiatric manifestations including anxiety 1
• Lead intoxication should be considered in appropriate exposure contexts 1
• Dysmenorrhea in women may present with cyclical anxiety symptoms 1

Laboratory Testing Approach

• Laboratory testing is not routine but should be obtained in collaboration with primary care when signs/symptoms suggest a medical condition 1
• Consider thyroid function tests (TSH, free T4) if hyperthyroidism is suspected 1
• Consider glucose monitoring if hypoglycemic episodes are suspected 1

Substance-Related Causes

Substance Intoxication

• Caffeine excess is a common and frequently overlooked cause of anxiety symptoms 1
• Stimulant medications (amphetamines, methylphenidate) and illicit stimulants (cocaine, methamphetamine) cause anxiety 2
• Cannabis can paradoxically cause anxiety, particularly in high doses or certain individuals 2

Medication Side Effects

• Corticosteroids commonly cause anxiety and agitation 3
• Bronchodilators (albuterol, theophylline) cause tremor and restlessness 3
• Thyroid hormone replacement in excess causes anxiety symptoms 3
• Decongestants containing pseudoephedrine or phenylephrine cause sympathomimetic effects 3

Substance Withdrawal

• Alcohol withdrawal causes severe anxiety with autonomic hyperactivity and requires immediate recognition 2
• Benzodiazepine withdrawal causes rebound anxiety and can be life-threatening 2
• Opioid withdrawal includes anxiety as a prominent symptom 2

Primary Psychiatric Disorders

Specific Anxiety Disorders

Panic Disorder is characterized by recurrent unexpected panic attacks with abrupt onset of intense fear reaching peak within 10 minutes, including at least 4 of 13 specific symptoms (palpitations, sweating, trembling, shortness of breath, choking, chest pain, nausea, dizziness, derealization/depersonalization, fear of losing control, fear of dying, paresthesias, chills/hot flushes), plus persistent concern about additional attacks 4, 5

Generalized Anxiety Disorder (GAD) involves excessive, uncontrollable worry about multiple life domains for at least 6 months, with at least 3 of 6 associated symptoms (restlessness, fatigue, difficulty concentrating, irritability, muscle tension, sleep disturbance) 4

Social Anxiety Disorder is marked by excessive fear of negative evaluation in social situations, with avoidance behavior and recognition that the fear is excessive 6

Specific Phobias involve anxiety reliably triggered by specific environmental stimuli (animals, heights, blood, enclosed spaces) with avoidance behavior 7

Separation Anxiety Disorder presents with developmentally inappropriate distress about separation from attachment figures, more common in children but can occur in adults 6

Agoraphobia involves fear of situations where escape might be difficult, often developing secondary to panic disorder 5

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive, unwanted thoughts (obsessions) and repetitive behaviors (compulsions) that are time-consuming and cause marked distress 5

Post-Traumatic Stress Disorder (PTSD) requires exposure to a traumatic event with subsequent reexperiencing (flashbacks, nightmares), avoidance, negative alterations in cognition/mood, and hyperarousal symptoms 5

Key Differentiating Features

• Panic disorder has discrete, episodic attacks versus the chronic, persistent worry of GAD 7
• Phobic disorders have identifiable, specific triggers versus the generalized nature of GAD 7
• Adjustment disorder with anxiety requires a clear precipitating stressor and symptoms that don't meet full criteria for other anxiety disorders 8

Psychiatric Comorbidities

Major Depressive Disorder is the most common comorbidity with anxiety disorders and must be systematically assessed using PHQ-9 or direct questioning about depressed mood, anhedonia, guilt, suicidal ideation 8

Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with anxiety, particularly in children and adolescents 1

Bipolar Disorder can present with anxiety during manic or depressive episodes 1

Eating Disorders commonly have comorbid anxiety, particularly social anxiety 1

Substance Use Disorders frequently co-occur and complicate anxiety treatment, requiring concurrent management 8

Personality Disorders, particularly avoidant and dependent types, overlap with anxiety presentations 7

Somatoform Disorders present with physical symptoms that may be manifestations of underlying anxiety 7

Pediatric-Specific Considerations

Medical Comorbidities in Children

• Children with anxiety disorders have higher rates of headaches, asthma, gastrointestinal disorders, and allergies 1
• The relationship between anxiety and physical disorders can be coincidental, causal (anxiety causing physical symptoms), or reactive (anxiety secondary to physical illness) 1

Developmental Considerations

• Anxiety symptoms must be developmentally inappropriate and excessive for age to be pathological 9
• Selective mutism in children often represents severe social anxiety 6
• School refusal may indicate separation anxiety, social anxiety, or panic disorder 6

Mental Status Examination Findings in Children

• Observable signs include poor eye contact, shy demeanor, clinginess, tremor, fidgetiness, hypervigilance, "nervous" habits, perseverative thinking, and irritability 1

Structured Assessment Approach

Screening Tools

• GAD-7 for generalized anxiety in adults and adolescents, with scores 0-4 (minimal), 5-9 (mild), 10-14 (moderate), 15-21 (severe) 8
• SCARED (Screen for Child Anxiety Related Emotional Disorders) for children, with parent and child versions 1
• Spence Children's Anxiety Scale (SCAS) for comprehensive anxiety assessment in youth 1

Diagnostic Interviews

• Anxiety Disorders Interview Schedule (ADIS) is the gold standard for comprehensive anxiety assessment, covering all DSM anxiety disorders plus comorbidity screening 1
• K-SADS-PL DSM-5 is a freely available structured interview for children and adolescents 1

Multi-Informant Approach

• Obtain information from patient, family members, teachers, and other collateral sources for comprehensive assessment, particularly in children and adolescents 1

Critical Safety Assessment

Immediate Red Flags Requiring Urgent Evaluation

• Suicidal ideation or self-harm behaviors require immediate psychiatric referral or emergency evaluation 8
• Severe agitation or psychotic symptoms warrant urgent specialist evaluation 8
• Confusion or delirium suggests medical emergency rather than primary anxiety 8

Common Diagnostic Pitfalls

• Missing medical mimics, particularly hyperthyroidism and cardiac arrhythmias, by attributing all symptoms to anxiety 6
• Overlooking substance use, including caffeine excess and alcohol use as self-medication 8
• Failing to screen for depression, which co-occurs in the majority of anxiety disorder patients 8
• Dismissing symptoms as "normal stress" when they meet criteria for clinical disorder 6
• Relying solely on patient report without collateral information, particularly in children 1
• Cultural variations in presentation, with non-Western populations more likely to report somatic rather than psychological symptoms 8