Is lethargy a typical symptom in an elderly male patient with amiodarone-induced thyrotoxicosis (AIT), low Thyroid-Stimulating Hormone (TSH) level, and elevated Prostate-Specific Antigen (PSA) level?

Is Lethargy Normal in Amiodarone-Induced Thyrotoxicosis?

Yes, lethargy is a recognized symptom in amiodarone-induced thyrotoxicosis (AIT), though it represents a paradoxical presentation that should prompt immediate evaluation for life-threatening complications or mixed thyroid dysfunction.

Understanding the Paradox of Lethargy in Thyrotoxicosis

While classic thyrotoxicosis typically presents with hypermetabolic symptoms (weight loss, palpitations, heat intolerance, tremors, anxiety, diarrhea), lethargy can occur in AIT through several mechanisms 1:

• Severe thyrotoxicosis with cardiac decompensation: Worsening of underlying heart disease is a clinical sign of hyperthyroidism, and in elderly patients with pre-existing cardiac disease, the metabolic demands of thyrotoxicosis can lead to heart failure and profound fatigue 2

• Beta-blocker masking: If your patient is taking beta-blockers for rate control, the typical hypermetabolic symptoms may be masked, leaving lethargy as a predominant symptom 1

• Type II AIT with destructive thyroiditis: This form involves inflammatory destruction of thyroid tissue, which can cause systemic inflammatory symptoms including fatigue and lethargy 3, 4

Critical Differential Diagnoses to Exclude Immediately

You must rule out concomitant hypophysitis or adrenal insufficiency, particularly if this patient has any history of immune checkpoint inhibitor therapy or other autoimmune conditions 1:

• Check morning (8 AM) cortisol and ACTH levels immediately
• Hypophysitis can present with fatigue and low free T4 with low/normal TSH, which differs from the expected high free T4 and suppressed TSH in AIT 1
• If both adrenal insufficiency and thyrotoxicosis coexist, steroids must be started before any thyroid treatment to avoid adrenal crisis 1

Life-Threatening Presentations Requiring Urgent Action

Lethargy in AIT can herald cardiovascular collapse, as demonstrated by case reports of cardiopulmonary arrest in AIT patients 5:

• Assess for signs of cardiac decompensation: worsening heart failure, refractory atrial fibrillation, or ventricular arrhythmias 2, 6
• In severe cases with deteriorating clinical status despite medical therapy, immediate total thyroidectomy should be considered rather than waiting for medical management to fail 5
• One case report documented a 49-year-old woman who developed cardiopulmonary arrest despite prednisolone treatment, requiring emergency thyroidectomy 5

Management Algorithm for Lethargic AIT Patient

Immediate steps 2, 4:

1. Discontinue amiodarone immediately if not essential for arrhythmia control—it can be stopped abruptly without tapering due to its 40-55 day half-life 2
2. Initiate beta-blocker therapy to control heart rate and prevent cardiac decompensation 2
3. Determine AIT type to guide specific treatment:
   • Type I: Thionamides plus potassium perchlorate 3, 4
   • Type II: Glucocorticoids (most effective) 2, 4
   • Mixed forms (common): Combination of thionamides, potassium perchlorate, and glucocorticoids 3, 4, 7

Common Pitfalls in Elderly Patients

• Apathetic thyrotoxicosis: Elderly patients may present with lethargy, depression, and apathy rather than classic hypermetabolic symptoms—this is a well-recognized atypical presentation in older adults 4

• Delayed recognition: The combination of beta-blockers masking symptoms and atypical presentations can delay diagnosis, allowing progression to life-threatening complications 1, 6

• Assuming hypothyroidism: Lethargy might prompt clinicians to assume hypothyroidism rather than thyrotoxicosis—always confirm with TSH and free T4 levels before initiating treatment 1

Monitoring and Expected Course

• Type II AIT is self-limiting and typically leads to permanent hypothyroidism after approximately 1 month of thyrotoxic phase and 2 months from immunotherapy initiation 1
• Repeat thyroid function tests every 2-3 weeks during the thyrotoxic phase 1
• Prepare to initiate levothyroxine replacement when hypothyroidism develops 2, 8
• Continue monitoring thyroid function every 4-6 weeks initially after starting replacement therapy 2

In this elderly male patient with cardiac disease, lethargy should be treated as a warning sign of potential cardiovascular decompensation rather than dismissed as a normal variant of AIT presentation.