Can hyperthyroidism (high thyroid hormone levels) and hypothyroidism (low thyroid hormone levels) coexist?

Can Hyperthyroidism and Hypothyroidism Coexist?

Yes, hyperthyroidism and hypothyroidism can coexist in the same patient, though this represents a rare clinical phenomenon driven by fluctuating autoimmune antibody activity, and more commonly, both conditions may be present simultaneously in patients with underlying heart failure from different causes.

Two Distinct Clinical Scenarios

1. Sequential Oscillation Between States (Rare Autoimmune Phenomenon)

The most striking form of coexistence involves spontaneous conversion between hypothyroidism and hyperthyroidism in patients with autoimmune thyroid disease, driven by alternating dominance of TSH-blocking antibodies (TBAb) and thyroid-stimulating antibodies (TSAb). 1, 2, 3

Key Clinical Features:

• Patients with long-standing hypothyroidism on levothyroxine can develop hyperthyroidism (Graves disease) despite years of stable thyroid replacement 2, 3
• The swinging dominance of inhibitory versus stimulatory thyroid antibodies creates cycles where patients alternate between hyper- and hypothyroid states 1
• Methimazole treatment may trigger TBAb dominance (causing hypothyroidism), while levothyroxine may trigger TSAb dominance (causing hyperthyroidism) 1

Diagnostic Pitfalls to Avoid:

• Do not assume persistent hyperthyroid symptoms in a hypothyroid patient on replacement therapy are simply due to overreplacement - this can delay recognition of true conversion to Graves disease 3
• Measure both TBAb and TSAb levels when oscillating thyroid function is suspected 1
• Repeated thyroid function testing every 2-3 weeks during treatment transitions is essential to detect these conversions 4

Management Approach:

• Definitive treatment with radioactive iodine ablation followed by levothyroxine replacement is the most effective strategy to end the oscillating cycle 1
• Antithyroid drugs and dose adjustments of levothyroxine often perpetuate the cycle rather than resolve it 1

2. Concurrent Presence in Heart Failure Patients (More Common)

Hypothyroidism and hyperthyroidism more commonly coexist as separate conditions in patients with heart failure from various underlying causes, rather than as simultaneous thyroid states. 5

Clinical Context:

• The American Heart Association guidelines explicitly state that "hypothyroidism and hyperthyroidism...more often coexist in patients with HF of various causes" 5
• This refers to thyroid dysfunction occurring alongside other cardiac pathology (ischemic, hypertensive, or valvular heart disease), not true simultaneous hyper- and hypothyroidism in the same thyroid gland 5

Screening Recommendation:

• Thyroid function tests are recommended in all patients presenting with heart failure due to the ease of diagnosis and availability of definitive treatments 5
• Both conditions can worsen cardiac function and precipitate heart failure, making detection critical for morbidity and mortality outcomes 5

Immunotherapy-Related Thyroid Dysfunction

Patients on immune checkpoint inhibitors can develop both hyperthyroidism and hypothyroidism, with hyperthyroidism often being transient and preceding hypothyroidism. 5

• Anti-PD-1/PD-L1 therapy causes thyroid dysfunction in 5-10% of patients, increasing to 20% with combination immunotherapy 5
• The hyperthyroid phase is typically transient and may precede permanent hypothyroidism 5
• TSH and FT4 should be monitored before every infusion or at least monthly 5

Bottom Line for Clinical Practice

Maintain high clinical suspicion for conversion between thyroid states in patients with autoimmune thyroid disease who develop persistent symptoms inconsistent with their current diagnosis. 1, 2, 3 The phenomenon is increasingly recognized in clinical practice despite being historically rare, and missing it leads to prolonged inappropriate treatment and patient suffering.