What is Thyrotoxicosis
Thyrotoxicosis is a clinical syndrome of hypermetabolism caused by excess circulating thyroid hormones (elevated free T4 or total T3 with low or normal TSH), regardless of the source of those hormones. 1
Key Distinction from Hyperthyroidism
It's critical to understand that thyrotoxicosis and hyperthyroidism are not synonymous terms:
- Thyrotoxicosis refers to any state of excess thyroid hormone, from any source 2
- Hyperthyroidism specifically refers to thyrotoxicosis caused by increased synthesis and secretion of thyroid hormones from the thyroid gland itself, almost always associated with increased radioactive iodine uptake 2
Biochemical Definition
The laboratory hallmark is elevated free T4 or total T3 with suppressed or normal TSH 1, 3. This biochemical pattern defines thyrotoxicosis regardless of whether symptoms are present 1.
Major Causes
Thyrotoxicosis can result from three main mechanisms:
1. True Hyperthyroidism (Increased Synthesis)
- Graves' disease (most common cause overall) 4
- Toxic multinodular goiter 4
- Toxic adenoma 4
- These conditions show increased radioactive iodine uptake 2
2. Destructive Thyroiditis (Hormone Release)
- Thyroiditis is the most frequent cause of thyrotoxicosis in patients on immune checkpoint inhibitors 1
- Inflammatory destruction releases preformed hormone without increased synthesis 2
- Shows low or absent radioactive iodine uptake 3
- Self-limiting, typically resolving within 2-14 weeks and often progressing to hypothyroidism 3
3. Exogenous Sources
- Excessive thyroid hormone ingestion (thyrotoxicosis factitia) 2
- Also associated with low radioactive iodine uptake 2
Clinical Presentation Spectrum
Most patients with thyrotoxicosis are actually asymptomatic, with diagnosis made through routine laboratory monitoring 1, 3. When symptomatic, the hypermetabolic state manifests as:
- Weight loss 1, 4
- Palpitations and tachycardia 1, 4
- Heat intolerance 1, 4
- Tremors 1
- Anxiety 1
- Diarrhea 1
- Muscle weakness 4
Important caveat: These symptoms may be masked in patients taking beta-blockers 1.
Severe Manifestation
Thyroid storm represents the most severe, life-threatening form of thyrotoxicosis, characterized by altered mental status and requiring immediate aggressive treatment 5, 6. Any patient with altered sensorium should have thyroid storm in the differential 6.
Diagnostic Approach
TSH measurement has high sensitivity and specificity for diagnosing thyrotoxicosis 4. The diagnostic algorithm proceeds as follows:
- Confirm biochemical thyrotoxicosis: Low TSH with elevated free T4 or total T3 1, 3
- Distinguish the cause using radioactive iodine uptake or Doppler ultrasound 3
- High uptake = hyperthyroidism (Graves', toxic nodules)
- Low uptake = thyroiditis or exogenous hormone
- Additional testing includes TRAb/TSI to identify Graves' disease, and TPO antibodies for autoimmune thyroiditis 1, 3