What is the possible diagnosis for a patient with elevated Triiodothyronine (T3), normal Thyroxine (T4), and normal Thyroid-Stimulating Hormone (TSH) levels, presenting with hyperhidrosis (excess sweating) and weight gain?

Diagnostic Evaluation for Elevated T3, Normal T4/TSH, with Hyperhidrosis and Weight Gain

Primary Diagnostic Consideration

This clinical presentation is atypical and does not fit standard thyroid disease patterns—the combination of elevated T3 with normal T4 and TSH alongside weight gain (rather than weight loss) suggests either laboratory error, T3 toxicosis with paradoxical weight gain, or a non-thyroidal cause for the symptoms.

Understanding the Biochemical Pattern

Classic Thyroid Dysfunction Patterns

• Overt hyperthyroidism presents with suppressed TSH (<0.1 mIU/L), elevated free T4, and/or elevated T3, typically causing weight loss, not weight gain 1
• T3 toxicosis (isolated T3 elevation) occurs with markedly subnormal TSH (≤0.1 mIU/L), normal free T4, but elevated T3—this is rare and typically associated with autonomous thyroid nodules 2
• Normal TSH with elevated T3 is biochemically inconsistent with primary thyroid disease, as TSH should be suppressed when T3 is truly elevated 3, 1

Critical First Step: Verify Laboratory Results

• Repeat thyroid function tests (TSH, free T4, total T3, and free T3 by equilibrium dialysis method) to confirm the pattern, as laboratory error or assay interference is possible 2
• Ensure testing was performed when the patient was not acutely ill, as non-thyroidal illness can cause spurious results 4
• Check for medications or supplements containing thyroid hormone (particularly T3/liothyronine) that could cause exogenous elevation 5

Differential Diagnosis Algorithm

If Repeat Testing Confirms Elevated T3 with Normal TSH/T4

Scenario A: True T3 Toxicosis (Rare)

• Obtain thyroid scan with radioactive iodine uptake to identify autonomous thyroid nodules (toxic adenoma or toxic multinodular goiter) 3, 2
• Perform thyroid ultrasound to evaluate for nodular disease 2
• Measure TSH receptor antibodies (TRAb) to exclude Graves' disease, though this would typically suppress TSH 1
• However: Weight gain argues strongly against true thyrotoxicosis, which characteristically causes weight loss 1

Scenario B: Assay Interference or Laboratory Error

• Consider heterophile antibodies or other assay interference causing falsely elevated T3 2
• Send samples to a different laboratory using alternative assay methodology 4
• Request free T3 measurement by tracer equilibrium dialysis, the gold standard method 2

Scenario C: Non-Thyroidal Etiology (Most Likely)

• The combination of hyperhidrosis and weight gain with this thyroid pattern suggests:
  • Insulin resistance/metabolic syndrome: Can cause hyperhidrosis and weight gain
  • Polycystic ovary syndrome (PCOS): If female patient, causes hirsutism, weight gain, and metabolic dysfunction
  • Pheochromocytoma: Causes episodic sweating, though typically with weight loss or stable weight
  • Carcinoid syndrome: Causes flushing and sweating
  • Medication effects: Certain drugs cause hyperhidrosis and weight gain

Clinical Pitfalls to Avoid

Common Diagnostic Errors

• Do not diagnose hyperthyroidism based on elevated T3 alone when TSH is normal—this violates basic thyroid physiology where elevated thyroid hormones suppress TSH 3, 1
• Do not treat with antithyroid drugs without confirming diagnosis with thyroid scan showing increased uptake 3
• Do not assume thyroid disease explains weight gain—thyrotoxicosis causes weight loss, not gain 1
• Do not overlook exogenous T3 intake—specifically ask about supplements, compounded hormones, or weight loss preparations 5

Critical Safety Considerations

• If TSH is truly normal with elevated T3, consider TSH-secreting pituitary adenoma (extremely rare), which would require pituitary MRI 3
• Rule out laboratory interference before pursuing invasive testing or treatment 2
• Assess for cardiac complications if true thyrotoxicosis is confirmed—check ECG for atrial fibrillation and consider echocardiogram 1

Recommended Diagnostic Workup

Immediate Next Steps

1. Repeat thyroid function tests with free T3 by equilibrium dialysis method at a reference laboratory 2
2. Obtain thyroid ultrasound to evaluate for nodular disease 2
3. Measure TSH receptor antibodies (TRAb) and thyroid peroxidase antibodies (TPO) 4, 1
4. Check for exogenous thyroid hormone intake—review all medications, supplements, and over-the-counter products 5

If Initial Testing Confirms Pattern

• Thyroid scan with radioactive iodine uptake to distinguish hyperthyroidism (high uptake) from thyroiditis or exogenous hormone (low uptake) 3, 2
• 24-hour urine metanephrines to exclude pheochromocytoma if episodic symptoms 3
• Fasting glucose, insulin, and HbA1c to evaluate for insulin resistance 4
• Pituitary MRI only if TSH remains inappropriately normal with confirmed elevated free thyroid hormones, suggesting TSH-secreting adenoma 3

Alternative Evaluation if Thyroid Disease Excluded

• Comprehensive metabolic evaluation for causes of hyperhidrosis and weight gain unrelated to thyroid
• Consider endocrinology referral for complex cases where biochemical pattern remains unexplained 2