For THYROID FUNCTION INTERPRETATION

• Inverse Log-Linear Relationship: Due to the classic negative feedback loop, serum TSH has an inverse relationship with the logarithm of Free T4.
• Physiological Mismatch: A significant fall in Free T4 without a corresponding massive surge in TSH (usually greater than 20 mIU/L) creates a mathematical discrepancy that often indicates laboratory error.
• Diagnostic Thresholds: Unless Free T4 is only marginally low, TSH must be greater than 20 mIU/L to definitively confirm a diagnosis of Primary Hypothyroidism.
• Disease Distribution: Demographics play a role in probability; for instance, the likelihood of hypothyroidism in a young male is statistically lower than in a middle-aged female.
• Clinical Correlation: Diagnosis should never rely on labs alone; a patient without classic symptoms like cold intolerance or constipation is considered Clinically Euthyroid regardless of suspicious initial reports.
• Limitations of T3 in Hypothyroidism: Free T3 is a poor indicator of hypothyroidism because levels are often maintained within the normal range by increased peripheral conversion of T4 to T3, even as the thyroid fails.
• T3 Utility in Hyperthyroidism: Free T3 is primarily useful when TSH is undetectable but Free T4 is normal, helping to identify specific T3 toxicosis.
• Non-Thyroidal Illness: In systemic illness, Free T3 often drops significantly as the body downregulates conversion from T4 to save energy, a state known as Sick Euthyroid Syndrome.
• Protein Binding Interference: Over 99 percent of T4 and T3 are bound to proteins like Thyroid-Binding Globulin; therefore, Total T4 levels can fluctuate based on protein levels in conditions like pregnancy or liver disease, leading to false results.