This article proposes a falsifiable unified framework for hypothyroidism centered on Functional Thyroid Insufficiency ≠ Thyroid Hormone Resistance. Pathophysiology is explained by insufficient functional capacity of the hypothalamic-pituitary-thyroid axis, framed as Total Thyroid Functional Deficit (TTFD). Clinical manifestations including fatigue, cold intolerance, weight gain, and metabolic slowing arise from inadequate thyroid functional reserve rather than primary cellular hormone resistance. This model unifies clinical phenotypes under a single mechanistic principle and aligns with homeostatic self-preservation without invoking biologically implausible immune-mediated destruction or cellular resistance.
FOO SENG ANG (Tue,) studied this question.