A patient with hyperthyroidism has elevated T3 and T4. Which mechanism explains the increased oxygen consumption and heat production in hyperthyroidism?

• A T3 directly activates mitochondrial uncoupling proteins (UCP2, UCP3), dissipating the proton gradient as heat
• B T3 directly inhibits ATP synthase, forcing ATP production through alternative pathways
• C T3 upregulates Na⁺/K⁺-ATPase expression, increasing futile cycling of Na⁺/K⁺ that consumes ATP and raises O2 consumption; also upregulates uncoupling proteins and mitochondrial biogenesis ✓
• D T3 activates beta-adrenoceptors directly, increasing catecholamine-driven thermogenesis

Explanation

Thyroid hormones (primarily T3, acting via nuclear TRα and TRβ receptors) increase the metabolic rate through multiple genomic mechanisms: (1) upregulation of Na⁺/K⁺-ATPase → increased active transport of Na⁺/K⁺ consuming ATP → more O2 consumed to regenerate ATP; (2) upregulation of mitochondrial uncoupling proteins (UCP1, UCP2, UCP3) dissipating the proton gradient as heat; (3) stimulation of mitochondrial biogenesis. T3 also increases the sensitivity of tissues to catecholamines by upregulating beta-adrenoceptors, but T3 does not directly activate adrenoceptors. T3 upregulates, not inhibits, ATP synthase.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.