Table 3.

Metabolic manifestations in resistance to thyroid hormone

	Genetic Defect	Hypothalamic-Pituitary-Thyroid Axis	General Manifestations	Metabolic Manifestations	Reference Nos.
RTH ß	Most commonly a mutation or deletion in ligand binding domain of TRβ, generally producing reduced ligand binding and irreversible interaction with corepressors	In most cases resistance to thyroid hormone feedback at the pituitary (mediated by TRβ)	Goiter	Enhanced metabolic rate	28, 178, 202
		Elevated serum T4 and T3, “inappropriately” normal range serum TSH	Generally euthyroid, except for tachycardia (unopposed action of the elevated serum T4 and T3 stimulating TRα in the atria)	Hyperphagia
		Elevated T4/T3 “compensate” for resistance to thyroid hormone	In some models; reduced linear growth, impaired hearing, defects in bone formation, and attention deficit disorder
RTH α	In the few reported cases, a mutation in ligand binding domain of TRα, analogous to those found in TRβ, generally producing reduced ligand binding and irreversible interaction with corepressors	Pituitary is predominantly TRβ, pituitary normally sensitive to feedback	Short stature	Elevated cholesterol	21, 258
		Normal T4, T3, and TSH	Developmental delay	Elevated BMI
		Elevated serum T3/T4 ratio compared with normal	Bony deformities
			Chronic constipation