Levothyroxine Use in Infants and Children with Congenital or Acquired Hypothyroidism

Contributing Editor: Marcia L. Buck, Pharm.D.; Editorial Board: Kristi N. Hofer, Pharm.D.; Michelle W. McCarthy, Pharm.D.


Pediatr Pharm. 2008;14(10) 

In This Article

Mechanism of Action

Release of T4 is regulated by the hypothalamic-pituitary-thyroid axis. Thyrotropin-releasing hormone (TRH) is released from the hypothalamus and triggers secretion of thyrotropin-stimulating hormone (TSH) from the anterior pituitary. The presence of TSH stimulates synthesis and secretion of T4 and L-triiodothyronine (T3) by the thyroid. When serum concentrations of T3 and T4 increase, secretion of TRH and TSH declines.[2,3]

While the exact mechanisms of action for T3 and T4 are not well understood, they appear to work through control of DNA transcription and protein synthesis. Both T3 and T4 have the ability to diffuse into the cell nucleus and bind to thyroid hormone receptor proteins on DNA. This binding results in their ability to regulate a variety of metabolic processes influencing normal growth and development, maturation of the central nervous system, and bone formation. Although both T3 and T4 are active, T3 is the predominate form throughout the body. The majority of circulating T3 (approximately 80%) is derived from T4, through deiodination in peripheral tissues. Levothyroxine serves as an alternate source of T4 in patients with impaired endogenous production.[2,3]


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