Combined hormonal treatment and lung maturation.
Despite the proven efficacy of glucocorticoids for the prevention of RDS, this treatment is not effective in every case. One possible approach to improving the outcome is combined treatment with thyroid hormone and corticosteroid. Thyroid hormones accelerate morphological development and surfactant production in animals after treatment in vivo. With lung tissue in culture, T3 enhances phospholipid synthesis, apparently acting at different biochemical sites from those stimulated by corticosteroids. The effects of T3 are mediated through nuclear receptors, indicating that physiologic concentrations of T3 are stimulatory in the fetal lung. Furthermore, the developmental pattern for endogenous T3, as well as effects of thyroidectomy in fetal lambs, support the concept that endogenous thyroid hormones contribute to the timing of normal lung maturation in vivo. Combined treatment with thyroid hormones and glucocorticoids produces additive or supra-additive effects on phosphatidylcholine synthesis in the fetal lungs of rats, rabbits, and humans. The enhanced and faster response with both hormones v glucocorticoid alone suggests that clinical benefit might occur after shorter treatment intervals than currently observed with corticosteroid therapy. As there is little placental transfer of T3 and T4 in humans, maternal treatment with these hormones is not likely to be a useful approach for fetal therapy. Potentially, such therapy could be achieved by intraamniotic injection of T3 or T4, maternal treatment with synthetic thyroid hormones that pass the placenta, or by maternal treatment with TRH. This latter approach has been shown to elevate T3 levels in the cord blood of infants at term, mimicking the normal surge immediately after birth. If additional animal studies confirm the benefit of combined therapy on pulmonary function, clinical trials with glucocorticoid plus thyroid hormone may be appropriate in the near future.
D000818:Animals; D004359:Drug Therapy, Combination; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D010713:Phosphatidylcholines / Q000096:biosynthesis; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D011988:Receptors, Thyroid Hormone; D012127:Respiratory Distress Syndrome, Newborn / Q000517:prevention & control; D013961:Thyroid Gland / Q000503:physiopathology; D013963:Thyroid Hormones / Q000627:therapeutic use*; D013970:Thyronines / Q000627:therapeutic use; D013974:Thyroxine / Q000627:therapeutic use; D014284:Triiodothyronine / Q000627:therapeutic use
D005938:Glucocorticoids; D010713:Phosphatidylcholines; D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D013970:Thyronines; D014284:Triiodothyronine; C022861:3,5-dimethyl-3'-isopropyl-L-thyronine; D013974:Thyroxine