Theophylline Treatment in the Neonate with Apnea: Effect on Growth Hormone, Thyroid Hormone and TRH Induced TSH Secretion

Abstract

Caffeine has been shown to markedly alter growth hormone (GH), thyroid stimulating hormone (TSH), and thyroid hormones in animal studies. Similar studies in the human are lacking. To determine the effect of theophylline treatment on endocrine function in neonates with apnea, 10 infants were studied prospectively pretreatment, immediately following therapeutic blood levels of theophylline, at 2, 4, and 6 weeks thereafter and finally 2 weeks after discontinuation of theophylline. T(4), free T(4), T(3), GH, and basal and stimulated TSH were measured at each study period. Results show no significant difference consequent to theophylline therapy on basal thyroid or GH secretion and thyrotropin-releasing hormone (TRH) induced TSH response at any study interval. We conclude there is no evidence to suspect abnormality occurring in growth, thyroid function and GH secretion in neonates receiving theophylline for breathing disorders.

Serum Thyroid Hormones in Preterm Infants: Associations with Postnatal Illnesses and Drug Usage

“…In the majority of adults and children, the result of therapeutic doses of theophylline is to increase plasma T 4 levels with variable increases in rT 3 and T 3 (54). A single dose of iv aminophylline to adult asthmatics is followed by acute increases in TSH and T 4 (55), whereas effects are absent after chronic administration (Ͼ2 wk) to infants (56). The effect of caffeine on neonatal thyroid hormones is unknown.…”

The measurement, definition, aetiology and clinical consequences of neonatal transient hypothyroxinaemia

“…61 Glucocorticoids, which are used to mitigate chronic lung disease in preterm infants, have various effects on the pituitary-thyroid axis. TSH secretion in adults is reduced, 62 peripheral deiodination of TT4 to TT3 is decreased 63 in hypothyroid adults and rT3 and TBG concentrations are reduced in healthy adult volunteers.…”

“…For example, aminophylline, which is used as a respiratory stimulant in preterm infants with recurrent apnoea, increases TSH, 59 TT4 58,59 and TT3 concentrations 58 whereas theophylline, a metabolite of aminophylline, increases plasma TT4 concentrations in adults and children, with inconsistent effects on TT3 and rT3; 60 although prolonged administration of theophylline to infants has no effect on thyroid hormone concentrations. 61 Glucocorticoids, which are used to mitigate chronic lung disease in preterm infants, have various effects on the pituitary–thyroid axis. TSH secretion in adults is reduced, 62 peripheral deiodination of TT4 to TT3 is decreased 63 in hypothyroid adults and rT3 and TBG concentrations are reduced in healthy adult volunteers.…”

Specificity of Co-Promoting Effects of Caffeine on Thyroid Carcinogenesis in Rats Pretreated with N-Bis(2-hydroxypropyl)nitrosamine

“…Caffeine (1,3,7-trimethylxanthine) occurs in more than 60 plant species throughout the world (Barone and Roberts, 1996) and is contained in various foods, beverages such as coffee, tea, or soft drinks and over-the-counter medications as one of the most commonly consumed neutrally active compounds (Graham, 1978). Experimentally, several investigators have reported the acute or chronic changes in growth hormone, thyroxine (T 4 ) 1 and thyroid stimulating hormone (TSH) after treatment (Wolff and Varrone, 1969;Clozel et al, 1983;Willett et al, 1987). We recently found that caffeine copromotes thyroid carcinogenesis with iodine deficiency (ID) in association with thyroid hormone changes in rats (Son et al, 2003).…”