Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone in juvenile obesity before and after hypocaloric diet

Abstract

This study was performed on 36 obese subjects aged 8.5-17.4 yr, 14 boys and 22 girls (prepubertal: 5 boys and 5 girls [stage I, according to Tanner]; BMI: 35.5 +/- 1.4 [mean +/- SEM] and 35 +/- 1.3 respectively; pubertal: 9 boys and 17 girls [stage IV-V]; BMI: 36.2 +/- 1.8 and 36 +/- 1.5 respectively) before and after 8 weeks of a 1000 kCal/day diet. The responses of serum TSH and PRL to TRH (200 micrograms iv as a bolus) were evaluated as Area Under the Curve (AUC) and net increase in respect to basal values (delta TSH and delta PRL). Serum T4, fT4 and rT3 were assayed at the baseline and T3 and fT3 at the baseline and 120' after TRH injection. A similar analysis was performed on 14 age- and sex-matched lean subjects as controls. In females at baseline fT4 serum levels were greater than controls and were significantly reduced after weight loss; rT3 increased after weight loss in the whole study group. In patients of both sexes the PRL peak after TRH injection was earlier but not greater (15') than in controls (30'). After weight loss PRL peak after TRH was found at 30' (as controls) in females only. Taking into consideration the stage of pubertal development, the results were the following: a) in puberal girls, after weight loss, TSH and PRL peaks after TRH were delayed with respect to baseline and to the other considered subgroups; b) in prepubertal girls TSH and PRL peaks, delta TSH, delta PRL, AUC-TSH and AUC-PRL were blunted with respect to pubertal ones; c) the other considered variables were unchanged after the period of caloric deprivation. No correlation between BMI and the AUC of TSH and PRL was found. These data suggest that thyroid function is substantially normal in adolescent obese subjects and not influenced by a prolonged period of caloric restriction, even though a reduced hypothalamic dopaminergic tone on pituitary thyreotrophs and lactotrophs could cause subtle alterations on TSH and PRL release, partially influenced by gender and sexual development.

Lack of Association Between Peripheral Activity of Thyroid Hormones and Elevated TSH Levels in Childhood Obesity

“…In normal-weight humans, monodeiodination of T4 produces approximately equal amounts of T3 and rT3. In obesity, production of T3 has been reported to be normal or increased (21,22), while data on rT3 are scarce and inconsistent (4,9,23,24). T3 increases energy expenditure in the organism and as a consequence, the availability of accumulated energy for conversion into fat is diminished.…”

“…The opposite situation has been described in obese patients by some authors, where over nutrition was associated with higher fT3 levels (1,6,8). However, studies documenting rT3 levels in obese children are scarce (9). In animal studies in diet-induced obese rats, increased rT3 instead of fT3 was reported, indicating presence of a mechanism that might impair the further increase in oxygen consumption (4,10).…”

Adaptive thermogenesis in humans

“…Both weight loss and the maintenance of a reduced body weight are associated with small but statistically significant decreases in circulating concentrations of triiodothyronine (T3) and increases in the circulating concentrations of its bioinactive enantiomer reverse T3 (rT3), suggesting that weight loss results in increased peripheral conversion of thyroxine (T4) to rT3 36 . Thyroid releasing hormone (TRH)-stimulated pituitary thyroid stimulating hormone (TSH) release is not diminished during caloric restriction 37 or after weight loss 38 in humans. The lack of increase in TSH with weight loss, despite the decrease in circulating concentrations of T3, indicates that hypothalamic TRH release is decreased following weight loss.…”

Thyroid Function and Obesity in Children and Adolescents

“…However, these former studies have just been performed with small numbers of obese children. Also, the results of TRH-stimulation tests were not conclusive [2, 3, 6, 7, 8]and further investigations seem to be necessary to understand the regulation of thyroid function in obesity. Yet, alterations of thyroid size and of thyroid function tests in children with obesity were described recently.…”