Introduction: ISS is defined as a condition in which the height of an individual is more than 2 SD score (SDS) below the corresponding mean height for a given age, sex, and population group without evidence of systemic, endocrine, nutritional, or chromosomal abnormalities. Several clinical trials demonstrated beneficial effects of GH treatment. (J Clin Endocrinol Metab 93: 4210?4217, 2008). In turn, the major systemic hormones that influence growth during childhood include not only GH/ insulin-like growth factor I (IGF-I) axis but also thyroid hormones (TH). The impact of TH action at tissue level is determined by TH availability as well as by TR expression at tissue level. We have previously reported (Clin Endocrinol 67, 629?636, 2007) that GH treatment to Turner Syndrome patients impaired peripheral TH mechanism of action. The aim of this study was to assess the effect of GH treatment on peripheral TH receptor expression in ISS patients.
Patients & Methods: Twenty diagnosed ISS patients (growth velocity <2 SD and normal GH secretion after pharmacological provocation tests), 10-14 y/o, were analyzed previous and after 6 and 12 months of GH therapy (50µg/kg/day). All patients were clinically and biochemically euthyroid. Peripheral blood mononuclear cells were obtained (Fycoll-Hipaque), total RNA extracted (Trizol) and TR mRNA levels determined by Real-time RT-PCR. In turn, thyroid function was tested by thyrotropin (TSH), total thyroxine(TT4), free thyroxine (FT4) and total triiodothyronine (TT3) serum levels and the biochemical response to GH treatment by osteocalcin (OC), â-crosslaps (â-CL) and IGF-I serum levels (all analytes were measured by electrochemiluminescence except for IGF-I that was determined by a immunoradiometric assay).
Results: As depicted in Table 1, results achieved showed a significant increase in TR mRNA expression in PBMC after both 6 and 12 months of GH treatment (ANOVA-Student-Neuman-Keuls, *p<0.05 vs pre GH treatment sample). In turn, no changes in thyroid function tests and significant increases in IGF-I, OC and â-CL were registered during the treatment.
| Table 1 | 6 months | 12 months |
| fold change in TR mRNA-level (after/before GH treatment) (mean±SD) | 1.41±1.15* | 1.90±1.61* |
Conclusions: These results indicate that GH treatment to ISS patients enhanced the peripheral expression of TR. It is not possible to conclude with surety whether results of TR expression in PBMC are predictive of the thyroid status in the whole organism. Nevertheless, the pivotal role of TH action for normal growth points out the importance of analyzing the evolution of thyroid signaling during GH treatment to ISS patients.
