Background: Normal TF is necessary for optimal growth. Changes in the hypothalamic-pituitary-thyroid (HPT) axis following GH therapy are reported. GH therapy has been suggested to centrally inhibit TSH production as well as peripherally increasing T4 to T3 conversion which increases negative feedback on TSH production. Hypothalamic dysfunction is a feature of PWS, therefore these patients may be at risk of developing central hypothyroidism associated with GH therapy.
Objective/Hypotheses: We evaluated the impact of GH therapy on thyroid status in children with PWS and we hypothesised that they may be at increased risk of central hypothyroidism during GH therapy.
Method: A retrospective review of children with PWS with growth data recorded on OZGROW (Australian GH database) was performed. FT4 (Free Thyroxine) and TSH (Thyroid Stimulating Hormone) was assessed before and after GH therapy. Between 2003 and 2014, 87 patients had at least one recorded FT4 and TSH test. FT4 and TSH results were standardized by expressing them as a % of the reference range (RR). x%=100×((x-L)/(U-L)), where x is the test result and U and L are the upper and lower values of the RR. Mean test % were compared to an expected mean of 50% for tests taken one year pre-GH and post-GT. We also assessed change in test % for those who had tests before and after GH commencement (Δ%) using a paired t test.
Results: In the year prior to GH, most FT4 and TSH were in the low normal range while 4 patients had FT4 below the RR (Table 1). Following GH therapy, FT4 and TSH decreased further. This effect was sustained for 3 years (Table 2).
|Baseline||1st Year of GH|
|Mean FT4 (sd)||33.1 (19.2) %a||21.7 (17.5)%a|
|Mean TSH (sd)||38.2 (22.7) %a||25.4 (22.6)%a|
|ap < 0.001, bp < 0.01, cp < 0.05.|
|1 year post GH||2 years post GH||3 years post GH|
|FT4 Δ% (sd)||−11.5 (23.0)%a||−8.9 (19.3)%c||−8.1 (15.5)%c|
|TSH Δ% (sd)||−12.9 (26.5)%a||−15.0(18.6)%a||−11.4(18.4)%b|
Conclusion: FT4 was significantly lower than expected in patients with PWS. This further decreased during GH therapy. Whether these changes have adverse clinical effects on growth is unclear. GH therapy has been suggested to decrease TSH by both a direct central and an indirect peripheral mechanism. Analysis of T3 levels is required to distinguish between these hypotheses and elucidate whether Thyroxine supplementation would be of benefit.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology