Predictors and Growth Consequences of Central Hypothyroidism in Pediatric Patients Receiving Recombinant Human Growth Hormone

Abstract

Objective: Although recombinant human growth hormone (rhGH) can unmask central hypothyroidism, few studies have investigated prevalence, predictors and growth consequences of evolving hypothyroidism in children receiving rhGH based on therapeutic indication. We hypothesized that children with GH deficiency (GHD) and greatest severity of GHD would be most likely to develop central hypothyroidism and decreased growth velocity (GV). Design: Retrospective chart review Patients: Children currently receiving rhGH with data available for at least 24 months after rhGH initiation (n=119). Indications included GHD, Prader-Willi syndrome, Turner syndrome, and idiopathic short stature (ISS) and SGA (n=60, 20, 19 and 20 respectively). Methods: We categorized patients as those hypothyroid at baseline (HYPO-B; n=13), those who developed hypothyroidism over 24-months of rhGH (HYPO-24; n=16), and those never hypothyroid (NO-HYPO; n=90). Groups did not differ for age or gender. Results: Central hypothyroidism developed in 25% of GHD patients. For all patients on rhGH, baseline IGF-1 (p=0.007), IGFBP-3 (p=0.006) and peak GH (p=0.02) differed between groups. HYPO-24 had lower baseline IGF-1, IGFBP-3 and peak GH than NO-HYPO, but did not differ from HYPO-B. Peak GH was <7 ng/ml in 100% of HYPO-24, 77% HYPO-B, and 71% NO-HYPO (p=0.01). GV SDS decreased between the first and second years in HYPO-24 in HYPO-24 compared with NO-HYPO. Conclusion: Evolution of central hypothyroidism is more likely in patients receiving rhGH for GHD than other indications, becomes more likely with greater severity of GHD and is associated with a reduction in GV SDS.

Treatment of Isolated Idiopathic Growth Hormone Deficiency in Children and Thyroid Function: Is the Need for LT4 Supplementation a Concern in Long-Term Therapy?

“…To our knowledge, this is the first study exploring predictive factors for hypothyroidism during rhGH therapy in a subset of children with isolated idiopathic GHD. Unadjusted comparison of patients who were treated with LT4 with those who were not, showed a slightly lower rhGH dose in the first group, which might be in line with the hypothesis that best responders to rhGH are also more prone to thyroid hormone variations; this is also in agreement with Wong et al [ 25 ], who evaluated patients with multiple GHD etiologies and reported lower doses of rhGH in patients who developed hypothyroidism.…”

“…Although the timing of hypothyroidism did not associate with somatropin doses, relevant thyroid function changes were associated with a better response to treatment. Other authors previously reported the need for LT4 during rhGH therapy [6,[15][16][17][18], that occurred earlier in the course of treatment [25], but only two studies directly evaluated patients with isolated idiopathic GHD [15,18]. Researchers suggest that clinically relevant hypothyroidism mostly arises in patients with MPHD, organic lesions on MRI or genetic defects causing GHD.…”

“…We evaluated the impact of GHD severity in the need of LT4, but the lower GH peak of two provocative tests did not associate with the appearance of clinically relevant hypothyroidism. However, Wong et al [ 25 ], who studied 119 patients treated with rhGH for multiple reasons, reported an association between GHD severity and the development of hypothyroidism.…”

“…The final height SDS of patients with properly treated hypothyroidism was similar to their counterparts without hypothyroidism, and both groups achieved a final height SDS that was not different from PAH SDS. Giavoli et al [ 12 ] reported a decline in GV before the start of LT4 supplementation and achievement of euthyroidism in patients with MPHD, Lippe et al [ 6 ] documented the need of LT4 to achieve maximal growth rate, and Wong et al [ 25 ] found decreased growth velocity SDS in patients with hypothyroidism. This evidence supports that adequate thyroid hormone replacement enhances the rhGH effectiveness in children with GH deficiency.…”

Thyroid Function in Adults with Prader–Willi Syndrome; a Cohort Study and Literature Review

“…Baseline characteristics of the 122 adults with PWS participating in the study are shown in Table 1. The median age was 29 years (IQR 21-39), and the median BMI was 29 kg/m 2 (IQR [26][27][28][29][30][31][32][33][34][35][36]. We included 58 males and 64 females.…”