Predictors and growth consequences of central hypothyroidism in pediatric patients receiving recombinant human growth hormone.
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).


METHODS
Retrospective chart review.


METHODS
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.


CONCLUSIONS
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.
Wong
Kara
K
Harvard Medical School, Boston, MA, USA.
Levitsky
Lynne L
LL
Misra
Madhusmita
M
D002648:Child; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000188:drug therapy; D005260:Female; D006130:Growth Disorders / Q000175:diagnosis / Q000188:drug therapy*; D013006:Growth Hormone / Q000009:adverse effects* / Q000172:deficiency; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D011218:Prader-Willi Syndrome / Q000188:drug therapy; D011994:Recombinant Proteins / Q000009:adverse effects*; D012189:Retrospective Studies; D014424:Turner Syndrome / Q000188:drug therapy
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone