Catch-up Growth in Prepubertal Children Treated for Juvenile Hypothyroidism and Growth Hormone Deficiency can be Modelled with a Monomolecular Function

Abstract

Objective: We hypothesized that modelling catch-up growth (CUG) as developed for coeliac disease (CD), might also fit CUG in adequately treated children with juvenile hypothyroidism (JHT) or growth hormone deficiency (GHD).

Methods: We used a monomolecular function for all available prepubertal data on height standard deviation score (HSDS) minus target height SDS (adjHSDS) in children with JHT (n=20) and GHD (n=18) on a conventional (CoD) or high GH dose (HD), based either on a national height reference with an age cut-off of 10 (girls) and 12 (boys) years (model 1) or prepubertal height reference values, if age (0) was ≥3, with no upper age limit (model 2).

Results: The models could be fitted in 83-90% of cases; in other cases the HSDS decreased after several measurements, which violated the assumption of an irreversible growth process. In JHT, the rate constant (k) and adjHSDS (0) were lower than in CD (p=0.02), but adjHSDS (end) was similar. In GHD (model 1), k was lower than for CD (p=0.004) but similar to JHT, while adjHSDS (0) and adjHSDS (end) were similar to CD and JHT. Thus, the shape of CUG is similar for children with JHT and GHD, while children with CD had less growth deficit at start and a faster CUG. The differences in CUG parameters between GH dose subgroups did not reach statistical significance.

Conclusion: Modelling CUG of prepubertal children with JHT and GHD can be used for assessing the adequacy of CUG and the influence of clinical treatment modalities on its speed and magnitude.

Keywords: Growth; catch-up growth; coeliac disease; growth hormone deficiency; hypothyroidism.

Figure 1

Modelled curves (uninterrupted lines) and raw data (open circles) describing catch-up growth [adjusted height standard deviation score (HSDS) versus age] for each child with juvenile hypothyroidism before reaching puberty, as well as adjusted adult HSDS. Stippled lines connect the last measurement before onset of puberty with adjusted adult HSDS JHT: juvenile hypothyroidism, Adj-HSDS: adjusted-height standard deviation score

Figure 2

Modelled individual curves and raw data describing catch-up growth of prepubertal children with juvenile hypothyroidism during three years, as well as the average curve JHT: juvenile hypothyroidism, Adj-HSDS: adjusted-height standard deviation score

Figure 3

Modelled curves and raw data describing catch-up growth for each child with growth hormone deficiency before reaching puberty Adj-HSDS: adjusted-height standard deviation score, GHD: growth hormone deficiency, HD: high dose, CoD: Conventional dose

Figure 4

Modelled individual curves and raw data describing catch-up growth of prepubertal children with growth hormone deficiency during three years, as well as the average curve. Panel A: conventional growth hormone dose. Panel B: high growth hormone dose Adj-HSDS: adjusted-height standard deviation score, GHD: growth hormone deficiency, HD: high dose, CoD: Conventional dose

Figure 5

Modelled mean adjusted-height standard deviation score of children with juvenile hypothyroidism, growth hormone deficiency (CoD and high dose, models 1 and 2) in comparison with the catch-up growth model for celiac disease Adj-HSDS: adjusted-height standard deviation score, CD: celiac disease, HD: high dose, GHD: growth hormone deficiency, JHT: juvenile hypothyroidism, CoD: Conventional dose

Suppl Figure 1

Modelled mean adjusted-height standard deviation score (adj-HSDS) of children with juvenile hypothyroidism in the first 3 years of L-thyroxine therapy, according to age at start (<5 or ≥5 years) and to adj-HSDS at start of therapy (<-3.5 or ≥-3.5). Values for the parameters A, B and k are indicated