Intradermal transgenic expression of granulocyte-macrophage colony-stimulating factor induces neutrophilia, epidermal hyperplasia, Langerhans' cell/macrophage accumulation, and dermal fibrosis

Bone age maturation and growth velocity were analyzed longitudinally by the TW2 RUS method standardized for Japanese children in 45 GH-treated boys with idiopathic GH deficiency (GHD). The patients were divided into three groups: Group I consisted of four isolated GHD patients who underwent spontaneous puberty without gonadotropin suppression treatment (GST) and had a mean final height of 151.9 cm; Group II consisted of 24 GHD patients with associated gonadotropin deficiency who received sex hormone replacement treatment (GRT) and had a mean final height of 165.3 cm; Group III consisted of 17 isolated GHD patients who underwent spontaneous puberty and had a mean final height of 158.3 cm after being treated with combined GH and GST. Bone age matured along with chronological age in Group I, whereas bone age in Group II decelerated significantly after a bone age of 12 years and did not reach a bone age of 14 years. Bone age maturation in Group III showed an intermediate pattern between Groups I and II; bone age decelerated significantly after a bone age of 12 years but mean bone age advanced beyond a bone age of 14 years. Height velocity in Group I during GH treatment decelerated rapidly after the pubertal growth spurt, as usually seen in normal puberty. A definite pubertal growth spurt was not observed in the height velocity of Group II during GH treatment before receiving GRT; the mean height velocity gradually declined, remaining at 3.5-4.5 cm/year even after 18 years. Mean height velocity in Group III during GH treatment and GST showed a similar tendency as Group II, but it declined more rapidly. Since a growth velocity of around 3 cm/year was preserved with GH treatment despite the decline in growth velocity, the slower the advance of bone age, the longer the treatment period and, therefore, the taller the final height achieved by GST compared to Group I. It is recommended to start GST at a bone age between 11.5 years and 13 years. The timing, namely when to start GRT in GHD with gonadotropin deficiency or when to stop GST in isolated GHD, can be estimated according to the patient's desired final height and bone age-growth potential.