[The impact of the 4-year human recombinant growth hormone treatment on growth, body composition and bone mineral density in patients with isolated growth hormone deficiency and multihormonal pituitary insufficiency].

BACKGROUND: In addition to stimulating bone growth in length, human recombinant growth hormone (rhGH) significantly affects in a direct and IGF-I-mediated manner body composition (body fat/lean body mass ratio) and skeletal maturation in vitro and in vivo. The direct role of rhGH on bone mineralization and its effect on bone mineral density is controversial. AIM: To compare growth and body composition, bone mineral density (BMD) and bone mineral content (BMC) in prepubertal children with isolated growth hormone deficiency (GHD) and congenital multihormonal pituitary deficiency (MPD), including MPD resulting from the PROP-1 gene mutation. MATERIAL AND METHODS: The study included 53 children (36 boys and 17 girls) aged 8.4 +/- 3.2 years with diagnosed GH deficiency. The subjects were divided into three groups. Group 1 consisted of patients with MPD resulting from the PROP-1 gene mutation: 14 children (8 girls and 6 boys) aged 6.4 +/- 2.1 years, Group 2 included children with MPD resulting from causes other than the PROP-1 gene mutation: 21 patients (5 girls and 16 boys) aged 9.6 +/- 3.9 years, while Group 3 represented children with GHD: 18 subjects (4 girls and 14 boys) aged 8.6 +/- 2.5 years. All the children were clinically and biochemically euthyreotic. The patients were assessed auxologically every three months. Their bone age was evaluated every year. Puberty stages were determined according to Tanner. BMI was calculated in keeping with the equation: kg/m2. Bone densitometry and body composition were determined by DEXA (DPX-IQ Lunar) prior to initiation of rhGH substitution and at yearly intervals in the course of rhGH treatment. RESULTS: Prior to commencement of rhGH substitution, the height of the PROP [+] patients was the lowest of all groups, with statistical significance demonstrated when comparing the above children to the GHD group (PROP [+]: -3.3 SD; PROP [-]: -2.8; GHD: -2.7 SD). Growth analysis in the three groups of patients showed a statistically significant improvement in each group, with the strongest effect in the PROP [+] group; the respective height increase in particular groups was: PROP [+]: 2.8 SD; PROP [-] 1.6 SD; GHD 1.9 SD. After 4-year rhGH substitution, patients with MPD PROP [+] and PROP [-] demonstrated an increase of BMC by 585.9 g and 350.2 g, respectively; no significant increase was observed in the GHD group. Prior to treatment, all the groups showed a comparable decrease of lumbar spine BMD (BMD LS): Z-score PROP [+] (-) 2.5 SDS; PROP [-] (-2.8) SDS; GHD (-) 2.0 SDS. In subsequent years of treatment, the BMD LS values were within normal range, i.e. above (-) 2.0 SD. A statistically significant increase of BMD LS by (+) 1.1 SD was noted in the PROP [-] patients. In all the groups, the mean total BMD values were within normal range, i.e. above (-) 2.0 SD prior to initiation of rhGH substitution and in subsequent years of follow-up. Prior to commencement of rhGH substitution vBMDLS SDS of the PROP [+] patients was the lowest of all groups, with statistical significance demonstrated when comparing the above children to the GHD group (PROP [+]:(-)2,8 +/- 1,6; PROP [-]:(-)1,9 +/- 1,8; GHD: (-)1,9 +/- 2,3 SD. After 4-year rhGH substitution lowest values of vBMDLS SDS were found also in PROP[+]: (-)1,6 +/- 1,3 SD, ans subsequently PROP[-]: (-)0,9 +/- 1,0 and SNP: (-)0,7 +/- 1,8 SD. Body fat percentage prior to rhGH substitution was the highest in the PROP [+] patients and the lowest in the GHD group: PROP [+]: 28%, PROP [-]: 26%, GHD: 20%, with the difference between PROP [+] and GHD being statistically significant. During all study period all children remained prepubertal. CONCLUSIONS: 1) Patients with MPD and the PROP1 gene mutation are characterized by a shorter stature, lower BMD and lower lean body mass as compared to MPD patients without PROP1 mutation and to GHD patients. 2) In comparison to children with GHD, rhGH substitution in patients with MPD exerted a more favorable effect on their growth, BMD and body composition.