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Table 2 Overview of the main studies that investigate the effect of vitamin D metabolites on GHD in children

From: Vitamin D and growth hormone in children: a review of the current scientific knowledge

Reference Study area, study design Number of patients Vitamin D metabolite considered At diagnosis After GH treatment Interrelation between vitamin D/GH Other remarks Limits
Wójcik [72] Poland, prospective cohort 121 GHD subjects (6–18 years old) 25(OH)D 71 subjects had vitamin D < 30 ng/mL despite rGH treatment and vitamin D3 supplementation Possible effect of vitamin D supplementation in caries prevention in GHD patients  
Hamza [73] Egypt, prospective case–control 50 idiopathic prepubertal GHD and 50 healthy controls (3.6–10 years old) 25(OH)D 42 GHD subjects had 25(OH)D < 30 ng/mL 23 GHD subjects remained with vitamin D < 30 ng/mL (all had an increase in 25(OH)D values) Positive association between 25(OH)D and peak GH levels Positive effect of 25(OH)D on height expressed in the SDS at diagnosis  
Delecroix [74] France, retrospective 50 GHD subjects due to pituitary stalk interruption syndrome (mean age: 5.4 ± 4.9 years old) 25(OH)D, 1,25(OH)2D 26 subjects had 25(OH)D < 30 ng/mL No relationship between 25(OH)D and IGF-1 values
Positive association of 1,25(OH) 2D and the 1,25(OH) 2D/25(OH)D ratio with peak GH levels
Retrospective
Not known if subjects underwent vitamin D supplementation before recruitment
Witkowska-Sedek [75] Poland, prospective cohort 53 GHD subjects (4.75–16.58 years old) 25(OH)D Mean 25(OH)D value 24.6 ± 7.54 ng/mL Mean 25(OH)D values after 6 months of rGH therapy 28.8 ± 8.09 ng/mL
Mean 25(OH)D values after 12 months of rGH therapy 27.2 ± 8.09 ng/mL
Positive effect of vitamin D supplementation dosage given in the first year of rGH therapy on BALP values during the first 6 months All patients in the first 12 months of rGH treatment received cholecalciferol supplementation
Witkowska-Sędek [76] Poland, prospective cohort 30 GHD subjects (4.8–16.6 years old) 25(OH)D Mean 25(OH)D value 24.2 ± 7.8 ng/mL 25(OH)D increases significantly after 6 months of rGH therapy to 28.5 ± 5.29 ng/mL Positive effect of 25(OH)D on GH Positive effect of 25(OH)D on ICTP values Vitamin D3 supplementation was recommended prior to and during rGH treatment
Witkowska-Sędek [77] Poland, retrospective 84 GHD subjects (4–17 years old) 25(OH)D 73–75 subjects had 25(OH)D < 30 ng/mL Positive association between vitamin D and baseline IGF-1 values No effect of vitamin D on the maximum peak of GH after a stimulus test  
Ciresi [78] Italy, prospective cohort 80 GHD subjects (mean age 10.3 years old) 25(OH)D 60 subjects had 25(OH)D < 30 ng/mL 40 subjects remained with vitamin D < 30 ng/mL (all had an increase in vitamin D values) Positive association between vitamin D and baseline GH values No effect of vitamin D on IGF-1 values  
Wei [79] Japan, prospective cohort 12 GHD subjects (7.5–13.8 years old) 25(OH)D 1,25(OH)2D Mean 25(OH)D value 26.3 ± 10.9 ng/mL
Mean 1,25(OH)2D value 59.4 ± 10.2 pmol/L
No variation in 25(OH)D values
1,25(OH)2D increase after rGH therapy
Positive association between 1,25(OH) 2D and an increase in IGF-1 values PTH values reduced after rGH treatment; the authors hypothesize a PTH-independent GH-Vitamin D correlation  
Boot [80] Netherlands, prospective cohort 40 GHD subjects (mean age 7.9 years old) 1,25(OH)2D Mean 1,25(OH)2D value 96.2 ± 25.8 pmol/L 1,25(OH)2D increases after rGH therapy Positive association between 1,25(OH) 2D and an increase in IGF-1 values Stable PTH values after rGH treatment; the authors hypothesize a PTH-independent GH-Vitamin D correlation  
Saggese [81] Italy, prospective cohort 26 GHD subjects (6.5–10.7 years old) 25(OH)D 1,25(OH)2D Mean 25(OH)D value 31.55 ± 7.01 ng/mL
Mena 1,25(OH)2D: 64.7 ± 15.8 pmol/L
No variation in 25(OH)D values
1,25(OH)2D increase at 12 months of therapy (not previously)
Positive effect of 1,25(OH) 2D on growth velocity Reference values are different from the most recent ones
Burstein [82] USA, prospective cohort 12 GHD subjects (mean age 10.5 years) 25(OH)D 1,25(OH)2D Mean 25(OH)D value 49.0 ± 2.4 ng/mL No variation in 25(OH)D
1,25(OH)2D increase only in the first week of high-dose hGH therapy
No effect of 25(OH)D 1,25(OH)2D on GH  
Chipman [83] USA, prospective cohort 7 GHD subjects (3.8–16.7 years old) 25(OH)D 1,25(OH)2D Mean 25(OH)D value 20.2 ± 6.5 ng/mL
Mean 1,25(OH)2D value 63.7 ± 19.3 pmol/L
No variation in 25(OH)D and 1,25(OH)2D values No effect of 25(OH)D 1,25(OH)2D and GH Stable PTH values after hGH treatment; the authors hypothesize a PTH-independent GH-vitamin D correlation Before hGH therapy, patients were treated with Ca, phosphorus and sodium supplementation
Gertner [84] USA, prospective cohort 9 GHD subjects (9–18 years old) 25(OH)D 1,25(OH)2D Mean 25(OH)D value 35.5 ± 8.9 ng/mL
Mean 1,25(OH)2D value 44.4 ± 27.9 pmol/L
No variation in 25(OH)D and 1,25(OH)2D values No effect of 25(OH)D 1,25(OH)2D on GH Stable PTH values after hGH treatment; the authors hypothesize a PTH-independent GH-vitamin D correlation Before hGH therapy, patients were treated with Ca supplementation