Deficiency of anterior pituitary hormones in Noonan syndrome and its impact on response to growth hormone therapy

Table 1 Clinical and biochemical parameters of the cohort with Noonan syndrome

Parameter	Median (IQR) or n (%) (No. of cases with NS = 11)
Age	10.5 (7.8, 13.0)
Height (cm)	117.5 (104.0, 124.5)
Ht-SDS	-3.43 (-4.18, -2.52)
Noonan specific Ht-SDS	-1.08 (-1.97, -0.61)
Bodyweight (kg)	18 (14, 25)
Bodyweight SDS	-2.93 (-4.38, -2.22)
BMI (kg/m2)	13.77 (12.69, 15.18)
BMI-SDS	-1.68 (-3.52, -1.00)
IGF-1 (ng/mL)	162 (135, 200)
IGF-1 SDS	-1.21 (-1.82, 0.22)
Height velocity in first year after GH	9.2 (7.5, 9.8)
Low IGF-1 (< -2 SDS)	4
GH deficiency seen on stimulation tests	5
IGF-1 SDS (%) increment in 1 year	75.21 (51.33, 83.85)
Genetic test ( n = 6)	PTPN11 mutation: 5
Cardiac defects (n = 8)	Pulmonary stenosis, n = 4
	ASD; n = 3
	HCM, n = 1
Chest deformity	9
Family history	1
Cryptorchidism	3/5 males
Mental retardation	2
Coagulation defects	1
Lymphatic dysplasia	3
Neuropsychological impairments, language delay	3

Data are expressed as median (interquartile range) and expressed as (25^th percentile, 75^th percentile) or as n (%). SDS: Standard deviation score; BMI: Body mass index; IGF-1: Insulin like growth factor 1; GH: Growth hormone; ASD: Atrial septal defect; IQR: Interquartile range; Ht: Height; HCM: Hypertrophic cardiomyopathy.

Table 2 Comparison between Noonan syndrome with and without combined pituitary hormone deficiency

Parameter	NS with CPHD (n = 5)	NS without CPHD (n = 6)	P value
Age	12.0 (11.0, 14.0)	8.8 (7.4, 10.1)	0.360
Height (cm)	117.5 (89.0, 126.0)	114.0 (106.5, 122.3)	0.790
Ht-SDS	-4.18 (-4.36, -4.17)	-2.52 (-2.76, -2.27)	0.009
Noonan specific Ht-SDS	-1.99 (-2.30, -1.59)	-0.61 (-0.74, 0.40)	0.020
Bodyweight (kg)	18 (10, 19)	19 (15, 27)	0.430
Bodyweight SDS	-5.05 (-6.32, -3.63)	-2.22 (-2.81, -1.99)	0.050
BMI (kg/m2)	13.37 (11.34, 13.77)	14.66 (13.21, 15.23)	0.330
BMI-SDS	-3.54 (-3.96, -3.49)	-1.00 (-1.59, -0.50)	0.009
IGF-1 (ng/mL)	149 (86, 179)	175 (154, 206)	0.330
IGF-1 SDS	-1.59 (-1.94, -1.10)	0.22 (-1.00, 1.17)	0.070
Height velocity in first year with GH	9.2 (8.4, 9.6)	5.5 (4.3, 6.0)	0.067
Ht-SDS (%) increment in 1 year	11.70 (5.09, 17.49)	3.32 (-3.82, 13.90)	0.430
Low IGF-1 (< -2 SDS)	2 (40)	2 (33)	0.990
GH deficiency seen on stimulation tests	4 (80)	1 (17)	0.080
IGF-1 SDS (%) increment in 1 year	78.45 (48.35, 89.26)	64.76 (59.53, 69.98)	0.860
Genetic test ( n = 5)	PTPN11 mutation: 3; POU1F1: 1	PTPN11 mutation: 2	> 0.990
Cardiac defects	4 (80); Pulmonary stenosis: 3; ASD: 2	3 (50); Pulmonary regurgitation: 1; ASD: 1; ASH: 1	0.550
Chest deformity	4 (80)	5 (83)	> 0.990
Family history	0	1
Cryptorchidism	50% of males	60% of males	> 0.990
Mental retardation	1 (20)	1 (17)	> 0.990
Coagulation defects	0	1 (17)
Lymphatic dysplasia	1 (20)	2 (33)	> 0.990
Neuropsychological impairments, language delay	1 (20)	2 (33)	> 0.990

Data are expressed as median (interquartile range) and expressed as (25^th percentile, 75^th percentile) or as n (%). NS: Noonan syndrome; CPHD: Combined pituitary hormone deficiency; SDS: Standard deviation score; BMI: Body mass index; IGF-1: Insulin like growth factor 1; GH: Growth hormone; ASD: Atrial septal defect; ASH: Asymmetric septal hypertrophy; Ht: Height.