Aim: To identify the distinctive features of GH Deficiency (GHD) and to assess the response to GH treatment (rhGH) in children with Septo-Optic-dysplasia (SOD) and Multiple Pituitary Hormone Deficiencies (MPHD).
Methods: Retrospective longitudinal single centre study of children with SOD (n:171) and MPHD (n:53). GHD was diagnosed in patients with growth failure by an insufficient GH response (≤6.7 μg/l) to provocation (Insulin Induced Hypoglycaemia or Glucagon) combined with low IGF1/IGFBP3. Neurosecretory GH dysfunction was diagnosed in children with low IGF1/IGFBP3, poor growth velocity (GV), structural Hypothalamo-Pituitary (H-P) abnormalities and abnormal nocturnal GH production characterised by fewer than 3 GH peaks > 6.7 ng/L on overnight profile (20 sampling for 12 hours).
Results: Within the SOD cohort, 132/171 (77.2%) had some degree of hypopituitarism. 11/132(8.3%) had preserved GH function (age range: 0.5215.46 years), whilst only 2/53(3.8%) MPHD were GH sufficient (ages: 0.57, 0.62 years). Of the patients with GHD, 9/121(7.4%) SOD and 3/51(5.9%) MPHD were born SGA. Despite being started on lower rhGH doses (25.61±7.61 vs 29.12±9.29 μg/kg/day; P=0.012), SOD had similar GV and IGF1 SDS after one and two years of treatment and similar delta between mid-parental height and height at the onset of puberty, as compared with MPHD. In MPHD only, there was a direct correlation between the starting rhGH dose and GV SDS after 2 years of treatment (r=0.475, P=0.003). Although not reaching statistical significance due to the small numbers (18 SOD and 6 MPHD), the final height SDS was lower in MPHD compared to SOD (−1.73±1.80 vs −0.82±1.66 SDS), whilst the delta between mid-parental height and final height was similar between groups (−1.12±1.74 vs −0.77±1.90 SDS). Neurosecretory GH dysfunction was diagnosed in 5/122(4.1%) SOD (but none of MPHD) (age at diagnosis: 2.5514.64 years). All 5 had small anterior pituitary, two had posterior pituitary absence, one had pituitary stalk interruption syndrome.
Conclusions: Although GHD is the most frequent deficiency in children with SOD and MPHD, it may not always be present at diagnosis. When compared with MPHD, SOD patients with GHD display similar growth responses and final height outcomes, despite the use of lower GH doses. In SOD with structural H-P abnormalities and normal GH responses to provocation, but with low growth rates and growth factor concentrations, an abnormality of the GH secretory pattern should be considered.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology