MRI findings and genotype analysis in patients with childhood onset growth hormone deficiency (coGHD). Correlation with severity of hypopituitarism

Objective: Childhood onset growth hormone deficiency may present as an isolated (severe or partial) form (SIGHD, PIGHD) or in association with multiple pituitary hormone deficiencies (MPHD). This study aimed to evaluate the relation between pituitary size, genotype and severity of growth hormone deficiency (GHD). Methods: We analyzed the magnetic resonance images of 44 patients with different forms of coGHD (34 males, 10 females; age 9.7±4.1 years) and screened for Pit1 and Prop1 mutations. Hormonal testing led to distribution of patients in the following subgroups: SIGHD (GH<5 ng/ml; n=14); PIGHD (GH 5–10 ng/ml; n=13); MPHD (n=17). Pituitary hypoplasia was assumed when pituitary volume was < –2 SD. Results: Pituitary abnormalities were noticed in 7/14 patients with SIGHD (50%), 11/17 patients with MPHD (64%) and in none of the patients with PIGHD. Mean pituitary height (PHT SD) was significantly lower in MPHD (-3.06±1.37) than in SIGHD (-0.09±1.93). PHT of both groups was significantly lower than the PHT of the patients with PIGHD (2.09±1.5). PHT SD correlated with IGF-I SD in the MPHD group (r=0.88) and in the SIGHD group (r=0.94). None of the patients with SIGHD or PIGHD showed mutations in the Pit1 and Prop1 genes. Among patients with MPHD we identified the AD deletion in position 301–302 in 5 related patients from a consanguineous Ucrainean family. The affected sibs had a significantly more severe short stature at diagnosis (–5.96±0.81 SD) than the other patients in the MPHD group (-3.77±0.39 SD), the bone age delay was significantly higher (5.92±2.91 ys) compared to 2.59±1.27 ys and the GH peak after combined stimulation was lower (0.75±0.54 ng/ml vs. 1.71±1.21 ng/ml). Conclusions: Pituitary malformations and hypoplasia correlated with the severity of growth hormone deficiency in our patients. Genetic alterations are known to be rare and were identified in 5 related patients, who presented a more severe short stature at diagnosis than the other patients in the MPHD group.