Associations between Pituitary Imaging Abnormalities and Clinical and Biochemical Phenotypes in Children with Congenital Growth Hormone Deficiency: Data from an International Observational Study

Abstract

Background/Aims: Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS. Methods: Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039). Results: Patients with hypothalamic-pituitary abnormalities had more severe phenotypes than patients with idiopathic GHD. Additional hormonal deficiencies were found in 35% of patients with structural abnormalities (thyroid-stimulating hormone > adrenocorticotropic hormone > luteinizing hormone/follicle-stimulating hormone > antidiuretic hormone), most frequently in patients with septo-optic dysplasia (SOD). Patients with the triad [ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia and stalk defects] had a more severe phenotype and better response to GH treatment than patients with isolated abnormalities. The sex ratio was approximately equal for patients with SOD, but there was a significantly higher proportion of males (approximately 70%) in the EPP, pituitary hypoplasia, stalk defects, and triad categories. Conclusion: This large, international database demonstrates the value of classification of GH-deficient patients by the presence and type of hypothalamic-pituitary imaging abnormalities. This information may assist family counseling and patient management.

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes

“…Slightly more than one-third of our analysed study population was girls. Similar gender proportions have been reported previously in GeNeSIS (12) and in other studies (24,25). This gender disparity has been attributed to ascertainment or referral bias, as short stature may be socially more detrimental to boys.…”

“…As described in a previous analysis of the GeNeSIS database (12) and other studies, patients with hypothalamic-pituitary genetic defects (13,14,15,16) or anatomical abnormalities of the hypothalamic-pituitary region (17,18,19) had more severe GHD and were more frequently diagnosed as MPHD. In our 4-year follow-up cohort seven of 22 patients with hypothalamic-pituitary genetic defects progressed to MPHD (32%), predominantly those with PROP1 mutations, but also two patients with GH1 mutation.…”

Auxologic parameters and response to 2-year therapy with recombinant human growth hormone in growth hormone deficient children with an ectopic posterior pituitary

“…12-14 among auxiliary diagnostics methods, MRi has been gaining an apparent role as an indicator of hormonal deficiencies of the pituitary. 4,5,[15][16][17] according to the guidelines of several endocrine societies, GH stimulation tests are not necessary in the event of co-existence of clinical signs of GHD and structural anomalies of the hypothalamic-pituitary area in the MRi. 2 Pituitary stalk interruption syndrome with ectopia of the posterior pituitary (PSiS), characterized by the hyperintensive T1 signal, is one of the typical qualitative alternations in the MRi related to GHD.…”

“…4,17,19 according to Coutant et al, children with GHD and abnormal MRi manifest greater height deficit and younger chronological age at initial diagnosis. 4 Moreover, Maghnie et al found bone age to be more delayed in this group of patients.…”

“…it can also be an indication for more stringent monitoring during puberty and vigilance with regard to putative development of other hormonal deficiencies of the hypothalamic-pituitary axis. 17,[22][23][24][25][26][27] it should be underlined, however, that normal anatomy of the pituitary does not exclude severe GHD and combined pituitary deficiency, as is found in the case of gene mutations of the pituitary transcription factors, POUF1F and PROP-1. 17,28 The results of this study demonstrate a beneficial effect of rhGH therapy both in patients with normal structure of the pituitary as well as in patients with midline defects of the hypothalamic-pituitary axis, provided that basic auxological criteria for the treatment are fulfilled.…”