Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement

Abstract

Background: Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966. Aims: Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes. Methods: The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients. Results: GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients. Conclusions: GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology.

Mutations Within the Transcription Factor <i>PROP1</i> in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency

“…Final height was achieved in nine of the PROP1 mutated patients, all of whom had final height SDS in the mid-parental target height SDS range. This result was in agreement with previous reports ( 10 , 35 , 36 ).…”

Needle-Free and Needle-Based Growth Hormone Therapy in Children: A Pooled Analysis of Three Long-Term Observational Studies

“…In our analysis, NAH was considered to have been attained if at least one of the two criteria was fulfilled, and notably, the majority of our patients who met the NAH criteria achieved a final height within the normal range comparable to other long-term studies of GHD [31]. Statistical analysis revealed a moderate, yet significant correlation between NAH (cm) and age at NAH.…”

Оцінка соматотропної функції в дітей із синдромом біологічно неактивного гормонa росту на основі проведення стимуляційних тестів iз клонідином та інсуліном

“…Hormone testing was performed in all patients, it included evaluation of basal and stimulated levels of STH, IGF-1, thyroid-stimulating hormone, free triiodthyronine, free thyroxine in the blood by radioimmunological method using standard IRMA kits (Immunotech, the Czech Republic). Insulin and clonidine tests were used to determine the stimulation level of STH by the standard methods in accordance with approved protocols of the Ministry of Health of Ukraine, which are consistent with the International consensus on the definition of somatotropic insufficiency and stimulation tests [1,2,10].…”

“…Growth pathology caused by somatotropic insufficiency is one of the most urgent problems in pediatric endocrinology. An increase in the growth hormone (GH) level less than 10 ng/ml was traditionally considered a criterion for diagnosing somatotropic insufficiency in patients with short stature, when performing provocation tests [1,2].…”