ESPE Abstracts

Introduction: This review summarizes the genetic findings in Growth Hormone Deficiency (GHD) versus Idiopathic Short Stature (ISS) and their effects on clinical, radiological, and laboratory outcomes.

Methods: A literature review was conducted to identify studies reporting genetic findings related to GHD and ISS.

Results: Genetic Findings in GHD: Mutations in GH-1, GH receptor, and other related genes were commonly found in GHD, leading to short stature, poor growth response, and varying degrees of GH insensitivity. Radiological findings often included pituitary hypoplasia and other MRI abnormalities. Laboratory data showed low GH peak levels and abnormal IGF-1 levels. For example, Goddard A et al. (1995) identified mutations in the GH receptor gene affecting GH binding, resulting in low serum concentrations of GH-binding protein and partial insensitivity to GH. Similarly, Carlsson L et al. (1994) found reduced GHBP concentration, contributing to short stature and possible GH resistance.

Genetic Findings in ISS: ISS presented similar genetic mutations, including SHOX gene mutations and other polymorphisms affecting growth plate paracrine factors. Clinical outcomes included short stature and skeletal abnormalities. Radiological findings varied, with some studies reporting normal pituitary size and structure. Laboratory data often showed normal or slightly abnormal GH and IGF-1 levels. Johnston LB et al. (1999) reported heterozygous GHR mutations in ISS, with various polymorphisms in the GHR gene leading to short stature and variable sensitivity to GH. Ahn J et al. (2021) identified various genetic variants via TNGS in ISS patients, indicating the utility of TNGS for determining genetic etiology. Both GHD and ISS demonstrated significant overlap in genetic mutations but differed in clinical and laboratory outcomes. The presence of genetic mutations in GHD often correlated with radiological findings like pituitary hypoplasia and abnormal MRI results, whereas ISS patients showed variable radiological findings. Laboratory data revealed distinct patterns, with GHD patients having low GH peak levels and abnormal IGF-1 levels, while ISS patients often had normal or slightly abnormal levels.

Discussion and Conclusion: The findings underscore the importance of genetic testing in differentiating GHD from ISS. Genetic mutations such as GH-1, SHOX, and GH receptor genes have significant implications for clinical management. These genetic differences are reflected in growth patterns, MRI findings, and hormone levels. The correlations between genetic mutations and clinical outcomes provide valuable insights for diagnosis and treatment.