Growth hormone deficiency and replacement in children

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Growth hormone deficiency and replacement in children Margaret C. S. Boguszewski 1 Accepted: 1 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Growth hormone deficiency (GHD) is a rare but treatable cause of short stature. The diagnosis requires a careful evaluation of clinical history, physical examination and appropriate interpretation of longitudinal growth, with specific features for each period of life. Other clinical findings, in addition to growth failure, may be present and can be related to the etiology and to associated hormone deficiencies. Despite more than 50 years since the first reports of provocative tests of growth hormone (GH) secretion for the diagnosis of GHD, the interpretation of the results remains a matter of debate. When GHD is confirmed, GH treatment is recommended. Treatment is effective and safe, but requires daily injections during many years, which can affect adherence. At the end of longitudinal growth, during the transition phase, it might be necessary to re-evaluate GH secretion. This review summarizes and updates the recent information related to GHD in children, as well the recommendations for treatment. Keywords Growth hormone . Short stature . Growth hormone deficiency . Growth hormone treatment . Transition phase

1 Introduction

2 Etiology

A full-term female neonate was evaluated due to persistent neonatal hypoglycemia and hypotonia. A term male neonate was evaluated with persistent neonatal hypoglycemia, hypotonia and micropĂȘnis. They were both diagnosed with congenital hypopituitarism, in a case series of five neonates with congenital hypopituitarism including growth hormone (GH) deficiency (GHD), all with abnormal magnetic resonance imaging (MRI) of the brain and pituitary [1]. A 5 years old girl was evaluated with short stature [Height Standard Deviation Score (SDS) -3.0], low insulin-like growth factor 1 (IGF-1) and low IGF binding protein-3 (IGFBP-3) but with normal GH peak during GH stimulation tests with arginine and clonidine. She carried a R183H mutation in GH1 gene and was diagnosed with isolated GHD (IGHD) type II [2]. These cases illustrate the variability of clinical and laboratory findings in children with GHD and the need for a careful and broad investigation. This review is a focused narrative of GHD and updates the information related to GHD in children, as well the recommendations for GH replacement.

It is beyond the scope of this article to review the etiology of GHD. Excellent reviews have been published [3, 4]. However, in order to discuss clinical manifestations and GH treatment, it is necessary to consider the main causes of GHD, whether congenital or acquired, isolated or associated with other hormone deficiencies. Among congenital causes are defects in genes associated with the somatotropic axis, genes associated with pituitary development and brain malformations. Examples of acquired conditions are midline tumors, cranial irradiation, infiltrative disorders, trauma, surgery, infection. When the etiology i