17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Somatotropin in the treatment of growth hormone deficiency and Turner syndrome in pediatric patients: a review

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Growth hormone (GH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotrophs of the anterior pituitary gland. The main action of GH is to stimulate linear growth in children; however, it also fosters a healthy body composition by increasing muscle and reducing fat mass, maintains normal blood glucose levels, and promotes a favorable lipid profile. This article provides an overview of the normal pathophysiology of GH production and action. We discuss the history of GH therapy and the development of the current formulation of recombinant human GH given as daily subcutaneous injections. This paper reviews two of the longest standing FDA-approved indications for GH treatment, GH deficiency and Turner syndrome. We will highlight the pathogenesis of these disorders, including presentations, presumed mechanism(s) for the associated short stature, and diagnostic criteria, with a review of stimulation test benefits and pitfalls. This review also includes current recommendations for GH therapy to help maximize final height in these children, as well as data demonstrating the efficacy and safety of GH treatment in these populations.

          Related collections

          Most cited references69

          • Record: found
          • Abstract: found
          • Article: not found

          The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis.

          Arcuate nucleus neurons are known to be responsive to a wide array of hormones and nutrients, including leptin, insulin, gonadal steroids and glucose. In addition to potential transport mechanisms, peripheral substances may access these neurons via arcuate cell bodies in and projections to the median eminence, a region considered to be a circumventricular organ. The arcuate is a potent site of leptin action, probably mediating a component of leptin's effects via arcuate neuropeptide Y/agouti-related peptide (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons, and implicating this structure in the long-term control of energy stores. However, ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, may also stimulate feeding and weight gain, in part through action on receptors in arcuate NPY neurons. Since ghrelin is secreted by the stomach upon content depletion, with a half-life of no more than an hour, the arcuate nucleus may also be important in sensing and responding to acute changes in nutrients. We have developed a system for recording from arcuate POMC neurons using a mouse containing a transgene in which the POMC promoter is driving expression of the green fluorescent protein (GFP). In these mice, 99% of the beta-endorphin positive neurons express GFP, making whole cell patch clamp recordings from the sparsely distributed POMC neurons facile. All of the POMC neurons appear to be activated by leptin, via two different mechanisms, while approximately 30-50% of the neurons appear to be inhibited by a gamma-melanocyte stimulating hormone (MSH) specific agonist. The latter result suggests that the melanocortin-3 receptor (MC3-R) may act as an autoinhibitory receptor on some POMC neurons. This hypothalamic slice preparation also confirms the responsiveness of arcuate POMC neurons to a wide variety of nutrients and hormones. Thus the arcuate melanocortin system is best described as a conduit of many diverse signals involved in energy homeostasis, with leptin acting tonically to regulate the responsiveness of the circuit to a wide variety of hormones and nutrients.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Holoprosencephaly

            Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Treatment of a pituitary dwarf with human growth hormone.

                Bookmark

                Author and article information

                Journal
                Clin Pharmacol
                Clinical pharmacology : advances and applications
                Dove Medical Press
                1179-1438
                2010
                01 June 2010
                : 2
                : 111-122
                Affiliations
                [1 ]Childrens Hospital Los Angeles, Keck School of Medicine of USC, Division of Endocrinology, Diabetes, and Metabolism, Los Angeles, CA, USA
                [2 ]Saban Research Institute, Childrens Hospital Los Angeles, Los Angeles, CA, USA
                Author notes
                Correspondence: Christina Southern Reh Fellow, Division of Endocrinology and Metabolism, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Mailstop, #61, Los Angeles, CA 90027, USA, Tel +1 323-361-8816, Fax +1 323-361-8152, Email csouthern@ 123456chla.usc.edu
                Article
                cpaa-2-111
                10.2147/CPAA.S6525
                3262362
                22291494
                a7d1b3a5-556f-4a8e-ad82-ee54086cc370
                © 2010 Southern Reh and Geffner, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                somatotropin,growth hormone,turner syndrome,pediatric patients

                Comments

                Comment on this article