Defects in the growth hormone (GH)-insulin-like growth factor (IGF)I axis may cause GH resistance characterized by IGFI deficiency and growth failure. The range of defects causing GH resistance is broad as are their biochemical and phenotypical characteristics. We propose that GH-IGFI axis defects form a continuum of clinical and biochemical effects ranging from GH deficiency to GH resistance. The pathophysiology of GH resistance is described followed by a scheme for investigation of the child with severe short stature and normal GH secretion. We critically discuss GH therapy for such patients and define acceptable growth responsiveness. Finally we discuss therapy with IGF-I within the limits of the USA Food and Drug Administration and European Medicines Agency labels for GH resistance.
Growth Disorders/physiopathology , Growth Disorders/therapy , Animals , Child , Growth Disorders/genetics , Hormone Replacement Therapy/methods , Human Growth Hormone/physiology , Humans , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/physiology , Insulin-Like Growth Factor I/therapeutic use , Receptors, Somatotropin/genetics , Receptors, Somatotropin/physiology
Idiopathic short stature is a condition in which the height of the individual is more than 2 SD below the corresponding mean height for a given age, sex and population, in whom no identifiable disorder is present. It can be subcategorized into familial and non-familial ISS, and according to pubertal delay. It should be differentiated from dysmorphic syndromes, skeletal dysplasias, short stature secondary to a small birth size (small for gestational age, SGA), and systemic and endocrine diseases. ISS is the diagnostic group that remains after excluding known conditions in short children.
Growth Disorders/diagnosis , Growth Disorders/epidemiology , Body Height/physiology , Diagnostic Techniques, Endocrine , Growth Disorders/etiology , Growth Disorders/genetics , Humans , Molecular Diagnostic Techniques
In the management of ISS auxological, biochemical, psychosocial and ethical elements have to be considered. In boys with constitutional delay of growth and puberty androgens are effective in increasing height and sexual characteristics, but adult height is unchanged. GH therapy is efficacious in increasing height velocity and adult height, but the inter-individual variation is considerable. The effect on psychosocial status is uncertain. Factors affecting final height gain include GH dose, height deficit in comparison to midparental height, age and first year height velocity. In case of a low predicted adult height at the onset of puberty, addition of a GnRH analogue can be considered. Although GH therapy appears safe, long-term monitoring is recommended.
Growth Disorders/drug therapy , Human Growth Hormone/therapeutic use , Age Determination by Skeleton , Body Composition , Body Height/drug effects , Clinical Trials as Topic/ethics , Clinical Trials as Topic/trends , Counseling , Growth Disorders/diagnosis , Growth Disorders/psychology , Human Growth Hormone/adverse effects , Humans , Puberty/drug effects , Puberty/physiology , Quality of Life , Treatment Outcome
Valtropin (somatropin, BioPartners and LG Life Sciences [LGLS]) is a recombinant human growth hormone (GH) preparation produced using a yeast expression system. An open single-arm phase III study was conducted to evaluate efficacy and safety at a dose of 0.16 IU/kg/day (0.053 mg/kg/day) s.c. for 12 months in the treatment of short stature in girls (n = 30, aged 2-9 years) with Turner's syndrome. The primary efficacy variable was height velocity (HV) at 12 months. Secondary efficacy variables included serum GH dependent growth factors. HV increased from 3.8 +/- 1.8 cm/yr at baseline to 9.7 +/- 1.6 cm/yr (mean +/- SD) after 12 months of treatment. Marked treatment effects were also observed on other growth parameters, serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). Treatment was well tolerated with no significant adverse events. It is concluded that Valtropin is as safe and effective as other human GH preparations for the treatment of growth failure in girls with Turner's syndrome.
Body Height/drug effects , Growth Disorders/drug therapy , Human Growth Hormone/therapeutic use , Turner Syndrome/drug therapy , Child , Child, Preschool , Female , Follow-Up Studies , Growth Disorders/complications , Humans , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/analysis , Recombinant Proteins , Treatment Outcome , Turner Syndrome/complications
Long-term administration of recombinant growth hormone (GH) increases growth, despite persistent acidosis, in mice with carbonic anhydrase II deficiency (CAD). In contrast, short-term administration of GH to acidotic rats fails to improve growth. To determine the factors affecting the rate of growth response to GH in acidosis, we analyzed serial measurements obtained during a randomized trial of GH in CAD mice and healthy controls. Administration of GH increased standardized growth progressively up to 5-9 weeks. These data suggest that assessment of the response to GH in rodents requires prolonged administration.
Acidosis/drug therapy , Growth Hormone/therapeutic use , Acidosis/pathology , Aging/physiology , Animal Nutritional Physiological Phenomena , Animals , Bicarbonates/blood , Body Height/drug effects , Body Weight/drug effects , Carbonic Anhydrases/deficiency , Eating/drug effects , Growth/drug effects , Mice , Mice, Mutant Strains , Multivariate Analysis , Osmolar Concentration , Recombinant Proteins/therapeutic use , Time Factors
