Growth Failure With Normal Serum Ria-Gh and Low Somatomedin Activity: Somatomedin Restoration and Growth Acceleration After Exogenous Gh

Abstract

Two three-year-old boys with dwarfism (height ages 1-4/2 and 1-11/12 years) and delayed bone ages (1-4/12 and 1-9/12 years) had normal growth hormone (GH) responses after stimulation and low levels of somatomedin. Unlike patients with Laron syndrome, the two patients generated normal levels of somatomedin after administration of exogenous hGH. Treatment with hGH (2 IU every other day) brought about a significant increase in the growth rate of both patients. The growth rate of the first patient increased from 2 cm/year before treatment to 12 cm/year on therapy. The growth rate of the second patient was 4.5 cm/year before treatment, and 8.3 cm/year while on treatment. The two cases represent a new syndrome of dwarfism which may be caused by secretion of a biologically inactive but immunoreactive GH.

Genetic control of growth

“…In its purest and most dramatic forms, primary IGFD has been identified with three classes of molecular defect: (1) GH insensitivity syndrome (GHIS) resulting from mutations within the GHR gene, primarily called Laron's syndrome (148,149), (2) genetic defects affecting the GH signalling pathway, mainly the Janus kinase 2 ( JAK2)/signal transducer and activator of transcription 5b (STAT5b) (150,151) and (3) deletions or mutations of the IGF-I gene itself (152). Further, the concept of dysfunctional GH variants and/or bio-inactive GH molecules has been proposed for years (153) and opens an interesting platform to study the elements between GHD and IGFD, as some of these patients excellently respond to the exogenous GH treatment. In addition, there are reports on abnormal GHR signalling in children with ISS in the absence of any GHR or GH gene alteration (154,155).…”

Quantitation of Urinary Growth Hormone in Children with Normal and Abnormal Growth

“…Many studies have suggested that children with idiopathic growth failure may be misjudged to be G H sufficient because they have normal G H responses to standard provocative agents (1)(2)(3)(4). In this population, the diagnosis of G H deficiency has been established by protocols that assess spontaneous G H secre-tion.…”

Bases Genéticas dos Distúrbios de Crescimento

“…descreveram duas crianças com fenótipo semelhante aos de crianças com deficiência de GH (baixa estatura severa e níveis baixos de IGF-I), mas que apresentavam secreção elevada de GH, e sugeriram que estas crianças possuíam uma molécula de GH biologicamente inativa (71). Mutações em heterozigose no gene GH-1 que causam a produção de uma molécula anômala de GH com estas características foram descritas em apenas dois casos na literatura (72,73).…”