Chemical pathology of growth disorders

Abstract

Growth disorders are characterized by two parameters - the absolute height measurement and the height velocity. The causes of growth failure can be classified as follows : endocrine, psychological, iatrogenic, chromosomal, nutritional, intrauterine, chronic disease and skeletal. I shall concentrate on the endocrine causes of disordered growth, in particular, abnormalities in the production of growth hormone (GH). Other endocrine abnormalities causing short stature include deficiency of thyroxine, excess Cortisol and delay in the production of sex steroids at puberty. GH is released from the anterior pituitary in a pulsatile fashion, with the greatest secretion occurring about one hour after the onset of sleep. Secretion of GH is stimulated by growth hormone releasing hormone (GHRH) and inhibited by somatostatin, both these peptides being released from the hypothalamus. GH exerts its growth promoting effects principally by acting on tissues, such as cartilage and muscle, to produce insulin-like growth factor I (IGFI) which probably acts locally in a paracrine fashion to stimulate growth. The clinical features of severe GH deficiency are relatively easy to recognize, but are less apparent in the child with partial lack of GH. The approach to the diagnosis of abnormal secretion of GH must include a complete clinical assessment, with appropriate auxological data and bone age. Provocation tests, to establish either partial or complete deficiency of GH, are based on either pharmacological or physiological stimuli. Other tests, used mainly for research, include measurement of the GH pulses over 24 hours, GHRH stimulation test and urinary GH excretion. 1GF1 measurement is of limited value in GH deficiency, but useful in states of GH excess. The introduction of biosynthetic GH has resulted in a broader spectrum of patients with growth disorders receiving treatment, and there is no longer the risk of transmission of slow virus infection, as occurred with the use of GH extracted from human pituitaries.