19 Familial Growth Hormone (GH) Deficiency

Abstract

Isolated GH deficiency has been observed in a number of instances, but its occurrence as a recessively inherited defect has been previously documented only in adult members of two families. The present study concerns a family of 9 in which the father and 4 siblings had growth retardation, truncal obesity, facial infantilism and impaired glucose tolerance. Plasma GH responsiveness to insulin-induced hypoglycemia and to bacterial pyrogen administration was absent in those whose growth was retarded, but indirect studies of thyrotropin and adrenocorticotropin demonstrated the presence of these pituitary factors in all members of the family. Human GH administration to the 18-year-old, dwarfed, sexually infantile, female sibling resulted in objective changes in sexual maturation, alterations in fat distribution and greatly accelerated growth. The similarly treated 9-year-old male sibling experienced marked increase in the rate of statural growth, but remained sexually infantile. No discernable change in urinary corticoid responsiveness to adrenocorticotropin and no measurable change in gonadotropin excretion occurred during the therapeutic period. Studies of glucose tolerance and plasma insulin responsiveness in 4 of the dwarfs revealed an increase in peripheral resistance to insulin during GH administration. It is concluded that this form of familial dwarfism is related to GH deficiency and that the defect is monotropic. The patients described clearly illustrate the natural course of the condition, wherein delayed adolescence is the rule rather than the exception. Observations presented support the possibility that GH alters responsiveness of endocrine end-organ tissues. Serious doubts are raised regarding the validity of diagnoses which exclude hypopituitarism in patients with retarded growth on the basis of eventual sexual maturation. (APS)