The extent to which autoimmunity contributes to thyroid dysfunction in Down Syndrome (DS) individuals has not been clarified. We studied 61 persons (34 males and 27 females) with DS (age 5 months to ...48 years) for the presence of thyroid autoantibodies (thyroid microsomal antibodies and thyroglobulin antibodies), pancreatic islet cell autoantibodies, gastric parietal cell autoantibodies, and adrenocortical autoantibodies. Thyroid function was determined by measurement of TSH. HLA-A, B and -DR typing was performed on 52 subjects. Forty of 61 subjects (66%) had thyroid dysfunction: elevated TSH values (greater than 5 mcIU/ml) were found in 35 of 61 individuals; 3 subjects had previously documented Hashimoto thyroiditis and were on therapy for hyperthyroidism; and 2 persons had Graves disease. No age or sex variation was detected. Seventeen (28%) subjects had thyroid autoantibodies. Fifteen of the 17 had thyroid dysfunction. Twelve of 25 subjects (48%) over 10 years with thyroid dysfunction had thyroid autoantibodies compared to only 3 of 15 (20%) under the age of 10 years. However, children less than of 10 years tended to have higher TSH values. Only 1 individual who had thyroid antibodies had gastric parietal cell autoantibodies present. Islet cell and adrenocortical autoantibodies were not found in any individuals. Neither thyroid dysfunction nor thyroid autoantibodies correlated with any HLA allele. These findings suggest that thyroid dysfunction in individuals with DS of all ages is a common heterogeneous disorder which cannot be solely explained on the basis of autoimmunity. We recommend that thyroid function be followed closely whether or not thyroid autoantibodies are present.
Molecular genetics has had a substantial impact on our understanding of inherited susceptibility to insulin-dependent diabetes mellitus. Alleles at the HLA-DQA1 and DQB1 loci appear to have the ...greatest influence on diabetogenesis. Other promising loci are present on chromosome 11 in the vicinity of the insulin gene. We have sought not only to improve our prediction of insulin-dependent diabetes mellitus but also to reveal the underlying immune and nonimmune defects that predispose to autoimmune beta-cell destruction. Continued advances in the field of genetics will aid in the prevention of insulin-dependent diabetes mellitus, which is our ultimate goal.
Childhood Diabetes Explosion MD, Michael S. Stalvey; MD, Desmond A. Schatz
Controversies in Treating Diabetes
Book Chapter
A century ago, the incidence of both Type 1 (T1D) and Type 2 (T2D) was very low. Worldwide epidemics of both T1D and T2D have placed tremendous burdens on both affected individuals and society. ...Disproportionate resources are spent on complications of the diseases. Although multiple etiologies have been promulgated, for T1D, causative factors and the precise mechanisms leading to the disease remain elusive. In contrast, the rising incidence of T2D in children is closely associated with the obesity explosion which is strongly linked to an increased food supply and decreased physical activity. The rising incidence of obesity has reached pandemic proportions with more than a billion people affected worldwide. Focus needs to be directed to understanding the complex interaction between genes, the environment, and the immune system culminating in T1D and tackling the obesity epidemic. This chapter will discuss the emergence of the diabetes explosion, the proposed pathogenic mechanisms, and potential interventions.
