ABSTRACT
Congenital adrenal hyperplasia is a disorder occurring in both sexes and is the commonest cause of ambiguous genitalia. It is a group of autosomal recessive disorders in which, on the basis of an enzyme defect the bulk of steroid hormone production by adrenal cortex shifts from corticosteroids to androgens. Autosomal recessive mutations in the CYP21, CYP17, CYP11B1 and 3betaHSD genes that encode steroidogenic enzymes, in addition to mutations in the gene encoding the intracellular cholesterol transport protein steroidogenic acute regulatory protein StAR can cause CAH. Each of the defects causes different biochemical consequences and clinical features. Deficiencies in 21 hydroxylase (21-OH) and 11beta-Hydroxylase (11beta-OH) are the two most frequent causes of CAH. All the biochemical defects impair cortisol secretion, resulting into compensatory hypersecretion of ACTH and consequent hyperplasia of the adrenal cortex. Research in recent years has clarified clinical, biochemical and genetic problems in diagnosis and treatment of the disorders. Expanding knowledge of the gene mutations associated with each of these disorders is providing valuable diagnostic tools in addition to the biochemical profile and phenotype. Genotyping is useful in selecting instances to provide genetic counseling and to clarify ambiguous cases.
Subject(s)
Adrenal Hyperplasia, Congenital/enzymology , Humans , Mutation , Phosphoproteins/deficiency , Steroid Hydroxylases/deficiencyABSTRACT
In addition to neuroendocrine abnormalities, women with polycystic ovary syndrome have insulin resistance and beta-cell dysfunction associated with a high frequency of metabolic syndrome components, such as glucose intolerance, type 2 diabetes mellitus (DM-2), dyslipidemia and a higher risk for endothelial dysfunction, haemostatic abnormalities, hypertension and cardiovascular disease. Obesity, a common finding in this disorder, plays an important role in the development of metabolic and cardiovascular disorders. Early identification of patients and prompt initiation of insulin sensitizing therapy by pharmacological agents or changes in life style such diet and exercise might improve the metabolic and endocrine abnormalities and reduce the risk of DM-2 and cardiovascular disease in these patients.