Hereditary male pseudohermaphroditsm

The anatomic, genetic, and endocrine features of hereditary male pseudohermaphroditism are summarized. On the basis of these characteristics, it is usually possible in the postpubertal state to arrive at a satisfactory diagnosis, recognizing certain limitations. For example, the family history may be uninformative. In addition, partial defects in testosterone synthesis (particularly defects that do not involve glucocorticoid synthesis such as 17,20-desmolase and 17β-hydroxysteroid dehydrogenase) may be particularly difficult to diagnose since, in the steady state, plasma testosterone values may be normal as the result of the rise of serum LH values. In the latter circumstance it is necessary to measure testosterone precursors, which tend to accumulate in a pattern corresponding to the block in question, such as the elevation of androstenedione levels in 17β-hydroxysteroid dehydrogenase deficiency. In the prepubertal state, particularly in infants with ambiguous genitalia and negative family histories, the arrival at a correct diagnosis can be particularly difficult. In instances of severe defects the diagnosis of defective androgen synthesis can be made by demonstrating an inadequate rise in testosterone levels following the administration of HCG. In other instances, it is useful to measure dihydrotestosterone formation and dihydrotestosterone binding in cultured skin fibroblasts. There is no question that many cases of male pseudohermaphroditism cannot be explained by the known causes of hereditary male pseudohermaphroditism. Some will prove to be the result of birth defects of multifactorial aetiology that influence testicular development. Others will prove to be the consequence of as yet uncharacterized mutations that influence androgen metabolism, androgen binding or more distal aspects of androgen action. Nevertheless, the formulation that male pseudohermaphroditism can result from abnormalities of androgen synthesis, androgen action, or mullerian regression will still provide a useful means of classifying these disorders.