Maria I New, MD

The primary research emphasis is on genetic steroid disorders. We continue to study two monogenic disorders: 21-hydroxylase deficiency and-hydroxylase deficiency, emphasizing genotype/phenotype correlation and prenatal diagnosis and treatment. A more precise definition of salt-wasting Congenital Adrenal Hyperplasia owing to 21-hydroxylase deficiency is being developed, in which mineralocorticoid secretion is evaluated by salt-deprivation studies. For the first time, patients who were treated in fetal life are old enough to participate in long-term outcome studies.

These studies will establish the safety of prenatal treatment, as they will include medical and psychoendocrine (gender) evaluations. We have made worldwide collaborations to study mutations in the CYP21A2 gene and have preliminary data indicating that mutations have ethnic specificity. Mice with a deletion of the CYP21A2 gene are being bred for studies and vectors are prepared for studies of gene therapy. As we have the largest population with Apparent Mineralocorticoid Excess (AME) owing to 11B-HSD2 deficiency, a disease Dr. New discovered in 1977, we are conducting medical follow-up searching for end organ disease. We have discovered a new mild form of AME, in which the phenotype is not as severe as the cases first described and the mutations in the 11B-HSD2 gene are different. This mild form may prove to be an important basis for low renin hypertension, which constitutes 40% of essential hypertension.

As hypertension is the second highest cause of death, detecting a genetic basis would provide new treatment modalities and would serve as a significant public health measure. Microarray studies are being utilized to study three newly discovered diseases whose genetic basis is unknown: a) Familial Hyperaldosteronism II; b) resistance to all steroids; c) a disorder of sexual differentiation in which a 46,XY SRY positive female (whose ovaries are also SRY positive) has given birth to a 46,XY female. After 50 years at Cornell, the Dr. New and her team moved to Mount Sinai in 2004, where the research in steroid disorders including clinical, hormonal and molecular studies has prospered.