Maria New

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Maria Iandolo New (1928-2024) was a professor of Pediatrics, Genomics and Genetics at Icahn School of Medicine at Mount Sinai in New York City. [1] She is an expert in congenital adrenal hyperplasia (CAH), a genetic condition affecting the adrenal gland that can affect sexual development. [2]

Contents

Medical education

New received her undergraduate degree from Cornell University in Ithaca, New York, in 1950, and her M. D. from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, in 1954. She completed an internship in medicine at Bellevue Hospital in New York, followed by a residency in pediatrics at the New York Hospital. From 1957 to 1958 she studied renal functioning under a fellowship from the National Institutes of Health (NIH). She was a research pediatrician to the Diabetic Study Group of the Comprehensive Care Teaching Program at the New York Hospital-Cornell Medical Center from 1958 to 1961, and had a second NIH fellowship under Ralph E. Peterson from 1961 to 1964, to study specific steroid hormone production during infancy, childhood and adolescence.[ citation needed ]

Career

In 1964, New was appointed Chief of Pediatric Endocrinology at Cornell University Medical College, a position she held for 40 years. In 1978, she was named Harold and Percy Uris Professor of Pediatric Endocrinology and Metabolism. In 1980, New was appointed Chairman of the Department of Pediatrics at Cornell University Medical College and Pediatrician-in-Chief of the Department of Pediatrics at New York-Presbyterian Hospital. She was one of the few women in the country to serve as Chair of a major division of a medical college, and her tenure lasted for 22 years. While Chairman, New founded and directed the 8-bed Children's Clinical Research Center, a clinical research center in pediatrics with groundbreaking research in pediatric endocrinology, hematology, and immunology, during the emergence of AIDS. In 2004, New was recruited to the Mount Sinai School of Medicine as Professor of Pediatrics and Human Genetics and Director of the Adrenal Steroid Disorders Program. [3] She is also currently Adjunct Professor of Genetics at Columbia College of Physicians and Surgeons, and Associate Dean for Research at the Herbert Wertheim College of Medicine at Florida International University.

New is recognized as one of the world's leading pediatric endocrinologists. [3] Her career links clinical and basic science. She has continued her scientific research, including the use of molecular genetic diagnosis, prenatal diagnosis and treatment. Although steroid physiology was well understood when New began her scientific career, little of the knowledge had been applied to the understanding of steroid disorders in children. New's research on the mechanism and genetics of steroid disorders has established standards for pre- and post-natal care for patients with congenital adrenal hyperplasia and apparent mineralocorticoid excess.[ citation needed ]

During a 43-year period, New held the longest continuously funded National Institutes of Health grant, "Androgen Metabolism in Childhood", which supported research characterizing the diverse clinical spectra of patients with rare steroidogenic enzyme defects, such as congenital adrenal hyperplasia, and their metabolic consequences. [4]

Her current primary research emphasis is on genetic steroid disorders. New continues to study three monogenic disorders: 21-hydroxylase deficiency, 11β-hydroxylase deficiency, and apparent mineralocorticoid excess, emphasizing genotype/phenotype correlation and prenatal diagnosis and treatment. She has published more than 640 academic articles in a wide range of prestigious journals and published a genetics book entitled Genetic Steroid Disorders in 2014. She has also received numerous awards recognizing her work treating mothers and children affected with the disorder. [5]

Principal discoveries

In 1977, New first described apparent mineralocorticoid excess (AME) in a Zuni girl. [6] Her team was the first to publish mutations on the 11β-hydroxysteroid dehydrogenase type 2 enzyme (encoded by the HSD11B2 gene) causing this potentially fatal form of low renin hypertension. New opened a new field of receptor biology by demonstrating the action of the 11β-HSD2 enzyme at the mineralocorticoid receptor of the distal renal tubule to metabolize cortisol to cortisone and thus protect the receptor. This was the first demonstration of the metabolism of a ligand to down-regulate its action on receptor activation.

In 1979, New described a form of mild steroid 21-hydroxylase deficiency called nonclassical 21-hydroxylase deficiency, which is characterized by diverse hyperandrogenic symptoms appearing postnatally in males and females. [7] The remarkable prevalence of 1 in 27 Ashkenazi Jews of a mild form of CAH was documented by New in 1985 and the genetic frequency of the mutation is 1 in 3 in the Ashkenazi Jewish population. [8] These studies established nonclassical 21-hydroxylase deficiency as the most frequent disorder of all autosomal recessive diseases in humans. While a spectrum of severity of congenital adrenal hyperplasia had always been observed, New was first to identify the mild form with specific molecular mutations.

Prenatal Dexamethasone

Ethical issues have been raised about New's research. Namely, it has been questioned whether pregnant women undergoing treatment for the possible effects of congenital adrenal hyperplasia on their unborn babies were properly informed concerning the treatments that were administrated to them. [2] In September 2010 the FDA found nothing worth pursuing. In a 2012 article Alice Dreger followed up on the issues involved. [9] Further research and long term studies are needed to establish the correct usage guideline.

Awards and honors

Elected Member of the US National Academy of Sciences, National Academy of Medicine, and the American Academy of Arts and Sciences

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Congenital adrenal hyperplasia</span> Genetic disorders of the adrenal gland

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. Most of these disorders involve excessive or deficient production of hormones such as glucocorticoids, mineralocorticoids, or sex steroids, and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults. It is one of the most common autosomal recessive disorders in humans.

<span class="mw-page-title-main">Adrenal insufficiency</span> Insufficient production of steroid hormones by the adrenal glands

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids, mineralocorticoids, and androgens. These hormones are important in regulating blood pressure, electrolytes, and metabolism as a whole. Deficiency of these hormones leads to symptoms ranging from abdominal pain, vomiting, muscle weakness and fatigue, low blood pressure, depression, mood and personality changes to organ failure and shock. Adrenal crisis may occur if a person having adrenal insufficiency experiences stresses, such as an accident, injury, surgery, or severe infection; this is a life-threatening medical condition resulting from severe deficiency of cortisol in the body. Death may quickly follow.

<span class="mw-page-title-main">Lipoid congenital adrenal hyperplasia</span> Medical condition

Lipoid congenital adrenal hyperplasia is an endocrine disorder that is an uncommon and potentially lethal form of congenital adrenal hyperplasia (CAH). It arises from defects in the earliest stages of steroid hormone synthesis: the transport of cholesterol into the mitochondria and the conversion of cholesterol to pregnenolone—the first step in the synthesis of all steroid hormones. Lipoid CAH causes mineralocorticoid deficiency in affected infants and children. Male infants are severely undervirilized causing their external genitalia to look feminine. The adrenals are large and filled with lipid globules derived from cholesterol.

<span class="mw-page-title-main">Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency</span> Medical condition

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is a form of congenital adrenal hyperplasia (CAH) which produces a higher than normal amount of androgen, resulting from a defect in the gene encoding the enzyme steroid 11β-hydroxylase (11β-OH) which mediates the final step of cortisol synthesis in the adrenal. 11β-OH CAH results in hypertension due to excessive mineralocorticoid effects. It also causes excessive androgen production both before and after birth and can virilize a genetically female fetus or a child of either sex.

<span class="mw-page-title-main">Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency</span> Medical condition

Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency is an uncommon form of congenital adrenal hyperplasia (CAH) resulting from a mutation in the gene for one of the key enzymes in cortisol synthesis by the adrenal gland, 3β-hydroxysteroid dehydrogenase (3β-HSD) type II (HSD3B2). As a result, higher levels of 17α-hydroxypregnenolone appear in the blood with adrenocorticotropic hormone (ACTH) challenge, which stimulates adrenal corticosteroid synthesis.

Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia (CAH) resulting from a mutation in the gene CYP17A1, which produces the enzyme 17α-hydroxylase. It causes decreased synthesis of cortisol and sex hormones, with resulting increase in mineralocorticoid production. Thus, common symptoms include mild cortisol deficiency, ambiguous genitalia in men or amenorrhea at puberty in women, and hypokalemic hypertension. However, partial (incomplete) deficiency often has inconsistent symptoms between patients, and affected women may be asymptomatic except for infertility.

<span class="mw-page-title-main">Congenital adrenal hyperplasia due to 21-hydroxylase deficiency</span> Medical condition

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a genetic disorder characterized by impaired production of cortisol in the adrenal glands.

<span class="mw-page-title-main">17α-Hydroxyprogesterone</span> Chemical compound

17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many other endogenous steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as neurosteroids.

<span class="mw-page-title-main">Aldosterone synthase</span> Protein-coding gene in the species Homo sapiens

Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by the CYP11B2 gene in humans.

<span class="mw-page-title-main">21-Hydroxylase</span> Human enzyme that hydroxylates steroids

Steroid 21-hydroxylase is a protein that in humans is encoded by the CYP21A2 gene. The protein is an enzyme that hydroxylates steroids at the C21 position on the molecule. Naming conventions for enzymes are based on the substrate acted upon and the chemical process performed. Biochemically, this enzyme is involved in the biosynthesis of the adrenal gland hormones aldosterone and cortisol, which are important in blood pressure regulation, sodium homeostasis and blood sugar control. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways which in humans ultimately lead to aldosterone and cortisol creation—deficiency in the enzyme may cause congenital adrenal hyperplasia.

<span class="mw-page-title-main">Steroid 11β-hydroxylase</span> Protein found in mammals

Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. The enzyme is involved in the biosynthesis of adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions.

<span class="mw-page-title-main">Adrenal gland disorder</span> Medical condition

Adrenal gland disorders are conditions that interfere with the normal functioning of the adrenal glands. Your body produces too much or too little of one or more hormones when you have an adrenal gland dysfunction. The type of issue you have and the degree to which it affects your body's hormone levels determine the symptoms.

<span class="mw-page-title-main">Isolated 17,20-lyase deficiency</span> Medical condition

Isolated 17,20-lyase deficiency (ILD), also called isolated 17,20-desmolase deficiency, is a rare endocrine and autosomal recessive genetic disorder which is characterized by a complete or partial loss of 17,20-lyase activity and, in turn, impaired production of the androgen and estrogen sex steroids. The condition manifests itself as pseudohermaphroditism in males, in whom it is considered to be a form of intersex, and, in both sexes, as a reduced or absent puberty/lack of development of secondary sexual characteristics, resulting in a somewhat childlike appearance in adulthood.

<span class="mw-page-title-main">Inborn errors of steroid metabolism</span> Medical condition

An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism.

<span class="mw-page-title-main">21-Deoxycortisol</span> Chemical compound

21-Deoxycortisol, also known as 11β,17α-dihydroxyprogesterone or as 11β,17α-dihydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid related to cortisol (11β,17α,21-trihydroxyprogesterone) which is formed as a metabolite from 17α-hydroxyprogesterone via 11β-hydroxylase.

<span class="mw-page-title-main">11β-Hydroxyprogesterone</span> Chemical compound

11β-Hydroxyprogesterone (11β-OHP), also known as 21-deoxycorticosterone, as well as 11β-hydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid and derivative of progesterone. It is a potent mineralocorticoid. Syntheses of 11β-OHP from progesterone is catalyzed by the steroid 11β-hydroxylase (CYP11B1) enzyme, and, to a lesser extent, by the aldosterone synthase enzyme (CYP11B2).

Walter L. Miller is an American endocrinologist and professor emeritus of pediatrics at the University of California, San Francisco (UCSF). Miller is expert in the field of human steroid biosynthesis and disorders of steroid metabolism. Over the past 40 years Miller's group at UCSF has described molecular basis of several metabolic disorders including, congenital adrenal hyperplasia, pseudo vitamin D dependent rickets, severe, recessive form of Ehlers-Danlos syndrome, 17,20 lyase deficiency caused by CYP17A1 defects, P450scc deficiency caused by CYP11A1 defects, P450 oxidoreductase deficiency.

Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia, is a milder form of congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.

<span class="mw-page-title-main">Androgen backdoor pathway</span> Series of interconnected biochemical reactions

The androgen backdoor pathway is responsible for the synthesis of physiologically relevant androgens. This process starts with 21-carbon steroids, also known as pregnanes, and involves a step called "5α-reduction". Notably, this pathway does not require the intermediate formation of testosterone, hence the term "bypassing testosterone" is sometimes used in medical literature as the hallmark feature of this way of androgen biosynthesis. This feature is a key distinction from the conventional, canonical androgenic pathway, which necessitates the involvement of testosterone as an intermediate in the synthesis of androgens.

References

  1. ↑ "Maria I. New, Icahn School of Medicine at Mount Sinai".
  2. 1 2 "Medical Ethics: Prenatal Dexamethasone Use Questioned". Time. 18 June 2010.
  3. 1 2 Slate "If Your Baby Girl Might Be Born With a Small Penis" August 15, 2015 http://www.slate.com/articles/double_x/doublex/2012/08/intersex_babies_should_you_treat_their_condition_with_prenatal_drugs_.html
  4. ↑ "The most comprehensive innovation search platform — Wellspring". www.collectiveip.com. Retrieved April 28, 2015.
  5. ↑ "Keynote Speaker, 2008 Eastern-Atlantic Student Research Forum, University of Miami Miller School of Medicine". Archived from the original on 2014-03-10.
  6. ↑ New, MI; Levine, LS; Biglieri, EG; Pareira, J; Ulick, S (May 1977). "Evidence for an unidentified steroid in a child with apparent mineralocorticoid hypertension". The Journal of Clinical Endocrinology and Metabolism. 44 (5): 924–33. doi:10.1210/jcem-44-5-924. PMID   870517.
  7. ↑ New, MI; Lorenzen, F; Pang, S; Gunczler, P; Dupont, B; Levine, LS (Feb 1979). ""Acquired" adrenal hyperplasia with 21-hydroxylase deficiency is not the same genetic disorders as congenital adrenal hyperplasia". The Journal of Clinical Endocrinology and Metabolism. 48 (2): 356–9. doi:10.1210/jcem-48-2-356. PMID   218988.
  8. ↑ Speiser, PW; Dupont, B; Rubinstein, P; Piazza, A; Kastelan, A; New, MI (Jul 1985). "High frequency of nonclassical steroid 21-hydroxylase deficiency". American Journal of Human Genetics. 37 (4): 650–67. PMC   1684620 . PMID   9556656.
  9. ↑ Dreger, A; Feder, E.K.; Tamar-Mattis, A (Jul 2012). "Prenatal Dexamethasone for Congenital Adrenal Hyperplasia: An Ethics Canary in the Modern Medical Mine". Journal of Bioethical Inquiry. 9 (3): 277–294. doi:10.1007/s11673-012-9384-9. PMC   3416978 . PMID   22904609.
  10. ↑ "Judson J. Van Wyk Prize".
  11. ↑ "Fred Conrad Koch Award". Archived from the original on 2013-08-28.
  12. ↑ "NICHD's First Grantees".
  13. ↑ "Citation for the 1995 Rhône-Poulenc-Rorer Clinical Investigator Award to Maria I. New". Endocr Rev. 16 (4): 551–2. Aug 1995. PMID   8521796.
  14. ↑ "Society for Endocrinology medallists" (PDF). Archived from the original (PDF) on 16 May 2013. Retrieved 27 August 2013.
  15. ↑ "Robert H. Williams Distinguished Leadership Award". Archived from the original on 2013-08-28.
  16. ↑ "Distinguished Graduate Award, Perelman School of Medicine, University of Pennsylvania". Archived from the original on 2015-03-02. Retrieved 2013-08-28.
  17. ↑ "St. Geme Lectureship, 2010" (PDF). Archived from the original (PDF) on 4 March 2016. Retrieved 27 August 2013.
  18. ↑ "Past presidents, Lawson Wilkins Pediatric Endocrine Society". Archived from the original on 2013-08-28. Retrieved 2013-08-28.
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