Profile of the Pediatric Endocrine Clinic at New YorkPresbyterian Hospital, New York Weill Cornell Center1
Maria I. New,
Jihad Obeid,
Robert C. Wilson,
Monina S. Cabrera,
Amanda Goseco,
Maria C. Macapagal,
Ian Marshall,
Saroj Nimkarn,
Jose B. Quintos,
Svetlana Ten,
Figen Ugrasbul,
Laurie Vandermolen and
Madeleine D. Harbison
Department of Pediatrics, Division of Pediatric Endocrinology,
Weill Medical College of Cornell University, New York, New York
10021
Address correspondence and requests for reprints to: Maria I. New, M.D., Professor and Chairman, Department of Pediatrics, Chief, Division of Pediatric Endocrinology, Harold and Percy Uris Professor of Pediatric Endocrinology and Metabolism, New YorkPresbyterian Hospital, 525 East 68th Street, Room M-622, New York, New York 10021. E-mail: minew{at}mail.med.cornell.edu
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Introduction
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IN 1927, THE CORNELL University Medical
College, now named The Weill Medical College of Cornell University, and
The New York Hospital (which in 1998 became the Cornell campus of the
merged New YorkPresbyterian Hospitals) formally integrated their
educational, research, and health care functions. The Medical College
is also formally affiliated or closely associated with Memorial
Sloan-Kettering Cancer Center, the Hospital for Special Surgery, and
Rockefeller University, which are adjacent medical institutions.
Together these institutions constitute one of the largest private
centers of medical care, education, and research in the world.
In 1964, Dr. Maria I. New was appointed the first Director of the
Division of Pediatric Endocrinology and established the university
hospitals first Pediatric Endocrine Clinic. In 1968, the National
Institutes of Health funded a grant to the College for an inpatient and
outpatient Pediatric Clinical Research Center, which has operated
continuously to the present.
There has been no published comprehensive profile of a pediatric
endocrine clinic profile since that in Lawson Wilkins (1) 1965
textbook on childhood and adolescent endocrine disorders. Hence, we
thought it valuable to present a modern clinic profile in a major
academic medical center, focusing on the past 5 years, which is the
culmination of the clinics dynamic 35-yr history at The New York
HospitalCornell Medical Center. In addition to the general endocrine
clinic, we have had a particular focus on steroid disorders. Currently,
our Division of Pediatric Endocrinology consists of the Director, six
academic full-time faculty members, and eight clinical fellows. We
shall review herein the philosophy, structure, and diagnostic patient
profile of the outpatient pediatric endocrine service for the past 5
years, from 1994 to the present.
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Clinic Description
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Operation of the clinic
Sixty-five percent of the endocrine service patients come from the
five boroughs of the New York metropolitan area. Twenty-eight percent
are referred from the remainder of New York State and the states of New
Jersey and Connecticut. Five percent are patients from the rest of the
United States, and 2% are referred from abroad.
The age distribution of our patients is shown in Fig. 1
. The large number of patients in the
newborn period reflects referrals from New York State Newborn Screening
Laboratories. The patients over 20 yr of age represent the cohort of
patients referred for abnormalities of androgen metabolism, relatives
of congenital adrenal hyperplasia (CAH) patients, the patients Dr. New
has continued to follow into adulthood, and adults with GH
deficiency.

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Figure 1. Histogram showing the number of patients
seen in each age category during the years of 19941999.
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Our outpatient endocrine service sees patients daily. There are three
formal clinics: the general Endocrine Clinic, Dr. News Steroid
Clinic, and a Diabetes Clinic. Approximately 10% of outpatients are
seen on the Childrens Clinical Research Center (CCRC). A total of
about 70 patients are seen each week.
Our outpatient service follows a conference clinic format in
which traineesconsisting of fellows, residents, and medical
studentsare supervised by a faculty member. Each patient on the
service is followed by a specific fellow and has an
attending-of-record. The patients clinical and laboratory data are
logged in a computerized database, which was developed by the
Informatics Section of the CCRC. The frequently used provocative tests
are shown in Table 1
.
In the Steroid Clinic, Dr. New sees her patients with disorders of
steroid metabolism and sexual differentiation, many of whom she has
followed since birth. She has developed a detailed form for following a
patient with CAH, which enables accurate tracking of steroid levels,
medication doses, linear growth, and bone age advancement (Fig. 2
). These collected data points are
entered into our informatics system.
Steroid patients are generally seen at 3-month intervals, at which time
an adrenal hormone profile is obtained. The Pediatric Steroid
Laboratory measures the following steroids: deoxycorticosterone,
corticosterone, cortisol, aldosterone, dehydroepiandrosterone,
dehydroepiandrosterone sulphate,
4-androstenedione, testosterone,
dihydrotestosterone, estradiol, progesterone, 17-hydroxyprogesterone,
17-
5-pregnenolone. The molecular genetic
laboratory conducts DNA analysis.
Weekly division conferenceeducation and training
A weekly conference is chaired by Dr. New and
attended by our entire Division, visiting scientists, residents, and
medical students. Frequently other members of our scientific team, such
as Dr. James German, geneticist and scholar in residence, and Dr. Leon
Bradlow, steroid biochemist, also attend the conference. Interesting
and/or enigmatic cases are presented to Dr. New and discussed in depth.
Dr. Jean Wilson, the world-renowned endocrinologist from the University
of Texas Southwestern Medical Center, attends on a regular basis. The
conferences attended by Dr. Wilson are so interesting and educational
that scientists come from many outside centers to participate. Guest
speakers are invited at regular intervals to present relevant and novel
research related to patients. Research-in-progress presentations are
periodically scheduled during this conference, in which fellows or
scientists in the department update the team on their research
findings; these talks are usually preparation for presentations at
national or international symposia and conferences.
Our Division has trained over 100 fellows since 1965, many of whom have
gone on to distinguished careers. Over 30 are endocrine chiefs or heads
of departments.
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Results
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Frequency of diagnosis
Using the Accreditation Council for Graduate Medical
Education categories for pediatric endocrinology patients, the most
frequent diagnosis of the approximately 3800 patients seen since 1994
was growth abnormalities, followed by thyroid pathology, disorders of
sexual development, and adrenal disorders (Table 2
). Patients with carbohydrate, bone
mineral, and anterior pituitary disorders made up a smaller group.
Posterior pituitary cases were rare. When these categories were
subdivided, the following pattern emerged (Table 3
). In the growth abnormalities category,
short stature was by far the leading diagnosis. Dysmorphic syndromes,
failure-to-thrive, and delayed puberty followed in frequency. Only a
very small number of patients were referred for tall stature. In the
anterior pituitary category, hypopituitarism including isolated GH
deficiency was the most frequent diagnosis. In the thyroid hormone
category, referrals to rule out hypothyroidism increased markedly,
owing to New York State laboratory newborn screening. Of these
referrals, the diagnosis of hypothyroidism was confirmed in one third
of the cases. Hyperthyroidism and goiter accounted for 10% of cases
referred for thyroid pathology.
Among the patients evaluated for adrenal disorders, CAH, comprising
various enzyme defects of steroid synthesis, was the most frequent
diagnosis, followed by patients being tested for suspected CAH. Of the
CAH patients, 92% had 21-hydroxylase deficiency.
Owing to our discovery of the disease, we are a major
international referral center for apparent mineralocorticoid excess
(AME), and we are one of the few centers in which an AME study
population has been examined clinically, biochemically, and
genetically. Remarkably, AME was diagnosed in 15 patients referred here
out of about 40 known cases in the world. Twenty-seven family members
of these patients were also studied.
The diagnoses falling into the category of disorders of sexual
differentiation were more evenly distributed, with evaluations for
precocious puberty, premature thelarche, and polycystic ovary disease
being the most common.
Among the calcium/phosphate disorders, vitamin D deficiency and
X-linked hypophosphatemic rickets were the main diagnoses.
Diabetes and obesity were frequent among the remaining endocrine
patients, whereas all other diagnoses were relatively rare.
Treatment with human GH (hGH)
The total number of patients treated with hGH in the last 5 years
was 347, with the number each year being similar (Table 4
). Table 5
shows the distribution of the number of GH-treated patients with
different diagnoses.
Molecular genetic diagnosis
The number of 21-hydroxylase-deficient CAH patients and their
families who have been genotyped by molecular genetic techniques was
152 since 1994. Since the molecular genetic laboratory was established
in 1992, a total of 198 families followed here have had DNA analysis
for 21-hydroxylase deficiency (Table 6
).
There are an additional 331 patients who are either probands in
families referred for prenatal diagnosis or consultation cases. These
patients also had molecular genetic analysis of CYP21. The
most frequent mutations in the CYP21 gene are the intron 2
and deletion mutations (Table 7
).
Prenatal diagnosis and treatment
The molecular genetic laboratory made possible the prenatal
diagnosis of 21-hydroxylase deficiency, 11ß-hydroxylase deficiency,
and AME. Since 1994, 241 fetuses and their families have had DNA
analysis of the 21-hydroxylase gene (CYP21). Altogether
since 1989, 330 fetuses have been tested for 21-hydroxylase deficiency
by molecular genetic techniques (Table 8
). Of these, 70 have been identified as
affected. Molecular genetic diagnoses have been used in two pregnancies
at-risk for 11ß-hydroxylase deficiency.
Patients never seen
As evidence that pediatric endocrinology has become a biochemical
and molecular genetic discipline, we receive two to three requests
monthly for consultation in which only blood or DNA is evaluated for
diagnosis.
CCRC
We owe the discovery of several diseases and advances in therapy
to our 32-yr-old federally funded CCRC. It has allowed us to integrate
clinical, biochemical, and genetic data in a controlled setting and has
permitted us to assemble statistically significant numbers of patients
of rare diseases. Furthermore, the data from these patients have been
logged into the CCRC informatics system.
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Discussion
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The profile of the Clinic reported in the 1965 edition of
the Lawson Wilkins (1) textbook indicates the referrals to the
best-known pediatric endocrinologist of his time: 3190 cases in 27
years. This contrasts with 3778 patients seen by this clinic in 5
years. Although the distribution of diagnoses has not changed
significantly, the great increase in the number of patients seen in
todays Pediatric Endocrine Clinic reflects the heightened awareness
of the role of hormones in health and disease in children. Several
other factors may account for the increase in the number of patients
referred to our clinic. For example, the development of bioengineered
GH has resulted in the availability and clinical use of GH in the
treatment of children. The impact of the advances in molecular genetic
analysis plus the interest of the director of the clinic in steroid
disorders probably account for the marked increase in the patients seen
with CAH. Thyroid screening in the state of New York has been
responsible for the increase in patients seen with hypothyroidism. The
marked increase in childhood obesity in the United States is also
paralleled in the Pediatric Endocrine Clinic.
Another change from the time of Lawson Wilkins is the marked increase
in the use of provocative tests. These tests are evidence of the more
biochemical approach to diagnosis. This has made possible the diagnosis
of the large number of patients never seen whose biological samples are
evaluated by biochemical or genetic tests.
The international character of our Clinic is reflected in the trainees,
the visiting scientists, and the patients. Referrals from abroad are no
longer rare. Fellows from 19911999 have originated from all over the
world, including Argentina, Iran, Brazil, the Philippines, India, the
Dominican Republic, Greece, Bangladesh, Egypt, Thailand, Croatia,
Turkey, and Russia. International visiting scientists (19941999),
bringing a world view to our clinic, and returning home with an
intimate awareness of our medical and scientific advances, have come
from Egypt, China, Iran, Brazil, Greece, Italy, and Germany.
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Conclusion
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Molecular genetic techniques and provocative endocrine testing
have changed the practice of pediatric endocrinology. However, in the
end, our patients remain our most important teachers. The rare and
complicated cases provide an arena for our trainees to learn
physiologic mechanisms and therapeutics. Our Division members are
taught to consider the ethical, social, and legal issues as vital to
the medical care of their patients. Unusual patients have become
"prismatic cases," leading to the discovery of diseases such as AME
(11ß-hydroxysteroid dehydrogenase type 2 deficiency) and the
mechanism of resistance to several steroids. Furthermore, by
inviting collaboration from our colleagues worldwide, we provide our
patients with cutting edge diagnostic and therapeutic techniques.
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Footnotes
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1 Significant sections of the work on which the data are reported
herein were supported by USPHS-NIH Grants HD-00072 and RR-06020. 
Received October 13, 1999.
Accepted October 15, 1999.
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References
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-
Wilkins L. 1965 The relation of extrinsic
genetic and endocrine factors to growth and development. In: Blizzard
RM, Migeon CJ, eds. The diagnosis and treatment of endocrine disorders
in childhood and adolescence, 3rd ed. Springfield, IL: Charles C.
Thomas; 311.