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The full ENDO2005 program may be viewed online at www.endo-society.org. Summarized
here are some highlights of interest to the editor.
Growth
A new cause of
short stature was reported by Olney et al from Jacksonville,
Cleveland, and Christchurch (OR43-4). They described acromesomelic
dysplasia, Maroteaux type (AMDM), a form of dwarfism
characterized by marked short stature with short arms and legs. These
patients had a mutation in the natriuretic C-type peptide (CNP)
receptor B gene that prevents cells from exerting the action of this
peptide to enhance growth, despite very elevated CNP levels. Patients
with AMDM were homozygous for the gene mutation, whereas family
members with one single gene copy mutation did not exhibit the
syndrome but had short stature and were about 9.5 cm shorter and had
an elevated CNP level 4 times higher than other family members who
did not have the CNP mutation. Researchers estimated that
approximately 1 in 700 people have a mutation in this gene. Thus,
this alteration may be present in up to 1.3% of short stature
children.
Naturally
conceived children have different growth patterns and lipid profiles
than those of children conceived by in vitro fertilization
(IVF), as reported by Miles et al from Auckland (OR54-6). They
studied 110 children, ages 4 to 10 years, 50 of them were born
following IVF. The IVF children were taller and had higher
growth-promoting hormones IGF-I, IGF-II and IGFBP3 and had a more
favorable cholesterol profile than those conceived naturally.
Countering
previous data, Maghnie et al from Pavia, Milano, Parma, Rome, and
Cagliari (P1-504) studied patients with multiple pituitary hormone
deficiencies (MPHD) and those with isolated growth hormone
deficiency (IGHD). They reported that both types reached the same
adult height. They studied 49 patients with MPHD and 39 with IGHD who
were diagnosed at a median age of 7 years and treated with GH. The
median adult height did not differ among the 2 groups. Adult height
of MPHD patients was positively correlated with both the time period
of GH treatment and with height at the time of diagnosis. The adult
height of IGHD patients was positively correlated with height at
diagnosis and with pubertal height gain.
A simple,
compact inhaler showed promise in easing delivery of human
growth hormone (hGH) as safely and effectively as by injection.
Chipman et al from Indianapolis, Cambridge, and London (OR33-3)
treated 12 healthy males, 21 years to 36 years of age, in a
cross-over design, with hGH given subcutaneously or by inhaler. Blood
levels of GH achieved with either method of administration were
similar among both groups. Mild side effects were similar and
infrequent in the 2 groups. This study showed evidence that
inhalation of large proteins may produce blood concentration-time
profiles and variability levels similar to those obtained by hGH
injection.
Geffner et al
from Los Angeles, Stockholm, Prague, London, and Antwerp (P2-505)
reported patients with childhood-onset growth hormone deficiency
(CO-GHD), who discontinued treatment after reaching adult height, but
later needed additional GH therapy. They stated that GHD patients
should resume treatment as soon as possible. Data from 210 patients
with severe CO-GHD followed in the Pfizer International Growth and
Metabolic database (KIGS and KIMS), who were off GH for more than 6
months during transition from childhood to adulthood therapy were
studied. There was a significant difference in IGF-I, cholesterol,
and triglyceride levels and quality-of-life scores after GH was
discontinued. The poorest results were among those with longer
intervals without GH. Thus, after retesting to confirm persistence of
GHD, GH treatment should be resumed promptly in adults with a history
of CO-GHD.
Obesity
Westphal et al
from Ulm, Leipzig, Luebeck (P2-149) reported a novel link describing
the connecting signaling pathways in adipose tissue with arterial
blood pressure. The connection was the JAK/STAT pathway that
inhibited 3-adrenergic crosstalk which down-regulated expression of
angiotensin II, thus contributing to the regulation of the
renin-angiotensin system. This crosstalk may represent the molecular
link between obesity and hypertension.
Flint et al from
Philadelphia (P1-705) determined that overweight children need repeat
evaluations of their glucose tolerance, as their ability to
metabolize glucose changes over time. Overall, 6 of the 44 children
studied demonstrated deterioration in glucose tolerance in 15 months.
In contrast, there was no significant change in the body mass index,
HOMA-1R, cholesterol, and triglyceride levels of these 6 children
over time. Longitudinal evaluation by oral glucose tolerance testing
was necessary to detect worsening glucose metabolism.
According to de
Zegher et al from Barcelona, Cambridge, and Leuven (OR34-4), small
for gestational age (SGA) infants who have rapid catch-up
weight gain, present with excess body fat by 2 to 3 years of age,
and may therefore already be on the path to type 2 diabetes (T2DM)
later in life. The authors compared a group of toddlers with body
composition measurements by DEXA, who were born small (SGA) and who
normalized their weight during infancy, with another group of
toddlers of average size at birth (AGA) and with normal weight in
infancy. The SGA infants accumulated more adipose tissue than lean
body mass; fat was deposited principally in the abdominal region and
noticed shortly after completion of their catch-up growth. The path
from early growth restraint to insulin resistance and later T2DM
emerges early in life.
Diabetes
For the first
time a developmental gene was discovered capable of reversing
autoimmune diabetes mellitus in mice by Yechoor and Chan et al
from Houston and Otsu (P1-10). The researchers treated mice with type
1 autoimmune diabetes (NOD/LtJ) with a single intravenous infusion of
an islet cell developmental gene (HDAd-ND and HDAd-BTC). This
reversed the disease and normalized the blood sugar levels. The in
vivo gene with nueroD along with betacellulin reversed the
autoimmune process and restored insulin secretion. This is a
promising and interesting alternative to islet cell transplantation.
According to
Milanesi et al from Winston-Salem and Padova (P1-14), amniotic
fluid stem cells showed promise in treating type 1 diabetes
by functional regeneration of pancreatic islets. The researchers
found that mouse amniotic fluid stem cells, taken from pregnant mice,
could induce pancreatic differentiation and formation of islet-like
clusters that expressed insulin in streptozotocine (STZ)-treated
NOD/SCID mice. When given the stem cells, these mice showed the same
number of islets as the healthy mice. Furthermore, the treated mice
maintained normal blood glucose levels and their pancreas’
showed normal islets that co-expressed insulin.
Steroids
This report by
Yazawa et al from Fukui and Saitama (P1-330) showed that stem
cells from adult bone marrow were able to create cells in the
testis and in adrenal glands. Mesenchymal stem cells or marrow
stromal cells were found to be engrafted and differentiated into
steroidogenic cells that were indistinguishable from Leydig cells
when transplanted into immature rat testes. Because adult stem cells
can be easily obtained from adult bone marrow by simple aspiration,
these findings may be of great potential as a stem cell resource that
may be used clinically for diseases associated with steroid
hormone-producing alterations.
Fima Lifshitz, MD
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Current GGH - Vol. 24 No. 1
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