Summary Highlights: Endocrine Society 87th Annual Meeting in San Diego, June 4-7, 2005
© 2005 Prime Health Consultants, Inc.
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