Highlights of the European Society for Paediatric Endocrinology 45th Annual Meeting, Rotterdam, Netherlands, June 30th-July 3rd, 2006

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The Annual ESPE Meeting was held in the Netherlands for the 4^th time, which is appropriate in view of the important contributions this country has made to the origins of pediatric endocrinology and to the significant advances during the development of the specialty. The scientific program stretched over 3 full days and the congress was attended by over 1700 delegates from 72 countries. The ESPE meeting has become a truly global pediatric endocrinology event. Under the presidency of Professor Stenvert Drop, the congress adopted the theme of ‘Pediatric Endocrinology: the impact of programming.’

Developmental Systems in Senescence

In the opening plenary session, Jan Hoeijmakers and Steven Lamberts, both from the Netherlands, discussed the growth hormone (GH)/insulin-like growth factor (IGF) axis in the process of aging. Delegates were reminded how human DNA is constantly subjected to minor alterations as a consequence of exposure to noxious agents. In order to counteract these changes, DNA repair systems have evolved; so-called ‘gene cleaning.’ However, defects in the same DNA repair system can give rise to different phenotypes associated with aging and may result in increased cancer risk. The role of circulating IGF-I in determining long-term cancer and cardiovascular morbidity was discussed. Data from the Rotterdam study of 7983 subjects showed that polymorphisms with 192 and 194 base pair alleles occurred in 80% of the population and were associated with the highest serum IGF-I levels, tall stature, and an increased relative risk of prostate cancer, but decreased risk for type 2 diabetes (T2DM). The general influences of IGF-I on human longevity remained unclear.

ESPE/LWPES Consensus Meeting on ‘Intersex’

This consensus meeting held in Chicago in October 2005 was summarized and the session moderated by the organizers; Ieuan Hughes (Cambridge, UK) and Peter Lee (Hershey, Penn, USA). A key outcome of the meeting was the agreement to revise the nomenclature and terminology used by healthcare workers. The general term of disorders of sex development (DSD) was adopted with 46,XX DSD or 46,XY DSD replacing the previously used ‘pseudohermaphroditism.’ The term ‘intersex’ was also felt to be inappropriate in many circumstances. Difficulties in assigning the optimal sex of rearing were described by Polly Carmichael (London, UK), who also emphasized the importance of a multi-disciplinary approach and of treating each patient and family individually. The consensus meeting decided that imposed reassignment of sex involving genital surgery should be performed before 18 months of age where possible. (For an additional review and comment on this meeting, see Consensus Statement on Management of Intersex Disorders by David Sandberg in this issue of GGH.)

Leendert Looijenga (Rotterdam, Netherlands) reviewed the subject of gonadal cancer risk in patients with DSD. Progress is being made in the definition of both low-risk and high-risk groups. The presence of the TSPY gene on the Y chromosome is a likely risk factor and immunohistochemical detection of OCT3/4 markers may also help to identify early malignant change.

SGA Consensus Meeting

Peter Clayton, the main organizer of the SGA consensus meeting held in Manchester, UK in December 2005, summarized the updated definition of ‘small for gestational age’ (SGA), which required birth weight and/or length to be <–2 SDS. This multi-system disorder requires early neurodevelopmental investigation and, where necessary, intervention. The consensus meeting arrived at the balanced view that routine surveillance of SGA adults was not indicated because of the only small influences of birth weight on adult BMI, blood pressure, coronary heart disease, and diabetes. Stefano Cianfarani (Rome, Italy) reported that there was only limited evidence of a programming effect of SGA in humans, and that genetic analyses of SGA subjects currently had limited diagnostic value. Alan Rogol (Charlottesville, Va, USA) summarized the growth deficit in SGA subjects and concluded that short SGA children should be followed in growth clinics. Treatment with GH had demonstrated a height gain of 1.2–2.9 SDS during the first 3 years of treatment.

Bone Health

In a symposium on bone health, Nick Bishop (Sheffield, UK) stated that pediatric bone disease can be divided into osteoporotic, osteolytic, rachitic, sclerotic, and dysplastic categories, and proceeded to make the point that each of these sub-types may require a different therapy. Bisphosphonates, possibly the most commonly used current therapy, have proven useful in disorders characterized by low bone mass, such as osteogenesis imperfecta, bone pain, high bone turnover, and osteolysis. Bisphosphonates increase bone mass and decrease fracture rate, particularly in the first year of therapy.

Cytokines and Growth in Chronic Disease

A highlight of the second day of the congress was a symposium on cytokines and growth in chronic disease. Stefan Bornstein (Dresden, Germany) described how the hypothalamic-pituitary-adrenal axis was a major site for both synthesis and action of numerous inflammatory cytokines. In severe inflammation, coordinated immuno-adrenal responses are essential for survival. The so-called Toll-like receptors (TLR), specifically types 2 and 4, have been identified as important links between the adrenal and immune systems. The TLR knock-out mice have impaired adrenal and immunological responses; TLR 2 and 4 are genetically polymorphic, which might explain the variable responses to anti-cytokine therapies in some inflammatory disorders.

Lars Sävendahl (Stockholm, Sweden) described how cytokines, specifically interleukin (IL)-1β, may interfere with growth plate function to suppress longitudinal growth. This model may be a target for IGF-I or IGF-I/IGF binding protein (BP)-3 therapy. The so-called biologic response modifiers (eg, Etanercept, a tumor-necrosis factor [TNF] inhibitor) have demonstrated in cultured fetal rat metatarsal bones to prevent cytokine-induced growth failure.

Faisal Ahmed (Glasgow, Scotland) described the clinical effects of chronic inflammation in inflammatory bowel disease and cystic fibrosis (CF), impairing both linear growth and puberty development. Specific therapy is somewhat disappointing because testosterone, GH, and anti-cytokine therapies induce only limited improvement. The possibility of IGF-I or IGF-I/IGFBP-3 therapy should be considered in such patients.

ESPE Young Investigator Award

The 2006 ESPE Young Investigator Award was presented to Dr. Mireille Castanet from the groups of Michel Polak and Paul Czernichow in Paris. Dr. Castanet presented data from a national French survey of thyroid dysgenesis patients demonstrating the genetic basis of this disorder. However, mutations of these genes are only present in a small number of familial cases.

ESPE Research Award

The 2006 ESPE Research Award was presented to Mikael Knip (Helsinki, Finland), whose lecture related to recent advances in the understanding of the pathogenesis of type 1 diabetes (T1DM). He described how the natural history of progressive beta cell autoimmune dysfunction varied widely among individuals. Because of early ‘programming’ of eventual beta cell failure in genetically susceptible individuals, primary preventive strategies should be commenced during infancy or as soon as possible after positive seroconversion.

Sleep Deprivation

Eve Van Cauter (Chicago, Ill, USA) gave an outstanding plenary lecture on the neuroendocrine effects of chronic partial sleep deprivation, which is becoming a major aspect of the lives of many young people, particularly adolescents. Sleep deprivation adversely effects glucose metabolism, appetite regulation, and energy expenditure, and may result in insulin resistance and weight gain, not to mention poor school performance.

Obesity: Hormonal Programming, Cytokines, and Genetics

A symposium was held to attempt to draw together these pathogenetic strands in the field of childhood obesity. Andreas Plagerman (Berlin, Germany) described how exposure of the fetus to abnormal hormone influences such as hyperinsulinemia could have a programming effect resulting in abnormal fat and glucose metabolism. The importance of the melanocortin (MC) system on body composition was stressed. This is demonstrated by the predisposing effects of MC3 and MC4 mutations towards obesity. Sadaf Farooqi (Cambridge, UK) described patients with leptin deficiency and MC4 genes. Patients with these disorders have hyperphagia associated with other endocrine abnormalities. MC4 deficiency accounted for 5% of patients with severe early-onset obesity. Ken Ong showed data from the ALSPAC (Cambridge, UK) study (6023 children), suggesting that genetic factors rather than programming per se might be responsible for early-onset weight gain. Maternal age of menarche was a strong predictive factor in offspring obesity (the earlier maternal menarche occurs, the more likely the subject is to develop rapid infantile weight gain and advanced growth, eventually resulting in shorter adult stature.

Endocrine Disrupters

A highlight of the third day of the congress was an in-depth look at the subject of endocrine disrupters. Richard Sharpe (Edinburgh, Scotland) described the effect of endocrine disrupters on the development of the male reproductive system. Any external influence which‘disrupts’ the secretion of key hormones, particularly testosterone, for male sexual development may cause under-masculinization such as cryptorchidism or hypospadias. Dr. Sharpe’s group has demonstrated that exposure of the rat to D-n(butyl) phthalate (DBP) may result in abnormalities to Leydig cells, germ cell development, and Sertoli cell proliferation.

Jorma Toppari (Turku, Finland) presented data from a longitudinal prospective baby cohort study set up to examine differing rates of cryptorchidism and characteristics of sperm counts between Finland and Denmark. Evidence was presented suggesting a degree of testicular dysgenesis in the Danish cohort which has a higher incidence of cryptorchidism. Differing exposure to environmental toxins in the 2 countries was also discussed. Katharina Main (Copenhagen, Denmark) presented data showing that exposure to most toxins, particularly phthalates, was higher in Denmark.

The Andrea Prader Prize Presentation

The 2006 Andrea Prader Prize, ESPE’s highest leadership award, was presented to Professor Ieuan Hughes from Cambridge, UK. Ieuan Hughes has made an enormous contribution to pediatric endocrinology over many years. Apart from being Secretary of ESPE for 5 years, he has contributed to fundamental scientific advances in the fields of adrenal diseases and sex differentiation disorders. He provided in his presentation an update on the latest molecular advances, particularly in his own field of androgen insensitivity.

Summary

The 2006 ESPE meeting provided evidence of the growing scientific stature of this Society. The range of symposia and the quality of oral presentations and prize lectures was impressive. The scientific program contained ‘something for everyone’ and Ze’ev Hochberg, Chair of the Organizing Committee, and Stenvert Drop, President of the meeting, can look back with satisfaction at 3 full days of vibrant and informative scientific interaction. The 2007 ESPE meeting will be held in Helsinki, Finland from June 27-30, 2007.

Martin O. Savage, MD

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Last Updated: 04/30/2008