The 2016 European Society of Paediatric Endocrinology (ESPE) conference kicked off this morning with the ESPE Working Groups, covering gynaecology, diabetes technology and therapeutics, Turner syndrome, bone and growth plate, and disorders of sexual development.

Exploring Turner syndrome

The Turner syndrome workshop opened with a look at pregnancy outcomes in Turner syndrome patients, presented by Sophie Christin-Maitre, from Hôpital Saint-Antoine in Paris, France. The physiological process of follicle depletion is accelerated in Turner syndrome women, leaving more than 95% with ovarian insufficiency, and oocyte donation or adoption as their only options for creating a family.

For those women who do become pregnant, complications are frequent. A study of 480 patients conducted by Christin-Maitre’s group found spontaneous menarche in 19.8% and spontaneous pregnancy in 5.6%, with 57.7% of these going to term, giving a spontaneous full-term pregnancy rate of 3.8%.

However, 31% ended in miscarriage, leading Christin-Maitre to urge delegates to “counsel your patients that the rate of miscarriage is high.” She also stressed that Turner syndrome women should be counselled about the increased risk of aortic artery dissection, which can be fatal.

The team’s comparison of patients who did and did not become pregnant found, unsurprisingly, indications of a milder phenotype among those who became pregnant. These women had achieved spontaneous menarche and had been diagnosed at a markedly older age than the other women, with nine being diagnosed during investigation for multiple pregnancy losses.

Two other presentations covered skeletal disproportion and impaired facial perception in Turner syndrome patients, and a third, from Helen Mijnarends (Centrum Chronisch Ziek en Work, Eindhoven, the Netherlands) demonstrated how coaching Turner syndrome patients to accept their limitations, while simultaneously gaining confidence in their qualities and competencies, can help them to succeed in their professional and family lives. And Mijnarends has the edge when it comes to coaching Turner patients: she is a Turner patient herself, giving her a unique insight and authority that other trainers lack.

The talk that generated probably the most discussion came from Theo Sas, from Sophia Children’s Hospital in Rotterdam, the Netherlands, who updated delegates on oestradiol supplementation in Turner syndrome.

In fact, Sas said, there is little to report on since the 2015 conference, although he noted that a consensus document is in progress, and his talk mainly focused on areas in which data are badly needed but hard to come by.

Firstly, he said, the evidence for the beneficial effects of low-dose oestradiol during childhood still comes from just one study and needs confirming before oestradiol can be recommended for girls under the age of 11 years.

Then he addressed the problem of administration, saying that a transdermal route is advised over oral administration for puberty induction, but there are no patches available for paediatric patients, no information on the stability and best storage of cut-down adult patches, and pharmacists are generally unwilling to cut them. Sas outlined the so far fruitless search for funding to investigate this, or for pharmaceutical companies willing to develop a paediatric patch, and appealed to companies to come forward.

In the meantime, he advises cutting patches rather than using a full-sized patch for 1 week with a 3-week break, which he stresses does not mimic physiological delivery. He noted that there is some evidence for the efficacy of the rather “less patient-friendly” approach of intramuscular injection, and that oestradiol gel is also an option, although with very little evidence.

This point was taken up during the discussion by a delegate who said her centre routinely uses gel and is very happy with the results. Besides different approaches to administering oestradiol, the discussion also centred on how to obtain the best available evidence and determine the optimal approach in the absence of research funding.

The bad and the good of progress

After the official welcome from current ESPE president Jean-Claude Carel, the plenary lectures commenced in the Grand Amphithéâtre with Barbara Demeneix (Muséum National d’Histoire Naturelle, Paris, France) outlining the evidence for the adverse effects of environmental chemicals on thyroid function. Barely a third of environmental chemicals have published data on their effects on thyroid function, she said, yet they are approved, on the market “and in your food”.

Jérôme Bertherat (Cochin Hospital, Paris, France) delivered the first few minutes of the second plenary without slides, thanks to a technical hitch, but then provided a comprehensive overview of how data-driven genetic research, made possible by modern mass-sequencing techniques, has identified genetic drivers of the adrenal tumours and hyperplasias that underlie Cushing’s syndrome.

Insights from nPOD

The afternoon symposia included the genetics of thyroid dysgenesis, a special session covering online education for paediatric endocrinologists, and paediatric autoimmune disease. This last included an overview of the JDRF nPOD study, a major collaborative effort set up to unpick the pathogenesis of Type 1 diabetes in human patients, rather than animal models.

To this end, the researchers obtain pancreases from deceased organ donors with Type 1 diabetes, or from patients who have received a transplant. The tissue is then distributed to various approved research projects studying viral infections, extracellular matrix components, autoimmunity, transplantation, islet isolation and ex vivo diabetic pancreatic function.

Presenter Alberto Pugliese, from the University of Miami in Florida, USA, particularly highlighted one finding to emerge from the work: that the destruction of islet cells in Type 1 diabetes patients is a chronic process. Insulitis affects only around 10% of islets at the point of diagnosis, and beta cell mass does not strongly correlate with insulitis, diabetes duration or age at onset.

Furthermore, insulin-producing cells are still detectable many years after diagnosis, suggesting that diabetes results from beta cell dysfunction as much as destruction.

This has major implications for the timing of interventions, said Pugliese, noting that prevention trials are necessarily very large and of long duration, while the point of diagnosis is a stressful time for patients and their families and not the ideal moment to enrol them into clinical trials.

Other nPOD project findings to date include evidence of chronic, low-grade viral infection of diabetic islets, a role for inflammation and stress and for several extracellular matrix components, and a marker that is highly expressed on infiltrating lymphocytes – representing a potential new target.

But for all these new findings, there is so far no “smoking gun”, said Pugliese. “We haven’t seen anything major that would radically change our perception of the disease.”

By Eleanor McDermid, Senior medwireNews Reporter

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