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Endocrinology research in focus

ESE publishes new guidelines on adrenal incidentaloma

The appropriate clinical response to adrenal incidentaloma should depend on the likelihood of malignancy, according to new guidelines published by the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumours (ENSAT).

The guidelines are based on a study first presented at ESE’s 2016 European Congress of Endocrinology earlier this year.

An adrenal incidentaloma is a tumour of the adrenal glands discovered through imaging performed for reasons other than a suspected adrenal tumour.

These incidentally discovered adrenal masses may be malignant or benign as well as functionally active (releasing hormones), or inactive. The majority found are benign, non-functioning masses. Due to a rise in the number of imaging procedures available, the frequency of diagnosis of these tumours is increasing. Despite this, no international guidelines exist on the topic.

In response, an interdisciplinary guideline working group made up of 10 international experts and led by Professors Martin Fassnacht and Olaf Dekkers determined to establish the best response to adrenal incidentaloma.

The working group used GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) to define key clinical questions surrounding the disease.

The group then carried out extensive literature research to address these questions, providing recommendations based on quality of evidence as well as outcomes, patient preferences, and feasibility of implementation.

“These guidelines are an important step in the handling of adrenal incidentaloma,” according to Prof Fassnacht.

 “We provide for the first time, evidence-based recommendations to avoid over-diagnostics and over-treatment, without missing relevant disease, such as adrenocortical carcinomas.”

Focusing on the assessment of malignancy, surgical intervention, follow-up recommendations, and the definition and management of low-level autosomal cortisol secretion, the guidelines provide a comprehensive overview of disease assessment, treatment, and follow-up.

 They state that the appropriateness of surgical intervention depends on the likelihood of malignancy, the presence and degree of hormone over-production, as well as the age, general health, and preference of the patient.

“The guidelines also provide recommendations on how to address bilateral incidentalomas (both adrenal glands) and tumours in patients with extra-adrenal malignancy (outside of the adrenal glands). They also clearly define that benign, non-functioning masses less than 4cm in size do not require follow-up imaging. Identification of this group is a major change to prior expert opinions.” The full guidelines can be downloaded free of charge from the European Journal of Endocrinology, the official journal of the ESE.

Preterm babies with low birth weight may be at increased risk of osteoporosis

Adults who were born prematurely or at a below average weight are more likely to have weaker bones and an increased risk of fracture and osteoporosis later in life, new research has shown.

A Norwegian study, presented at the 2016 European Congress of Endocrinology, could lead to recommendations that high-risk individuals follow diets rich in calcium, vitamin D, and protein, and undertake weight-bearing exercise.

Worldwide, approximately 10 per cent of babies are born preterm and are subject to multiple health risks later in life.

The human body concentrates calcium for bone development during the third trimester of pregnancy; if this is interrupted due to premature birth, babies may risk suffering poor bone health later in life.

This study by researchers at the Norwegian University of Science and Technology, examined the bone mass of 186 adults, of both genders. Peak bone mass is achieved between 20 and 30 years of age and is a good indicator of fracture risk; the sample was therefore made up of adults of 26-28 years of age. Of these 186 individuals, 52 were born prematurely with very low birth weight (1265g) and 59 were born at term, but with low birth weight (2950g). The further 75 – who were born at term with average birth weight (3700g) – formed a control group. The researchers found that both low birth weight groups had a lower peak bone mass than controls. However, once height – a factor which greatly influences bone mass – was adjusted for, this lower bone mass was accounted for in the group born at term; the research showed that low bone mass in this group was partly due to smaller body size. This was not the case in the preterm, very low birth weight group where body size alone could not account for the low bone mass, highlighting this group as particularly high-risk. Differences in physical activity and calcium intake were also adjusted for and differences in bone mass between groups still persisted. Smoking habits did not differ between the groups, and the occurrence of previous fractures was also similar.

Dr Chandima Balasuriya,  who led the study, emphasised that follow-up of these children is important.

“Ensuring children with low birth weight have a diet rich in calcium, vitamin D, and protein, in combination with exercise regimes involving weight-bearing physical activities, will help reduce risk of bone fractures later in life.” The next stage for the research will be to look at what causes babies to be born with low birth weights.

“We want to examine the ultrasounds to determine whether low birth weight babies are genetically programmed to be smaller, or if it might be a result of growth restriction. We are also analysing mothers’ blood to see how vitamin A and D status might relate to their children’s bone health,” said Dr Balasuriya.

New breath tests could be developed to detect low blood glucose levels

A chemical exhaled in the breath could provide a flag to warn of dangerously low blood glucose levels in patients with type 1 diabetes, according to new research from the University of Cambridge, UK.

 The finding, published in the journal Diabetes Care, could explain why some dogs can be trained to spot the warning signs in patients.

Given the reports of dogs alerting owners to blood glucose changes, researchers at the Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, believed that certain naturally occurring chemicals in exhaled breath might change when glucose levels were low. In a preliminary study to test this hypothesis, the scientists gradually lowered blood sugar levels under controlled conditions in eight women, all aged in their 40s, and all with type 1 diabetes. They then used mass spectrometry – which look for chemical signatures – to detect the presence of these chemicals.

The researchers found that levels of the chemical isoprene rose significantly at hypoglycaemia – in some cases almost doubling. They believe that dogs may be sensitive to the presence of isoprene and suggest that it may be possible to develop new detectors that can identify elevated levels of isoprene in patients at risk.

“Isoprene is one of the commonest natural chemicals that we find in human breath, but we know surprisingly little about where it comes from,” says Dr Mark Evans, Honorary Consultant Physician at Addenbrooke’s Hospital, University of Cambridge. “We suspect it’s a by-product of the production of cholesterol, but it isn’t clear why levels of the chemical rise when patients get very low blood sugar.

“Humans aren’t sensitive to the presence of isoprene, but dogs with their incredible sense of smell, find it easy to identify and can be trained to alert their owners about dangerously low blood sugar levels. It provides a ‘scent’ that could help us develop new tests for detecting hypoglycaemia and reducing the risk of potentially life-threatening complications for patients living with diabetes. It’s our vision that a new breath test could at least partly – but ideally completely – replace the current finger-prick test, which is inconvenient and painful for patients and relatively expensive to administer.”

In Ireland, there is also work underway on the theory by Ms Susan O’Neill, who is training dogs to detect low blood glucose levels in people.

Ms O’Neill is looking for volunteers with type 1 diabetes to supply a breath sample to her when their blood glucose levels are low. See www.diabetes.ie for more information.

Hormone treatment in transgender persons could shed light on role of sex hormones in bone density

Male-to-female (MtF) transgender persons have a greater increase in bone mineral density than female-to-male (FtM) persons in their first year of hormone treatment. The research, presented at the 2016 European Congress of Endocrinology in Munich, helps researchers to further understand the roles sex hormones play on bone development and maintenance in both sexes.

As the number of people seeking gender reassignment treatment continues to increase globally, there is an ever-greater need for scientists and clinicians to understand the effects of cross-gender hormonal treatment on the human body, according to the study authors.

Within the first year of gender transition, applicants are treated with sex hormones: MtF persons receive oestrogen, whilst FtM persons receive testosterone.

It is known that oestrogen increases bone density, however, whilst it is known that testosterone increases bone size, its effects on bone density are still unknown.

To further investigate, a research team from VU University Medical Centre in Amsterdam completed an observational study of 188 adults undergoing hormone treatment for gender reassignment. Bone mineral density was measured both before and after one year of hormone treatment; the results showed that MtF persons receiving oestrogen had an average increase in spine bone density of 3.72 per cent, compared to only a one per cent increase in FtM persons receiving testosterone.

These results confirm the understanding that oestrogen increases bone density and suggest that testosterone does not, or does so to a lesser extent.

In FtM transgender persons who were post-menopausal with low pre-treatment oestrogen levels, bone density of the spine was seen to increase by 4.5 per cent following testosterone treatment.

“As this increase was only found in those with low pre-treatment oestrogen levels, it might suggest that in biological adult women (pre-menopause) testosterone primarily affects bone density through its conversion into oestrogen,” said Dr Chantal Wiepjes, lead author of the study.

“Our next steps will be to investigate what the long-term effects of hormone treatment are on bone density. Patients undergoing hormone therapy routinely have bone density scans, which might give them the impression that hormone treatment can have adverse effects on their bones. Therefore, a more solid molecular long-term understanding of the changes may reassure them,” continued Dr Wiepjes.

“I also think transitioning patients should be aware that the changes caused by these hormones aren’t just external – their internal structure changes too.”

As well as improving understanding of treatments within the transgender community, the team hopes to more clearly understand the role of oestrogen in biological males and the role of testosterone in biological females. Whilst it should be noted that the observational study did not compare results to a control group, the team feel that differences seen in post-menopausal FtM persons suggest that it is unlikely the changes in bone density seen were merely due to age or timing.

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