Happy International Women’s Day!

This year, in celebration of International Women’s Day, we reached out to some of the female members who are an integral part of our Society (44% of our membership base!) to find out know what motivates, drives and inspires them, and what their proudest moments are. Notepad in hand, we interrupted their busy schedules to ask them some questions. Here’s what they said:

Dr Anna Crown and Dr Helen Simpson both completed their PhDs whilst starting a family and value the career support they received:

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“I think this is an example of how it is possible to achieve a ‘work life balance’ and a reminder to senior colleagues of how important and influential their backing and encouragement can be”, says Anna.

Helen adds, “I frequently thought I would never finish my PhD. I will be eternally grateful for the support received”. Despite the challenges, Helen’s research achieved a citation for Excellence in Published Clinical Research in the Journal of Clinical Endocrinology & Metabolism.

Louise Hunter agrees that support is one of the essential ingredients for career success:

“My biggest achievement has been securing my MRC Clinical Research Training Fellowship. It made me value the faith others had in me, and taught me the importance of persevering towards a goal!”

Other members value being mentors or good role models. Lisa Shepherd’s proudest moment was becoming SfE Chair of the Nurse Committee, “representing, supporting and educating Endocrine Nurses in the UK. This also led to my becoming one of the founding members of the Federation of International Nurses in Endocrinology.”

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Professor Karen Chapman has several proud moments: “They have all been every time one of my PhD students or RAs have won a prize or recognition for their research. That’s a wonderful feeling.”

Dr Antonia Brooke was proud to be told by one of her male trainees that she was his role model, and likes to think that she leads by example: “I’m training programme director and Clinical Lead whilst running a household and a family (and being the major breadwinner).”

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And acknowledgement never goes amiss – For Professor Maralyn Druce, “my proudest career moment was the first time that anyone sent me a party invitation addressed to ‘Professor Druce’. – That was pretty cool.”

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Anna Crown and Karen Chapman have previously contributed to The Endocrinologist, submitting some of their thoughts about women in science. Anna also shared some tips on how to survive endocrinology as a woman with The Endocrine Post.

Be Bold for Change

This year’s International Women’s Day campaign tag line, ‘Be Bold For Change’ prompts all of us to continue to push the agenda for gender parity. So what are our members doing to ‘be bold’?

Here’s some tips on following their example: 

    • Act as a mentor for men and women
    • Share tips on how to juggle responsibilities to achieve a work-life balance (e.g. challenge out of hours career-related meetings)
    • Promote women’s networking or leadership events
    • Create opportunities for women to discuss the challenges they face in their careers
    • Attend inspirational talks or events by successful women in any career path
    • Raise the issue of equal representation in boards or committees.
    • Recommend or nominate women for committees, talks or chair sessions.

Do you know an amazing endocrinologist you’d like to nominate for a Society Committee? We’d love to hear about them! Find out how to nominate them. 

From small seeds grow mighty oaks: how the Endocrine Nurse community is growing together to share knowledge

Lisa Shepherd, an Endocrinology Advanced Nurse Practitioner at Heart of England NHS Foundation Trust and Chair of the Society for Endocrinology Nurse Committee, discusses continuing education opportunities and the value of networking for endocrine nurses.

Endocrinology is a fascinating but complex area and nurses often work in isolation, so opportunities to develop and update their knowledge, benchmark their practice and network with other nurses are invaluable. The Society for Endocrinology Nurse Committee supports a number of strategies that promote networking amongst the Endocrine Nurse community.

Social media is increasingly used to build professional networks, so the Nurse Committee have set up an invite-only group on Facebook for endocrine nurses, which is a fast and easy way for the community to share protocols and information. Nurse Members of the Society also have a Twitter feed where training opportunities, research and nursing practice can be promoted to the wider community.

Face-to-face networking remains an effective means of sharing experience and learning from others, so a ‘nurses lounge’ was recently introduced at the SfE BES conference, to give nurses a dedicated space to meet each other in person. As many nurses are working in isolation it is valuable to provide a variety of opportunities, across different media that encourages endocrine nurses to support and learn from each other.

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Endocrine Nurse Update (ENU) is coming up soon. This yearly update is designed by nurses for nurses and offers a varied and active programme of endocrinology topics. I am very excited that this year’s ENU will feature the inaugural Endocrine Nurse Award lecture by winner, Nikki Kieffer. This award was introduced to recognise excellent nursing practice that can be shared to advance knowledge and understanding in the discipline. Nikki is an endocrine nurse specialist at Leicester Royal Infirmary and led the project that developed the Competency Framework for Adult Endocrine Nursing. This project is a great example of nurses working together to share best practice and Nikki will deliver the prize lecture at ENU 2017 in March.

There are also great benefits to networking with other closely related communities and this year, for the first time, ENU will include a workshop run collaboratively between clinician and nurse colleagues, Dr Richard Quinton, Dr Channa Jayasena and Dr Andrew Dwyer. Whether you are a nurse new to endocrinology or a nurse with many years of experience, the ENU programme, in combination with Clinical Update has something to offer all. I hope you can join us at the meeting or follow us online, to learn from your colleagues and share your experience.

Nominations for the 2018 Endocrine Nurse Award are open until 16 June 2017, find out more.

Travel grants are available for ENU 2017, apply before 15 March.

View the ENU 2017 programme.

 

12 endocrine news stories that you may have missed in 2016 – Part 3

In the final blog post in our series looking back over the endocrinology news you may have missed in 2016, we explore news on the effects of the contraceptive pill, drug pricing and more.

Find Part 1 and Part 2 here.

September: Contraceptive pill explains falls in ovarian cancer

It’s generally agreed that the pill offers protection against ovarian cancer. In September we got a better idea of just how strong this effect is, as a study published in Annals of Oncology looked back at the potential cases prevented since the pill was introduced in the 1960s. Between 2002 and 2012, the rate of ovarian cancer fell dramatically in the EU, US and Oceania, with deaths falling 10% in 28 EU countries.

The declines were particularly marked in countries such as the UK (22%), Denmark (24%) and the USA (18%), where the pill was more widely used after its introduction in the early 60’s.

“There are noticeable differences between countries such as Britain, Sweden and Denmark, where more women started to take oral contraceptives earlier – from the 1960s onwards – and countries in Eastern Europe, but also in some other Western and Southern European countries such as Spain, Italy and Greece, where oral contraceptive use started much later and was less widespread,” said lead researcher Professor La Vecchia.

The effects were also more pronounced in younger and middle aged women compared to older women. “This is possibly due to the fact that women who are middle-aged or elderly now were less likely to use oral contraceptives when they were young,” he added.

 Media headlines causing a buzz:

Making babies without eggs may be possible, say scientists (BBC)

Testosterone could treat prostate cancer (The Times)

Common contraceptive hormone could protect women from flu (The Telegraph)

First ‘three person baby’ born using new method (BBC)

 

October: The pill and depression

October was a busy month for reproductive endocrinology. Scientists found evidence that ovaries can grow new eggs and we came a step closer to a male contraceptive injection. However, the story causing the biggest stir was an association between use of hormonal contraceptives and depression. Published in JAMA Psychiatry, the study showed that women who used hormonal contraception were more likely to be prescribed an antidepressant, and to be diagnosed with depression.

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In a statement widely covered by the media, Society member Dr Channa Jayasena said: “This study raises important questions about the pill. In over a million Danish women, depression was associated with contraceptive pill use. The study does not prove (and does not claim) that the pill plays any role in the development of depression. However, we know hormones play a hugely important role in regulating human behaviour.”

“Given the enormous size of this study, further work is needed to see if these results can be repeated in other populations, and to determine possible biological mechanisms which might underlie any possible link between the pill and depression. Until then, women should not be deterred from taking the pill,” he added.

 

Media headlines causing a buzz:

Evidence suggests women’s ovaries can grow new eggs (The Guardian)

Male contraceptive jab ‘effective’, but side effects are common (NHS Choices, Bazian)

Zika virus could cause infertility in men, new study suggests (The Telegraph)

Prostate cancer sufferers who have hormone treatment ‘double’ their risk of dementia ( Daily Mirror)

Researchers discover the role of hormone in ‘creating fat’ (NHS Choices)

Boys conceived through IVF technique have lower than average fertility (The Guardian)

 

November: Yoyo dieting might not be your fault

While you were at the Society’s 70th annual conference in Brighton, you may have missed a study in Nature that provides some understanding into why people often regain weight after weight loss, and why yo-yo dieting is so ineffective. It appears that stubborn gut bacteria may retain a “memory” of obesity.

Scientists created a yo-yo dieting mouse model, which was cycled from high fat chow to low fat chow continuously, leading to cycles of weight gain and weight loss in the mice.

“As observed in recurrently dieting humans, a preceding obesity-weight loss cycle rendered mice susceptible to accelerated secondary weight gain, even after fully returning to baseline weight,”

The mice which had been on the “yo-yo” diet gained even more weight than mice which had eaten the high fat food the entire time. When the altered “yo-yo” gut microbiome was transferred into healthy mice on a normal diet the mice showed accelerated weight gain, which suggests the altered gut microbiome is causing the accelerated weight gain. So unfortunately, even if you lose weight, your guy microbiome might make it more difficult to keep the weight off – but it is possible! The researchers said that eventually, the microbiome goes back to normal, but this could take months, even years in humans.

 

Media headlines causing a buzz:

Infections not antibiotics may be tied to childhood obesity (New York Times)

Zika virus — concerns for male fertility (Nature)

Discovery of alcohol-regulating hormone could lead to pill which prevents cravings (The Telegraph)

 

December: Hydrocortisone price hike

This new story really got endocrinologists talking. Actavis, producer of hydrocortisone tablets, has been accused of overcharging the NHS after hiking prices from 70p per pack to £88. The accusation comes one week after Pfizer was given an £84.2m fine for similar price hikes for an epilepsy drug.

In 2008 Actavis gained the right to make generic hydrocortisone tablets which are not subject to price regulation.

“We allege that the company has taken advantage of this situation and the removal of the drug from price regulation, leaving the NHS – and ultimately the taxpayer – footing the bill for the substantial price rises,” said the Competition and Markets Authority senior responsible officer Andrew Groves.

Hydrocortisone is a life-saving drug for patients with Addison’s disease, where the body does not produce enough steroid hormone.

Normally only patent drugs are subject to price regulation. When patents expire, and other companies can create generic versions, the competition between competitors keeps prices low. In this case, lack of competitors meant prices could be elevated.

“This is a lifesaving drug relied on by thousands of patients, which the NHS has no choice but to continue purchasing,” said Andrew Groves.

 

Media headlines causing a buzz:

Pregnancy alters woman’s brain ‘for at least two years’ (BBC)

Some baby teething toys may contain hormone-disrupting chemicals (Washington Post)

Prostate cancer sufferer ‘cured’ by blasting tumours with testosterone (The Independent)

Exercise boosts men’s sperm count (BBC)

Babies made from three people approved in UK (BBC)

Autism linked to vitamin D deficiency during pregnancy, researchers find (The Guardian)

Man, I feel like a woman

The Journal of Molecular Endocrinology is the only Society-owned basic science journal dedicated to looking at hormones at the cellular and molecular level. In a series of blog posts, we look back at some of the most cutting-edge research published by our members in our journals. This first piece was written by Douglas Gibson (@douglasagibson), a postdoctoral research at University of Edinburgh.

Remember that members can now publish in JOE, JME and ERC free of charge!

We often think of hormones as ‘male’ or ‘female’ because of how they shape the features we associate with each sex. So androgens – the ‘male’ hormones – might make you think of ‘manly’ things like body hair, muscles and deep voices, but what if I told you that they play an important role in women becoming pregnant too?

It’s difficult to separate androgens from their macho reputation, particularly when examples of androgen excess in women, such as in athletic doping, also produce masculinizing effects. Despite this, androgens have long been known to be important in controlling many processes in female physiology. Indeed, androgens can be detected at significant concentrations in the blood of women and in some cases may even exceed those of men! However, although androgens are abundant in the blood they are usually only activated in specific tissues when they are needed. In this clever way they don’t have widespread and uncontrolled effects.

One surprising place where androgens were recently found to be activated is inside the womb. Every month, the structure of the womb lining – known as the endometrium – is reorganised to create an environment that can support and sustain pregnancy. However, without the right hormonal signals, the endometrium will not provide the conditions required for a fertilised egg to implant.

Recent studies have found that hormones produced inside the womb play a pivotal role in the early stages of pregnancy. It was previously thought this vital role was carried out solely by hormone signals from the ovary but new research has found that ‘male’ hormones (androgens) help to prepare the womb lining to encourage a successful pregnancy.

In our study, we wanted to understand how the signals inside the womb lining affected the early stages of pregnancy. In fact, we found that androgens can act in two key ways; by acting as a direct signal in the womb but also by being converted into ‘female’ hormones (estrogens) in the early stages of pregnancy. We found that estrogens within the womb signal to cells that control blood vessel development which is essential for promoting exchange of nutrients between mother and baby.

So amazingly, androgens seem to provide a delicate balance to control key changes in the womb in pregnancy. However as fewer of these key hormones are produced as women age, this could partly explain why some older women find it difficult to conceive. Our research is now focussing on how changes in the availability of androgens can affect the way the womb lining prepares for pregnancy. We hope to be able to apply this new understanding to improve fertility treatments which in the future may mean that older women seeking motherhood may have a better chance of successfully conceiving.

Life as a young lab head

Earlier this year, the Endocrine Society and the Endocrine Society of Australia published a paper titled ‘Career advancement: Meeting the challenges confronting the next generation of endocrinologists and endocrine scientists‘. Endocrinologists are facing challenges in reduced funding, competing responsibilities and gender issues. Giving us the personal side of the story, Australian prostate cancer researcher Luke Selth tells us about the ups and downs of life as a young lab head…


“As I sit down to write this, there is a foul odour permeating my cancer research lab. I know what you’re thinking: one of the PhD students has left a Bunsen burner on and I’m on butane high. I wish it was so simple.

No, the stench is a heady mixture of stress and worry. I am expecting the outcomes of two National Health and Medical Research Council (NHMRC) Project Grant applications this week. We also have two research papers currently under review at a prominent journal in the field of cancer biology (seriously, how can it take 62 days to review a paper?).

It feels as though the next week could literally make or break my career. Is this an exaggeration? Well, no, actually. Let me break it down for you…

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The grant applications

My lab’s research is focused on identifying the molecular mechanisms underlying prostate cancer progression, and developing new therapeutic strategies for this important disease. Both of my Project Grant applications are in this field and, realistically, there’s every chance neither will be funded.

I’d like to stress that this isn’t because they are bad applications. ‘You’re biased’, I hear you muttering, and I can’t argue with that – of course everyone thinks their own research is the most novel and exciting. However, I have evidence to back this notion up: both have made it through the dreaded ‘Not for further consideration’ cut, which means they were ranked in the top 50% of applications.

So we are through the first hurdle. However, given that last year’s success rate was 13.7%, this means that both grants still only have around a 1 in 4 chance of being funded. Of course, that’s if the success rate doesn’t decrease even further this year – there’s every indication that it will. When I started writing NHRMC grant applications 5 years ago, 22.9% of applications were being funded. This worrying trend, largely due to the lack of real increase in the overall NHMRC budget, has caused a lot of scientists to change professions or leave the country – a “brain drain” that will be difficult to recover from.

The low success rate means the outcomes often feel like a bit of a lottery. All of the applications still in the hunt are strong; it’s extremely difficult for a review panel to choose the best. In a perfect world (or, more accurately, a perfect Australian economy), most of them would be funded. But this isn’t a perfect world, and so some randomness ensues. This process of assessing applications in this type of funding scheme has been studied: Fang and colleagues provided evidence that the peer review process used by the National Institute of Health (USA) does not necessarily fund the best science – and that using a lottery-style system to awards grants would actually yield equivalent, if not better, research outcomes.

In short, a bit of bad luck could see both of my applications – which collectively took around 2 months of full-time work to prepare – down the drain.

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The papers

The old mantra of “publish or perish” is stronger than ever in Australian science. Consistently publishing in high quality journals is required for grant success, which in turn is required to keep consistently publishing in high quality journals; it’s a feedback loop that sadly consumes much of my attention.

The two papers that are currently under review are both strong bodies of work. But, again, there’s every chance they will be rejected – the current acceptance rate at the journal I have submitted to is around 20-25%.

The possible outcomes

OK, so what happens if my grant applications and research papers are both tossed out like old agar plates? Well, I will have just enough funding to keep my small research group going next year, but virtually nothing for the following year (not even my salary). The stench of worry in my lab will become even more pungent. I’m a passionate guy, and in such a situation I’d like to allow myself the release of smashing a glass beaker or two – but I couldn’t afford the cost of replacements…

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Alternatively, there is the possibility that I win the lottery. Sure, there’s been a lot of work done by my group, but in the end I truly believe there is a significant amount of luck involved. If the papers are accepted and grants are funded, suddenly the lab’s future and finances will look flush again. There will be no need to let anyone go, and I can cancel that online barista course I signed up for!

This roller-coaster we call a science career

Of course I’ve simplified things. There is a whole spectrum of possibilities between total failure and total success. But what I’m hoping to convey is the reality of life for a young lab head trying to make his or her way in the world of biomedical research. This job is a bloody roller-coaster, and it seems perverse that I spend up to half of my time applying for money so that I can simply do my job.

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I’m often asked by my close friends and family why I stick with it. One response is that I’m not sure any café would want a washed-up scientist as their barista! Seriously though, I love my job for many reasons, the most important being that I have a scientific curiosity that can probably only be sated by this type of research and a vision to improve outcomes for cancer patients. Fortunately, the satisfaction of discovery, coupled with a real chance to improve the health of our society, far outweigh my grant- and paper-related pessimism.

So, even if the grants and papers don’t come through this week, I’m going to persist – and I have many inspirational colleagues and mentors who do the same, year in and year out.

References:

  1. Fang FC, Bowen A, & Casadevall A (2016) NIH peer review percentile scores are poorly predictive of grant productivity. Elife 5.

Meet your new Society President

 Meet your new President…

 A new era begins for the Society as Professor Graham Williams takes over as President at SfE BES 2016. Associate Editor of The Endocrinologist, Amir Sam, finds out more about Graham’s background, reflections and aspirations for the Society for Endocrinology. The full interview will be published in the winter issue of The Endocrinologist.

Tell us about your background

I worked as an SHO in Kidderminster and did my general medicine rotation at the Queen Elizabeth and Birmingham General Teaching Hospitals. I then got an MRC Training Fellowship with Michael Sheppard and Jayne Franklyn in Birmingham to work on thyroid hormones.  I did a year of my PhD there and then completed it at Harvard Medical School with Reed Larsen and Greg Brent at the Brigham and Women’s Hospital in Boston, where I also did some of my post-doctoral training.

I came back with an MRC Clinician Scientist Fellowship and started as a Lecturer in Birmingham with a completely empty lab and had to start from nothing!  About six months before I left Boston, I had a meeting with Reed, who was very happy to support me but said that I shouldn’t work on the same subject that he was working on because it was too small a field and it was important I develop my own independence.  He urged me to read the literature and find a new area to pursue.

I had been working on the biochemistry of transcriptional activation by thyroid hormone and retinoid X receptors and wanted to apply the basic science to clinically and physiologically important questions.  I decided to find a relevant thyroid hormone responsive target tissue that wasn’t being studied; most people were working on pituitary, heart and liver and other labs were getting into the brain. I spent a lot of time talking to various people and eventually settled on the skeleton, a clearly important target organ that had not been investigated in the context of thyroid hormones in any detail.  Having not known anything about bone, I had a blank canvas and started from scratch!  In 1995 I was approached by Raj Thakker and James Scott to move to Hammersmith as a senior lecturer.

When did you know you wanted to be an endocrinologist?

When I qualified from medical school I was all set to do surgery, but realised pretty quickly that I did not have the dexterity to be any good.  My first house job was in endocrinology at the Queen Elizabeth Hospital in Birmingham with David London. At the time there were some really fascinating cases, and working with him got me enthused and hooked on endocrinology straight away. He was definitely the biggest influence on my career selection.

By the time you finish your term of office as President, you will have held major roles at the Society for Endocrinology for over a decade.  How has the Society changed over the time?

The financial aspect of the Society has substantially increased over time. When I took over the treasurer’s role the gift aid to the Society from Bioscientifica was around £100,000 per year, and when I ended my term as treasurer it had grown to about £1 million per annum. The Society has grown incredibly in terms of its diversity; it is reaching out further to different countries and continents in a way that was never possible and is now a very professional and superbly run organisation.

How do you see the Society developing over the next few years?

We have a much greater role in education and the development of opportunities for young endocrinologists. I don’t think my plans for the future will be to fix anything in particular because I think the Society is functioning extremely well. We need to develop it further along these roles for the benefit of the next generation. We have to support our younger scientists and clinicians, retain them and hopefully attract more people to the discipline with the ultimate aim of benefiting our patients and endocrine science. We also need to strengthen our international collaborations, both scientifically and clinically.

Post-Radioiodine Graves’ Management: The PRAGMA Study

Petros Perros is a Consultant Endocrinologist at Newcastle Hospitals, and Honorary Senior Lecturer at Newcastle University. He is the Project Lead for the PRAGMA Study, a Society for Endocrinology research project which compares the incidence of dysthyroidism in post-radioiodine patients treated with difference management strategies.

Petros will be presenting the PRAGMA study’s latest findings next week in Brighton, which is hosting this year’s SfE BES conference. Ahead of the event, we asked him to write about the project and why it’s such an important Society project.

For more information, be sure to check out Petros’ talk at 16.45 on Tuesday 8 November in Syndicate One. Our Scientific Programme has more details.

Project Background

Grave’s Disease, an autoimmune condition, is the most common cause of hyperthyroidism. Radioiodine (RI) is an effective, safe and cheap treatment for hyperthyroidism, though it results in most patients with RI-treated Graves’ disease requiring life-long thyroid hormone replacement.

Ideally the transition from hyperthyroidism to a stable thyroid status (through thyroid hormone replacement) should be rapid and smooth. However, in practice fluctuations in thyroid status in the first year after RI are not uncommon.

In an attempt to achieve and maintain euthyroidism (in which the thyroid gland is functioning normally) after RI, endocrinologists employ different strategies. These will eventually include the introduction of levothyroxine, a synthetic thyroid hormone chemically identical to thyroxine. The two most typical treatment strategies are:

  • The use of anti-thyroid drugs for a period of time after RI. These are used either alone or in combination with levothyroxine – with levothyroxine is known as the “block and replace” strategy
  • Watchful monitoring and introduction of levothyroxine when required

This variation in management in response to fluctuations in thyroid status following RI was the inspiration for the PRAGMA Study. We set out to determine the extent of thyroid instability after RI, and to explore whether different strategies of management are associated with different degrees of thyroid instability.

The study was funded by the Clinical Endocrinology Trust and was included in the NIHR portfolio.

What has been achieved so far?

Thirty-four hospitals in the UK have recruited 812 patients over 2 years. One of the most striking findings was that a very large proportion of patients – 67.2% – had at least one episode of hypothyroidism within the first year after RI, and 36% had an episode of hyperthyroidism. Patients treated with the “block and replace” regimen after RI were least likely to experience hypothyroidism and gain weight, though hypothyroidism was still experienced in 26% of cases.

What next?

We continue to collect data in the management of this condition. Additional interventions need to be identified and implemented to improve outcomes for patients with Graves’ disease treated with RI, and this study provides us with great possibility.

The level of engagement of colleagues with the PRAGMA Study proves that large scale studies addressing common, simple, clinically relevant questions can be conducted with ease and minimal cost. It is a great asset to the field of clinical endocrinology research.

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Should prednisolone be the first line for glucocorticoid replacement in adrenal insufficiency?

At 18.30 on Monday 7 November Professor Jeremy Tomlinson is chairing a debate on the treatment of adrenal insufficiency at SfE BES 2016. Ahead of the debate, we asked Professors Stafford Lightman and Karim Meeran to give you a little taste of their stance on this hot topic in endocrinology.

 

Professor Jeremy Tomlinson, University of Oxford – Chair

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The optimal strategy for glucocorticoid replacement in patients with adrenal insufficiency remains a contentious issue. In the majority of cases, hydrocortisone is used, but there are issues relating to the need for three times a day administration alongside the high costs of treatment. Are there alternatives?

Prednisolone is significantly cheaper, has a longer duration of action and therefore can be administered twice daily. However, it is a synthetic glucocorticoid that does not act in an identical way to hydrocortisone.

Head-to-head comparisons with meaningful clinical end points are lacking, and in the modern NHS, treatment costs play an increasingly important role.

Let the debate begin!

 

Professor Stafford Lightman, University of Bristol – AGAINST

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The evolution of Homo sapiens from early mammals has taken about 200,000,000 years. During this time we have developed many highly specialised physiological systems –including the key homeostatic system we call the Hypothalamo-Pituitary-Adrenal axis. This system maintains key cognitive, metabolic and immunological systems in optimal state and is also a rapid response system to protect us against stress. The hormone that has evolved to do this is cortisol.

In the absence of endogenous cortisol no-one would disagree that the gold standard therapeutic hormone replacement should be the closest we can get to normal physiology, so if we have to go second-best and provide a different steroid or pattern of plasma steroids it is incumbent on us to prove that this alternative treatment is as good as the best possible therapy available with the native compound.

Prednisolone differs from cortisol in many ways. Not only does it have different characteristics of glucocorticoid mediated gene transcription with no simple dose response comparison to cortisol, but its plasma half-life and metabolism are also unphysiological.

During the debate, I shall demonstrate why these aspects of prednisolone replacement are potentially disadvantageous at cognitive, metabolic and immunological levels. I will explain why I feel it would be dangerous to submit patients to such long duration therapy unless appropriate long term studies are able to show non-inferiority of this regime.

 

Professor Karim Meeran, Imperial College London – For

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Patients with endocrine deficiency need replacement therapy.

We are getting better at making new analogues of replacement hormones that are more patient friendly and improve compliance by lasting longer. Thus for insulin, we have moved away from normal human insulin to analogues of insulin that have variable half-lives, but are a totally different molecule. There is no evidence that the new analogues are any better than native insulin, but production of some preparations of native human insulins have ceased and many of us use these new insulin analogues. Vasopressin is replaced with a modified molecule, 1-desamino-8-D-arginine vasopressin; the D-enantiomer is used (which never occurs in nature) because it lasts longer. The argument in some quarters that “natural” cortisol would be better thus has no basis.

Similarly, rather than give hydrocortisone several times a day, we need to modify the molecule slightly by inserting a double bond, which increases its half-life and potency, and enables once daily administration. A slow release preparation has been developed and costs £400 per month, but it is far better to use a drug that has an appropriate half-life.

We don’t need to develop one because, remarkably, prednisolone has a half-life that is perfect for a once-daily administration. It happens to be extremely cheap, but that should not deter us from using it!

We now have an assay available for prednisolone, and present data at a number of posters at the BES in November confirming that a once-daily dose of prednisolone 3mg is equivalent to hydrocortisone 10mg plus 5mg plus 5mg. I have converted several patients, who regularly report how well they feel on prednisolone 3mg, and how much easier it is to take.

The main reason that patients should take once-daily prednisolone is its convenience. Added benefits for those in the UK are the low price of prednisolone compared to hydrocortisone, which is substantially more expensive in the UK than in other countries because of a peculiar licensing issue, and the fact that the NHS is not allowed to import it.

We have a serious problem in the UK with the cost of hydrocortisone, and every patient who is switched to prednisolone will save over £100 per month.