16 May 2023
AMEND at World MEN 2023
WORLD MEN 2023 MEETING, MARSEILLE (27-29 APRIL)
By AMEND CEO, Jo Grey
The very early start (4am) and flight (7am) meant that my first day at World MEN 2023 was a bit of a struggle, but it certainly helped that the sun was shining warmly in Marseille, as did the many familiar and friendly faces there from around the world. The focus for the meeting was ‘unmet needs’, and many of these are long-standing! However, rest assured that progress is being made. I was honoured to be invited to speak about unmet needs from the patients’ perspective (more on this below), but first, a summary of some of the interesting snippets gleaned from this fantastic meeting.
Phaeo/Para (PPGL): in this session, Prof. Anne-Paule Gimenez-Roqueplo from Paris introduced us to two new genetic mutations that cause paraganglioma syndromes; DNMT3A, which can predispose those affected to Head & Neck paragangliomas, and DLST, which can predispose those affected to multiple paragangliomas in the abdomen and chest areas. She concluded that gene testing of both blood (germline) and tumour cells (somatic) will eventually allow for the use of therapies tailored to the individual, but that many more trials are needed before we reach this point.
[Gimenez-Roqueplo, A., Robledo, M., & Dahia, P. L. M. (2023). Update on the genetics of paragangliomas, Endocrine-Related Cancer, 30(4), e220373. Retrieved May 2, 2023, from https://doi.org/10.1530/ERC-22-0373]
Prof Hervé Lefebvre from Rouen in France presented an interesting piece of research that has shown that the pregnancy hormone human chorionic gonadotropin (hCG), is responsible for stimulating present but ‘silent’ phaeochromotycomas to over-produce epinephrine (adrenaline). Together with colleagues, he tested this theory on phaeo cells to conclude that hCG secreted during pregnancy may therefore be responsible for the surges of catecholamines and hypertensive crises that can occur. He also explained that the anti-sickness medicine, metoclopramide, which is sometimes prescribed for morning sickness, can also stimulate catecholamine production in pregnant women with phaeochromocytomas. This emphasises the potential dangers of pregnancy in a woman with an undiagnosed phaeo and why patients with gene mutations that can cause phaeochromocytomas (MEN2, MEN3, PPGL) should consult with their endocrinologist, preferably before becoming pregnant.
[Expression of LHCGR in Pheochromocytomas Unveils an Endocrine Mechanism Connecting Pregnancy and Epinephrine Overproduction, Antoine-Guy Lopez et al, Originally published 22 Feb 2022, https://doi.org/10.1161/HYPERTENSIONAHA.121.18864, Hypertension. 2022;79:1006–1016]
Medullary Thyroid Cancer: the team from MD Anderson in Houston, Texas, were involved in this session. Surgeon, Prof. Steven Waguespack called for a change in language from ‘prophylactic thyroidectomy’ to ‘early thyroidectomy’ since, and especially when children with MEN2 and MEN3 have a delayed diagnosis, ‘prophylactic’ surgery (to avoid a future problem), is rarely achieved. He also queried the current recommendations for age of surgery in some children, suggesting that it may be possible to wait until calcitonin rises to a specific level before embarking on an operation. Given the number of members we have where the mutation is thought not to be aggressive, and yet the course differs from that expected, this felt like an unnecessary risk to me. Other speakers from the conference also showed how resilient children can be about testing and treatments when prepared properly. We also heard how, in sporadic MTC, resistance to TKI therapies is caused by tumours developing new mutations, thus highlighting the value of somatic tumour mutation testing. New therapies are in the pipeline that hope to get around these mutations.
Parathyroid Adenomas: Dr Omair Shariq, a surgeon from the USA, emphasised the challenge of trying to predict how an MEN1 mutation would affect a patient (genotype-phenotype correlation). Parathyroid hyperplasia (PHPT) is the most common problem to occur in MEN1 (70% by age 18). On the balance of risk vs benefit, the operation of choice in MEN1 is subtotal parathyroidectomy (SPTX) when 3 ½ parathyroid glands are removed, leaving a remnant behind. This approach is done to avoid both long periods of high calcium levels (hyperparathyroidism) and low calcium (hypoparathyroidism). In addition, Dr Shariq’s study found three new MEN1 gene mutations. MEN1 patients from 5 international centres were included in this study which is a great example of international collaborative research.
[Shariq OA, Lines KE, English KA, Jafar-Mohammadi B, Prentice P, Casey R, Challis BG, Selberherr A, Boon H, Cranston T, Ryan FJ, Mihai R, Healy U, Kurzawinski T, Dattani MT, Bancos I, Dy BM, Lyden ML, Young WF Jr, McKenzie TJ, Richards D, Thakker RV. Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomes. Surgery. 2022 Jan;171(1):77-87. doi: 10.1016/j.surg.2021.04.041. Epub 2021 Jun 26. Erratum in: Surgery. 2022 Jun;171(6):1708-1711. PMID: 34183184.]
Pancreatic Neuroendocrine Tumours: a presentation looked at treatments for PNETs that have spread to the liver (metastasised). Radiological treatment, SIRT, is the most promising, but the dose must be individualised (See AMEND patient information booklet on MEN1). SIRT is less toxic than other therapies and can even be given in an outpatient setting. It has been found to be okay for patients to receive SIRT after they have tried PRRT but have had disease progression. Unmet needs in this area include the inclusion of MEN1 PNETs in research and clinical trials (there is shockingly little), and more individualised treatments. For the future, prospects include other treatments, and also combination therapies (e.g. PRRT plus SIRT). SIRT is not routinely available in the UK for pNETs on the NHS but can be “self-funded” in some centres, meaning that patients can pay for the treatment.
Patient Perspectives: I was delighted to be in a session with Dr Ana Hoff from Sao Paolo from Brazil who has an interest in Quality of Life in MEN2, along with our host, Professor Frederic Castinetti from Marseille who also has an interest in this topic and presented on the impact of Cushing’s Disease. My own talk echoed much of Dr Hoff’s own research, although I used data from AMEND’s Member Survey (2022), our Counselling Service data (2021) and results from the Perception of Quality of Care Survey results by the European MEN Alliance, to highlight the difficulties in diagnosis for our rare diseases, as well as the necessity for psychological support to be embedded in the patient pathway from diagnosis onwards. The session was well-received and is always a good reminder to the audience of the ‘end user’ of their research.
[Correa FA, Farias EC, Castroneves LA, Lourenço DM Jr, Hoff AO. Quality of Life and Coping in Multiple Endocrine Neoplasia Type 2. J Endocr Soc. 2019 Apr 15;3(6):1167-1174. doi: 10.1210/js.2018-00371. PMID: 31139763; PMCID: PMC6532676.]
New MEN1 Guidelines: The new Guidelines for MEN1 are due to be published in early 2024. We were given a status update by the team from Utrecht in The Netherlands who are part of the Core development group. The Guidelines will include recommendations for the treatment and management in MEN1 of non-functioning pancreatic neuroendocrine neoplasms (NFpanNEN), primary hyperparathyroidism (PHPT), and the pituitary neuroendocrine neoplasm (PitNEN), prolactinoma.
Here is their problem: to review and update the Guidelines, good quality research studies are required, and to date, there are almost none (e.g. they found only 2 useful studies about panNENs in MEN1!). Therefore, a different approach is being taken, which is to survey the view of an Experts Panel (the Delphi Method) in several rounds. To make a recommendation, it must be agreed by a large majority of those surveyed. I think the lack of good quality studies came as a surprise to many, and I believe that this has once again highlighted the need for experts to work together internationally to ensure that this is not the case the next time that the Guidelines need updating. The final draft should be available towards the end of 2023, at which point we hope to be invited to review and comment on them.
So, in conclusion, there was a great energy to this meeting, not least because it was finally being held in person, but also because of the dedicated clinicians and researchers who attended. New connections have been made, and the ‘to-do’ list has grown slightly. Excitingly though, there finally appears to be a real desire for international, collaborative research, and this can only change the trajectory of future care and treatments in our rare diseases for the better.