IOPTH monitoring in the 21st century; A validation study in progress!

Dear Ultrafast Hormones Followers

 

A few months ago I posted a message about a new instrument able to measure parathormone (PTH) concentration during parathyroid surgery in 5 minutes using whole blood rather than plasma samples. The machine is small, fast, precise and most importantly simple to operate, which opens the possibility of PTH measurements being performed by medical staff already present in operating theatres. Current methods of intraoperative PTH monitoring (IOPTH) require the involvement of biochemists performing measurements either in the main laboratory or in theatres. The new NBCL platform offers an opportunity to change this paradigm. Simplifying the logistics of IOPTH should encourage more surgeons to use this technique routinely to the benefit of their patients.

Two of the NBCL instruments are now installed in London and are undergoing thorough laboratory and clinical validation at the University College Hospital and London Clinic. The initial results of the precision and accuracy studies are very encouraging and further assessments of linearity, limits of detection and quantitation are ongoing. Eight members of our team at University College Hospital and London Clinic including biochemists, nurses, surgeons and anaesthetists are now trained and certified to use it. We have already performed parathyroidectomies using the NBCL system in parallel with our “gold standard” methods (Future Diagnostics and main Roche platforms). A correlation graph of our first patient is shown below. As you can see, although absolute concentrations of PTH are slightly different on each of the platforms (as expected), there is a good correlation between changes in PTH concentration and a 50% reduction in circulating PTH, main (Miami) criteria confirming biochemical cure, were similar for all 3 platforms.

 

A big thanks to the laboratory and clinical teams at both hospitals, especially to Christina Soromani and Sujiwa Morley, for performing the validation study. We hope to present a full report of our work at the next annual conference of the British Association of Endocrine and Thyroid Surgeons (BAETS) in Leeds in October.

 

Watch this space and please contact us if you require more information

Patients with parathyroid conditions during COVID pandemic – Parathyroid UK survey.

Coronavirus affected everybody in the world, but it has been a particularly difficult time for patients with pre-existing medical problems. Liz Glenister, CEO of Parathyroid UK, should be congratulated for conducting an online survey about the experiences of patients with parathyroid conditions during the Covid pandemic.

A survey was run during the first 2 weeks in November 2020, and 570 patients from the UK (81% from England)  replied to it. This very large number of participants reflects not only the fact that parathyroid conditions are common but also highlights the strength of “Parathyroid UK” and the active participation of patients in the works of their advocacy group.

Two-thirds of responders had hypoparathyroidism, mostly postsurgical, and were younger, while those with hyperparathyroidism were often over the age of 50. The survey revealed several important aspects of how the coronavirus pandemic has affected these patients.

Firstly, there was significant anxiety about whether they should be classified as Extremely Clinically Vulnerable (ECV). Only 11% of responders were classified as such by their doctors, but 45% felt that they should be included in this group. The worry about contracting coronavirus was so significant that 35% of patients choose to shield independently. The inconsistency of UK Government rules which changed the classification of vulnerability, did not help and caused confusion and frustration. About ¼ of respondents felt they had Covid, mostly mild or moderate, but about 4% had severe symptoms requiring admission to hospital or ITU. The hospital stay varied from overnight to up to three weeks.

There were also serious concerns about Long Covid and potential confusion between post-viral long-term symptoms and problems relating to parathyroid conditions.

Secondly, the majority of patients (85%) were very worried about becoming ill due to their parathyroid condition and needing hospital treatment during the pandemic. 63% felt that the stress of Covid had adversely affected their health. Interestingly, most responders did not feel that they are more more likely to get infected but that if they get infected, fighting the Covid would be more difficult because of their parathyroid problems. 27% experienced difficulty with work, especially stress, anxiety and fatigue, particularly in jobs requiring direct interaction with the general public. Depressingly, there were complaints about unsupportive bosses and colleagues “who did not believe in Covid”.

Thirdly, access to medical advice was maintained despite pandemic, and 36% of patients called the NHS helpline, 49% spoke to their GP and 23% to their consultant. Consultations were mostly on the telephone or internet, but some  (14%) face to face consultations took place as well. 22% had their consultations cancelled.

Most patients (71%) were able to get a blood Calcium test done. About half of the tests were done in their GP practice.

Sadly, only 1/3 of patients with hyperparathyroidism who had their surgery scheduled during the pandemic had an operation. Operations were postponed or delayed, and many are still waiting for the date. The backlog of cancelled operations in the UK will be a huge challenge this year.

Despite limitations relating to possible misunderstanding or lack of answers to some questions and the fact that the survey was anonymous, therefore it was not possible to tell if anyone had answered more than once, it represents unique experiences of patients with parathyroid conditions during Covid.

Evidence highlighted by the survey should help medical professionals to understand better the difficulties experienced by these patients and have a positive impact on their education and treatment.

 

New Era in IOPTH monitoring has arrived

Dear All

After years of international research instrument which can measure PTH in under 5 minutes has finally arrived. 

And I have got two!
It works with whole blood and is incredibly simple to use. Anybody in the operating theatre can do it, nurse, surgeon or even the anaesthetist!FI have spent the last 7 years trying to build such a device using the lateral flow platform. Quite a few teams around the world have tried as well. With the help of many friends and collaborators, I have achieved some interesting and encouraging results but never had enough financial resources and engineering expertise to build a commercially viable system. However, I have learned a lot in the process and became “an expert”.

All credit for this new instrument goes to engineers and entrepreneurs from NBCL  (nbcl.nl) who were successful in financing and developing an amazing technology that fulfils all the modern requirements for parathyroid surgery. The instrument is small, fast, reliable, and simple to operate. For now, in my opinion, the race to build the best instrument for Intraoperative PTH monitoring is over, and I am glad I have been beaten by such a formidable side. In the future, I am certain there will be more exciting developments in this field.

For the last year, I have been collaborating with NBCL, and I have just received 2 new instruments which we are going to validate and train our team to use. This is going to happen next week.  I will be publishing our results and share them on social media with others, so follow Ultrafasthormones (ultrafasthormones.co.uk) news  on Linkedin and Twitter. If you are interested in looking at this new system, we can talk on the phone or organise a Zoom. Instruments already have CE certifications, and we are working on registering them with MHRA (Brexit). Therefore, these instruments cannot be used in the UK for a few months.

I am certain that they could be purchased and installed in your hospital this year. However, it is very important that you and your team undergo appropriate training and have a certificate confirming your ability to perform PTH measurements. After all, successful parathyroidectomy will depend on both surgical skills and accurate measurements of PTH. Theatre staff will take over the laboratory staff responsibility of doing it well, so training is essential.

Please get in touch with me if you would like to take it further.

Best wishes

Tom

#research #parathyroid  #healthcare #endocrine #surgery

Imaging Aldosterone Driven Hypertension – New Research Project at UCL/UCLH

Primary Hyperaldosteronism (PHA) also known as Conns Syndrome is a severe form of hypertension caused by the overproduction of the hormone aldosterone in the adrenal glands and affects 1 in 10 people with high blood pressure. If left untreated it often leads to life threatening conditions, such as heart attack, stroke, kidney disease and dementia.

Hypertension in patients with PHA is difficult to control and they need to take a number of medications (3-5 drugs) for the rest of their life. However, in about half of them removal of the single adrenal that produces too much aldosterone can cure the high blood pressure and reduce the need for medications lowering blood pressure. 

Current diagnostic pathways stratifying for curative adrenalectomy is cumbersome, time consuming and costly It is therefore not surprising that only 1 in 1000 patients with this condition is correctly identified and appropriately treated. It is estimated that in the UK alone there is at least half a million of patients with PHA but only fewer than 300 adrenalectomies for unilateral form of PHA are performed each year.

UCL Centre for Radiopharmaceutical Chemistry has developed a highly selective aldosterone synthase PET tracer which we called AldoView and which could be used as a diagnostic tool to better identify and stratify patients with PHA for surgery. The aim of our research is to validate AldoView in two interlinked projects, laboratory study based on working with human adrenal tissue samples (d’ART) and first in human AldoView PET scanning (IDEAL). This research is funded by DPFS Biomedical Catalyst MRC (MRC Reference: MR/S037349/1).

D’ART

Development of Novel Positron Emission Tomography Adrenal Radio-Tracer for Diagnosis and Image Guided Therapy in Patients with PHA” (d’ART) is a laboratory study in which we will correlate the amount of aldosterone synthase detected by autoradiography ([18F]UCB2) and immunohistochemistry (CYP11B2) in resected adrenal glands from patients with PHA, Cushing and Phaeochromocytoma and kidney donors. In particular, we will analyse how well the radiotracer performs to (i) distinguish diseased areas of the adrenals (with abnormally high levels of aldosterone synthase) from healthy areas, (ii) differentiate PHA from other diseases caused by lesions in the adrenal glands, and (iii) detect tiny, but potentially very aggressive lesions that are easily missed in the current diagnostic procedure. 

IDEAL

Image-Derived Enzymatic Adrenal Lateralisation of Primary Hyperaldosteronism” (IDEAL). is the “first-in-human” clinical study where 12 patients with PHA will have PET/CT with AldoView and adrenalectomy. The aim of this study is to gather pilot data regarding the in vivo quantification of aldosterone synthase (CYP11B2) expression confirmed by histopathological analysis. In order to achieve this, we first need to understand tracer binding in the adrenal glands, to determine the optimal time window for imaging, and understand the biodistribution and dosimetry of the tracer. For this we will image patients and take venous blood samples at various time points to create Time-activity curves. This feasibility study will allow us an estimate of the effect size and its standard deviation, which will help to inform a sample size calculation for a subsequent clinical trial.

Diagnosis and treatment of Primary Hyperparathyroidism in a young female patient: a rare disease misdiagnosed.

A 14 year old patient presented to her local hospital in North Africa with hip and knee pain. She has been well until 2 years previously but then she became weak and was unable to walk. Genu valgum and bilateral slipped femoral epiphyses were diagnosed and underwent a series of bilateral orthopaedic operations.

Subsequently, she was found to have high blood calcium (2.9 mmol/l) and PTH (>263, hypercalciuria (urine Ca/Creatinine ratio 3.73) and low Vitamin D (13 nmol/l). 

She was transferred to London, UK where she was diagnosed with Primary Hyperparathyroidism, the skeletal survey showed vertebral compression fractures, low bone density and other multiple skeletal abnormalities. Renal ultrasound showed no kidney stones and Sanger sequencing of MEN1 gene did not identify any mutation.    

The Sestamibi CT SPECT scan showed a single, enlarged right lower parathyroid adenoma. At operation, an abnormal parathyroid gland was removed.

 Postoperative recovery was excellent with no complications apart from severe hypocalcaemia which required large doses of alfacalcidol and calcium. 

  Five months after parathyroidectomy she was well and able to walk. Her calcium and PTH were normal and there was an improvement of bone mineralisation on Dexa scan and healing of vertebral compression fractures on X rays.