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Full of the joys of spring! - A report on the Joint Spring Meeting of the ACB Northern Ireland Region and ACB Ireland held on 19th April 2013.

The ACB Ireland and Northern Ireland meeting was held this year in the Elliott Dynes building, a former care of the elderly unit, in the Royal Victoria Hospital in Belfast. Chair for the morning session was Dr Peter Sharpe (chairman of the NI region), who welcomed attendees from both sides of the border.

To network or not to network?

First speaker was Jennifer Welsh, chair of the NI Pathology network since 2010. She provided a concise overview of the NI pathology network to date. The network was officially launched on 20th October 2009 and progress has been made on strengthening our culture of evidence-based practice. This includes a regional screening programme for familial hypercholesterolaemia. In December 2011, the DHSSPSNI released the ‘Transforming Your Care’ document: a review of local health and social care. Jennifer highlighted the importance of being mindful of this release, particularly recommendation 78 (regarding implementation of the pathology network) to ensure that the interest in pathology is maintained. Prior to this publication, the board had no clinical members. Network decisions are made for the greater good and chemical pathologist Michael Ryan is now the network’s clinical lead. Positive news for trainee scientists is that a new fund for their training has been supported by the Chief Medical Officer. When the network is prioritising potential projects, from the current list of 44, the aim is to reach a consensus amongst people actually delivering the services.

Why is this blood glucose so low?

Next was a highly instructive talk from Gwen Wark, director of the regional peptide lab in Guildford. Her subject was insulin and the investigation of hypoglycaemia. She reminded us to think of proinsulin, as some tumours only produce this precursor peptide. The main clinical indication for measuring insulin levels is in the work-up of hypoglycaemia, but it is being increasingly being requested in patients suspected of insulin resistance. The JCEM guidelines from 2009 are the port of call for those who would like further elaboration. Drugs, alcohol and critical illness are common causes. If both insulin and C peptide are elevated in hypoglycaemia, then the aetiology is narrowed to sulfonylureas or insulinoma. To avoid confusion, it is crucial to clarify whether the reference interval is for a healthy or a hypoglycaemic population. The blood glucose is essential to enable result interpretation and she always measures C peptide concurrently to check the source of the insulin. It can be helpful for insulin assays to be less specific as tumours can produce 100% insulin, 100% proinsulin or a mixture. ELISA can provide a quantitative result for proinsulin. The mainstay of insulin analysis, however, is the immunoassay and insulin was actually the first substance measured by this method. Failure to appreciate the hook effect can lead to falsely low results. Haemolysis is unfortunately a big problem as peroxisome protease, found in erythrocytes, chews up insulin, but not C peptide. The enzyme’s activity is much slower when frozen. She then presented some case scenarios, which illustrated various clinical pitfalls. For instance, enzyme assays should be able to pick up animal as well as human insulin. She also reminded us to consider the potential access to insulin, e.g. a healthcare worker or diabetic pets.

Help with those tricky thyroid results

There followed an illuminating presentation on unusual thyroid results, by local trainee in endocrinology, Dr Helen Wallace. She presented a case of thyroid hormone resistance, an autosomal dominant condition, affecting only one in 50,000 live births. This is a rare differential when free T4 is elevated and TSH is normal or elevated. Next came a similar pattern, but with a different explanation. This time a TSHoma, showing a typically blunted response in the TRH test. The patient’s results normalised after treatment with pituitary surgery. The final case was one of a macroadenoma presenting with bitemporal hemianopia, with post-op blood results indicative of primary hyperthyroidism. This lady had been receiving enoxaparin for the treatment of recent multiple pulmonary emboli. Enoxaparin interferes with protein binding, thereby increasing free T4. TSH is an unreliable indicator in somebody with pituitary surgery.

So kidneys are important then?

Clinical scientist Peter Auld was up next, discussing the introduction of a scoring system for that oft neglected medical emergency, acute kidney injury. The idea is to highlight to clinicians results for which immediate action is required, but without crying wolf. About one in five of all acute hospital admissions suffer from this condition, which kills 200 times more people than MRSA. The NCEPOD 2009 report observed that only 50% of AKI patients receive good care. Last November, there was a consensus conference at RCP Edinburgh, which emphasised that 12000 lives could be saved a year, given optimal care. The MDRD reversal technique was highlighted as an estimate of a patient’s baseline creatinine. A 10 day pilot study was performed in the Royal, which found 13 episodes of AKI, one of which had been missed by clinical staff. The pilot allowed improvement of the initial e-alert system, to ensure visualisation. The system has the potential to reduce morbidity and mortality. NICE have recently released draft guidelines for consultation and in the words of Donal O’Donoghue, “Don’t let them die from AKI.” Why not download the London AKI app today?

Hypertension: not just essential!

Marguerite MacMahon stimulated us with the utility of mass spectrometry in evaluating hypertension. It has greater specificity than the more widely used immunoassay and can handle complex mixtures, so many compounds can be measured in just one run. It is slower than immunoassay however, and requires significant sample preparation, for example dilution or protein precipitation. A quarter of the Western population are hypertensive, meaning endocrine causes are more common than you might think. Mass spectrometry is much better at detecting catecholamine metabolites than immunoassay and this is more important than whether the sample was plasma or urine (a useful 2013 discussion can be found in Clinical Chemistry). Methoxytyramine, a marker of metastatic phaeochromocytoma, can also be measured. Urinary free cortisol can boast 100% recovery, with a turnaround time of only 2 days, and an impressive intra- and inter-assay CV of only 3%. Finally, aldosterone and rennin can also be measured and it is noteworthy that primary hyperaldosteronism confers a higher cardiovascular mortality when compared to those with similar blood pressure.

To screen or not to screen?

Next Jennifer Cundick talked about neonatal screening. First she reminded us that the classic WHO screening criteria of Wilson and Jungner were not designed for neonates. Next came a history of neonatal screening locally, starting with PKU screening in 1969, hypothyroidism in 1981 and CF in the early 1980’s (cf 2005 for remainder of UK). The introduction of tandem mass spectrometry at the tail end of the last century led to a quickening of pace. MCADD screening came in August 2009. She suggested considering the combined prevalence of inherited metabolic disorders when considering the utility of neonatal screening. Food for thought was provided in the example of the benign condition histinidaemia, when patients were subjected to the significant risks of liver biopsies to what gain?

A condition in its screening infancy

Screening for the autosomal recessive condition sickle cell anaemia was introduced in Northern Ireland in March 2012 (England: 2001 and Scotland: late 2010) and we were given a succinct overview of the story so far by Gareth McKeeman. Over 25000 children have been screened to date and a case has yet to be found. The clinical consequences of this condition occur due to the hypoxic polymerisation of HbS leading to painful vaso-occlusive ischaemia. The method used is ion-exchange HPLC, with the more positively charged measurands eluting later. Variants are confirmed by isoelectric focussing. 18 SC carriers have been found and 9 HbD carriers have been found; of note D-Punjab is the only clinically significant variant. When considering the merits of screening, one must always weigh up cost versus equality.

It is time to fight for obesity treatment

The educational components of the day finished with a bang, with the inimitable presentational style of Dr Michael Ryan. He warned us of the rising prevalence of obesity and stated that it is the most significant health problem of this century. BMI is a tool prone to error in individuals with higher than average muscle mass. It must not be glossed over that obesity increases the risk of many cancers and increases the risk of death and cardiovascular disease. Abdominal obesity has been relatively ignored, when compared to its more popular cousins of smoking, diabetes and hypertension. If a person weighs 100kg and they manage to shed 10kg, their risk of death falls by over 20%. Dr Ryan believes that a pathological relationship with food is the root cause and reminds us that excess calories are stored as triglycerides. Blood markers of calorie overload include GGT, triglycerides, LDL, HDL and CRP. The ubiquitous fatty liver should not be confused for a benign phenomenon as it is a serious predictor of early death. He mentioned some pharmacological treatments including lorcaserin and the anticonvulsant topiramate. He also pulled out the statistic that about 97% of type 2 diabetes is due to weight. He mentioned the incretin system and the diabetic drugs available such as GLP1 agonists. He recommended the Nature review article on these hormones from 2006. He told us that behaviour modification really works and concluded by reminding us of the potency of weight loss: 6% weight loss has similar effects on HDL as fibrates and on LDL as ezetimibe. Bariatric surgery, he told us during the questions, can reverse diabetes, but patients do need long-term follow-up and it is not yet known the long term benefits.

The final part of the day was a celebration of two retiring chemical pathology consultants: Pooler Archbold and the afore mentioned, Dr Ryan.

(This page is maintained by the ACB Northern Ireland Region)

Updated 20th August 2013

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