Reported by Maryam Khan, Bristol

 

Bristol hosted a stimulating and fun autumn scientific meeting – despite another endocrine meeting happening simultaneously just across the bridge in Newport (hosted by my old much-loved Cymraeg colleagues!), an impressive number of delegates attended. It just goes to show: we all love endocrinology!

 

Dr. Wolf Woltersdorf (Bristol Royal Infirmary) chaired the morning session, which started with a talk by Dr. Liz Crowne (Bristol Children's Hospital) about the new developments in the understanding of puberty. Recent advances have looked at the neuroendocrine and genetic factors involved in the control of the onset of puberty. There is a complex network of neurones responsible for the secretion of LHRH, and thus the initiation of puberty. A number of genes (KAL1, FGFR1, NELF) required for the correct migration of these neurones have been identified, and studies in deficient mice are expanding our understanding of this process. Several other factors affecting the timing of puberty were discussed, including diet, energy expenditure, stress, gonadal steroids, environmental chemicals and migration. The incidence of premature adrenarche and precocious puberty appears to be increasing, which has been associated with the obesity epidemic, and there is a hypothesis that pubertal onset is influenced by insulin resistance. Despite our increased understanding, the old controversy still exists – what age is “normal” for puberty? Although in the majority of cases, the cause of early puberty may be idiopathic, Dr. Crowne described two cases of children who had presented with central precocious puberty in whom subsequent MRI scanning showed the presence of rare neuronal tumours, therefore demonstrating the necessity for thorough investigation.

 

We were grateful to Dr. Geoff Beckett (Edinburgh Royal Infirmary), an ACB representative on the panel for the UK Thyroid Function Tests Guidelines, who flew down for the morning, to answer some of our questions on how we should be dealing with TFT results. He focused on a few of the keys points from the guidelines, primarily: (i) the debate around TSH vs TSH+fT4 for first-line screening, (ii) treatment of subclinical hypothyroidism, and (iii) pregnancy. With regard to thyroid function testing, the financial pressures are significant, and one key issue is the need for us, with the support of local endocrinologists, to consult with our GPs to agree on best practice. Finally, we were reminded that these are just guidelines – and ultimately, we should be treating the patient, and not just the numbers.

 

The afternoon session, chaired by Dr. Peter Astley (North Bristol), began with a very informative talk on the skeletal and non-skeletal effects of Vitamin D deficiency by Dr. Theresa Allain ( Southmead Hospital ). The definitions of vitamin D deficiency are constantly evolving, and the new concept of Vitamin D “insufficiency” has now been introduced. There is probably huge overlap between the classification of “deficiency” and “insufficiency”, and clinically, making this distinction is not very helpful. Dr. Allain emphasised that we cannot necessarily diagnose deficient patients based on biochemistry or clinical characteristics; indeed, subjects with histological osteomalacia may have normal serum biochemistry. Some of the non-musculoskeletal actions of Vitamin D were discussed. Vitamin D deficiency is associated with increased risk of malignant disease and infection, and increased susceptibility to autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease and type I diabetes. Therefore the clinical implications of Vitamin D are much greater than previously realised (and not just skeletal). The pharmacological dilemmas still exist: what dose and formulation of Vitamin D should we be giving? And, whom should we be treating?

 

Our next speakers were Mr. Jim Clarke and Dr. Raji Parasuraman (Early Pregnancy Unit, Royal Devon & Exeter Hospital ), who discussed the use of serum progesterone and hCG in the management of ectopic pregnancy. There is an increasing incidence of ectopic pregnancies in the UK , probably due to the increased incidence of Chlamydia infection. The diagnostic test is the transvaginal ultrasound, although in 8-31% of cases, the ultrasound scan gives insufficient information and a diagnosis cannot be made at initial presentation. Therefore, other diagnostic markers are required to aid management of these patients. Serial hCG measurements are often used, although this is not always reliable since 17% of ectopics will show a normal hCG rise, and 15% of viable intrauterine pregnancies have an abnormal hCG rise. Mr. Clarke explained that these patients pose a very difficult management decision – although delaying treatment always comes with the worry of severe haemorrhaging, intervention will involve a laparotomy, which requires inpatient stay, the patient will be off work, and the worry that future pregnancies may be affected. Therefore, the decision to operate is not taken lightly, and ideally, we would want to avoid unnecessary surgical procedures. Measurement of serum progesterone levels may provide reassurance in managing these cases. Serum progesterone levels are usually stable early in pregnancy, and a low progesterone level indicates a nonviable pregnancy, regardless of location. Mr. Clarke's group are investigating the use of different progesterone cut-offs, which will be assay- and population- specific. This was a very colourful presentation, with plenty of interesting kinetic 3D images!

 

Although the programme was running late, delegates were more than keen to stay to hear Dr. Mike Wheeler (Exmouth) talk about “Grumpy old men and testosterone measurement” – and indeed, he provided a most entertaining and worthwhile last hour for the audience! Laboratories appear to be receiving many more requests for testosterone analysis in older men – why is this? There is a greater awareness of A ndrogen D eficiency in the A geing M ale (or ADAM), which gives rise to the typical andropause symptoms of reduced potency, reduced libido, reduced muscle strength and increased fatigue. There have been significant improvements in testosterone preparations available; treatment will alleviate symptoms and may reduce the period of frailty and dependency in these individuals, and therefore the cost of long-term care. There are several issues for the laboratory regarding testosterone measurements, including: (i) awareness of circadian rhythm at different ages; (ii) variations in manufacturer's kits quoted reference ranges. Unnecessary over-investigation is undesirable. With reference to the recent Annals paper (Ho et al , 43 : 389-97), Dr. Wheeler highlighted that the best estimate of testosterone is the calculated free testosterone concentration, and stressed the need for laboratories to derive their own calculations and reference ranges based on their own assay methods. The talk stimulated lots of discussion points, including who should be involved in the decision to prescribe testosterone, and the possible future use of tandem MS for testosterone analysis.

 

The Bayer Award competition was popular this year, with 5 keen participants, female dominated – as is often the case! All trainees presented work from their recent MSc projects, which included lots of hands-on method development work. The presentations were of a very impressive high quality, which left the judges with a difficult decision to make over lunch. The winner was Karolina Witek ( Southmead Hospital ) who had given a very clear and enthusiastic presentation of the GC-MS method she has developed and validated for the analysis of galactose-1-phosphate. A second prize was awarded to Natasha Porcu ( Southampton General Hospital ), who has developed an in-house assay for measuring salivary 17-OHP, which provides great potential in the monitoring of patients with CAH.

 

Many thanks to our organisers, Roberta Goodall and Roy Fisher, the Bayer judges, Keith Wakelin, John O'Connor and Allan Thompson and our sponsors, Bayer Diagnostics and Waters Corporation, for a very enjoyable meeting.

 

 

Programme