posted 12 Jan 2012 14:41 by Katie Wynne
 The study analyzed the effects of tight glycemic control on regenerative potential of myocardium during acute myocardial infarction.
Seventy-five patients with their first acute myocardial infarction undergoing CABG were studied:
Control - 25 patients with glycemia <140 mg/dl (<7.8mmol/l)
Hyperglycemic patients (glucose >140 mg/dl) randomized to :
1. intensive glycemic control (80–140 mg/dl) (4.4-7.8mmol/l),
2. conventional glycemic control (180–200 mg/dl) (10-11.1mmol/l), or
3. glucose-insulin-potassium (180–200 mg/dl) before surgery, using insulin infusion followed by sc insulin treatment.
Biopsies from the peri-infarcted area were taken during CABG. Number of myocyte precursor cells, DNA oxidation, senescent myocyte precursor cells and cycling cardiomyocytes were analyzed.
Patients with intensive glucose control had higher MPC and cycling myocytes, as well as less oxidized and senescent MPC compared with both CGC and GIK patients.
Tight glycemic control, by reducing senescent MPC, may increase regenerative potential of the ischemic myocardium.
This work provides very useful evidence for tight glycaemic control during MI and complements the findings of the previous DIGAMI studies well. Any clinician caring for MI patients, not just endocrinologists, should be made aware of the importance of tight glycaemic control.
The control group had significantly more myocyte precursor cells and less oxidative damage than any of the three hyperglycaemic groups. This may reflect the chronic effects of glucose on the myocardium in diabetics.
Findings from the intensive control group may have been attenuated by the presence of hypos.
Marfella et al. Second University of Naples, 80138 Naples, Italy
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posted 6 Dec 2011 14:00 by Katie Wynne
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updated 6 Dec 2011 14:03
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Some patients with intermediate thyroid FNA cytology wil have a chance of cancer:
- AUS/FLUS – Thy3 (predicted probability of cancer 5-15%).
- FN/SFN – Thy3 (predicted probability of cancer 15-30%).
- SMC – Thy4 (predicted probability of cancer 60-75%)
The current BTA/ATA guidelines suggest a diagnostic lobectomy for a biopsy desingated 'Thy3' with completion of thyroidectomy if histology is positive for cancer as 10–40% will prove to have malignant potential. A thyroidectomy is recommended for Thy4 lesions.
This study aims to answer whether an FNA can distinguish between a benign nodule and cancer preoperatively, to allow planning of definitive surgical management. The revised American Thyroid Association’s guidelines suggest that units consider a 'mutational panel' for nodules with indeterminate FNA cytology to help guide clinical management.
Objective: Study the clinical utility of molecular testing of thyroid FNA samples with intermediate cytology.
Method:
- From April 2007 to April 2009, 1056 consecutive residual FNA samples from 762 patients with indeterminate cytology diagnoses were prospectively tested for mutations.
- Cytological diagnosis was established before molecular testing.
- A retrospective analysis was performed with correlation between the results of cytological evaluation, histological diagnosis and molecular testing
Results:
- 967 FNA samples adequate for mutational analysis.
- 479 thyroidectomies provided a histopathological diagnosis for 513 FNA samples.
- Total of 85 mutations were detected.
- Molecular testing has a PPV of 87–95% for predicting thyroid cancer.
- RAS mutation (85% risk of malignancy).
- BRAF V600E, RET/ PTC, PAX8/PPAR mutations (associated with malignancy in close to 100% of nodules)s
Yuri E. Nikiforov et al. suggest a total thyroidectomy for any positive genetic test result in this panel. THey recommend a partial thyroidectomy in FN/SFN (Thy 3) and SMC (Thy 4) nodules that are mutation negati
Imperial Centre for Endocrinolgoy felt that this was:
- Easy, reproducible, does not prolong medical procedures.
- Definitive surgical care in the first surgical procedure: 121/479 patients in this study, ie 25.3%.
- The group does not actually propose no surgery vs total (definitive) thyroidectomy, but provides an algorithm to save patients a repeat surgical procedure vs those that will only undergo diagnostic lobectomy.
- For this study, each FNA sample was considered independently. In practice patients with indeterminate cytology have repeated FNA, which may yield different result.
- Histopathologist not blinded to the results of molecular testing.
- Paper does not make clear how many patients had diagnostic vs total vs cpmpletion of thyroidectomy and implies that all 479 operations were lobectomies.
- 51 patients actually had SMC (Thy4) cytology, which should have been total thyroidectomy according both to BTA and ATA guidelines, but seem to have had diagnostic lobectomy in this cohort – why?
- Negative predictive value of molecular testing: In this paper FN/SFN NPV 14%, SMC NPV 28%, best reported has been 6%. However, for these markers to change practice, ie avoid surgery overall, the NPV needs to be almost 0, since only then can you say to a patient with indeterminate/Thy3 cytology that they do not require surgery overall. Most patients would not accept a conservative approach with a 6% risk that they have a cancer.
Yuri E. Nikiforov et al
J Clin Endocrinol Metab, November 2011, 96(11):3390–3397
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posted 20 Nov 2011 12:25 by Katie Wynne
 This is the largest study to date of patients examining the relationship between anti-thyroid drugs (ATDs) and bone marrow suppression in the form of agranulocytosis and pancytopenia. The study estimated the incidence of these complications in patients on ATDs at 0.3% for agranulocytosis and 0.01% for pancytopenia. This is in keeping with the previous literature. The onset of these complications was at any point during treatment course however the cumulative incidence plateaued at 100 days post initiation. The study failed to determine any statistically significant risk factors and this is in keeping with the consensus that these the immunological mechanisms involved cannot be predicted by background factors. 100% of patients in the agranulocytosis group (n=50) were successfully treated with currently available treatments (including GCSF, steroids and supportive therapy). 80% of patients who developed pancytopenia (n=5) had prior agranulocytosis. And in this group one patient died.
Imperial Centre for Endocrinology felt that:
- This is an excellent paper representing the largest study to date and hence contains information useful to our daily clinical practice.
- Clinicians should remain vigilant throughout for these adverse reactions as they can occur at any moment in the treatment course.
- In this study there were 4 patients with agranulocytosis who were not symptomatic, purely being picked up by routine FBC. However the paper does not detail their clinical course (except that they all were treated successfully) and this represents a 0.0001% of patients on ATDs. Hence it is difficult to advocate routine FBC monitoring.
- Reassuringly currently available treatments were successful in treating all patients with agranulocytosis.
- The study could have looked at daily/cumulative ATD doses as a risk factor for developing bone marrow suppression.
- It would have been useful if the paper had detailed the management of their hyperthyroidism after the development of bone marrow suppression.
Antithyroid Drug-Induced Hematopoietic Damage: A Retrospective Cohort Study of Agranulocytosis and Pancytopenia Involving 50,385 Patients with Graves' Disease
Watanabe N, Narimatsu H, Noh JY, Yamaguchi T, Kobayashi K, Kami M, Kunii Y, Mukasa K, Ito K, Ito K.
J Clin Endocrinol Metab. 2011 Nov 2. [Epub ahead of print]
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posted 3 Oct 2011 13:50 by Katie Wynne
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updated 3 Oct 2011 14:06
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Graeme Eisenhofer, Jacques W.M. Lenders, Henri Timmers, Massimo Mannelli, Stefan K. Grebe, Lorenz C. Hofbauer, Stefan R. Bornstein, Oliver Tiebel, Karen Adams, Gennady Bratslavsky, W. Marston Linehan and Karel Pacak
In the absence of characteristic clinical stigmata and family history, plasma metanephrine, normetanephrine, and methoxytyramine may be useful in guiding genetic testing.
Germline mutations account for roughly 30% of phaeochromocytomas/paragangliomas. Nine tumour-susceptibility genes have been identified so far; von Hippel-Lindau tumour suppressor (VHL); succinate dehydrogenase complex, subunit B, iron sulfur (SDHB); and succinate dehydrogenase complex, subunit D, integral membrane protein (SDHD).
About a quarter of phaeochromocytomas/paragangliomas patients are likely to carry a germline mutation and hence routine genetic testing is recommended, particularly in young patients, even in the absence of family history. A full genetic screen testing for all known mutations is expensive. This study assessed whether measurements of plasma metanephrine, normetanephrine, and methoxytyramine, might aid rationalisation of genetic testing.
Plasma metanephrine, normetanephrine, and methoxytyramine were measured in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF1), 66 with von Hippel-Lindau (VHL) syndrome, and 59 with mutations of SDHB or SDHD. While patients with MEN and NF1 mutations secreted increased metanephrines (suggestive of increased epinephrine production), patients with VHL showed a solitary increase in normetanephrines and 70% of patients with SDH mutations presented with raised methoxytyramine in addition to normetanephrine. The authors were able to discriminate between patients with NF1 and MEN 2 from those with VHL, SDHB, and SDHD gene mutations in 99% of cases by using a combination of normetanephrine and metanephrine. Methoxytyramine was useful in differentiating between SDH mutations andVHL mutations in 78% of cases.
Imperial Centre for Endocrinology felt:
1. Units should analyse their own internal data of urine catecholamines, methoxytyramine and metanephrines
2. Urine metanephrines, which the paper suggest have comparable efficacy, may be as useful in clinical practice.
3. Since metanephrines are released at a steady rate, it may be possible to discriminate using single void spot urines.
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posted 26 Sep 2011 11:44 by Katie Wynne
 BMJ Sep 2011 Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence Shakila Thangaratinam, Alex Tan, Ellen Knox, Mark D Kilby, Jayne Franklyn, Arri Coomarasamy BMJ 2011:342:d2616
In 1990, a study was carried out looking at the causes of post-partum thyroiditis (1). This uncovered, by chance, an association between the presence of thyroid autoantibodies (thyroid peroxidase antibody) and the rate of miscarriage and preterm birth. At the time, this association was largely disregarded as a plausible causative hypothesis did not exist. Twenty one years later, a wealth of studies carried out support the initial observation. This meta-analysis on 31 studies (case control and cohort) demonstrates an increased risk of both miscarriage and preterm birth with the presence of thyroid peroxidase antibodies.
In an attempt to determine whether treating the positive antibody status with thyroxine leads to any benefit, the authors cite two studies. Both these studies, carried out by the same group of investigators, have some serious flaws. First of all, the antibody positive group are older, secondly, one of the studies is not placebo controlled and thirdly, the studies are carried out in Italy, in an iodine deficient population. However, both studies demonstrated a significant reduction in miscarriage and preterm birth with thyroxine treatment.
Many GP’s and endocrinologists are currently checking the thyroid antibody status on infertile or subfertile women. The question about whether or not to treat these women with thyroxine is hotly debated. Some feel that thyroxine will do no harm and may be beneficial. Others feel that the appropriate evidence for treatment is not yet available. An important caveat in all of this would be to remember that rendering a pregnant woman hyperthyroid could also have serious metabolic consequences to mother and unborn child.
1. Stagnaro- Green A. et al. Detection of at risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 1990; 264: 1422-5
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posted 11 Aug 2011 12:19 by Katie Wynne
The COR-BMOD Trial Weight Loss With Naltrexone SR/Bupropion SR Combination Therapy as an Adjunct to Behavior Modification
The COR-BMOD Trial was a Phase III Study looking at combination of Naltrexone and Buproprion (Contrave) for weight loss. It was a well designed study with good comparison between groups. 66% vs 42% achieved >5% wt loss with statistically significant changes in cardiometabolic risk factors. However, safety issues surrounding patients' final blood pressure reading and increased pulse rate were cited in the FDA Approval Committee which rejected Contrave without more long term trial data.
Obesity (2011) 19, 110–120. doi:10.1038/oby.2010.147
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posted 9 Aug 2011 13:09 by Katie Wynne
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updated 10 Aug 2011 11:46
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7 – 9 November 2011
Hilton Sheffield, Victoria Quays, Sheffield, UK
The Society for Endocrinology’s Clinical Update training programme provides essential training for trainees and new consultants in endocrinology and diabetes.
Over a three-year period, the programme covers the national curriculum in endocrinology and diabetes and is indispensable for those preparing to sit the Federation of Royal Colleges of Physicians’ Specialty Certificate Examination. The 2011 event is in the second year of the cycle, although attendance at CU10 in NOT a prerequisite.
The three-day residential course compromises lectures and interactive workshops. The small group workshops (50 delegates maximum) are targeted to specific topics on the curriculum. They begin with a short introductory presentation by a leader in the field, followed by routine cases presented by delegates. The majority of the time is spent on discussing best clinical practice with these day-to-day scenarios.
or contact BioScientifica, 22 Apex Court, Woodlands, Bradley Stoke, Bristol, BS32 4JT, UK.
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posted 28 Jun 2011 14:05 by Katie Wynne
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updated 28 Jun 2011 14:24
]
 Bristol-Myers Squibb and AstraZeneca have reported two-year data on their SGLT-2 inhibtor dapagliflozin. Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2), which is responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine.
Although this data supports the efficacy of dapagliflozin as a diabetes therapy, reports have highlighted a higher number of cancers found among patients taking the drug. Of 5000 patients who took the new drug, 18 developed breast and bladder cancer, compared to only two cases in the control arm. Clearly, the overall number of cancers was very low and is thought to be unlikely to stop FDA approval; but this data may mandate a post-marketing safety study. Researchers have noted that there was no evidence of an increased cancer risk in preclinical animal studies designed for this purpose.
Bristol-Myers Sqibb also posted Phase III data showing that dapagliflozin+metformin XR significantly reduced blood sugar levels compared to dapagliflozin or metformin XR alone. Michael A. Nauck,the principal investigator of the study reported that "Two-year data demonstrated patients taking dapagliflozin added to metformin sustained reductions in blood sugar levels over an extended period of time."
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posted 21 Jun 2011 14:04 by Katie Wynne
 This paper systemically assessed the iodine status in UK schoolgirls aged 14-15 years attending secondary schools in nine UK centres. Mild iodine deficiency impairs cognition in children and this study focused in female schoolchildren as they are most likely to proceed to pregnancy in the short-to-medium term and their offspring are most susceptible to the adverse effects of iodine deficiency.
WHO, International Council for Control of Iodine Deficiency Disorders, and UNICEF recommend that the median urinary iodine from representative samples of spot urine collections can be used to define a population’s iodine status for national surveys of iodine nutrition. This cross-sectional survey measured the urinary iodine concentration and tap water iodine concentration in summer and winter of 2009. A validated diet questionnaire was also recorded.
Mild iodine deficiency were present in 51% (n=379) of participants, moderate deficiency in 16% (n=120), and severe deficiency in 1% (n=8) in a total of 810 participants. Low urinary iodine excretion was independently associated with sampling in the summer (p<0.0001), UK geographical location (p<0.0001) and low intake of milk (p=0.03). Among the nine UK centres, Belfast has the highest prevalence of iodine deficiency (85%, n=135). There was no positive association between tap water iodine content and urinary iodine concentration.
The reason for iodine deficiency in UK may be due to a fall in milk consumption and increased consumption of processed food that is lacking iodine. The seasonal variation in urinary iodine concentration in the study reflects the greater use of iodine-rich artificial feed to cattle during winter. It is noted that UK commercially-purchased salt is not iodised.
Imperial Centre for Endocrinology felt that the findings of this study are of potential major public health importance. Mandatory salt iodisation has been used in Australia and New Zealand to tackle iodine deficiency. Although high iodine intake can be associated with very small increases in the incidence of subclinical hypothyroidism and autoimmune thyroiditis, it is important to ensure adequate iodine intake in the UK population, particularly in young women of reproductive age.
Mark P J Vanderpump, John H Lazarus, Peter P Smyth, Peter Laurberg, Roger L Holder, Kristien Boelaert, Jayne A Franklyn, on behalf of the British Thyroid Association UK Iodine Survey Group
The Lancet Vol 377 June 11, 2011 |
posted 17 Jun 2011 12:56 by Katie Wynne
Bariatric surgery (gastric bypass and banding) are increasingly performed on merely overweight, rather than obese people. Findings presented at the American Society for Metabolic and Bariatric Surgery Meeting suggested that the less obese patients may benefit most from surgery.
Researchers reviewed the outcomes of 981 people (BMI <35 - >50kg^m2) who had gastric bypass surgery. The lower-BMI patients "had better outcomes" than the higher-BMI patients in that they "lost more weight and had higher rates of remission of diabetes."
Current guidelines suggest that surgery should only be offered for patients whose BMI is >35kg^m2 with an obesity-related health conditions or BMI >40kg^m2. This preliminary research suggests that perhaps the guidelines are too strict and more patients could benefit from surgery before they become obese.
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