Charlotte Elder

The short Synacthen test: a questionnaire survey of current usage

Background Supported by meta-analyses, the low-dose Synacthen test (LDST) has gained in popularity, with many believing it to be more sensitive than the supraphysiological standard (250 µg) short ST (SSST), particularly when assessing children prescribed high-dose inhaled corticosteroids (HDICS). However, consensus is lacking about its specific clinical application, what is considered ‘low dose’ and how that dose is made up. Methods To ascertain current use of the short Synacthen test (SST), a questionnaire was emailed to members of the British Society of Paediatric Endocrinology and Diabetes in the UK and Ireland (N=257), requesting a response from each department (N=92). A reminder was sent a month later to members of departments which had not responded. Results The authors received 39 replies, giving a response rate of 42%. All departments use the SST: 82% use an LDST, 87% use the SSST and 69% use both. The 1 µg dose was used by 44% of hospitals, with the other 56% using seven different doses based on age, weight and body surface area. There were 14 different methods of preparing the low dose test. Additionally, variations in the timings of cortisol sampling and the diagnostic cut-offs for adrenal insufficiency were found. Increased requests for SSTs in children with asthma prescribed HDICS were noted by 44% of respondents, with 67% reporting the detection of adrenal suppression in this group. Conclusion Standardisation of the SST is required to address the considerable variation in the methodology and application of this test in the UK and Ireland.

Hydrocortisone for adrenal insufficiency.

Thomas Addison first described Addisons disease in 1855 in patients who had adrenal tuberculosis, highlighting the importance of the adrenal cortex to survive. In 1952, a decade after the medical landmark discovery of cortisone as a treatment for inflammatory conditions, the first case of adrenal crisis and death in a patient on glucocorticoid therapy undergoing surgery was described,1 and thereafter, a spate of such cases was published;2 ,3 recommendations as to how these patients should be investigated and managed followed.4 ,5 It is now widely acknowledged that patients on long-term corticosteroids require increased steroid cover at times of stress, such as major surgery and significant febrile illness. A knowledge of how to treat adrenal insufficiency during times of (patho) physiological stress is paramount to prevent complications andϕ death. The hypothalamic-pituitary-adrenal (HPA) axis is integral to the bodys maintenance of baseline homeostasis and its response to stress. The physiological secretion of cortisol is regulated by the main circadian oscillator in the suprachiasmatic nucleus, located in the hypothalamus.6 Each of the main components of the HPA axis is secreted in a pulsatile, circadian manner. The central clock is synchronised to the environment through signals from the retina, and efferent projections from the central clock induce the release of corticotropin-releasing hormone (CRH), which drives the HPA axis. In turn, cortisol induces the expression of peripheral clock genes, thus synchronising peripheral tissues with central circadian control. The height of the pulse amplitude for hypothalamic CRH and arginine vasopressin is characteristically at 4:00 a.m., with adrenocorticotropic hormone (ACTH) peaking between 4:00 a.m. and 6:00 a.m., and the resultant cortisol surge seen at 8:00 a.m. Circadian rhythm is absent in newborn babies and starts to establish itself during infancy but may not fully mature until 3 years of age or older. …

Early glycaemic control is predictive of long-term control: a retrospective observational study

There is a paucity of long‐term data examining the relationship between early glycaemic control, in children and young people diagnosed with type 1 diabetes mellitus (T1DM), and long‐term control. We wanted to determine whether early glycaemic control can predict long‐term control. In addition, we examined whether initial presentation with ketoacidosis predicts future control.

Time to end the routine testing of growth hormone and cortisol on hypoglycaemia screens

We prospectively studied 124 consecutive hypoglycaemia screens performed on children attending our emergency department over a 27-month period (March 2006 to May 2008). In keeping with most other paediatric services in the UK, we routinely collect a number of samples to permit investigation of low blood sugar, including metabolic investigations, and a random cortisol and growth hormone. Most of these patients have an intercurrent illness and are subsequently thought to have had an episode of “physiological hypoglycaemia”. There is a paucity of published data examining how cortisol and growth hormone respond to hypoglycaemia and no previous work looking at …

Use of salivary cortisol and cortisone in the high and low dose synacthen test

Salivary cortisone reflects serum cortisol levels, is more sensitive than salivary cortisol at lower values of serum cortisol and is noninvasive.

HbA1c league tables: might assay variability encourage foul play?

The mean or median HbA1c of patients within a diabetes clinic or GP practice is increasingly being utilised by commissioners as a metric by which to assess the quality of diabetes care provided. Publication of this data may lead to the construction of performance ‘league tables’ which are likely to reach the public domain. However the variability between different HbA1c assays and its influence on these metrics is often not fully appreciated. In 2006, when evaluating a number of replacement analysers, our clinic samples were run on several different systems. Our clinic average HbA1c on the existing Primus analyser was 8.4% (SEM 0.19); on the two possible replacement laboratory analysers it was 9.1% (Tosoh; SEM 0.21) and 7.6% (DCA Vantage; SEM 0.42). Two point of care analysers tested produced clinic averages of 8.9% (Vitros; SEM 0.25) and 8.4% (Affinion; SEM 0.38). Our clinic average HbA1c therefore ranged from 7.6% to 9.1%, dependent entirely on the assay. Figure 1 illustrates the impact of this on our potential position in any future national league table and on our perceived performance. All systems were ‘DCCT-aligned’, with correlation coefficients of 0.97, and internal control solutions were used. But what does DCCT (Diabetes Control and Complications Trial) alignment mean? A manufacturer obtains DCCT-alignment if 95% of their results are within 61% of specific standardsdbut a 1% HbA1c variation is clinically relevant. Our experience is not unique. Within the UKNEQAS programme (a quality assurance programme) variability of results is common. In a recent monthly report participating laboratories reported results between 6.9% and 8.3% for the same 7.5% standard. The new IFCC (International Federation of Clinical Chemistry) reference method recently introduced (which reports HbA1c as mmol/mol rather than % HbA1c) is unlikely to alter this variation as the underlying assay methodology remains the same. For GPs, 27 of the 30 available Quality and Outcomes Framework (QOF) points for diabetes relate to glycaemic control, with each QOF point increasing the practice income. Payment by results may see hospital clinics vying for position in league tables and there may be a temptation to select a more flattering assay. HbA1c is rightly seen as a key indicator of quality, but we believe further standardisation of assays is required before it can be reliably used to compare the performance of different centres and determine remuneration. We suggest either national adoption of a single assay or employing a correction factor to aid comparison between varying assays.

International survey on high- and low-dose synacthen test and assessment of accuracy in preparing low-dose synacthen

The short synacthen test (SST) is widely used to assess patients for adrenal insufficiency, but the frequency and protocols used across different centres for the low‐dose test (LDT) are unknown. This study aimed to survey centres and test the accuracy of ten different synacthen preparation strategies used for the LDT.

Letter in response to Chitale et al.: determining the utility of the 60‐minute cortisol measurement in the short synacthen test

Dear Editors, We read with interest the paper by Chitale et al. and agree that the 60-minute sample is essential to the standard 250-mcg short synacthen test (SSST), in contrast to the low-dose short synacthen tests (LDSSTs), and welcome any research helping to clarify the optimal use of the short synacthen test in terms of dose, sampling times and diagnostic cut-offs. A recent survey of UK paediatric endocrinologists demonstrated 82% using a form of LDSST and 87% the SSST. All centres (N = 39) sampled at 0 and 30 minutes but 18% did not perform a 60-minute sample. There were a number of additional samples taken at different time points, with a mean of 3 8 samples per SSST for all centres. In keeping with national practice, our tertiary paediatric endocrinology service is predominantly performing LDSST; however, on analysis of the SSSTs undertaken between January 2011 and May 2012 (N = 20), we have found similar results to Chitale et al. in our paediatric cohort. Of the 20 tests analysed, the 60-minute cortisol value was higher than the 30-minute sample in 90%, on average 84 1 nmol/l higher (SD 70 6 nmol/l) supporting the use of a 60-minute sample to guard against false-positive results. Discrepant results, that is, those where the patient would be felt to have adrenal insufficiency based on the 30-minute cortisol value but not on the 60-minute result or vice versa depend on the cut-off value applied. Our national survey revealed that 54% of responding centres use 500 nmol/l and 44% 550 nmol/l. Employing a cut-off of 500 nmol/l, 32% of our patients undergoing an SSST would have been misdiagnosed with adrenal insufficiency without the 60-minute sample and 10% using 550 nmol/l. In conjunction with our laboratory colleagues, we have recently revised our diagnostic cut-off to 450 nmol/l following the introduction of a new cortisol assay and welcome the authors’ view that local reference ranges need to be determined rather than historically set values that may not reflect laboratory advances and variability.

Borderline peak plasma cortisol following Synacthen stimulation - single-centre analysis of three years' data

References 1. Cross AS et al. International survey on high and low-dose synacthen test and assessment of accuracy in preparing low-dose synacthen. Clinical Endocrinology 2018; 88: 744-751. 2. Park et al. The diagnosis and treatment of adrenal insufficiency during childhood and adolescence. Archives of Disease in Childhood 2016; 101(9): 860-865. 3. Kline et al. Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay. Clinical Biochemistry 2017; 50(9): 475-480. 4. Hawcutt DB et al. Adrenal responses to Low Dose SST in children with asthma. Clinical Endocrinology 2015; 82: 648-656. Aim

The use of a radiolucent template to improve bone age X-ray quality (BASIC study)

Abstract Background: Left hand and wrist X-rays are conventionally used to assess skeletal maturity using methods such as Tanner-Whitehouse 3 (TW3). We noted a number were poor quality, caused by difficulty with hand placement. We introduced a simple radiolucent hand template to assist in hand positioning and assessed changes in X-ray quality and repeat X-ray rates. Methods: The position of fingers, thumb and overall clarity of bone age X-rays were prospectively scored. In the absence of a validated tool to assess quality a 1–3 scale (poor, borderline, good) was devised. A radiolucent hand template was introduced for use in the intervention group. Need for repeat X-ray was determined by set criteria. Results: The intervention improved scores. More patients scored 3 (good) for positioning of fingers (89.29% and 85.33%, p=0.38), thumb (98.21% and 89.96%, p=0.06) and overall clarity (76.79% and 70.27%, p=0.41) for the intervention (n=56) and control groups (n=259), respectively. No patient required repeat X-ray from the intervention group, compared with 28 in the control group (p=0.007). Conclusions: Achieving good quality bone age X-rays is more difficult than previously assumed. The use of a radiolucent hand template has been shown to improve hand position and significantly reduce the need for repeat X-ray.