http://www.pathology.leedsth.nhs.uk/dnn_bilm/Misc/Syntheticglucocorticoidsandcortisolassays.aspx Further information At our institution, we measure the serum ACTH levels before ACTH administration. This later helps to differentiate between primary and secondary adrenal insufficiency in those who show insufficient cortisol response. The objective of this study was to determine the current clinical practice involved in performing SST and to establish a standardized test protocol. 2 Objectives We have therefore undertaken a retrospective analysis of repeat SSTs performed in patients with potentially reversible causes of AI to determine if there are features of the SST results (basal, 30-minute, or delta cortisol) that might both guide a strategy for repeat testing and in addition help to identify groups of patients in whom HPA axis function is likely (or unlikely) to be restored. Materials and Methods Patient selection Importantly, in our study there are some limitations. This is a retrospective analysis of clinical data obtained from electronic patient records, and therefore there is the potential for selection bias in those individuals undergoing short Synacthen testing. We do not have accurate data on the dose and duration of exposure to glucocorticoids, and therefore we are unable to answer questions that relate to cumulative exposure that might predict AI. However, this does represent the largest analysis of this kind published to date. Our data extend to approximately 4 years of follow-up and therefore it is not possible to say whether further recovery of the HPA axis may occur after this time point. The algorithm that we have proposed is designed to guide and help the clinician, but is only derived from this data set and has not been tested or validated in other cohorts. As a result, it is important that individual clinicians use their discretion and clinical judgment in the frequency and interpretation of dynamic assessments of HPA axis function. Plumpton and Besser investigated the cortisol response to hypoglycemia by undertaking ITT in healthy individuals; they showed that the maximum response ranged from 21 to 48 μg/dL and therefore proposed 20 μg/dL (550 nmol/L) as the minimum threshold level for a normal cortisol response to insulin-induced hypoglycemia. [1] They used an immunofluorescent assay, which measures cortisol and corticosterone levels and therefore has a 20% to 30% positive bias. Carr et al later compared radioimmunoassay (RIA) with immunometric assays. In 154 basal and stimulated serum cortisol samples, they observed that the mean result obtained with an RIA was 23% lower than those obtained with an immunometric assay. [2] They observed a similar correlation in the results of patients who underwent either a short Synacthen test (SST) or ITT. Moore et al compared different assays for cortisol, and observed lower cortisol levels with RIA. [3]

Send both blood samples to the laboratory at ambient temperature. If unavoidable can be refrigerated overnight. Required information Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394 ± 286.58, 722 ± 327.11, and 827 ± 369.30 nmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (n = 72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550 nmol/L at 60 minutes. This particular subgroup's mean change (240 nmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152 nmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226 nmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST ( P-value < .0001).We invited endocrinologists and internists, including those in other associated sub-specialties registered with the Saudi Medical Council. We extended the invitation to consultants, associate consultants, assistant consultants, registrars, and endocrinology training fellows. Section 37(1A) of the 2001 Act defines the “relevant period” for the purposes of conversion to an SST as follows: Ensure that you have read the contraindications and precautions as given in the Synacthen product information sheet. Having done so it is the responsibility of the investigating medical officer to decide whether it is safe to proceed with this investigation.

Kaplan-Meier plots estimating time to recovery of HPA axis function in 110 patients with AI due to exposure to suppressive doses of glucocorticoid therapy stratified by (a) basal (0-min) cortisol of the same test, (b) 30-min cortisol, and (c) delta cortisol (30-min – basal cortisol) of their initial SST. (d) ROC curve analysis to determine the ability of the characteristics of the initial SST to predict eventual recovery of adrenal function. Give the 250 ug of Synacthen by either intravenous (i.v.) or intramuscular (i.m.) injection (there is no difference in cortisol response between i.v. and i.m. administration). A total of 13% of the clinicians reported encountering cortisol levels below the pass threshold and peak cortisol levels being reached only 60min after the ACTH injection. Other studies have reported similar results and have suggested that 60-min cortisol measurement is integral to the SST protocol. 4, 5, 6, 7, 8The patients’ characteristics are presented in Table 1, including the relevant clinical indications as well as the number and timing of the SSTs performed. A total of 776 subjects were recruited, all with potentially reversible causes of AI. A subgroup analysis was performed in 110 patients with AI secondary to treatment with suppressive doses of glucocorticoids. We conducted the study from mid-January 2021 to the end of February 2021. After the initial invitation, we sent three further reminders, each 1 week apart. We concluded the survey 6 weeks after the initial invitation, then proceeded with data analysis. We collaborated with the institutional biostatistics department in the design of the questionnaire survey and the data analysis. The results of the analysis were not altered when corrected for both age and sex. In addition, a further analysis was undertaken in which only patients that failed their first test were included (n = 248), and the results were not different from those presented above ( Supplemental Figs. 1 and 2). HPA axis recovery in glucocorticoid-exposed patients A normal response does not exclude ACTH deficiency which requires an endocrine referral if suspected. Our study has the following strengths including: a large sample size with generalizability in terms of age, sex, body habitus, and reflected daily clinical practice; it is the largest study on this subject to the best of our knowledge; and no previous studies have reported on this subject from our geographical area. Therefore, this research adds valuable information to the literature. Since different cortisol assays have different sensitivity and specificity, we used the same assay to perform all tests to ensure accuracy of the results.

The increasing use of glucocorticoid therapy has led to a dramatic increase in the awareness and diagnoses of secondary AI in the context of “iatrogenic Cushing syndrome.” It is estimated that 2% to 3% of the population of the United Kingdom and United States are taking prescribed glucocorticoids, and these are most commonly used in the more elderly populations and at doses that are known to suppress the HPA axis ( 25). Data on recovery of the HPA axis after exposure to a suppressive dose of glucocorticoids are limited and often in studies that have recruited small numbers of patients (ranging from n = 1 to 49) ( 10, 26–35). In addition, much of the published literature has been in pediatric populations ( 35–40), and therefore simple extrapolation into the adult setting is not straightforward. These studies are limited not only in the variability of the populations that they have studied, but also in the differences in duration and dose exposure to glucocorticoids. As a result, the published literature that is currently available does not allow us to determine whether the duration, dose, or cumulative glucocorticoid exposure are the main drivers to the development of secondary AI in this context ( 9). There is substantial variability between individuals in their susceptibility to the development of the adverse metabolic effects associated with glucocorticoid use, and it is highly likely that the same will apply to the development (and subsequent potential for recovery) of HPA axis suppression.

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As well as the utility of the peak cortisol value post-SST, the authors highlight the importance of the delta cortisol to predict future recovery of AI. It is perhaps not surprising that in a group of patients with suppressed adrenal function post exogenous GC therapy as opposed to a “normal” population being evaluated for adrenal sufficiency, the incremental change in cortisol was clinically useful. However, it is important to stress that the SST in this context has yet to be validated against the ITT; Kane et al. ( 25) in a small series of GC treated rheumatology patients highlighted differences between the performance of the SST and ITT in patients with TAI; 8/22 patients failing the SST but passed the ITT.

The reliance on the 30-minute serum cortisol value stems from studies done with ITT and how it relates to serum cortisol levels attainted 30 minutes after an adrenocorticotrophic hormone (ACTH) injection. [5] However, Dorin et al showed that ACTH concentration remains well above the threshold for maximal cortisol secretion for up to 2 hours following cortisol sampling, after IV SST. He showed that serum cortisol continues to rise and peaks 60 minutes after the ACTH injection in normal healthy adults. This provides a rationale for measuring 60-minute serum cortisol rather than just up to 30 minutes in patients who undergo SST. [6] Alia et al studied the profile of serum cortisol in 10 healthy volunteers after the low and standard doses SST with at least 1 week between each test; they observed that cortisol continues to rise, reaching a peak after 30 minutes irrespective of the ACTH dose. [7] Longui et al drew a similar conclusion when they examined 64 healthy adults with a standard dose SST and determined that peak serum cortisol was attained, 60 minutes after the injection. [8] A variety of SST protocols are used. Some protocols involve the measurement of serum cortisol at 30 and 60min after ACTH injection, whereas others involve just a 30- or 60-min cortisol measurement after the injection. Likewise, some protocols include baseline serum cortisol and ACTH measurement before the ACTH injection, whereas other protocols do not require this step.

Herein, we surveyed clinicians to understand the different SST protocols used in KSA. Our objectives included the following: Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250 μg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level. Abbreviations: ACTH = adrenocorticotropic hormone, ANOVA = analysis of variance, HPA = hypothalamic-pituitary-adrenal, ITT = insulin tolerance test, SST = short Synacthen test. Our survey results showed similarities and differences between our single center 1 and the multicenter national practice. Data collection and curation: Hadeel Aljamei, Lama Amer, Muhammad Sohaib Khan, Eman Alrajhi, Anhar Alnassar, Reem Alahmed, Mohammed Abufarhaneh, Fayha Farraj Abothenain, Dina Mahmoud Ahmad Aljayar.