scholarly journals MON-189 Evaluation of Adrenal Insufficiency and Recovery in Rheumatology Patients on Long-Term Glucocorticoid Therapy

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rebecca Sagar ◽  
Sarah Mackie ◽  
Paul Michael Stewart ◽  
Afroze Abbas
Keyword(s):  
Adrenal Insufficiency ◽  
Glucocorticoid Therapy ◽  
Published Data ◽  
Baseline Cortisol ◽  
Time Period ◽  
Significant Difference ◽  
Show Evidence ◽  
Synacthen Test ◽  
Short Synacthen Test

Abstract Background Long-term glucocorticoid (GC) therapy is commonly used to treat rheumatological conditions. This may result in tertiary adrenal insufficiency, as a result of suppression of the HPA axis, when GC doses are weaned/withdrawn. There is little published data about tertiary adrenal insufficiency in this group. This study aims to further evaluate prevalence, characteristics and recovery of adrenal insufficiency in these patients at a large UK teaching hospital. Methods We retrospectively identified patients seen in outpatient clinics between January 2014 and September 2019 who had received tapering doses of long-term GC to treat their underlying condition (largely patients with polymyalgia rheumatica, giant cell arteritis or other vasculitis) and had either had a 9am cortisol or short synacthen test (SST). Data were collected using a standardised proforma. Results There was a total of 238 patients, median age of 71 years with a female preponderance (75%). Mean duration of glucocorticoid use was 63.3 months. Mean peak dose of glucocorticoid was 29.2mg. 142 patients had 9am cortisol as the first line test to assess adrenal function. 65% of these were considered sub-optimal based on local protocol (cortisol <350nmol/L). 38% of these patients went on to have SST, of which 56% continued to show evidence of sub-optimal cortisol production. All patients where baseline 9am cortisol was <100nmol/L failed to reach stimulated cortisol of >500nmol/L on SST, whereas 31% failed SST if 9am cortisol was 250-350 nmol/L. In total 138 SSTs were performed of which 51% (n=70) were abnormal (cortisol <500nmol/L post synacthen). When baseline cortisol was <100nmol/L on SST, all patients had a suboptimal peak response. However, where baseline cortisol on SST was >350 nmol/L only 3% had a sub-optimal peak cortisol. 32 of these patients with an abnormal baseline SST went on to have a repeat SST within 2 years. 50% (n=16) continued to be suboptimal. Of the 32 patients, 38% (n=12) were switched to hydrocortisone with 33% showing complete adrenal recovery, average time to recovery of 25 months. 62% (n=20) patients did not switch, with 60% demonstrating recovery within the same time period (p=0.05). Mean ACTH levels in patients who had sub-optimal SST were 23.1 ng/L (n=19). ACTH levels were not different between those who recovered and those who did not (p=0.23). Conclusion Our study suggests that tertiary adrenal insufficiency is highly prevalent in this cohort of patients with rheumatological conditions requiring long-term glucocorticoid therapy. A 9am cortisol threshold of greater than 350nmol/L excludes most patients with adrenal insufficiency. These data also suggest no significant difference in adrenal recovery if switched to hydrocortisone versus continuing on prednisolone. ACTH levels were not fully suppressed in patients with adrenal insufficiency and did not predict recovery.

scholarly journals P77 What is the role of cortisol and short Synacthen testing in patients weaning off long term glucocorticoids?

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Ruth Smith ◽  
Mohammed Akil
Keyword(s):  
Adrenal Insufficiency ◽  
Serum Cortisol ◽  
Prednisolone Dose ◽  
Morning Cortisol ◽  
Starting Dose ◽  
Synacthen Test ◽  
Short Synacthen Test ◽  
Age Range

Abstract Background Many rheumatological conditions are treated with steroids. Patients on long-term steroids are known to be at risk of adrenal insufficiency especially when withdrawing them. Sheffield Teaching Hospital (STH) Endocrinologists advised the following protocol for patients reducing steroids to determine hypothalamic pituitary adrenal status and confirm safe onward withdrawal of steroids:- After 1 month on 3mg prednisolone measure 9am serum cortisol and ACTH (after 24 hours off steroid)- If cortisol <150nmol/L or < 200nmol/L and ACTH <10pg/mL - refer Endocrinology- If cortisol 200-430nmol/L (or > 150nmol/L and ACTH >10pg/mL) arrange short Synacthen test (SST). If 30-minute cortisol <430nmol/L - refer Endocrinology. If 30 minute cortisol >430nmol/L - stop steroids and monitor for adrenal insufficiency (give hydrocortisone 20mg TDS to cover illness for 3 months after stopping prednisolone). Methods We performed a retrospective review of records of rheumatology patients having morning cortisol level checked July 2017-January 2019 to determine how many tests were abnormal and to what degree the results changed management. Results 160 cortisol tests were performed. 36 were excluded from further analysis. Of the 124 cases reviewed: 80 females and 44 males. Age range 18-87; mean 64 years. Starting dose of prednisolone 5-60mg. Duration of steroid use 6 months to > 10 years; modal duration 13-24 months (49 patients/40%). 59 patients/48% were taking other immunosuppressants. Prednisolone dose at cortisol testing 1-5mg; modal value 3mg (89 patients/72%). 12 patients/10% had a normal morning cortisol. 9 patients/7% fell into the group ‘cortisol <150nmol/L refer Endocrinology.’ 103 patients/83% fell into the group requiring SST. 79 patients had an SST (out of an expected 112). 58/73% were normal. 17 patients/81% with abnormal SST were referred to Endocrinology. 11/65% were advised to wean prednisolone as per normal rheumatology practice of 1mg per month; 1/6% to continue prednisolone and repeat SST in 2-3 months; 3/18% to commence hydrocortisone. 2/12% had not yet been seen. Of the patients with abnormal SST: 8 females and 13 males. Age range 32-87; mean 67 years. Starting dose of prednisolone 5-40mg. Duration on steroids 6 months to > 10 years; modal duration 13-24 months in 9 patients/43%. 12 patients/57% were on other forms of immunosuppression. Conclusion Endocrinology guidance changed the management of 3 patients/2% by the introduction of hydrocortisone compared with previous rheumatology standard practice of weaning prednisolone by 1mg per month or similar. No distinctive characteristics were identified in patients with abnormal SST, except for a greater proportion of men (35% of whole group: 62% of abnormal SST group). Given the limited impact of the investigations, and the shortage of Synacthen, a new protocol has been implemented: if morning cortisol <300nmol/L, or 300-350nmol/L and symptoms - contact Endocrinology for SST; if 30 minute cortisol <430nmol/L - refer Endocrinology; otherwise wean prednisolone as normal. Disclosures R. Smith None. M. Akil Honoraria; AbbVie, Actelion, Celgene, Astra Zenica, Lilly and UCB.

scholarly journals Pharmacodynamic studies of nasal tetracosactide with salivary glucocorticoids for a noninvasive Short Synacthen Test

2020 ◽  
Vol 105 (8) ◽  
pp. 2692-2703 ◽  
Author(s):  
Charlotte J Elder ◽  
Ruben Vilela ◽  
Trevor N Johnson ◽  
Rosie N Taylor ◽  
E Helen Kemp ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Salivary Cortisol ◽  
Plasma Cortisol ◽  
Pharmacokinetic Analysis ◽  
Healthy Children ◽  
Noninvasive Test ◽  
Pediatric Study ◽  
Significant Difference ◽  
Synacthen Test ◽  
Short Synacthen Test

Abstract Context The Short Synacthen Test (SST) is the gold standard for diagnosing adrenal insufficiency. It requires invasive administration of Synacthen, venous sampling, and is resource-intensive. Objective To develop a nasally administered SST, with salivary glucocorticoids measurement, to assess the adrenal response. Design We conducted 5 studies: 4 open-label, sequence-randomized, crossover, pharmacodynamic studies testing 6 doses/formulations and a repeatability study. Additionally, pharmacokinetic analysis was undertaken using our chosen formulation, 500 µg tetracosactide with mucoadhesive chitosan, Nasacthin003, in our pediatric study. Setting Adult and children’s clinical research facilities. Participants A total of 36 healthy adult males and 24 healthy children. Intervention We administered all 6 nasal formulations using an European regulator endorsed atomization device. The IV comparators were 250 µg or 1 µg SST. Main Outcome Measures We analyzed paired blood and saliva samples for plasma cortisol and salivary cortisol and cortisone. Results The addition of chitosan to tetracosactide and dose escalation increased peak cortisol response (P = 0.01 and 0.001, respectively). The bioavailability of Nasacthin003 was 14.3%. There was no significant difference in plasma cortisol at 60 minutes between 500 µg Nasacthin003 and 250 µg IV Synacthen (P = 0.17). The repeatability coefficient at 60 minutes was 105 nmol/L for IV Synacthen and salivary cortisol and cortisone was 10.3 and 21.1 nmol/L, respectively. The glucocorticoid response in children was indistinguishable from that of adults. Conclusions Nasal administration of Nasacthin003 generates equivalent plasma cortisol values to the 250-µg IV SST and, with measurement at 60 minutes of salivary cortisol or cortisone, provides a noninvasive test for adrenal insufficiency.

scholarly journals Recovery of the Hypothalamo-Pituitary-Adrenal Axis After Transsphenoidal Adenomectomy for Non–ACTH-Secreting Macroadenomas

2019 ◽  
Vol 104 (11) ◽  
pp. 5316-5324 ◽  
Author(s):  
Riccardo Pofi ◽  
Sonali Gunatilake ◽  
Victoria Macgregor ◽  
Brian Shine ◽  
Robin Joseph ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Hpa Axis ◽  
Secondary Adrenal Insufficiency ◽  
Baseline Cortisol ◽  
Transsphenoidal Adenomectomy ◽  
Synacthen Test ◽  
Acth Secreting ◽  
Short Synacthen Test ◽  
Pituitary Adrenal Axis ◽  
Hpa Function

Abstract Context Secondary adrenal insufficiency is a potential complication of transsphenoidal adenomectomy (TSA). Most centers test recovery of the hypothalamo-pituitary-adrenal (HPA) axis after TSA, but, to our knowledge, there are no data predicting likelihood of recovery or the frequency of later recovery of HPA function. Objective To assess timing and predictors of HPA axis recovery after TSA. Design Single-center, retrospective analysis of consecutive pituitary surgeries performed between February 2015 and September 2018. Patients Patients (N = 109) with short Synacthen test (SST) data before and at sequential time points after TSA. Main outcome measures Recovery of HPA axis function at 6 weeks, and 3, 6, and 9 to12 months after TSA. Results Preoperative SST indicated adrenal insufficiency in 21.1% Among these patients, 34.8% recovered by 6 weeks after TSA. Among the 65.2% (n = 15) remaining, 13.3% and 20% recovered at 3 months and 9 to 12 months, respectively. Of the 29% of patients with adrenal insufficiency at the 6-week SST, 16%, 12%, and 6% subsequently recovered at 3, 6, and 9 to 12 months, respectively. Preoperative SST 30-minute cortisol, postoperative day 8 cortisol, and 6-week postoperative SST baseline cortisol levels above or below 430 nmol/L [15.5 μg/dL; AUC ROC, 0.86]; 160 nmol/L (5.8 μg/dL; AUC ROC, 0.75); and 180 nmol/L (6.5 μg/dL; AUC ROC, 0.88), were identified as cutoffs for predicting 6-week HPA recovery. No patients with all three cutoffs below the threshold recovered within 12 months after TSA, whereas 92% with all cutoffs above the threshold recovered HPA function within 6 weeks (OR, 12.200; 95% CI, 5.268 to 28.255). Conclusion HPA axis recovery can occur as late as 9 to 12 months after TSA, demonstrating the need for periodic reassessment of patients who initially have SST-determined adrenal insufficiency after TSA. Pre- and postoperative SST values can guide which patients are likely to recover function and potentially avoid unnecessary lifelong glucocorticoid replacement.

Do we need 30 min cortisol measurement in the short synacthen test: a retrospective study

2019 ◽  
Vol 96 (1138) ◽  
pp. 467-472
Author(s):  
Rajeev Kumar ◽  
Peter Carr ◽  
Kimberley Moore ◽  
Zeeshan Rajput ◽  
Louise Ward ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Adrenal Insufficiency ◽  
Late Response ◽  
Inadequate Response ◽  
Insufficient Response ◽  
Group A ◽  
Synacthen Test ◽  
Cortisol Levels ◽  
Group B ◽  
Short Synacthen Test

ObjectiveThe short synacthen test (SST) is widely used across the UK to assess adrenal reserve but there remains no consensus on the timing of cortisol sampling to help diagnose adrenal insufficiency. The main objective of our study was to see if both 30 and 60 min sample are required following administration of synacthen to investigate suspected adrenal insufficiency (AI).DesignThis was a single-centre retrospective study of 393 SSTs measuring 0, 30 and 60 min cortisol levels after administration of 250 µg of synacthen.Patients and methodsAll the SSTs for patients suspected of primary or secondary AI between April 2016 and October 2018 were included in this study. The tests were performed as per our hospital protocol. A post-adrenocorticotropic hormone (ACTH) cortisol response of 420 nmol/L at any time point was considered adequate to rule out AI. The data were analysed to ascertain the proportion of patients who achieved this level at 30 and/or 60 min.ResultsA total of 393 SST results were included in this study. Patients were divided into two groups depending on whether (group A) or not (group B) they were on steroids. Overall, a total of 313 (79.6%) subjects achieved cortisol level of ≥420 nmol/L at 30 and 60 min while 19 (4.8%) had late response (ie, insufficient 30 min cortisol levels, rising to ≥420 nmol/L at 60 min). Another 61 subjects (15.5%) showed insufficient response at both 30 and 60 min (ie, failed to achieved level of ≥420 nmol/L). Importantly, there was no patient in either group who had adequate response at 30 min and then failed at 60 min. Patients in group A were more likely to have inadequate response at both 30 and 60 min while patients in group B were more likely to have normal response at both time points.ConclusionsOur results suggest that about 5% of people undergoing SST may be inappropriately diagnosed as having AI (and subjected to long-term unnecessary steroid treatment) if the 60 min sample is not maintained. We suggest that 30 min sample does not add any additional diagnostic utility and can be omitted thus simplifying SST even further and saving on cost and resources. We propose that single measurement after 60 min of administration of synthetic ACTH is a sufficient screening test for AI.

scholarly journals P.089 Recovery from chronic secondary adrenal insufficiency in patients with pituitary disorders

2016 ◽  
Vol 43 (S2) ◽  
pp. S41-S41
Author(s):  
V Munro ◽  
B Tugwell ◽  
S Doucette ◽  
DB Clarke ◽  
A Lacroix ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Tumour Size ◽  
Pituitary Surgery ◽  
Complete Recovery ◽  
Glucocorticoid Therapy ◽  
Hormone Deficiency ◽  
Secondary Adrenal Insufficiency ◽  
Glucocorticoid Treatment ◽  
Acth Secreting

Background: Patients with pituitary disorders may be placed on steroid replacement for secondary adrenal insufficiency (SAI), generally after pituitary surgery; however, data regarding recovery of long-term SAI are lacking. We conducted a study to assess the longer term recovery rate of SAI in patients with pituitary disorders. Methods: We identified all SAI patients from prospectively entered data in the Halifax Neuropituitary Database from November 1, 2005 to September 30, 2014, who had required glucocorticoid therapy for >3 months, and a minimum follow-up of 6 months. Exclusion: ACTH-secreting adenomas; peri-operative glucocorticoid treatment only; glucocorticoids for non-pituitary conditions. Results: 55 patients fulfilled the criteria, 41 (75%) of which had transsphenoidal surgery. Nine (16.4%) patients had complete recovery of SAI over a median of 20 months (range: 8–51). Smaller tumour size and initial cortisol >175 nmol/L had increased likelihood of recovery; those with secondary hypogonadism or growth hormone deficiency were less likely to recover. Conclusions: This is the first study to examine long-term recover of SAI in patients with pituitary disorders: approximately 1 in 6 patients recover adrenal function, up to 5 years after diagnosis. Consequently, patients with SAI should undergo regular testing to prevent unnecessary chronic glucocorticoid therapy.

scholarly journals Comparing the utility of 30- and 60-minute cortisol levels after the standard short synacthen test to determine adrenal insufficiency

Medicine ◽  
2020 ◽  
Vol 99 (43) ◽  
pp. e22621
Author(s):  
Muhammad Imran Butt ◽  
Nouf Alzuhayri ◽  
Lama Amer ◽  
Muhammad Riazuddin ◽  
Hadeel Aljamei ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Synacthen Test ◽  
Cortisol Levels ◽  
Short Synacthen Test

scholarly journals No Improvement in Survival for T-PLL Patients over the Last Two Decades

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1552-1552
Author(s):  
Matthew J Cross ◽  
Monica Else ◽  
Ricardo Morilla ◽  
Mark Edward Ethell ◽  
Michael Potter ◽  
...  
Keyword(s):  
Complete Blood Count ◽  
Single Agent ◽  
Diagnostic Techniques ◽  
Published Data ◽  
Cell Transplant ◽  
Trisomy 8 ◽  
Prolymphocytic Leukemia ◽  
Karyotypic Abnormality ◽  
Significant Difference

BACKGROUND: T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive, post thymic lymphoid malignancy, with an incidence of approximately 0.1/100,000 people. T-PLL accounts for ~2% of all mature lymphocytic leukaemias in adults >30 years. Median overall survival (OS) ~20 months and long term remissions are infrequent. Intravenous alemtuzumab, a monoclonal antibody directed against CD52 remains the most effective treatment in T-PLL. At the Royal Marsden Hospital (RMH) we have been using alemtuzumab for T-PLL since the early 1990s. We describe our experience over the last 3 decades. METHODS: We included 174 T-PLL patients that were diagnosed or treated at RMH between 1989-2019. Immunophenotyping data was available through our hematological malignancy diagnostic service (HMDS) from 1998 onwards. Kaplan-Meier analysis was used for OS and disease free interval (DFI) RESULTS: There were 174 patients in total. Mean age at diagnosis was 61 years old (range 32-88) and M: F ratio was ~2:1 (113:61). 90 patients had reliable information on complete blood count (CBC) at diagnosis with median white blood cell count of 74 x 109/L (range 10-918), median hemoglobin 126 g/L (range 59-175) and median platelet count 116 x 109/L (range 7-513). Sufficient immunophenotyping data was available for analysis in 135/174 patients. The results showed predictably high expression of CD2, CD3, CD5, CD7, CD52 and TCRαβ. CD25 was positive in 67/135 (50%) of cases which is higher than the 18-35% seen in the current literature. CD4+/CD8- cases comprised 83/135 (61%) with CD4-/CD8+ 19/135 (14%), CD4+/CD8+ 32/135 (23%) and CD4-/CD8- 2/135 (2%). These results are summarized in table 1. Karyotyping/FISH (fluorescent in-situ hybridization) records showed a clonal result in 84 patients and of these 65/84 (77%) had an aberration of chromosome 14. These comprised 48/65 with inv(14), 6/65 t(14;14), 2/65 t(X;14), 1/65 TCL1 gene rearrangement by FISH and 8/65 with TRA/TRD involvement by FISH. Other frequent abnormalities seen were i(8)(q10) in 31/84 (39%) and complex karyotypic abnormality in 40/84 (48%). Lower frequency abnormalities seen were monosomy 11 in 8/84 (9%), monosomy 12 in 8/84 (9%), trisomy 8 in 6/84 (7%), 17p loss in 5/84 (6%) and mononsomy 13 in 4/84 (5%). Alemtuzumab was used in 116 patients, 69/116 (59%) receiving it as frontline treatment and 47/116 (41%) as salvage therapy. In 50/116 (43%) alemtuzumab was used as single agent, the remaining 66/116 (57%) receiving combination therapy, mostly pentostatin. Mean time from diagnosis to receiving alemtuzumab was 6.8 months (range 0-53 months). Overall response rate (ORR) to alemtuzumab was 94/116 (81%) with complete remission (CR) 69/116 (59%), partial remission (PR) 25/116 (22%) and no response (NR) 20/116 (17%). Alemtuzumab produced better response rates when used as frontline therapy. Table 2 summarizes these results and OS and DFI are shown in figures B and C. Allogeneic stem cell transplant (allo-SCT) was performed in 34 patients. Median OS post allo-SCT was 22 months and median DFI 31 months. Relapse rate post allo-SCT was 47%, non-relapse mortality 38% and transplant related mortality 29%. Figures D and E show OS and DFI post allo-SCT. Although relapse rates are high post allo-SCT there is a small cohort of patients who are achieving long term remission. We analysed OS by decade of diagnosis covering 3 decades 1990-1999, 2000-2009 and 2010-2019. The median OS for the whole cohort was 20.6 months with median OS of 21 months, 23 months and 19 months for each decade respectively. Results are shown in figure A. There was no statistically significant difference between the curves by log-rank analysis. DISCUSSION: Immunophenotyping results were similar to previous published data on T-PLL except for an increase in CD25 expression at 50%. Our data shows that outcomes in T-PLL have remained unchanged since the first decade of alemtuzumab usage, with no improvement in OS in the last 20 years. Despite improvements in diagnostic techniques and supportive care median OS is static at approximately 20 months. These results highlight the need for novel therapies in T-PLL. Given the rarity of T-PLL, international, multi-center, randomised trials are needed to improve outcomes. Disclosures Cross: Royal Marsden Cancer Charity: Other: MD Residency, Research Funding. Iyengar:Abbvie: Honoraria; Janssen: Honoraria. Dearden:Janssen: Honoraria; Genentech: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria.

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