scholarly journals THE ICET-A SURVEY ON CURRENT CRITERIA USED BY CLINICIANS FOR THE ASSESSMENT OF CENTRAL ADRENAL INSUFFICIENCY IN THALASSEMIA: ANALYSIS OF RESULTS AND RECOMMENDATIONS

2016 ◽  
Vol 8 ◽  
pp. 2016034
Author(s):  
Vincenzo De Sanctis

Introduction: In March 2015, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) implemented a two-step survey on central adrenal insufficiency (CAI) assessment in TM patients and after analysis of the collected data,  recommendations for the assessment of hypothalamic-pituitary- adrenal (HPA) axis in clinical practice were defined.Methods: To ascertain the current practice for assessment of CAI in thalassemia, the Coordinator of ICET-A sent two questionnaires by email: i) The first to evaluate the current interpretation of basal serum cortisol level (first step) and ii) The second to evaluate the current usage of ACTH test and the variability in practice" (second step). Based on the surveys the core ICET-A group prepared the recommendations for the assessment of suspected CAI in thalassemia (third step).Results: A total of 19 thalassemologists/endocrinologists have participated in the first survey and 35 specialists participated in the second step questionnaire. The survey demonstrated a considerable variability in almost all aspects of relevant current criteria used for the diagnosis of CAI.  A ROC analysis using peak value > 20 μg/dl (> 550 nmol/L), after ACTH stimulation test, was performed with the aim of identifying the optimal basal serum cortisol cut-off. The optimal threshold that maximizes sensitivity plus specificity for morning basal cortisol against peak post-ACTH value >20 μg/dl (>550 nmol/L) was 10 μg/dl (275 nmol/L).,Furthermore, the values associated with highest negative predictive value (NPV) and highest, positive predictive value (PPV) were 4.20 (115 nmol/L) and 18.45 μg/dl (510 nmol/L), respectively.Surprisingly, 20 specialists in thalassemia working in blood bank, thalassemia centres (day hospital), internal medicine, hematology and onco-hematology had poor knowledge and experience in testing for CAI and stopped filling the questionnaire after the second question. In contrast, 9 endocrinologists (8 pediatricians) and 6 hematologists working in collaboration with endocrinologists completed the questionnaire.Conclusions: While waiting more extensive adequately powered and targeted studies, physicians should adopt an acceptable policy for accurate assessment of HPA in TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are also recommended. The ICET-A recommendations are reported in order to facilitate for interested physicians the approach to successful assessment of adrenal function in thalassemia. Key words: Thalassemia, adrenal insufficiency, pitfall in the diagnosis, ACTH stimulation test, guidelines.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5640-5640
Author(s):  
Aimaz Afrough ◽  
Amy Sidorski ◽  
Roberto Salvatori ◽  
Ivan Borrello

Abstract Introduction: Glucocorticoids (GC's) are major drugs in the treatment of multiple myeloma (MM). Chronic administration of supra-physiological doses of GC's suppresses the hypothalamus-pituitary-adrenal (HPA) axis and is associated with secondary adrenal insufficiency (AI). In MM, GC's are usually administered in weekly high dose pulses. Due to long GC-free periods in such therapy, GC-induced AI is not usually considered to be a consequence of GC therapy in MM (Krasner, AS. JAMA, 1999. 282(7): p. 671-6). Here we report on the incidence of AI in MM patients treated at our center with pulse-dose GC. Methods: This is a retrospective cross-sectional study of patients with MM treated with GC-based regimens. Patients were required to have at least a random serum cortisol or a standard 250 mcg ACTH stimulation test result available in their medical record during dexamethasone-based chemotherapy. Patients were excluded if they were on dexamethasone more than 1 day a week, were lost to follow-up, had prior use of synthetic progestational agents such as megestrol or had been on oral glucocorticoids for any other medical indication. Diagnosis of AI was established by a frankly low AM serum cortisol level (<3 ug/dL) or an inadequate cortisol response to ACTH stimulation test (Salvatori, R. JAMA, 2005. 294(19): p. 2481-8). Results: A total of 45 patients were included in this study with median age of 62 (range, 49-89). Fifteen (33.3%) of patients were diagnosed with AI. The median random cortisol level in AI group was 2.3 ug/dL (range, 0.3-7.4 ug/dL) compared to 9.9 ug/dL (range, 1.0-21.2 ug/dL) in the non-AI group. The median time between the last dexamethasone dose and the serum cortisol assay was 5 days (range, 1-21). The median number of GC-based chemotherapy cycles taken before diagnosis of AI was 15 (range, 2-60). The median cumulative dexamethasone consumption was 1280 mg (range, 180-5220 mg). There was no correlation between developing AI and dose or duration of dexamethasone treatment. We observed clinical trend between cumulative doses of ≥1500 mg (P= 0.055) or use of clarithromycin (P=0.079) and developing AI, without reaching a statistically significant difference. Conclusion: The rate of AI was 33% among patients with MM on weekly pulse-dose dexamethasone. As such, patients should be periodically evaluated for this to enable early detection and proper management. Disclosures Borrello: BMS: Honoraria, Research Funding; WindMIL Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Lara Albert ◽  
Joaquím Profitós ◽  
Jordi Sánchez-Delgado ◽  
Ismael Capel ◽  
José Miguel González-Clemente ◽  
...  

Purpose. The prevalence of adrenal insufficiency (AI) in patients with decompensated liver cirrhosis is unknown. Because these patients have lower levels of cortisol-binding carrier proteins, their total serum cortisol (TSC) correlates poorly with free serum cortisol (FC). Salivary cortisol (SaC) correlates better with FC. We aimed to establish SaC thresholds for AI for the 250 μg intravenous ACTH test and to estimate the prevalence of AI in noncritically ill cirrhotic patients. Methods. We included 39 patients with decompensated cirrhosis, 39 patients with known AI, and 45 healthy volunteers. After subjects fasted ≥8 hours, serum and saliva samples were collected for determinations of TSC and SaC at baseline 0’(T0) and at 30-minute intervals after intravenous administration of 250 μg ACTH [30’(T30), 60’(T60), and 90’(T90)]. Results. Based on the findings in healthy subjects and patients with known AI, we defined AI in cirrhotic patients as SaC-T0< 0.08 μg/dL (2.2 nmol/L), SaC-T60 < 1.43 μg/dl (39.5 nmol/L), or ΔSaC<1 μg/dl (27.6 nmol/L). We compared AI determination in cirrhotic patients with the ACTH test using these SaC thresholds versus established TSC thresholds (TSC-T0< 9 μg/dl [248 nmol/L], TSC-T60 < 18 μg/dl [497 nmol/L], or ΔTSC<9 μg/dl [248 nmol/L]). SaC correlated well with TSC. The prevalence of AI in cirrhotic patients was higher when determined by TSC (48.7%) than by SaC (30.8%); however, this difference did not reach statistical significance. AI was associated with sex, cirrhosis etiology, and Child-Pugh classification. Conclusions. Measuring SaC was more accurate than TSC in the ACTH stimulation test. Measuring TSC overestimated the prevalence of AI in noncritically ill cirrhotic patients.


2019 ◽  
Vol 181 (6) ◽  
pp. 639-645 ◽  
Author(s):  
Abilash Nair ◽  
Chellamma Jayakumari ◽  
Geena Susan George ◽  
Puthiyaveettil Khadar Jabbar ◽  
Darvin V Das ◽  
...  

Objectives Injectable tetracosactide hexa-acetate, ACTH 1-24 (Synacthen), is not marketed in many countries including India, whereas Injectable long acting porcine sequence, ACTH 1-39 (Acton Prolongatum®) is easily available and much cheaper. This study aimed to find the diagnostic accuracy of ACTH stimulation test using i.m. Acton Prolongatum® (acton prolongatum stimulation test, APST) in comparison with Synacthen (short synacthen test, SST) for the diagnosis of glucocorticoid insufficiency. Methods Subjects with a suspicion of adrenal insufficiency based on clinical features underwent a SST with 250 µg Synacthen followed by APST using 30 units of Acton Prolongatum®. Serum cortisol levels were measured at 60 and 120 min following injection of Acton Prolongatum®. Stimulated peak cortisol of less than 18 µg/dL on SST was considered as adrenal insufficiency. Results Forty seven patients with mean age of 36.7 ± 14.4 years were enrolled for the study. Based on SST, twenty (n = 20) persons were classified as having adrenal insufficiency, whereas twenty-seven (n = 27) were found to be normal. Area under the curve of APST (at 120 min) was 0.986 when compared to SST, thus proving its high accuracy. A serum cortisol cut off value of 19.5 µg/dL at 120-min following stimulation with Acton Prolongatum® showed a sensitivity of 100% and specificity of 88%. Conclusion ACTH stimulation test using Acton Prolongatum® is an economical and accurate alternative to the short Synacthen test.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Amit Kumar ◽  
Maria Ghosh ◽  
Jubbin Jagan Jacob

Abstract Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) &lt;135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na &gt;30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of &lt;18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.


2020 ◽  
Vol 56 (2) ◽  
pp. 2001478
Author(s):  
Brian Lipworth ◽  
Rory Chan ◽  
Chris RuiWen Kuo

2020 ◽  
Vol 67 (1.2) ◽  
pp. 95-101
Author(s):  
Worapaka Manosroi ◽  
Pichitchai Atthakomol ◽  
Supawan Buranapin ◽  
Nipawan Waisayanand ◽  
Mattabhorn Phimphilai ◽  
...  

2020 ◽  
Vol 56 (2) ◽  
pp. 2002149
Author(s):  
Alexandra M. Nanzer ◽  
Grainne D'Ancona ◽  
Philip A. Kelly ◽  
David J. Jackson

Endocrines ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 125-137
Author(s):  
Shogo Akahoshi ◽  
Yukihiro Hasegawa

The present review focuses on steroid-induced adrenal insufficiency (SIAI) in children and discusses the latest findings by surveying recent studies. SIAI is a condition involving adrenocorticotropic hormone (ACTH) and cortisol suppression due to high doses or prolonged administration of glucocorticoids. While its chronic symptoms, such as fatigue and loss of appetite, are nonspecific, exposure to physical stressors, such as infection and surgery, increases the risk of adrenal crisis development accompanied by hypoglycemia, hypotension, or shock. The low-dose ACTH stimulation test is generally used for diagnosis, and the early morning serum cortisol level has also been shown to be useful in screening for the condition. Medical management includes gradually reducing the amount of steroid treatment, continuing administration of hydrocortisone corresponding to the physiological range, and increasing the dosage when physical stressors are present.


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