title: The ICET-A Survey on Current Criteria Used by Clinicians for the Assessment of Central Adrenal Insufficiency in Thalassemia: Analysis of Results and Recommendations.
abstract: BACKGROUND
  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 assess 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 study demonstrated a considerable variability in almost all aspects of relevant current criteria used for the diagnosis of CAI. An 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 the 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 for 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 a successful assessment of adrenal function in thalassemia.
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authors.affiliation: Department of Pediatrics, Division of Endocrinology, Hamad General Hospital Doha, Qatar and Department of Pediatrics, Division of Endocrinology, Alexandria University Children's Hospital, Alexandria, Egypt.
authors.forename: Ashraf T
authors.initials: AT
authors.lastname: Soliman
authors.affiliation: Department of Pediatrics, Ain Shams University, Cairo, Egypt.
authors.forename: Heba
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authors.affiliation: Endocrinology and Diabetes Department of Elias Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
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authors.affiliation: Head Division of Pediatric Hematology Oncology, Deputy Chair of Hematology & Head Section of Hematology Research Lab, King Fahd Medical Research Center Department of Hematology Faculty of Medicine, King Abdulaziz University Jeddah, Kingdom of Saudi Arabia.
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authors.affiliation: Head of Pediatric Endocrine Unit, Department of Child Health, Sultan Qaboos University Hospital, Al-Khoud, Sultanate of Oman.
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authors.affiliation: Thalassemia Unit, Maternal and Child Department, Garibaldi Hospital, Catania, Italy.
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authors.affiliation: Director of Thalassemia Diagnosis Center of Mediterranean Blood Diseases Foundation Antalya, Turkey.
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authors.affiliation: Department of Oncology, University of Turin, Mauriziano Hospital, Turin, Italy.
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authors.affiliation: Emeritus Director in Pediatrics, Children's Hospital "Santobono-Pausilipon", Naples, Italy.
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authors.affiliation: Department of Pediatrics, Ain Shams University, Cairo, Egypt.
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authors.affiliation: Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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authors.affiliation: Department of Pediatrics, Endocrinology Unit, Alexandria University Children's Hospital, Egypt and Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman.
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authors.affiliation: Çukurova University, Medical Faculty, Department of Pediatric Hematology, Adana, Turkey.
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authors.affiliation: Professor Pediatric Hemato-Oncology, Christian Medical College and Hospital, Ludhiana Punjab, India.
authors.forename: Praveen
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authors.forename: Iva
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authors.affiliation: First Department of Paediatrics, University of Athens, Athens, Greece.
authors.forename: Christos
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