Letters to the Editor Indian Pediatrics 2005; 42:733-734 |
Diagnostic Adrenal Dysfunction in Thalassemic Children: A Note of Caution |
1. While using 1 µg ACTH stimulation tests, it is the 30 minute cortisol and not the 60 minute cortisol that forms the basis of diagnosis of adrenal insufficiency(2). Although the authors have mentioned that one patient had adrenal insufficiency by 1 µg ACTH test, the absolute values are not given in the article. 2. Standard commercial preparation of 1 µg ACTH is not available. It is usually prepared by diluting 250 µg ACTH. These are stored over time and used as and when patients are tested. However, ACTH is easily degradable and the biological activity decreases over time. The activity of the ACTH preparation has to be determined at the end of the study as described by Gandhi, et al.(3) 3. The authors have used basal cortisol <400 mmol/L (14.5 µg/dL) to define abnormal adrenal function. This is a rather high value for making a conclusive diagnosis of adrenal dysfunction despite the explanations given by the authors. A very low early morning plasma cortisol (<138 nmol/L, 5 µg/dL) is highly suggestive of adrenal insufficiency, but lacks sensitivity because most patients with adrenal insufficiency have cortisol values exceeding this value. Sensitivity is increased by raising the cut off value for a presumptive diagnosis to 275 nmoL/l (10 µg/dL), but this considerably decreases the specificity(2). Hence using 400 nmol/L as cut off would reduce the specificity further. Furthermore, at least in the evolution of adrenal dysfunction due to primary adrenal insufficiency, stimulated cortisol values become abnormal earlier than basal cortisol values(4). Hence there is no reason to believe that it is different in secondary adrenal insufficiency, where the trophic action of ACTH is lost. In the absence of normal controls to substantiate the basal cortisol values, the authors should refrain from using the term "adrenal dysfunction" to describe patients with basal cortisol <400 nmol/L. Hence, it is incorrect to classify a patient with "low" basal cortisol (<400 nmol/L) and normal post ACTH cortisol as having adrenal insufficiency. Obviously, such a state has no therapeutic implication. Further, it gives an impression that adrenal dysfunction is very common (9 out of 20 patients) in thalassemics who have received multiple transfusions. Mathew John,
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