We thank Dr. Mathew John for his interest in our article(1). His comments are very meaningful. The following paragraphs address the suggestions/comments:

Regarding the 1 µg ACTH test, only freshly prepared dilution of the standard preparation was used and it was not stored for further use. The 30 min value was used in the 1µg test to define adrenal insufficiency, in accordance with the current recommendation, though the 60 min response was also assessed. In the solitary patient, who had failed the 1µg ACTH stimulation test, the basal and 30 min cortisol levels were 230 and 300 nmol/L, respectively.

We agree with the comment that the baseline cortisol values alone cannot be used to diagnose adrenal insufficiency. It is precisely for this reason that we carefully avoided the use of the term "adrenal insufficiency" in the concluding paragraph. Instead we designated it as a subtle abnormality of adrenocortical function.

Though the baseline cortisol cut off value of 400 nmol/L may appear arbitrary but it was based on published evidence on adrenal function during stress of illness or pharmacological stress. Stewart, et al. had shown that no patient with a morning cortisol value >14 mg/dL (~400 nmol/L) failed an insulin tolerance test(2). Similarly it has been shown that random cortisol value below 13 mg/dL (~360 nmol/L), during severe stress is a predictor of increased mortality with potential benefit with glucocorticoid supplementation(3). Since thalassemics are chronically stressed with anemia, hypoxia and multiple organ dysfunction, we proposed that a baseline cortisol value of <400 nmol/L is inappropriately low for these patients. Any intermittent acute ilnness has the potential to precipitate adrenal insufficiency. Though adrenal insufficiency, by accepted criteria of stimulation tests, is less common in thalassemics, a high index of suspicion is warranted to diagnose and treat this condition in thalassemics in an appropriate clinical setting.

R.K. Marwaha,
Advanced Pediatrics Center,
PGIMER, Chandigarh 160 012, India.
E-mail: rammarwaha1@rediffmail.com

1. Srivatsa A, Marwaha RK, Muralidharan R, Trehan A. Assessment of adrenal endocrine function in Asian thalassemics. Indian Pediatr 2005; 42: 31-35.

2. Stewart PM, Corie J, Seckl JR, Edwards CRW, Padfield PL. A rational approach for assessing the hypothalamopapituary adrenal. Lancet 1988; 11: 1208-1210.

3. Grinspoon SK, Biller BMK. Laboratory assessment of adrenal insufficiently. J Clin Endocrinol Metab 1994; 79: 923-931.