High prevalence of "biochemical" adrenal insufficiency in thalassemics: is it a matter of different testings or decreased cortisol binding globulin?

Abstract

Context: High prevalence of "biochemical" adrenal insufficiency (AI) in thalassemics has been reported. However, "clinical" AI is rare.

Aim: The aim was to determine whether cortisol binding globulin (CBG) or tests used in assessing adrenal function contributed to the abnormally high prevalence of biochemical AI.

Setting: The study was conducted at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Participants: Participants included 56 children and adolescents with thalassemia and 44 controls.

Main outcome measures: Serum CBG and adrenal function test results assessed by 1 μg cosyntropin test and insulin tolerance test (ITT) were measured. Free cortisol index (FCI) calculated by total cortisol (TC)/CBG and calculated free cortisol (cFC) were determined.

Results: Mean (sd) CBG levels were comparable between patients and controls [45.2 (11.0) vs. 47.0 (8.6) mg/liter]. Peak TC, FCI, and cFC after cosyntropin test were lower in thalassemics [TC, 15.2 (4.0) vs. 18.9 (3.1) μg/dl; FCI, 3.4 (0.8) vs. 4.2 (1.2) μg/mg, P <0.001; and cFC, 1.03 (0.38) vs. 1.44 (0.61) μg/dl, P = 0.008]. Thirty of 56 thalassemics (53.6%) had AI, defined as having peak TC of less than 16 μg/dl. ITT was performed in 26 of those 30 patients. Five of 26 patients had peak TC after an ITT of at least 20 μg/dl. As a result, the estimated frequency of AI in the entire patient group was reduced by approximately 10%.

Conclusion: The 1 μg cosyntropin test could be an adrenal function screening test in thalassemics. However, for definite diagnosis, ITT should be performed in those having peak total cortisol of less than 16 μg/dl after the 1 μg cosyntropin test.