Eight patients with
beta-thalassemia who were given long-term treatment with combined multiple transfusions and
chelation therapy underwent adrenal testing. The six male and two female patients ranged in age from 7 to 19 years. Six of eight patients had delayed bone ages and height greater than 2.5 SDs below the mean. Of the six patients more than 13 years of age, two had clinical evidence of isolated adrenarche and only one had evidence of true puberty.
Cortisol levels were similar in patients and controls at zero time (10.6 +/- 1.8 micrograms/dL [292 +/- 50 nmol/L] vs 10.8 +/- 1.4 micrograms/
dL [298 +/- 39 nmol/L]) and at 60 minutes (26.6 +/- 2.5 micrograms/dL [734 +/- 69 nmol/L] vs 24.9 +/- 1.9 micrograms/dL [687 +/- 52 nmol/L]) after
insulin hypoglycemia (all values are the mean +/- SE). During an eight-hour infusion of
ACTH,
cortisol responses in the patients with
thalassemia were not significantly different from those of controls. Baseline levels of the adrenal
androgens dehydroepiandrosterone (
DHEA) and
dehydroepiandrosterone sulfate (
DHEA-S) were significantly lower in the subjects with
thalassemia compared with controls of similar bone age and pubertal status. The prolonged
ACTH infusion caused a significant increase in the
DHEA level (79.2 +/- 14.7 ng/dL [2.74 +/- 0.51 nmol/L] vs 538.6 +/- 38.1 ng/dL [18.67 +/- 4.79 nmol/L]) and the
DHEA-S level (37.5 +/- 10.8 micrograms/dL [1.02 +/- 0.29 mumol/L] vs 70.5 +/- 18.3 micrograms/dL [1.19 +/- 0.50 mumol/L]) in the patients. The patients' peak stimulated levels of
DHEA-S were significantly lower than those of the controls, whereas peak levels of
DHEA were similar in the patients and the controls. These results indicate that combined multiple transfusions and
chelation therapy preserve the integrity of the
ACTH-
cortisol axis in patients with
thalassemia. The reduced levels of adrenal
androgens, short stature, and
delayed puberty noted in our patients suggest, however, that alternative approaches to the
therapy of
thalassemia are needed.