Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients.
OBJECTIVE
Previous studies suggested that in patients with thalassemia major, initiating deferoxamine (DFO) therapy before puberty can prevent iron-induced failure of growth and puberty. However, early initiation of chelation has also been associated with DFO toxicity. The aim of this retrospective study was to determine the prevalence rates of endocrine complications and DFO bone toxicity in our thalassemia major patients and to correlate them with the degree of iron chelation.


METHODS
Thirty-nine patients with thalassemia major were followed for a median of 16.3 yr (range 2-28). Individual mean serum ferritin level during the study period was calculated using repeated annual measurements. Bone DFO toxicity was assessed by wrist and spine radiographs; endocrine dysfunction by anthropometric measurements and pubertal stage; and hypogonadotropic hypogonadism by lack of luteinizing hormone response to gonadotropin-releasing hormone.


RESULTS
Chelation therapy was initiated at median age 4.9 yr. Mean serum ferritin level during the study period was 2698 +/- 1444 ng/mL. Hypogonadism was noted in 59% of the patients who reached pubertal age, and short stature was found in 36% of patients who reached final height. Mean ferritin level of 2500 ng/mL during puberty was the cut-off for hypogonadism, and ferritin level of 3000 ng/mL during prepuberty was the cut-off for final short stature. None of the patients who attained final height had signs of DFO bone toxicity.


CONCLUSIONS
High serum ferritin levels during puberty are a risk factor for hypogonadism, and high serum ferritin levels during the first decade of life predict final short stature. It remains to be determined whether improving chelation by earlier initiation of DFO or by the combined use of DFO and deferiprone will lead to better growth and sexual development without DFO toxicity.
Shalitin
Shlomit
S
Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Carmi
Doron
D
Weintrob
Naomi
N
Phillip
Moshe
M
Miskin
Hagit
H
Kornreich
Liora
L
Zilber
Rama
R
Yaniv
Isaac
I
Tamary
Hannah
H
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003676:Deferoxamine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005293:Ferritins / Q000097:blood*; D006130:Growth Disorders / Q000097:blood / Q000209:etiology; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000209:etiology; D007223:Infant; D007501:Iron / Q000097:blood; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D011379:Prognosis; D011627:Puberty / Q000097:blood*; D012189:Retrospective Studies; D012307:Risk Factors; D017086:beta-Thalassemia / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology
D015415:Biomarkers; D007502:Iron Chelating Agents; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine