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Chapter 40 Thalassemia Syndromes 559

40 the mean serum ferritin level in the entire group was 3500 ng/mL,
35.0% indicating persistence of a high level of excess iron burden in most
35 of this group.
Vertebral fractures (%) 25 17.6% frequently allows a normal onset of puberty and development of
Regular chelation therapy started early in the first decade of life
30
274
secondary sexual changes. Administration of recombinant human
growth hormone in conventional doses increases height velocity in
20
275,276
Normal or higher
patients with growth hormone deficiency.
15
doses of recombinant human growth hormone increase growth
10
277,278
levels of insulin-like growth factor I.
For patients with a func-
5 7.7% 8.5% velocity in patients with normal growth hormone reserve but low
tional hypothalamic–pituitary axis, treatment with gonadotropin-
279
0 releasing hormone may induce pubertal changes. In others,
10–15 >15–20 >20–30 >30 administration of sex steroids is necessary to induce secondary sexual
(n = 65) (n = 47) (n = 17) (n = 20) characteristics.
Age (y)
Fig. 40.9 FRACTURE RISK IN THALASSEMIA BY AGE GROUP. Diabetes Mellitus
Thalassemia patients have increased risk of vertebral fractures by age group.
(Adapted from Pontipa Engkakul, Pat Mahachoklertwattana, Suphaneewan Jaovi- Abnormal carbohydrate metabolism is common in older patients
sidha, Ampaiwan Chuansumrit, Preamrudee Poomthavorn, MD, Niyata Chitrapazt, with thalassemia major. Prepubertal children usually have normal
MD, and Suporn Chuncharunee, MD: Unrecognized vertebral fractures in adolescents glucose metabolism, but pubertal patients exhibit impaired responses
and young adults with thalassemia syndromes. J Pediatr Hematol Oncol 35:212–217, to glucose load. Higher than normal insulin levels despite normal
280
2013.) glucose levels are also encountered during puberty. The defect in
these patients appears to be related to insulin resistance, with insulin
deficiency developing later in the progression to diabetes. Rates of
190
diabetes are reported close to 6% to 8%. Diabetes occurs more
frequently in patients with hepatitis C and hepatic dysfunction. 281–283
Oral hypoglycemic agents have been used to regulate hyperglycemia
and may reduce the rate of further deterioration of glucose
metabolism. 284
Laboratory findings of hypothyroidism and hypoparathyroidism
are present in approximately 14% of patients with thalassemia
major. 285–289 Clinical findings associated with these deficiencies are
uncommon. 290
Liver and Gallbladder
Hepatomegaly occurring before the initiation of transfusion therapy
in severely affected patients is primarily a consequence of extramedul-
lary hematopoiesis. With the amelioration of the anemia, the liver
diminishes in size. However, as transfusion therapy continues, iron
Fig. 40.10 COMPRESSION FRACTURE OF L2 VERTEBRA IN A accumulation provides a new reason for hepatomegaly and resultant
PATIENT WITH SEVERE β-THALASSEMIA. (From Pearson HA, Benz EJ liver injury. Iron deposition, first present in the Kupffer cells, ulti-
Jr: Thalassemia syndromes. In Miller DR, Baehner RL, McMillan CW, editors: mately engorges the parenchymal cells, resulting in an appearance
Smith’s blood diseases of infancy and childhood, ed 5, St. Louis, 1984, CV Mosby, that is indistinguishable from that of idiopathic hemochromatosis. 291–293
p 439.) The hepatocellular injury of iron overload may be attributable to the
liberation of hydrolases resulting from initiation by the ferrous form
294
of iron and peroxidative damage of lysosomal membrane lipids.
Fibrosis is usually followed by cirrhosis and an increased risk of
Growth and Endocrine Status hepatocellular carcinoma. The risk of liver damage and the rate of
progression may be increased by the concomitant presence of exces-
270
Growth retardation, including skeletal and dental deformities, was sive iron with viral hepatitis.
common even in young children until the use of hypertransfusion Regular chelation therapy is the key to maintaining normal or
regimens restored relatively normal growth during the first decade. near-normal hepatic iron concentrations and preventing iron-induced
Without iron chelation therapy, the adolescent growth spurt is often hepatic fibrosis and cirrhosis. Treatment with deferoxamine slows or
delayed or absent; most patients, even those well maintained by prevents iron-induced liver damage and may reduce the severity of
transfusion, may not attain normal stature, partly because of iron- preexisting fibrosis in some cases. 148,161,295 Results of treatment of
induced damage to the hypothalamic–pituitary axis. 78,271,272 Menarche hepatitis C in patients with thalassemia major are similar to those
is frequently delayed. Breast development may be poor, and many found in other patients. Sustained viral responses occur in 28% to
female patients have primary or secondary amenorrhea. Boys are 40% of patients treated with interferon alone and, in two smaller
frequently immature, with sparse facial and body hair. Although series, 46% to 72% of patients treated with interferon and
spermatogenesis may be normal, libido is often decreased. A multi- ribavirin. 296–300 Transfusion requirements increase by 30% to 40% in
center study of 250 adolescent patients in northern Italy showed that patients treated with ribavirin as a result of drug-induced hemoly-
despite hypertransfusion and 7 to 10 years of deferoxamine iron sis. 297,299,300 Lower levels of viral RNA and non-1 genotypes are associ-
chelation therapy, two-thirds of male patients and one-third of female ated with better responses. Higher iron levels adversely affect the
patients older than 14 years of age were 2 standard deviations or more response to antiviral therapy in some studies but not in others. 296,298,301
273
below the mean for height. Many adolescents between 12 and 18 The Thalassemia Clinical Research Network studied the use of
years of age lacked any secondary sexual changes of puberty. However, pegylated interferon and ribavirin in 16 thalassemia patients. Fifty