The Growth Hormone-IGF-1 Axis in Patients with
Thalassaemia Major:
The studies on growth hormone (GH)
secretion in patients have shown both normal and reduced response to a variety of pharmacological
stimuli. Normal or subnormal spontaneous growth hormone secretion has been
reported in thalassemic patients.
The growth hormone response to growth hormone releasing hormone (GHRH) has been
reported to be normal or reduced. In patients with delayed puberty, the GH
response to GHRH was reported to be impaired, but the response improved with
the onset of spontaneous or induced puberty with sex steroids or gonadotropin. In thalassemic patients with impaired GH response to
GHRH, the combination of GHRH with either pyridostigmine or arginine restored
the GH response to stimulation to a level comparable to that observed in normal
controls. This finding suggests that the impaired GH secretion in some
thalassemic patients may be due to an increase in the somatostatinergic tone on
GH release (Low, 2005).
The serum IGF-1 and IGFBP-3 levels have
been shown to be low in patients with transfusion dependent thalassemia major.
The low serum IGF-1 level in patients with thalassemia has previously been
attributed to a decreased hepatic synthesis due to liver damage from
transfusion hemosiderosis but this is unlikely to be the important causative
factor. No evidence for a defect in growth hormone binding to liver membranes
was found in patients with thalassemia major (Postel et al., 1989). The low serum IGF-1 and IGFBP-3 concentrations in
short thalassemic patients with normal GH reserve and serum GHBP levels suggest
a secondary GH insensitivity state (Low 2005).
Diagnosis
requires careful clinical evaluation to establish:
-
Slow growth rate:
growth velocity expressed in cm/year, below the 1SD for age and sex (based on
growth velocity charts).
-
Short stature: hight
below the 3rd centile for sex and age (based on national growth
charts).
-
Signs of other
pituitary hormone deficiencies (e.g., gonadotrophins).
-
Other causes of
retarded growth (De Sanctis, 1999).
The first step in the
investigation of short stature or retarded growth is the regular (six-monthly
interval) and accurate measurement of the standing and sitting height, pubertal
staging and bone age, including examination of the metaphyses. Interpretation
of absolute height must take into account the height of the parents. It is
important to bear in mind that desferrioxamine toxicity is an important cause
of delayed growth.
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