Growth Hormone and Some Other Parameters Estimation in Thalassemia major Patients

This study is a cross-sectional study, included forty eight male subjects, during the period from the beginning of December 2013 to the beginning of April 2014 at Azadi teaching Hospital in Kirkuk City in Iraq. Questionnaire was administered, patients were examined, blood sample was collected and examined, data gathered and analysis (SD, T test & P value and Pearson correlation was employed for analysis of the relationship between variables). Growth hormone (GH), Serum Ferritin(SF), Hemoglobin (Hb) and packed cell volume(PCV), also body weight &height as well as body mass index were evaluated in 33 male patients (aged 10–20 years old) with β thalassaemia & in 15 subjects at the same age and sex as a control group. This study revealed that there was highly significant decrease in all parameters in thalassemic patients (except serum ferritin was highly significant increase in patients) as compare with controls (P< 0.001). Positive correlation found between GH and both Hb and PCV, while negative correlation was found between GH and ferritin level.


Introduction
Growth hormone (hGH, somatotropin),secreted from the anterior pituitary [1]. Of all the hormones produced by the hypophysis, GH is the most abundant. The pituitary gland contains an amount of GH that is 20 to 40 times greater than that of corticotropin and 50 to 100 times greater than that of PRL [2].
It's a polypeptide with two intra-chain disulfide bridges, which circulates free or bound to number of different GH-binding proteins [1]. About half of the GH in the plasma is bound to a protein that consists of a cleavage product of the GH receptor. This provides a reservoir that compensates for the wide fluctuations in the rate of secretion and the short half-life (6-20 minutes) of GH [3].
Several forms of growth hormone have been identified [1]with the major being of molecular weight 22,000 daltons [4] containing 191 amino acid residues . A 20,000-dalton variant, which posses all known biological actions of GH, has also shown to be important . The primary biological actions of the hormone are indirect growth promoting . GH exerts its effect directly on target organs such as bones and muscles; indirectly through the release of somatomedins ,a family of insulin like growth factor (IGF)hormones , produced in the liver . In particular somatotropin C (IGF-1) is essential for bone growth during childhood. [5] The clinical usefulness of the measurement of growth hormone (GH) in children has been well established in ascertaining linear bone growth along the epiphyseal plate. Abnormally elevated levels lead to gigantism while complete absence slows the rate of growth one-third to one half of normal. In adults, the epiphyseal growth plates had fused so hGH excess gradually produces acromegaly, a cross thickening of the bones of the skull, hands and feet [6].
Growth retardation has been reported to occur in most patients with thalassemia major [7].
Defective somatomedin activity has been suggested [8,9] as one of the causes of this growth failure, since endocrine studies did not show a significant suppression of GH secretion in all patients. Functional damage to the hypothalamic structure for GH control, with a markedly decreased GH response to GHRH, has also been reported recently [10]. The pathogenesis of growth failure is multifactorial. Key contributing factors to stunted growth in patients with Thalassemia Major may include chronic anemia, transfusional iron overload, hypersplenism, and  [11]. Other contributing factors include hypothyroidism, hypogonadism, GH deficiency/insufficiency, zinc deficiency, chronic liver disease, undernutrition and psychosocial stress [12].
The classic pattern of constitutional growth delay is normal birth weight and length. A subtle decrease in growth velocity occurs about second year of life. Thereafter, stature remains below the fifth percentile through childhood. However, growth velocity remains appropriate for the skeletal age. Linear growth is considered to be decreased when a child's height falls more than 2 standard deviation (SD) below the mean height for age [13].
The aim of the study is to evaluate the influence of age at the onset of blood transfusion, iron chelation therapy, and serum ferritin levels on growth and , and the prevalence of this endocrine complication with respect to pituitary somatotropic function among a group of male thalassemic patients in Kirkuk city.

Patients and Methods
Clinical information collected from 60 patients with β-thalassemia major who attended Azadi -
Short stature has been reported as a common complication in transfusion dependent thalassemia [28]. Many factors are involved in the growth retardation of patients with thalassemia, the main ones are chronic anemia , iron overload, hypersplenism, folate deficiency, endocrine disorders secondary to iron overload (hypogonadism, hypothyroidism), and bone dysplasia secondary to DFX toxicity. [24,27,29] GH secretion is also operative.
Studies on GH secretion in patients with thalassemia have shown both normal and reduced GH response to stimulation tests, and reduced spontaneous secretion (neurosecretory dysfunction).

Conclusions
In conclusion ,poor compliance with chelating therapy is the main reason for low growth hormone level, which is the main cause of stunted growth.

Recommendations
Timing of regular blood transfusion and iron chelation therapy influence the growth in these patients. We recommend new chelating therapy that insures good compliance of patients with the drug. Also early detection of low GH level to be treated early.