Growth Hormone Deficiency – A Case Report

Growth hormone is an anabolic hormone released in pulsatile manner in the circulation. It is one of the uncommon causes of short stature in children and is largely idiopathic. The case report is about a 12 years old boy who presented with short stature. He was diagnosed to have Growth hormone deficiency. Growth hormone was started after diagnosis was made.


Introduction
Growth hormone has a well-defi ned role in promoting childhood growth and in maintaining normal adult body composition.Growth Hormone defi ciency can be isolated or associated with pituitary disturbances¹.Epidemiological studies suggest that idiopathic isolated growth hormone defi ciency occurs more frequently than multiple pituitary hormone defi ciency in children whereas in adult onset GH defi ciency is frequently due to pituitary adenomas, surgeries and irradiation².Synthetic human growth hormone (somatropin) shows improvement in children with isolated cases of growth hormone defi ciency if started early provided that it should be administered under strict supervision.

The Case
A 12 year old male presented to Nepal Medical College Teaching Hospital in April, 2008 with the complaints of not gaining height and weight.There was no history of perinatal insult, constitutional delay or history suggestive of any systemic causes of short stature.Birth weight and length were adequate and according to race.Dentition was however delayed.On examination the boy was alert with stable vitals and no abnormalities detected in systemic examination.There was no signs of dysmorphism.The anthropometric measurements showed; weight-18 kgs and height 110 cms.His height for age was below 3 rd percentile (NCHS) i.e. 73% of an expected (height age: 5 1/2 years) and weight for age was also below 3 rd percentile (NCHS) i.e. 45% of an expected (weight age: 5 years).However his weight for stature was between 25 th and 50 th percentile (NCHS).The mid parental height was 158.25cms.Head circumference was 50 cm.The ratio of upper and lower segment and arm span suggested to be proportionate short stature.Growth velocity was less than 4cm/year.Penile length was 2.5 cm and there were no secondary sexual characteristics.
Investigations showed no abnormalities in routine blood, stool and urine examinations.The blood glucose, renal function test, liver function test and thyroid function tests were all normal.No abnormalities were present in the chest X-ray.However, his bone age was delayed (Bone age: 7 years).Clonidine stimulation test (Growth hormone assay) was done which was consistent with Growth hormone defi ciency.Hormone binding factors were found to be within normal limits.Pituitary gland was unremarkable on MRI study.
Growth hormone (Genotropin) 1.5 Units was started subcutaneously, once daily, 5 days in a week in the patient along with Calcium.Growth hormone was to be continued till fi nal height was reached.A reasonable approach to stop Growth hormone therapy is to assume that near fi nal height is reached in boys by the age 16.Regular follow-up was advised so that frequent blood glucose levels and thyroid hormonal assay could be monitored.There was a signifi cant increase in his height on follow up after a year and the height velocity was 11 cms following growth hormone therapy.(Fig. 1) growth hormone defi ciency could be due to CNS tumors including (craniopharyngiomas) and malformations 7 perinatal trauma, lack of oxygen at birth 3,8 , Septo-optic dysplasia 3,7 , Leukemias, CNS trauma, CNS radiation 7 , abnormalities in the hormone receptors and very rarely it may be due to a genetic defects, which in some instances may also be heredity.Children with GHD usually present with short stature and a low growth velocity for age and pubertal stage.Alternative causes of poor growth needs to be considered and excluded.Age at presentation can vary from the fi rst few months of life to adolescence.Typically the GH-defi cient child has increased subcutaneous fat especially around the trunk.The face is immature with a prominent forehead and depressed midfacial development; this is related to the lack of GH effect on endochondral growth at the base of the skull, occiput, and the sphenoid bone.Dentition is delayed.In males the phallus may be small, and the average age of pubertal onset is delayed in both boys and girls 3 .Radiograph shows bone age lower than the chronological age.Growth hormone levels and binding protein levels (IGF-I and IGFBP-3) will show whether the growth problem is caused by a problem with the pituitary gland.MRI of the head can show the hypothalamus and pituitary glands 9,10 .Treatment with growth hormone will usually result in marked acceleration of linear growth.This is most pronounced in the fi rst two years of therapy.In one study of more than 12,000 children, growth hormone replacement therapy was started at an average age of 9.2 ± 4.1 years and produced an increase in growth velocity from 4.4 cm per year to 10.0 cm per year.The younger the patient at the initiation of treatment and the more severe the growth defi ciency, the better the response to early therapy 5 .

Discussion
Natural growth hormone is released in a pulsatile manner from the adenohypophysis spontaneously and in response to various physiologic stimuli 6 .Its production is stimulated by growth hormone-releasing factor and inhibited by somatostatin, which are both produced by the hypothalamus.Growth hormone binds to receptors on hepatic tissue and other cells, stimulating the production of insulin-like growth factor-I either locally or at the site of growing bone.Growth hormone binds to a specifi c growth hormone-binding protein (GHBP) and circulates.This GHBP is the extracellular portion of the growth hormone receptor.IGF-1 binds to one of several IGF-binding proteins (IGFBPs) and circulates almost entirely (>99%) in the bound state.IGFBP-3 accounts for most of the IGF-I binding and this binding protein directly depends on growth hormone 5,7 .Growth hormone defi ciency is an uncommon cause of short stature.In one study done in England and Wales, the approximate incidence of growth hormone defi ciency was only 1 in every 30,000 births, about half of the patients had idiopathic defi ciency and half had defi ciency secondary to intracranial disease.These patients with low serum growth hormone levels associated with maternal deprivation were excluded 4 .Several cases apart from being idiopathic causes for a

Fig 1 :
Fig 1: Growth chart showing increase in height after Growth hormone therapy