Presentation title

Dr. Md. Shah Shamiul Alam

Portfolio Manager

a Novartis company
Human growth hormone

• Human growth hormone (hGH), which is also called somatotropin,

is a hormone produced in the anterior pituitary gland.
• Advances in recombinant DNA technology over the last 25 years
have enabled companies such as Sandoz to produce complex human
peptides and proteins in large quantities.

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Mechanism of action of GH

• It is crucial to understand that GH has two distinct types of effects.

• GH acts directly by binding to its receptors on target cells.
• The indirect effects of GH are mediated by other molecules, the
most important of which is IGF-I (insulinlike growth factor-I).
• IGF-I is secreted from the liver and other tissues in response to GH.

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Mechanism of action of GH

• GH acts directly by interacting with receptors on target cells in

various tissues, including:
 hepatocytes
 adipocytes (fat cells)
 fibroblasts
 lymphoid cells (Leung et al. 1987).
• IGF-I is produced by the liver, cartilage and other tissues in response
to GH stimulation (Bier et al. 1991).
Stimulation of IGF-I secretion is a major factor in the actions of GH.

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Action of GH

• GH has important physiological and metabolic effects in both pre-

pubertal children and in adolescents and adults who have reached
their final height.
 Increases bone density
 Increases lean tissue
 Decreases adipose tissue (especially visceral)
 Improves cardiac contractility
 Improves mood and motivation
 Enhances exercise capacity.

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Indication of GH

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Clinical features

• Children with GHD typically have short

stature - this may be the only clinical feature
(AACE).
• Other signs of GHD include:
 decreased growth velocity
 immature facial appearance
 increased subcutaneous fat mass
 Children who are very much shorter than their
peers may experience psychosocial problems

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Diagnosis

A detailed physical examination and review of the medical and

family history and diet
• Sequential measurements of height, weight and growth rate than
normal.
• Hormonal measurements
• Imaging techniques are used to assess bone age and also to
investigate whether there are structural

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Blood hormone measurements

• Stimulation tests are used to diagnose GHD because basal levels of

GH in blood are often undetectable
• An agent such as arginine, clonidine, insulin and glucagon, which
stimulates the production of GH from the pituitary gland, is injected.
• Blood samples are taken at frequent intervals over next 2 hours and
the concentration of GH is measured.
• In normal individuals the peak GH concentration in a stimulation
test is >10 mg/mL.
• In those with GHD, the pituitary gland does not produce as much
GH so that the peak GH concentration
is <10 mg/mL.

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Growth charts

• Growth charts enable clinicians to compare an individual child’s

growth with normal values for their
peer group.
• Individuals with suspected GHD should be measured at regular
intervals (preferably every 3 months) and their height plotted on an
appropriate growth chart.
• Growth below the normal range is indicative of GHD.
There is no universal standard growth chart – different countries use
charts that are appropriate for their populations

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GH therapy

• GH therapy is used to replace the missing endogenous hormone and

ensure that the child achieves normal
growth.
• Treatment is continued until final height is achieved, the epiphyses
have closed or the child no longer
responds to GH. .
• The recommended dose of GH for children is up to 0.3 mg/kg
bodyweight per week.

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GH therapy

• Children with severe GHD will show an increase in growth rate

within months of starting GH therapy. In the first year of treatment a
child may show ‘catch up’ growth and grow much more quickly than
normal
• In subsequent years the growth rate slows but usually remains higher
than normal, so that the child may eventually achieve a height within
the normal range.
• Increased muscle strength and decreased fat may also be observed
after GH replacement therapy.

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Adult GH deficiency

• The prevalence of adult-onset GHD is 1 in 10,000 people.

• Clinical features of adult GH deficiency (GHD) include (AACE):
 Increased body fat, especially visceral adipose tissue;
 Decreased lean tissue;
 Decreased bone density;
 Increased cardiovascular risk factors (including adverse lipid
profiles and insulin resistance).

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Adult dose

• A daily dose of 0.006 mg/kg body weight by sc injection is

recommended for adult patients with GH deficiency at the start of
therapy with OMNITROPE®.
• The dose may be increased progressively according to individual
patient requirements to a maximum of
0.01 mg/kg body weight.
• Younger patients require higher doses than older patients.
• Women require higher doses of GH than men.
• Oestrogen replacement therapy may also affect the sensitivity to GH
(AACE).
• A 50 year old man may require doses of 0.2 to 0.5 mg/day
• A 50 year old woman may require 0.4 to 1.0 mg/day.
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Turner Syndrome

• Turner syndrome (TS) is a genetic disorder that only affects females

• TS occurs when one of the two X chromosomes normally found in
females is missing or incomplete
• Approximately 1 in 2,500 females are affected
• TS is named after Dr Henry Turner who described it in the 1930s
• Females have two X sex chromosomes (46XX) and individuals with
TS have all or part of one of these X chromosomes missing.

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Clinical features of Turner syndrome

• Short stature is the most common feature of TS. Girls with TS have
decreased growth rates from infancy to puberty
• Without GH treatment they have a very severe reduction in height,
reaching a mean final adult height
of ~142 cm.
Primary amenorrhoea
 Webbing of the neck
 Low hairline at the back of the neck
 Drooping of the upper eyelid (ptosis)
 Broad chest

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GH therapy in Turner Syndrome

• Growth hormone therapy will improve growth velocity and final

adult height in girls with TS.
• The recommended daily starting dose of Omnitrope® for children
with TS is 0.05 mg/kg body weight.

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Chronic renal insufficiency (CRI)

• Growth failure is a significant problem in children with congenital

causes of CRI (NICE guidelines).
• GH therapy prior to kidney transplantation is therefore an important
part of the treatment strategy for these patients.
• GH therapy is stopped after transplantation.
• Growth should have been followed for a year preceding beginning
therapy with OMNITROPE® in order to verify the presence of
growth disturbance.

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Prader-Willi syndrome

• Prader-Willi syndrome (PWS) is a genetic disorder that affects

approximately 1 in 15,000 children.
• PWS involves a deletion of chromosome 15.

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PWS – Clinical Feature
• Children with PWS have altered physical and mental development.
 Excessive appetite and overeating (hyperphagia)
 Hypogonadism
 Short stature,
 Hypoventilation
 Behavioural problems (NICE guidelines).
 Low muscle tone
 Emotional instability
 Learning disabilities (sometimes very mild)
 Obesity is a common feature of PWS

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PWS -Dose

• GH therapy is used in children with PWS to

increase their final height
improve their body composition.
• GH therapy should not be started until a child with PWS is 2 years
of age
• The recommended dose of GH is 0.24 mg/kg body weight per week
for patients with PWS

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Small for gestational age

Birth weight of <2,500 g at a gestational age of >37 weeks

 Growth and height are assessed in the same way as for children
suspected with GHD.
 It is not necessary to measure GH levels before initiating GH
therapy in short SGA children.
The indications for GH therapy in a short SGA child are:
Birth size < 2 SDS below normal
Height < 2 SDS below normal (≥ 1 SDS below target height)
Age over 4 years
Height velocity <0 SDS

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Small for gestational age

• SGA children represent 20% of all children with short stature.

• In short SGA children, GH therapy can:
Induce catch up growth
Normalize growth
Improve adult height
• The recommended dose of Omnitrope® for short SGA children is
0.035 mg/kg/day

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Side effects

• The major side effects reported in early clinical trials in adults were:
 Arthralgia (joint pain)
 Myalgia (muscle pain)
 Oedema (fluid retention)
 Paresthesias (abnormal sensation such as numbness, tingling)
 Carpal tunnel syndrome
• Adults are more susceptible to adverse events associated with GH
therapy than children
• Older adults are less able to tolerate GH therapy than younger adults

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Side effects

Benign intracranial hypertension –

 headaches,
 visual changes, nausea and vomiting.
 Symptoms usually develop during the first 4months of therapy.
 The risk of this complication increased in children receiving GH
for chronic renal insufficiency.
Slipped capital femoral epiphysis
Scoliosis
 GH has not been associated with an increased risk of cancer in
childhood.

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 One pen days
Weight Dosage @ mg/kg Cost per Month
coverage
(Kg) (Range) Tk. (Range)
(Range)

8 0.2 0.28 25 18
9,000 12,600

10 0.25 0.35 20 14
11,250 15,750

12 0.3 0.42 17 12
13,500 18,900

14 0.35 0.49 14 10
15,750 22,050

16 0.4 0.56 13 9
18,000 25,200

18 0.45 0.63 11 8
20,250 28,350

20 0.5 0.7 10 7
22,500 31,500

25 0.625 0.875 8 6
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28,125 39,375
Omnitrope® is the first biosimilar product approved in Europe
and USA represents a new class of medicines.
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