Effect of hyposecretion of Growth Hormone…

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Effect of hyposecretion of Growth Hormone
BY Prof. M.Y. Jan
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THE GROWTH AXIS

• Higher CNS centers
• Hypothalamus
• ? Somatostatin
• ? GHRH (GH releasing
  hormone)
• Pituitary (specific receptors for somatostatin
  and GHRH )
• ? GH (circulate 30 bound to GH
  binding protein )
• Liver and other Tissues ( specific receptors for
  GH )
• ? IGF-I
• ? IGF-BP
• Peripheral tissues
• ? respond to IGF-I (and to
  lesser extent to GH directly)
• ? mitogenic and metabolic
  effects
• IGF-I and IGF-BP
• ? IGF-I is a peptide which is GH,
  nutrition and age dependent
• plasma level increase during
  childhood to peak during puberty
• ? IGF-I is tightly bound in the
  plasma, 6 bindings proteins are so far identified
• ? IGF-BP 3 is the major carrier
  protein in plasma and its
• regulation is similar to IGF 1

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GH - Deficiency

• GHD may result from disruption of the GH axis in
  the following sites
• higher brain
• hypothalamus
• or pituitary
• This dysfunction can be
• congenital
• acquired

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• Congenital GHD may be associated
  with
• an abnormal pituitary gland
• be part of a syndrome such as
• septo-optic dysplasia
• which may include other pituitary
  deficiencies, optic nerve
• hypoplasia, and absence of the septum
  pellucidum

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• Acquired GHD may result from
• tumor (e.g. Craniopharyngioma)
• trauma
• infections (eg, encephalitis, meningitis)
• cranial irradiation (somatotrophs
  appear to be the most radiation-sensitive cells
  in the pituitary)

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• While most instances of isolated GHD are
  idiopathic,
• specific etiologies cause most GHD
  associated with other pituitary deficiencies

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Growth Hormone Hyposecretion

• GHD or Hyposomatotropism
• 1- effects on bone mass, delayed bone maturation
• 2- GH regulates muscle mass, muscle strength
• 3- body composition lipid and carbohydrate
  metabolism, and impaired cardiac function
• 4- Patients with GHD typically manifest
  hyperlipidemia, increased body fat, premature
  atherosclerotic plaques

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Growth Hormone Hyposecretion

• Currently, GHD in adults is recognized as a
  distinct clinical syndrome that encompasses
• 1- reduced psychological well being
• 2- specific metabolic
  abnormalities such as
• hypertension
• central
  obesity
• insulin
  resistance
• dyslipidemia
• coagulopathy

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Growth Hormone Hyposecretion

• Symptoms and Signs in General 1-
  Behavioral and educational difficulties
• 2- Peripheral vascular disease and reduced
• myocardial function3- Reduced muscle
  strength, lean body
• mass, and reduced exercise capacity
• 4- Reduced thermoregulation5- Abnormal
  thyroid hormone metabolism6- Impaired
  psychosocial well being7- Decreased bone
  mineral content

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Growth Hormone Hyposecretion

• Physical
• Congenital
• Normal to subnormal length at birth
• Later Short stature
• Midline defects
• Cleft lip
• Cleft palate
• Blindness
• Single central maxillary incisor
• Hypogonadotropic hypogonadism
• Hypoglycemia

• - Shaking
• - Irritability
• - Lethargy
• - Hypotonia
• - Diaphoresis
• - Tachycardia
• Pallor

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Growth Hormone Hyposecretion

• Acquired
• Short stature
• Characteristic facies
• Frontal bossing
• Flattened nasal bridge
• Forehead prominence
• Delayed dental eruption
• Delayed bone age
• Increased weight-to-height ratio
• Poor muscle tone (motor delay may result)
• Laryngeal hypoplasia
• Poor hair and nail growth
• Delayed puberty
• Normal genitalia
• Normal skeletal proportions

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Assessment of short stature

• History (family, prenatal, system review)
• Growth data must be graphed on growth chart
• Physical examination
• Full blood count
• Electrolytes, creatinine, calcium, phosphorus
• Bone age
• Chromosomes in short girls
• Coeliac screen
• Thyroid function test
• Growth hormone (GH) tests

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• Clinical Manifestation
• Infants (born at term) with Cong. GHD have
• Normal Birth weight
• Normal Birth Length

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• The growth rate slows after birth
• They tend to have an elavated weight for height
  ?
• Chubby and short
• A patient with classic GHD appears Cherub
  (chubby and immature)
• High-pitched voice (from immature larynx)
• Hypoglycemia ( Gluconeogenesis)

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• GH Resistence
• LARON SYNDROME
• Autosomal recessive
• GH receptor or post receptor defect
• MALNUTRITION
• Severe LIVER disease
• High GH level
• Low IGF1 level

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GH Stimulation tests

• Stimulation tests are needed to prove a diagnosis
  of GH deficiency because GH is secreted in
  pulsatile fashion
• There are usually 3 4 nocturnal and
• 2 3 day time pulses, the nocturnal pulses
  coinciding with stage ¾ sleep
• Random blood tests for GH levels may miss a pulse
  and not very informative
• Stimulation tests may be either physiological or
  pharmacological

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Physiological tests for GH secretion

• For stimulation of a pulse of GH secretion do
• ? Sleep (stage ¾ deep sleep)
• ? Exercise ( to the point of exhaustion ? 20
  min on exercise bicycle)

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Pharmacologic tests for GH secretion

• A pulse of GH can be stimulated by use of either
  of the following
• ? Arginine
• ? Insulin induced hypoglycemia
• ? Clonidine
• ? Propranolol
• ? Glucagon

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Pharmacologic tests for GH secretion

• Single Agent stimulation test
• e.g. 1- Arginine
• 2- Insulin
• Combined Agent Stimmulation test
• e.g. 1- Clonidine Glucagon
• 2- Propranolol Exercise test