SOMATROPIN SEDICO

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SOMATROPIN (SEDICO)

• Growth hormone 4IU

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SYNTHESIS

• GH is the most abundant anterior pituitary
  hormone, and GH-secretion somatotrope cells
  constitute up to 50 of the total anterior
  pituitary cell population.
• the pituitary GH gene produces two alternatively
  products that give rise 22-kDa GH(191 amino
  acids) and a less abundant, 20-kDa GH molecule,
  with similar biologic activity.

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SECRETION

• GH secretion is controlled by complex
  hypothalamic and peripheral factors. GHRH is
  stimulates GH synthesis and release Ghrelin or
  gastric-derived peptide, as well as synthetic
  agonists of the GHRP receptor stimulate GHRH and
  also directly stimulate GH release. Somatostain
  somatotropin-release inhibiting factor (SRIF)
  is synthesized in the medial preoptic area of the
  hypothalamus and inhibits GH secretion. GHRH is
  secreted as discrete spikes that elicit GH pulses
  whereas SRIF sets basal GH tone.
• IGF-I, the peripheral target hormone for GH,
  feeds back to inhibit GH, estrogen inducis GH,
  whereas glucocorticoid excess suppresses GH
  release.

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• GH secretion is pulsatile, with greatest levels
  at night. Generally correlating with the onset of
  sleep. GH secretory rates decline markedly with
  age so that hormone production in middle age is
  about 15 of production during puberty. These
  changes are paralleled by an age-related decline
  in lean muscle mass.
• GH secretion is also reduced in obese
  individuals, though IGF-I levels are usually
  preserved, suggesting a change in the set point
  for the feed back control. elevated GH levels
  occur within an hour of deep sleep onset as well
  as after exercise, physical stress, trauma and
  during sepsis.
• Integrated 24-h GH secretion is higher in women
  and is also enhanced by estrogen replacement.
  Using standard essays, random GH measurements are
  undetectable in50 of daytime samples obtained
  from healthy subjects and are undetectable in
  most obese and elderly subjects. Thus, single
  random GH measurements do not distinguish
  patients with adult GH deficiency from normal
  persons.

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• GH secretion is profoundly influenced by
  nutritional factors. Using newer ultra sensitive
  chemiluminescence's-based GH assays with a
  sensitivity of 0.002µg/L, a glucose load can be
  shown to suppress GH togt 0.7µg/L in female and
  togt 0.07µg/L in male subjects. Increased GH pulse
  frequency and peak amplitudes occur with chronic
  malnutrition or prolonged fasting. GH is
  stimulated by high-protein meals and by
  L-arginine. GH secretion is induced dopamine and
  apomorphine ( a dopamine receptor agonist), as
  well as by a-adrenergic pathways, ß-adrenergic
  blockage induces basal GH and enhances GHRH- and
  insulin-evoked GH release.

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• GH induces protein synthesis and nitrogen
  retention and impairs glucose tolerance by
  antagonizing insulin action. GH also stimulates
  lipolysis, leading to increased circulating fatty
  acid levels, reduced omental fat mass and
  enhanced lean body mass. GH promotes sodium,
  potassium and water retention and elevates serum
  levels of inorganic phosphate. Linear bone growth
  occurs as a result of complex hormonal and growth
  factor actions, including those of IGF-I.

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INSULIN-LIKE GROWTH FACTORS

• Through GH exerts direct effects in target
  tissues, many of its physiological effects are
  mediated indirectly through IGF-I, a potent
  growth and differentiation factor. The major
  source of circulating IGF-I is hepatic in origin.
  Peripheral tissue IGF-I exerts local paracrine
  actions that appear to be both dependent and
  independent of GH. Thus, GH administration
  induces circulating IGF-I as well as stimulating
  IGF-I expression in multiple tissues.

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PHYSIOLOGY

• though IGF-I is not an approved drug.
  Investigational studies provide insight into its
  physiologic effects. Injected IGF-I(100µg/Kg)
  induces hypoglycemia and lower doses improve
  insulin sensitivity in patients with severe
  insulin resistance and diabetes. in IGF-I
  infusion enhances nitrogen retention and lowers
  cholesterol levels. Bone turn over may also be
  stimulated by IGF-I.
• IGF-I side effects are dose-dependent, and
  overdose may result in hypogycemia, hypotension,
  fluid retention, temporomandibular jaw pain and
  increased intracranial pressure. All of which are
  reversible.

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DISORDERS OF GROWTH AND DEVELOPMENT

• Skeletal Maturation and Somatic Growth
• The growth plate is dependent on a variety of
  hormonal stimuli including GH, IGF-I, sex
  steroids, thyroid hormones, paracrine growth
  factors. The growth-promoting process also
  requires caloric energy, amino acids, vitamins
  and trace metals and consumers about 10 of
  normal energy production.
• Bone age is delayed because of GH deficiency,
  hypogonadism, thyroid hormone deficiency and
  elevated pubertal sex steroid levels.

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GH deficiency in children

• GH deficiency isolated GH deficiency is
  characterized by short stature, micropenis,
  increased fat, high-pitched voice.
• GHRH receptor mutations recessive mutations of
  the GHRH receptor gene in subjects with severe
  proportionate dwarfism are associated with low
  basal GH levels that cant be stimulated by
  exogenous GHRH, GHRP or insulin-induced
  hypoglycemia.

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• Growth hormone insensitivityThis is caused by
  defects of GH receptor structure or signaling.
  homozygous or heterozygous mutations of the GH
  receptor are associated with partial or complete
  GH insensitivity and growth failure (laron
  syndrome) this diagnosis is based on normal or
  high GH levels
• Nutritional short statureCaloric deprivation
  and malnutrition, uncontrolled diabetes and
  chronic renal failure represent secondary causes
  of GH receptor function. Children with these
  conditions typically exhibit features of acquired
  short stature with elevated GH and low IGF-I
  levels. Circulating GH receptor antibodies may
  rarely cause peripheral GH insensitivity.

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• Psychosocial short statureEmotional and social
  deprivation lead to growth retardation
  accompanied by delayed speech, discordant
  hyperphagia and attenuated response to
  administered GH.

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Presentation and diagnosis

• Short stature should be comprehensively evaluated
  if a patients height islt 3SD below the mean for
  age or if the growth rate has decelerated.
  Skeletal maturation is best evaluated by
  measuring a radiological bone age, which is based
  mainly on the degree of growth plate fusion.

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Laboratory investigation

• GH deficiency is best assessed by
  examining the response to provocative stimuli
  including exercise, insulin-induced hypoglycemia
  and other pharmacologic tests which normally
  increase GH tolt7µg/L in children.

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Adult GH deficiency (AGHD)

• This disorder is usually caused by hypothalamic
  or pituitary somatotrope damage. Acquired
  pituitary hormone deficiency follows a typical
  sequential pattern whereby loss of adequate GH
  reverse foreshadows subsequent hormone deficits.
  The sequential order of hormone loss is usually
• GH FSH/LH TSH
  ACTH

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Presentation and Diagnosis

• The clinical features of AGHD include changes in
  body composition, lipid metabolism and quality of
  life and cardiovascular dysfunction.
• Impaired quality of life decreased energy and
  drive, poor concentration, low self-esteem,
  social isolation.
• Body composition changes increased body fat
  mass, central fat deposition, increased waist-hip
  ratio, decreased lean body mass

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• Reduced exercise capacity
• Cardiovascular risk factorsImpaired cardiac
  structure and function, abnormal lipid profile,
  decreased fibrinolytic activity, atherosclerosis,
  omental abesity.

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Laboratory investigation

• Testing should be restricted to patients with the
  following predisposing factors
• Pituitary surgery
• Pituitary or hypothalamic tumor or granulomas
• Cranial irradiation
• Radiological evidence of a pituitary lesion
• Childhood requirement for GH replacement therapy
• The most validated test is insulin-induced(0.05to0
  .1U/Kg) hypoglycemia. and peak GH release occurs
  at 60min. and remains elevated for up to 2hr.
  About90 of healthy adults exhibit GH responseslt
  5µg/LAGHD is defined by peak GH response to
  hypoglycemia ofgt 3µg/L

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Treatment

• In childrenWith growth hormone deficiency, the
  usual dose in the U.K is0.5to0.7 units\Kg
  body-weight, or 12to20 units\m2 body-surface
  weekly. This weekly dose may be given by
  intramuscular injection in 3 divided doses or by
  subcutaneous injection, usually in6or7 divided
  doses.
• In adultsWith growth hormone deficiency lower
  doses are recommended. A suggested initial dose
  is0.125 units\Kg weekly, divided into daily
  subcutaneous injection, and increased according
  to requirements up to a max. of 0.25 units\Kg per
  week.