Clinphar 2

• GROWTH HORMONE

  -AKA Somatotropin

  most abundant hormone produced by the anterior pituitary lobe
• Hypothalamus- releases growth hormone releasing hormone (GHRH)

  thus stimulates the liver and other peripheral target tissues to produce insulin-like growth factors (IGFs).
• IGF-I is responsible for growth of bone and other tissues

  IGF-II is primarily responsible for regulating fetal growth.
• anterior pituitary - is the front load of your pituitary gland which is a small pea sized plant located at the base of your brain below your hypothylamus
• insulin like growth factor or igf - is a polypeptide or peptide hormone that functions primarily to stimulate the growth but that also possesses some ability to decrease the blood glucose levels.
• Acromegaly

  Growth Hormone Excess
• growth plates of the long bones are usually close near the end of puberty so for GIRLS this is usually when they're turning 13 to 15 and for BOYS it is usually during their 15 to 17.
• Gigantism - refers to growth hormone excess that occurs during childhood before epificial closure and results in excessive linear growth.
• coarsening of facial features- lack of definition of main features of the face such as the eyebrows, nose, lips, mouth and chin, the features are not clearly defined instead they are round and heavy in face.
• impotence - abnormal physical or psychological state male, characterized by inability to engage in sexual intercourse because of failure to have or maintain an erection.
• Carpal tunnel syndrome is caused by pressure on the median nerve. The carpal tunnel is a narrow passageway surrounded by bones and ligaments on the palm side of the hand. When the median nerve is compressed,symptoms can include numbness, tingling, and weakness in the hand and arm.
• 75-g oral glucose challenge

  • Primary biochemical test for diagnosing acromegaly 1* Postprandial hyperglycemia inhibits secretion of GH
  • If GH concentration is greater than 1 ng/mL, the patient is diagnosed with acromegaly
• IGF-I serum concentration

  Elevated IGF-I serum concentration helps to confirm the diagnosis because IGF-I serum concentrations are relatively stable and correlate positively with mean GH concentrations
• Computed tomography and MRI

  Computed tomography and magnetic resonance imaging of the pituitary are important diagnostic tests to confirm the presence of a pituitary adenoma.
• Surgical Treatment

  -Surgical resection of the pituitary tumor through transsphenoidal pituitary microsurgery is the treatment of choice for most patients with GH-producing pituitary adenomas.
• surgical resection of the pituitary tumor through the transsphenoida pituitary micro surgery- most common way to remove the pituitary tumors / done through the sphenoid sinus hollow space in the skull behind the nasal passages and below the brain) is the treatment of choice for most patient with growth hormone producing pituitary adenomas
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  Radiation therapy is an important adjunctive therapy in patients with residual GH excess after surgery or pharmacologic therapy.Treatment involves the use of radiation to destroy rapidly growing tumor cells, and often results in a reduction in tumor size.

  • A major complication of radiation therapy is hypopituitarism, requiring lifelong hormone replacement.
• Somatostatin Analog

  GH-Inhibiting Hormone

  • Ex: Octreotide
  • These agents mimic endogenous somatostatins and bind to somatostatin receptors in the pituitary to cause potent inhibition of GH, insulin, and glucagon secretion.
  • Long term treatment can sustain GH suppression, alleviate soft tissue manifestations, and reduce tumor size
• Growth Hormone Receptor Antagonist

  Ex: Pegvisomant

  • Pegvisomant is recommended in patients who have inadequate response to somatostatin analogs, or as an adjuvant for patients who have only a partial response to somatostatin analogs
  • The long-term use of Pegvisomant appears to be well tolerated with a low incidence of adverse effects, including self-limiting injection-site reactions and elevated liver enzymes.
• Dopamine Agonist

  Ex: Bromocriptine

  • Suppress GH release from the tumorAE: Gl discomfort and orthostatic hypotension
• prolactin- is a polypeptide hormone that is responsible for lactation, breast development, and hundreds of other actions needed to maintain homeostasis.
• PROLACTIN

  • Prolactin is secreted in a pulsatile fashion by the lactotroph cells of the anterior pituitary, with the highest peak concentrations observed during sleep.
  • The secretion of prolactin is regulated primarily by tonic hypothalamic inhibitory effects of dopamine.
  • During pregnancy, prolactin serum concentrations rise substantially above normal
• Hyperprolactinemia is a state of persistent serum prolactin elevation.

  Prolactin concentrations >20 mcg/L observed on multiple occasions are generally considered indicative of Hyperprolactinemia
• Bromocriptine

  • directly binds to the D2 dopamine receptors
  • normalizes prolactin concentration
  • restore menses and fertility in women and improve testosterone secretion, sperm count and erectile function in men
  • may also improve visual field defects associated with macroadenomas
  • AE: nausea, dizziness, and orthostatic hypotension
• Pergolide

  dopamine-receptor agonist with affinity for both D1- and D2-receptors
• Cabergoline

  higher affinity for D2 dopamine receptors than bromocriptine and possesses a long half-life, allowing for once- or twice-weekly administration

  It is also effective in treating hyperprolactinemia in patients who are resistant to or intolerant of bromocriptine and in men and women with micro prolactinomas and macroprolactinomas.
• Cushing's syndrome is a disorder that occurs when your body makes too much of the hormone cortisol over a long period of time.
• Cortisol is sometimes called the "stress hormone" because it helps your body respond to stress. Cortisol also helps maintain blood pressure, regulate blood glucose, thus also called blood sugar.
• Steroidogenic Inhibitors

  • These agents are used primarily in preparation for surgery, as adjunctive treatment after unsuccessful surgery or radiotherapy, or for refractory patients who are not surgical candidates.

  Examples: Metyrapone, Aminoglutethimide, Ketoconazole, Etomidate
• Metyrapone

  • Inhibits 11- hydroxylase activity, resulting in inhibition ofcortisol synthesis.
  • Increase in androgenic and mineralocorticoid hormones results in hypertension, acne, and hirsutism.
  • Nausea, vomiting, vertigo, headache, dizziness, abdominal discomfort, and allergic rash.
• Aminoglutethimide

  Inhibits cortisol synthesis by blocking the conversion of cholesterol to pregnenolone early in the cortisol pathway.

  AE: severe sedation, nausea, ataxia, and skin rashes
• Ketoconazole

  • It is highly effective in lowering cortisol in Cushing's disease, and patients can be maintained successfully on therapy for months to years.

  AE: Reversible elevation of hepatic transaminases and Gl upset
• Etomidate

  Imidazole derivative similar to ketoconazole that inhibits 11-hydroxylase

  Because it is only available in a parenteral formulation, its use is limited to patients with acute hypercortisolemia awaiting surgery.
• Adrenolytic Agents

  • Example: Mitotane
  • Inhibits the 11-hydroxylation of 11-desoxycortisol and 11-deoxycorticosterone in the adrenal cortex.
  • Nausea and diarrhea are common at doses >2 g/day and can be avoided by gradually increasing the dose and/or administering it with food.
  • Lethargy, somnolence, and other CNS effects are also common.
• Neuromodulators of ACTH Release

  Examples: Cyproheptadine, Tretinoin, Bromocriptine, Cabergoline, Valproic acid, Octreotide, and Rosiglitazone.
• Glucocorticoid-Receptor Blocking Agents

  Mifepristone is a progesterone, androgen-, and glucocorticoid receptor antagonist that inhibits dexamethasone suppression and increases endogenous cortisol and ACTH values in normal subjects.
• Adrenal Insufficiency (Al) is an endocrine or hormonal condition in which the adrenal glands fail to produce sufficient amounts of steroid hormones.

  The main hormone affected is cortisol, a hormone that plays an important role in helping the body respond to stress. However, other hormones, such as aldosterone and androgens, are also often affected.
• acute adrenal insufficiency.

  HPA-axis disregulation results in downstream physiological consequences, increasing risk or immune system dysfunction, mood disorder, metabolic disease and cardiovascular disease.
• Primary adrenal insufficiency

  Also referred to as Addison's disease

  Primary adrenal insufficiency is characterized by the inability of the adrenal glands to produce enough Cortisol
• Secondary adrenal insufficiency

  This is the most common type of adrenal insufficiency.

  Secondary adrenal insufficiency occurs when the pituitary gland is unable to make enough adrenocorticotropin hormone (ACTH)