Endocrine System Random Flashcards

Endocrine System and Drugs

• The endocrine system is vital for life, controlling:
  • Reproduction
  • Metabolism
  • Immune function
• Insulin:
  • In the fed state, insulin stimulates glucose uptake.
  • Stimulates fatty acid uptake.
  • Nearly every cell has insulin receptors.
• Oxytocin:
  • Causes parturition, childbirth, and milk let-down reflecting its role in reproductive functions.
  • Found in the brain, involved in sexual pleasure.
  • Few cells have oxytocin receptors.
  • Regulates stress and reward pathways.
• Hormone Excretion:
  • Mainly controlled by negative feedback loops: The product inhibits its own synthesis.
  • When hormone levels drop, synthesis increases; when levels rise, synthesis decreases.
  • Insulin example:
    • Increased plasma glucose leads to increased insulin secretion by the pancreas.
    • This increases insulin in the plasma, increasing glucose and fatty acid uptake.
    • Resulting in a decrease in plasma glucose and a subsequent decrease in insulin secretion.
• Constant use of pharmacotherapy disrupts normal feedback loops.
  • Testosterone example:
    • Increased muscle mass.
    • Testicular atrophy (sterility).
    • The individual becomes sterile and stops producing testosterone.
• Why use hormones in therapy?
  • To replace hormones not being produced, for example, after pituitary removal due to a tumor.
  • To decrease the size of hormone-responsive tumors.
    • Estrogen can be used to decrease the size of prostate tumors.
    • Testosterone can be used to decrease breast tumors.
  • To achieve an exaggerated response, e.g., using prednisone to amplify the normal cortisol response.
• The hypothalamus and pituitary control hormone secretion.

Hypothalamus and Pituitary

• Hypothalamus:
  • POMC (Pro-opiomelanocortin) neurons in the hypothalamus regulate energy balance and food intake.
    • POMC is a protein made in the anterior pituitary by corticotrope cells.
    • POMC is converted into several hormones:
      • MSH (Melanocyte-stimulating hormone): Affects skin pigment.
      • ACTH (Adrenocorticotropic hormone): Stimulates the adrenal glands to produce cortisol.
      • BLPH??
      • E-endorphin: Released during pain or stress.
      • Met-Enkephalin (also known as OGF): Suppresses tumor growth, specifically in colon cancer.
      • Lipotropin:
        • Stimulates Melanocytes (Skin pigment).
        • Stimulates Steroidogenesis (steroid hormones synthesis).
        • Stimulates Lipolysis (lipids breakdown).
• Posterior Pituitary:
  • Makes ADH (Vasopressin).
  • Makes Oxytocin.
  • These hormones are produced by neurons.
• Anterior Pituitary:
  • Utilizes the hypophyseal portal system: a specialized portal vein carries stimulating hormones from the hypothalamus to the anterior lobe of the pituitary.
  • GNRH (Gonadotropin-releasing hormone) from the hypothalamus increases FSH and LH.
    • In males, this results in the inhibition of testosterone biosynthesis (chemical castration).
      • Decreases testosterone.
      • Decreases sex drive.
      • Decreases sexual urge.
• Growth Hormone:
  • Can be abused.
  • Expensive.
  • Considered unsportsmanlike.
  • Somatotropin (Humatrop):
    • Increases muscle growth.
    • In children, increases all kinds of growth.
    • Increases metabolism.
    • MOA: Direct stimulation of growth hormone receptors, stimulates the release of insulin-like growth factor from the liver (IGF1).
  • Given to children who are hormone deficient before growth plate closure.
  • Not approved for athletic use (adding muscle while decreasing fat).
    • Other uses: anti-aging.
  • Too much growth hormone results in Acromegaly.
    • Richard Kiel (Jaws, James Bond, Happy Gilmore) is an example.
    • Causes enlarged bones in feet, face, and skull.
    • Sloping forehead.
    • Broad nose.
    • Excessive height.
    • Treatment:
      • Octreotide (Sandostatin): Decreases Growth Hormone and IGF1.
      • Bromocriptine (Parlodel): D2 agonist.
• ADH (Antidiuretic Hormone):
  • Controls hydration, regulates water balance and blood pressure.
  • Increases water absorption at the kidney collecting duct.
  • Mainly active at night, but controlled by ANG II.
  • Potent vasoconstrictor, increasing blood pressure.
  • Diabetes Insipidus:
    • Rare condition with depressed ADH synthesis.
    • Leads to the loss of large volumes of water.
    • Results in dilute urine and a strong thirst mechanism.
    • Treatment:
      • Desmopressin (Stimate): Artificial vasopressin/ADH.
      • Lasts 2-4 hours.
      • Increases blood pressure by decreasing arterial diameter (increases vasoconstriction).
      • Affects the uterus and GI tract.
      • Can be used to treat clotting disorders:
        • Von Willebrand disorder
        • Factor VIII disorder
        • Hemophilia A

Thyroid Hormones

• The hypothalamus senses cold and stress.
• Thyroxine: exists in T3 and T4 forms.
• Thyroid Gland:
  • Active TH:
    • T3: Active form (3 iodides).
    • T4: Inactive (4 iodides).
    • Binds to thyroid-binding globulin (TBG), which increases during pregnancy.
• TH:
  • Controls Basal Metabolic Rate (BMR).
  • Impacts GI function.
  • Impacts heart function.
  • Affects neuromuscular function.
  • Increases myelination (increases myelin basic protein synthesis) in children.
• Thyroid Gland:
  • Follicular cells: Secrete TH, T3, and T4.
  • Parafollicular cells: Secrete calcitonin (involved in Calcium homeostasis).
  • High amounts of iodine suppress thyroid activity.
    • Lugol's solution works this way.
    • Radioactive iodine exposure: Take potassium iodide to shut down and protect the thyroid gland.
• Hypothalamus:
  • Thyroid releasing hormone.
  • The pituitary releases thyroid-stimulating hormone.
  • Goes to the thyroid.
• Primary Hypothyroidism:
  • Autoimmune destruction of the thyroid (Hashimoto’s disease).
  • Symptoms:
    • General weakness.
    • Dry skin.
    • Temperature tolerance issues (always cold).
    • Bradycardia.
    • Weight gain.
    • Decreased taste and smell.
    • Muscle cramps.
• Secondary Hypothyroidism:
  • Decrease in TRH and TSH due to a hypothalamic or pituitary issue.
  • Treated by giving:
    • Levothyroxine (Synthroid): T4, which is then converted to active T3.
• Hyperthyroidism:
  • Graves’ Disease.
  • Treated by destruction or removal of the thyroid with I131.
  • Propylthiouracil (PTU):
    • Used since 1947.
    • Pregnancy Category D.
    • Inhibits thyroid peroxidase, involved in the formation of thyroglobulin, which is broken down into T3 and T4.
    • Also inhibits iodinase, which converts T4 to T3.
  • Methimazole - NOT ON THE LIST.
• Thyroid Storm:
  • Life-threatening condition with excessive thyroid hormone levels.
  • 89% mortality rate.
  • Symptoms:
    • Increased fever.
    • Heart failure.
    • MI.
    • Angina.
    • Tachycardia.
    • CNS effects.
  • Treatment:
    • Electrolytes.
    • Lugol's solution - a medication containing iodine.
    • Antithyroid drugs: Propylthiouracil (PTU) and Methimazole (though methimazole is NOT ON THE LIST).

Adrenal Glands

• Involved in the sympathetic response (fight or flight).
• Innervated by the sympathetic nervous system.
• Secrete:
  • Epinephrine (75-80%).
  • Norepinephrine (20-25%).
• What adrenal glands make:
  • Mineralocorticoids: Aldosterone.
    • Regulates plasma volume via the renin-angiotensin-aldosterone system.
    • Increases aldosterone leads to increased sodium retention, increased water retention, leading to higher plasma volume and increased potassium.
  • Androgens.
  • Glucocorticoids: Cortisol.
    • Increases glucose in the blood by increasing liver production.
    • Increases lipid and protein breakdown.
    • Decreases immune response.
    • Decreases bone mineralization.
    • Increases bronchial dilation.
    • Increases sensitivity of vascular smooth muscle to Ang II.
• Adrenal Insufficiency:
  • Primary: Adrenal Gland issue.
  • Secondary: Hypothalamus/Pituitary.
  • Addison’s Disease: No aldosterone, no cortisol (President Kennedy had it).
    • Treatment:
      • Hydrocortisone (Coref).
      • Fludrocortisone: Cortisone with a fluorine atom, giving it mineralocorticoid activity.
• Adrenal Hyper state:
  • Cushing Syndrome:
    • Moon Face.
    • Females may experience facial hair (hirsutism/bearded lady).
    • Buffalo hump.
    • Cataracts.
    • Diabetes.
    • Osteoporosis.
    • Blood pressure issues.
    • Increased glucose levels.
• Receptors are nuclear; when they bind to the hormone, they increase gene expression.
• Controls 20% of gene transcription.
• When using Prednisone or any glucocorticoid, gradually wean the patient off to avoid adrenal gland atrophy/insufficiency.