Thyroid

• Endocrine system

  Releases hormones into the bloodstream, which carries chemical messengers to target cells throughout the body
• Hormones


  Have a much broader range of response time than nerve impulses, requiring from seconds to days, or longer, to cause a response that may last for weeks or months
• Nerve impulses


  Generally act within milliseconds
• Hypothalamus


  Connects the nervous system with the endocrine system via the pituitary gland

  
• Hormones secreted by the hypothalamus and the pituitary

  • Peptides
  • Glycoproteins

  
• Releasing/inhibiting factors or hormones

  Produced in the hypothalamus, reach the pituitary by the hypophyseal portal system

  
• Hormone production


  1. Interaction of releasing hormones with receptors

  2. Activation of genes that promote synthesis of protein precursors

  3. Posttranslational modification to produce hormones

  4. Release into circulation
• Pituitary hormone preparations


  Used for specific hormonal deficiencies, but have limited therapeutic applications
• Administration of pituitary hormones

  Intramuscularly, subcutaneously, or intranasally (not orally due to susceptibility to proteolytic enzymes)

  
• Adrenocorticotropic hormone (ACTH)


  Product of posttranslational processing of proopiomelanocortin precursor
• ACTH is released from the pituitary in pulses with a diurnal rhythm, with the highest concentration in early morning and the lowest in late evening
• Stress


  Stimulates ACTH secretion
• Cortisol


  Acting via negative feedback, suppresses ACTH release
• Mechanism of action of ACTH

  1. Binds to receptors on adrenal cortex

  2. Activates G protein-coupled processes

  3. Stimulates rate-limiting step in adrenocorticosteroid synthesis (cholesterol to pregnenolone)

  4. Ends with synthesis and release of adrenocorticosteroids and adrenal androgens

  
• Therapeutic uses of ACTH

  • Diagnostic tool for differentiating primary and secondary adrenal insufficiency
  • Treatment of infantile spasms and multiple sclerosis
• Adverse effects of ACTH

  Short-term use usually well tolerated, but longer use has toxicities similar to glucocorticoids (hypertension, edema, hypokalemia, emotional disturbances, increased infection risk)
• Growth hormone (GH)


  Released by anterior pituitary in response to GH-releasing hormone, inhibited by somatostatin

  
• GH secretion decreases with age, accompanied by decrease in lean muscle mass
• Mechanism of action of GH

  Many effects exerted directly, others mediated through somatomedins (IGF-1 and IGF-2)
• Exogenous GH


  Synthesized by gene technology, used as injection; animal GH ineffective for humans
• Effects of GH over-secretion


  • Gigantism (before puberty)
  • Acromegaly (after puberty)

  
• Effects of GH under-secretion

  • Dwarfism
• Functions of GH


  • Glycogenolysis (↑ blood sugar)
  • Lipolysis
  • Protein synthesis
  • Increase in cell number and density, including bone and cartilage
• Therapeutic uses of somatropin (synthetic GH)

  • GH deficiency
  • Growth failure in children
  • Treatment of HIV patients with cachexia
  • GH replacement in adults with confirmed deficiency
• Somatrem (synthetic GH)


  Has longer half-life than natural GH, used in dwarfism before puberty to avoid acromegaly after puberty
• Adverse effects of somatropin

  • Pain at injection site
  • Edema
  • Arthralgias
  • Myalgias
  • Nausea
  • Increased diabetes risk
• Somatostatin


  Binds to pituitary receptors to suppress GH and TSH release, also inhibits insulin, glucagon, and gastrin

  
• Octreotide and lanreotide

  Synthetic somatostatin analogs with longer half-lives, used in acromegaly and carcinoid tumors
• Adverse effects of octreotide

  • Bradycardia
  • Diarrhea
  • Abdominal pain
  • Flatulence
  • Nausea
  • Steatorrhea
  • Asymptomatic cholesterol gallstones with long-term use
• Gonadotropins (FSH and LH)

  Produced in anterior pituitary, regulate gonadal steroid hormones, used in infertility treatment

  
• Menotropins (hMG)


  Obtained from urine of postmenopausal women, contain both FSH and LH
• Urofollitropin


  FSH obtained from postmenopausal women, devoid of LH
• Follitropin alfa and follitropin beta

  Recombinant human FSH products
• Human chorionic gonadotropin (hCG)

  Placental hormone, effects identical to LH

  
• Use of gonadotropins in infertility

  1. Menotropin for follicular growth and maturation, followed by hCG for ovulation induction in women

  2. hCG for maturation of external sexual organs, followed by menotropin for spermatogenesis induction in men

  
• Adverse effects of gonadotropins

  • Ovarian enlargement
  • Ovarian hyperstimulation syndrome (potentially life-threatening)
  • Multiple births

  
• Prolactin


  Peptide hormone secreted by anterior pituitary, stimulates and maintains lactation, decreases sexual drive and reproductive function

  
• Regulation of prolactin


  Stimulated by thyrotropin-releasing hormone, inhibited by dopamine acting at D2 receptors

  
• Drugs that increase prolactin

  Dopamine antagonists (e.g. metoclopramide, some antipsychotics)
• Hyperprolactinemia


  Associated with galactorrhea and hypogonadism, treated with D2 receptor agonists (bromocriptine, cabergoline)