place of storage for thyroid hormones (T3, T4)

(clinical app.- this is why if synthesis stops, we dont get symptoms until 2-3 months)

• jagged edged/scalloped edge and small thyroid follicle cells
  • colloid is reabsorbed

1. iodine moves into cell via iodine trap (active transport)
2. moves into lumen and is oxidized
3. leads to tyrosine being iodinized within thyroglobullin
4. produces 2 DIT's and MIT
   1. 2 DIT's produce T4
   2. 1 DIT and 1 MIT produce T3
5. TG endocytosed into follicle cell and proteolysis occurs
   1. allows for recycling of iodide
   2. allows for T4, T3 release

Many steps where process can be blocked and drugs can work.

1. T4 and T3 circulate bound to thyroid binding proteins
   1. equilibrium between bound and free hormone
   2. if you increase T4 production, you would expect the equilibrium to shift to plasma bound T4
2. FREE T4, T3 transported into cell via active transport
3. T4 is converted to T3 via 5'deiodinase enzyme
   1. T3 is more biologically active
4. Move into nucleus to have effects

• T4
  • 75 micrograms produce a day
  • 99.96% bound
  • half life of 7 days
• T3
  • 25 micrograms produce a day
  • 99.6% bound
  • biological potency- four times that of T4
  • half life of 1 day

increase size, secretion, and number of thyroid cells

Higher in evening with small, rapid variation

Increases BMR

• mitochondria number
• respiratory enzyme
• ATPase

• increase carbohydrate and fat metabolism
• increase glucose absorption and cell intake
• increase lipolysis

• increase protein synthesis (anabolic effect)
  • clinical app.- if too much thyroid hormone (hyperT), you get protein breakdown
• increase beta adrenergic receptor (increase number, sensitivity)
  • increase HR, CO (increase cardiac contractility, so increase SV)
• normal growth and development
• increase mental speed and irritability
  • enter brain, increase response to catecholamines (esp. Reticular activating system)

• lose weight
• increase heat generation
• increase heart rate, CO
• atrial fibrilation
• tremor
• increased BMR
• exophthalmos (buldging eyes)
• goiter

• gained weight
• decrease heat generation
• decrease HR, CO
• lethargy
• decrease BMR
• drooping eyelids
• goiter
• inhibits physical and mental perinatal growth

• lack of physical and mental growth (cretinism)
• due to Hypothalamic thyroid disorder in newborn
• cause- iodine deficiency in mother or Ab's crossin placenta

• Graves disease (increase thyroid stim. Igs)
• thyroid tumor
• excess TSH
• exogenous thyroid hormone (dose to large medically to correct hypoT)

• thyroiditis (autoimmune or Hashimotos thyroiditis)
• iodine deficiency
• congenital
• decrease TSH or TRH (secondary hypoT)

• PTU (propylthiouracil)- inhibit syn.
• radioactive iodine
• thyroidectomy
• beta antagonists

• prevent radioactive iodine from killing thyroid by diluting the iodide pool by
• saturating membrane sites
• see high iodine levels and lower thyroid synthesis

• ex: propanolol
• thyroid hormone does increase beta receptor activity, so it is blocking the cardiovascular effects (also reduces tremors and sweating)

• bone resorption
• kidney
  • decreased phosphate reabsorption
  • increased calcium reabsorption
• intestines- increase calcium reabsorption

• increased excitability of nerves and muscle (lower threshold)
  • tingling and numbness (sensory neurons)
  • muscle twitches (motor neurons)

• zona glomerulosa- secrete mineralcorticoids (Aldosterone)
• zona fasiculata- secrete glucocorticoids (cortisol)
• zona reticularis- secrete androgens and some glucocorticoids

1. precursor protein is POMC (Pro-opiomelanocortin) found in paraventricular nucleus in hypothalamus
   1. input from amygdal, SCN, nociceptive pathways
   2. inhibited by baroR activity via NTS
2. broken down to produce:
   1. ACTH
   2. alpha melaonocyte stimulating hormone
3. ACTH stimulate cholesterol desmolase 

Increased ACTH associated with increased melanocyte stimulation.

1. cholesterol to pregnenolone via cholesterol desmolase
2. prenenolone to 17 hydroxypregnenolone via 17 alpha hydroxylase
   1. major precursor of cortisol

95% bound

5% free and active

• cortisol- 95% of glucocorticoid activity with slight mineralcorticoid activity
• corticosterone- 4% glucocorticoid activity with slight mineralcorticoid activity

dexamethanson

methylprednisone

prednisone

cortisone

stress

diurnal cycle

1. cortisol will dissociate from cortisol binding globulin (CBG)
2. diffuses into cell as free steroid
3. binds to receptor within the cytosol
4. steroid receptor dimer (activated) goes into the nucles and effects a hormone response element

• carb metabolism- increase blood glucose
  • increase gluconeogenesis
  • lower glucose utilization (except in brain)
• protein- increase proteolysis
• immune/inflammatory response- inhibit inflamation and suppress immune cells
• endocrine
  • supress ACTH, TSH, LH, GH
  • enhance norepinepherine response
• weak Ald effect (slight increase in water and sodium reabsorption)

• Cushings syndrome (due to adrenal hyperplasia or pharmacological administration)
  • increase blood glucose, could lead to diabetes
  • muscle weakness- atrophy, fatigue, bruising due to protein breakdown
  • thin skin due to protein breakdown
  • fat redistribution to face and trunk
  • growth supression
  • poor healing
  • infection
  • peptidic ulcer
  • hypertension and HF

• hypoglycemia
• high ACTH
• increase skin pigmentation (ACTH increase melanocyte number)
• hypotension (decrease mineralcorticoids)

• hypoglycemia
• low ACTH
• NO HYPOTENSIONOR SKIN PIGMENTATION
  • mineralcorticoid less affected by less ACTH

• stress related
  • severe (major surgery, trauma, delivery)- 100-150 mg IV
  • moderate (infection, minor surgery)- double usual oral dose
  • exceptional (hike, excam)- 5-10 mg hydrocortisone

1. stressful situation
2. stimulate preganglionic symp. nerves
   1. one set goes to chromaffin cells and produce norepi, epi
   2. another connect to postganglionic symp. cells and produce norepi

80% epinepherine

20% norepinephrine

• heart- stimulates increase in HR, SV, CO and contractility

• norepinephrine- stimulates alpha cells to vasoconstrict
• epinephrine
  • stimulates alpha receptors to vasoconstrict the bv's
  • inhibits beta 2 receptors, leading to DECREASE VASOCONSTRICTION

• tumor of chromaffin cells (increased catecholamines)
• symptoms
  • HTN
  • tachycardia
  • glucose intolerant
  • headache
  • sweating
  • anxiety
  • tremor