LMP301 2014 Lecture 9.pdf

6 Pages
110 Views

Department
Laboratory Medicine and Pathobiology
Course Code
LMP299Y1
Professor
Kenneth Yip

This preview shows pages 1 and half of page 2. Sign up to view the full 6 pages of the document.
Description
    Lecture  9  :  Thyroid  Diseases   Goiter   -­‐ Enlarged  thyroid  gland   o May  be  associated  with  hypo,  hyper  or  eu -­‐thyroid  (no  thyroid  problem)   o Malnutrition?  Thyroid  gland  would  try  to  enlarge  the  number  of  cells  to  produce  more   tissues  and  accumulate  more  iodine  from  diet   à  goiter  is  adaptation  to  environment     Thyroid  Gland  and  Thyroid  Hormones   -­‐ thyroid  gland  secretes  mostly  T4  and  some  T3   -­‐ the  peripheral  tissues  (e.g.  the  liver  and  kidney  –  can  convert  T4  to  T3)  deiodinate    T4  to   produce  2/3  of  the  circulating  T3  (peripheral  conversion)   -­‐ thyroid  hormones  bind  to  receptors  and  triggers  the  hormonal  effects   -­‐ T3  is  more  biologically  active  than  T4 ,  but  at  a  lower  concentration  in  plasma  (2nmol/L  for  T3   vs  100nmol/L  for  T4)   -­‐ Reverse  T3  (rT3)  is  an  inactive  form  metabolized  from  T4   -­‐ T3  binds  to  receptor  and  triggers  target  cell  to  promote  metabolism   -­‐ Local  thyroid  status  can  be  modulated  b y  the  relative  production  of  T3  and  rT3   -­‐ Thyroid  hormones  are  essential  for  the  normal  maturation  and  metabolism  of  all  tissues  in  the   body     Synthesis  of  Chemical   1) tyrosine  (amino  acid)  is  a  precursor   2) from  diet,  thyroid  gland  accumulates  iodine  à  gets   converted  to  a  more  active  form  so  it  can  bind  to  a   tyrosine  molecule   3) If  there  is  only  1  iodine  attached  =   monoiodotyrosine  (MIT)   • If  there  is  2  iodines  attached  =  diiodotyrosine   (DIT)   4) If  2  of  the  diiodotyorsine  is  coupled  together  =  T4   • There  are  4  iodines  attached  to  the  2  DITs   5) If  there  is  1  monoform  and  1  diiodoform  coupled   together  =  T3   • From  T4,  they  can  also  lose  one  of  the  iodine  to   form  T3   6) In  rT3,  iodine  is  in  a  different  position  and  one  is   active,  another  is  inactive   -­‐ peripheral  tissue  (by  adjusting  how  much   conversion  to  T3  or  rT3  =  fine  tuning  of  local  thyroid  hormone  effect)       Hypothalamus-­‐Pituitary-­‐Thyroid  Axis   1) hypothalamus  produces  TRH   2) TRH  stimulates  the  Anterior  Pituitary  to  release  TSH   3) TSH  goes  to  the  thyroid  gland  and  binds  the  TSH  receptor   à  promote  thyroid   gland  to  release  T4  and  T3   -­‐ thyroid  hormones  connect  the  feedback  to  the  pituitary  ad  hypothalamus   à   when  there  are  enough  thyroid  hormone  in  the  circulation,  they  will  reduce  TRH   and  TSH  production   -­‐ same  mechanism,  TSH  can  also  have  a  negat ive  feedback  to  the  hypothalamus  to   adjust  TRH  release   -­‐ fine  tuning  of  T3  and  rT3  production  in  peripheral  tissues   à  locally  adjust  response  to  thyroid  hormone     Total  vs.  Free   -­‐ in  the  circulation,  most  of  thyroid  hormones  bind  to  their  binding  proteins   -­‐ reversibly  bound  to  carrier  proteins   o e.g.  T4-­‐binding  globulin  (TBG),  some  will  bind  to  albumin       -­‐ only  very  small  fraction  is  unbound  and  free  for  biological  activity  à  these  are  the  active  hormones  à  bind  receptors   to  cause  biological  effect     • only  0.03%  of  T4’s  are  in  the  free  form   • 0.3%  of  T3’s  are  in  the  free  form   -­‐ alterations  in  the  concentration  or  affinity  of  binding  proteins  may  change  the  concentration  of  thyroid  hormones   o in  the  circulation,  if  there  is  a  change  in  the  binding  protein  concentration,  or   binding  protein  affinity  to  the   hormone  à  balance  between  bound  and  free  will  also  change   -­‐ FT4  and  FT3  vs.  total  T4  and  total  T3   –  which  are  the  better  markers  in  routine  assessment  of  thyroid  function?     Changes  of  TBH  Binding  Affects  Thyroid  Function  Tests   Cause   Compound   Effects   Increase  TBG   Estrogen   ↑  T4,  T3  /  ↔  FT4,  TSH   (by  increasing  liver  production)   -­‐  can  decrease  TBG  synthesis  in  the  liver   à  when  there  is  an  increase   -­‐  less  binding  protein  (less  T3  and  T4  bound  to  the  binding   level  of  TBG  in  the  circulation   protein  =  bound  form  is  decreased)   à  more  binding  protein  =  more   -­‐  but  because  the  normal  patient  with  functioning  thyroid  can   thyroid  hormone  bound     immediately  respond  to  change  of  hormone  status,  they  can   à  but  in  a  normal  patient  with   maintain  normal  thyroid  status   à  adjust  T4  level  to  be  normal   a  normal  thyroid  function,  they   à  total  hormone  (because  bound  fraction  has  been  decreased)   can  maintain  normal  thyroid   à  adjust  total  hormone  level  in  response  to  bound   hormone  status  =  free  T4  is   increase/decrease  à  maintain  free  hormone  to  be  normal   maintained  as  normal,  but  total   (therefore,  TSH  also  maintained  to  be  normal   à  feedback   hormone  level  is  increase   pathway)   (bound  is  increased)   Oral  contraceptive   Decrease  TBG   Androgen   ↓  T4,  T3  /  ↔  FT4,  TSH   Glucocorticoids   Inhibit  binding  of  T4/T3  to   Salicylates   ↓  T4  /  ↔  FT4   TBG   -­‐  medication   -­‐  inhibit  binding  of  thyroid  hormones  to  TBG  à  decrease  binding   affinity   -­‐  same  effect  as  decrease  in  binding  =  l ess  bound  form   -­‐  but  because  this  medication  has  nothing  to  do  with  the  thyroid   gland  à  assume  in  normal  subject,  the  thyroid  gland  can  respond   to  change  in  binding  to  return  free  t4  to  normal,  and  decrease   total  T4  levels   -­‐  free  hormone  is  more  important  to  biological  effect  of  thyroid   gland  and  thyroid  hormone  status   -­‐  the  total  hormone  fluctuates  through  the  binding  protein   change   -­‐  measure  FT4/FT3  in  the  laboratory   MYXEDEMA:  Dry,  Waxy  Swelling  of  the  Skin,  with  A bnormal  Deposits   of  Glucosaminoglycans  (unbranched  polysaccharides )   -­‐ change  in  the  appearance  of  an  untreated  hypothyroid   female  over  11  year  period   -­‐ this  dramatic  change  reflects  thyroid  function  (not  just  age)  -­‐   hypothyroidism   -­‐ myxedema:  skin  accumulates  in  deposits  of  unsaturated   polysaccharides     -­‐ enlarged  thyroid  gland  due  to  iodine  deficiency     Symptoms  and  Signs  of  Hypothyroidism  –  Hypometabolic  Syndrome   -­‐ low  thyroid  hormone     -­‐ symptoms  and  signs:   o weight  gain   o easy  fatigue  (less   energy  and   o depression   energy,  less  thyroid   metabolism)   hormone  to  produce   o lethargy       o cold  intolerance   o deep,  hoarse  voice   o Bradycardia  (slow   o hair  loss   o dry,  coarse  skin   heart  rate)  à  less   o constipation  (less   o myxedema   hormone  to  produce   intestine  movement)   o high  cholesterol   heart  beat  and  less   o growth  retardation   (decrease  in  LDL   metabolism in  children   receptors)     Cause  of  Hypothyroidism   -­‐ primary  hypothyroidism  (targets  endocrine  gland  –  thyroid  gland)   o autoimmune  destruction  of  the  thyroid  gland     § thyroid  gland  failed  to  produce  thyroid  hormone   § Hashimoto’s  Disease:  auto-­‐antibody  targets  the  thyroid  gland   • Destroys  the  thyroid  gland  so  it  cannot  function  and  produce  hormones   o Radioiodine  or  surgical  treatment  of  hypothyroidism   o Iodine  deficiency   o Congenital  defects  in  hormone  biosynthesis  and  action   o Transient  hypothyroidism  due  to  drug  therapy  (antithyroid  drugs)   § After  stop  of  treatment,  thyroid  gland  can  go  back  to  normal   -­‐ secondary  hypothyroidism  (targets  the  pituitary)   o pituitary  disease   o pituitary  fails  to  produce  TSH   à  thyroid  gland  does  not  get  enough  TSH   à  cannot  produce  hormone   o giving  TSH  =  thyroid  gland  goes  back  to  normal  to  produce  hormones   -­‐ tertiary  hypothyroidism   o hypothalamic  disease  (caused  by  the  hypothalamus)   o hypothalamus  fails  to  produce  TRH     Diagnostic  Strategy  for  Suspected   Hypothyroidism   -­‐ if  suspected  of  hypothyroidism,  screen   test  for  TSH  and  fT4   • high/normal  TSH  and  high   fT4  =  not  hypothyroid   • high  TSH  and  low  fT4  =   primary  hypothyroidism   § low  fT4  =  less  thyroid   hormone  =   hypothyroidism   § pituitary  is  functioning,  but  thyroid  gland  failed   • high  TSH  and  normal  fT4  =  subclinical  hypothyroidism   § not  hypothyroidism  yet   § but  high  TSH  –  fT4  not  enough  to  maintain  normal  thyroid  hormone  requirements   • low/normal  TSH  and  low  fT4  =  secondary  hypothyroidism   § caused  by  the  pituitary  =  secondary  hypothyroidism     § isn’t  enough  TSH  to  promote  T4  production     Complications  of  Hypothyroidism   -­‐ depending  on  when  during  life  a  patient  is  hypothyroid,  clinical  outcomes  vary   -­‐ pregnancy:  if  the  pregnant  women  develops  hypothyroidism  =  irreversible  fetal  malformation,  
More Less
Unlock Document

Only pages 1 and half of page 2 are available for preview. Some parts have been intentionally blurred.

Unlock Document
You're Reading a Preview

Unlock to view full version

Unlock Document

Log In


OR

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


OR

By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.


Submit