Ftplectures Endocrine system Lecture Notes

ENDOCRINE

Medicine made simple

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Ftplectures Clinical Medicine
Copyright 2014

Adeleke Adesina, DO
Clinical Medicine

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Title:  Adrenal  gland  physiology  
 
Objectives  for  learning:  parts  of  adrenal  gland  
 
Parts  of  adrenal  gland  
Adrenal  gland  has  two  parts-­‐    
 
1) outer  layer  cortex-­‐  The  cortex  has  3  zones  which  are  
• Zona  glomerulosa-­‐  salt  –  aldosterone  -­‐  sodium  absorption  to  keep  up  blood  pressure  
• Zona  fasciculata-­‐  sugar  –  glucocorticoids  like  cortisol  
• Zona  reticularis  –  sex  –  testosterone  -­‐  related  to  sexual  function  
 
2) Inner  layer  medulla  
• chromaffin  cells  
 
The  acronym  is  GFR  (similar  to  glomerular  filtration  rate).  An  easier  way  to  remember  is  to  
think  salt,  sweet  and  sex  for  the  three  zones.  The  deeper  it  goes,  the  sweeter  it  gets.    
Zona  glomerulosa  produces  the  hormone  aldosterone  that  is  related  to  sodium  absorption  
(salty).  Zona  fasicculata  produces  glucocorticoids  (sugary)  like  cortisol  and  zona  reticularis  
produces  sex  hormones  like  testosterone.  Medulla  has  chromaffin  cells.  
 
Steroid  pathway  
Cholesterol  is  a  steroid  and  it  gets  converted  to  pregenenolone  under  the  action  of  
desmolase.  The  enzyme  desmolase  is  activated  by  ACTH  (adrenocorticotropic  hormone).  
Pregenenolone  breaks  down  to  progesterone.  Under  the  action  of  21  alpha  hydroxylase  
progesterone  gets  converted  to  11-­‐  deoxycorticosterone  which  again  is  converted  to  
corticosterone  under  the  action  of  11  beta  hydroxylase.  Under  the  effect  of  aldosterone  
synthase  corticosterine  gets  converted  to  aldosterone.  The  whole  pathway  occurred  in  Zona  
Glomerulosa.  
Pregenenolone  gets  converted  to  17-­‐OH  pregenenolone  under  the  action  of  17  alpha  
hydroxylase.  17-­‐OH  pregenenolone  converts  to  DHEA  (dehydroepialdosterone).  17-­‐OH  
pregenenolone  and  progesterone  (under  the  action  of  17  alpha  hydroxylase)  get  converted  
to  17-­‐OH  progesterone.  21  alpha  hydroxylase  mediates  the  conversion  of  17-­‐OH  
progesterone  from  11-­‐deoxycortisol.  11  beta  hydroxylase  converts  11-­‐deoxycortisol  to  
cortisol.  This  part  of  the  pathway  takes  place  in  Zona  Fasciculata.  
17-­‐OH  progesterone  gets  converted  to  androstenedione  which  in  turn  gets  converted  to  
testosterone.  Androstenedione  gets  aromatized  to  form  estrone.  Testosterone  gets  
aromatized  to  form  estradiol  and  under  the  action  of  5  alpha  reductase  it  gets  converted  to  
dihydrotestosterone  (DHT).  This  part  of  the  pathway  takes  place  in  Zona  Reticularis.  
(Important  terms  in  the  cycle  are  marked  in  bold  letters)  
 
Adrenal  medulla  
The  chromaffin  cells  of  adrenal  medulla  are  under  the  action  of  sympathetic  nerve  fibers.  
These  presympathetic  fibers  contain  acetylcholine  that  act  on  chromaffin  cells  so  that  they  
contract  and  produce  epinephrine  and  norepinephrine.  They  are  called  as  catecholamines.  
Adrenal  medulla  produces  80%  of  epinephrine  and  20%  norepinephrine.  The  venous  
drainage  from  adrenal  cortex  has  a  high  quantity  of  cortisol  and  increases  the  transcription  
of  PNMT,  an  enzyme  that  catalyses  the  conversion  of  epinephrine  to  norepinephrine.  
In  a  way  cortisol  is  responsible  for  the  conversion  of  epinephrine  to  norepinephrine.  
Norepinehrine  causes  vasoconstriction,  thereby  increase  the  blood  pressure.  
 
How  steroid  hormones  act?  
Steroids  are  lipid  soluble  with  a  phospholipid  bilayer.  A  steroid  molecule  penetrates  the  
cellular  cytoplasm  and  binds  to  the  steroid  binding  protein  (globulin).  The  complex  of  
steroid-­‐protein  enters  the  nucleus  and  bind  to  the  DNA.  DNA  gets  transcribed  into  mRNA  
which  in  turn  makes  a  protein  (enzyme).  
 
Functions  of  cortisol  
1. Anti-­‐inflammatory  agent-­‐  It  prevents  the  activation  of  arachidonic  acid  pathway.  In  
arachidonic  acid  pathway,    

                                                   PLA2  is   arachidonic  

inhibited  by  corZsol   acid  

cycloxygenase   lipoxygenase  
pathway   pathway  

leukoZenes  
PGE2,D,I2   TA2   A,B,C,D  

 
Phospholipase  A2  acts  on  arachidonic  acid  to  start  of  the  two  pathways  that  eventually  form  
mediators  of  inflammation.  Cortisol  inhibits  PLA2,  so  causes  anti-­‐inflammation.  
 
2. Gluconeogenesis,  lipolysis  and  proteolysis  
Glucose    

  PEP(  phosphoenoplyruvate)  
 
 
  Pyruvate              PEP  carboxylase                                                                    cortisol  
 
  Acetyl  CoA  
     
  TCA  cycle  
oxaloacetate  
 
Cortisol  acts  on  PEP  carboxylase  and  reverses  the  glycolytic  pathway  by  producing  glucose.  
Cortisol  breaks  down  fats  and  proteins  also.  
 
3. Decreases  your  immunity-­‐  it  reduces  the  neutrophilic  function.  It  reduces  the  
capacity  of  adhesion  of  neutrophils  to  the  endothelial  cells  of  the  capillaries.  This  
way  the  neutrophils  keep  on  floating  in  the  blood  and  make  the  person  
immunosuppressive.  
4.  Maintain  your  blood  pressure-­‐  Epinephrine  gets  converted  to  norepinephrine  under  
the  influence  of  cortisol.  If  there  is  a  drop  in  B.P.,  cortisol  causes  the  preload  and  
afterload  to  increase,  the  cardiac  output  increases,  heart  rate  increases  and  blood  
pressure  increases.  This  way  the  B.P.  is  maintained.  
5. Decreases  bone  formation-­‐  The  patients  are  predisposed  to  osteoporosis.  
Adrenal  insufficiency  

Definition  

It  is  the  decreased  level  of  adrenal  gland  hormones  like  aldosterone  and  cortisol.  

Types  

Primary   Secondary   Tertiary  

Adrenal  gland  is  affected   Pituitary  gland  is  affected   Hypothalamus  is  affected  
1. Addison  disease   Abrupt  discontinuation  of   Less  production  of  CRH  
-­‐ Cause  of  adrenal   steroids   -­‐ A  rare  cause  
insufficiency  in   -­‐ The  most  common   -­‐ When  
industrialized  world.     reason  for  adrenal   corticotrophin  
-­‐ autoimmune  disorder   insufficiency.   releasing  hormone  
-­‐ Antibodies  generated   -­‐ A  person  put  on   is  not  released  from  
against  adrenal  gland.   prolonged  periods   hypothalamus,  
of  steroid   ACTH  will  not  be  
administration   produced  by  
should  never  stop   pituitary.  Hence,  
steroid  use   cortisol  will  not  be  
abruptly.     released  from  the  
  adrenal  gland.  

2. Infection   -­‐ His  adrenal  glands   Since  aldosterone  is  not  

-­‐ Cause  of  adrenal   are  atrophied   affected  by  ACTH,  the  level  will  
insufficiency  in  third   because  of  disuse   remain  in  the  same.  
world  countries   for  a  long  time.  
-­‐ Tuberculosis  like    
infections  
3. Iatrogenic   -­‐ So  tapering  of    
-­‐ Cause  of  adrenal   steroids  is  
insufficiency  is   recommended  
bilateral  adrenal  gland   instead  of  abrupt  
removal     discontinuation  
 
4. Metastasis      
-­‐ From  lung  or  breast  
cancer,  metastasis  can  
take  place  to  adrenal  
gland  
 

 
Clinical  features  

-­‐ These  patients  have  ↑  ACTH  levels.  

-­‐ They  have  high  levels  of  MSH  (melanocyte  stimulating  hormone)  
-­‐ So  such  patients  are  hyperpigmented.  

↓aldosterone  
HYPONATREMIA  

hyperkalemia-­‐    causes  weakness,  faNgue  and  

arrythmias  

hypovolumia,  decreased  renal  perfusion    

hypotension,  ↓ CO, ↓ perfusin to brain, shock,

syncope  
 

Secondary  adrenal  insufficiency  

↓ corNsol  

hypoglycemia  or  ↓ level of glucose  

orthostaNc  hypertension  

non-­‐specific  gastrointesNnal  symptoms  like  nausea,  vomiNng  

CNS  Symptom  like    lethargy,  psychosis  and  confusion  

 

Diagnosis  

-­‐ Test  the  level  of  cortisol  

-­‐ If  the  level  is  low,  check  for  level  of  plasma  ACTH.  
-­‐ If  the  level  is  high,  it  is  primary  adrenal  insufficiency  
-­‐ If  the  level  is  low,  it  is  secondary  adrenal  insufficiency  
-­‐ On  ordering  standard  ACTH  stimulation  test,  there  will  be  no  change  in  the  level  of  
cortisol  in  both  primary  and  secondary  cases  initially.  
-­‐ The  same  test  is  repeated  about  5  to  6  days  later  and  if  there  is  an  increase  in  the  level  
of  cortisol,  it  is  definitely,  secondary  adrenal  insufficiency.    
-­‐ Imaging  methods  like  MRI  of  brain  can  be  done  to  find  out  the  cause  of  pituitary  or  
hypothalamus  malfunction  

Treatment  

For  primary  adrenal  insufficiency-­‐  

• Prednisone  (which  is  a  glucocorticoid  and  acts  as  cortisol)  

• Fludrocortisone  (which  is  a  mineralocorticoid  and  acts  as  aldosterone)  
For  secondary  adrenal  insufficiency  

• Do  not  stop  your  steroid  intake  abruptly.  

• Taper  it  down  so  that  there  is  sufficient  production  of  cortisol  in  the  body.  

 
Title:  Diabetes  Insipidus  

Definition  

Kidney  does  not  respond  to  ADH.  There  are  2  types-­‐  

a. Central  DI-­‐  The  brain  is  affected.  There  is  low  or  no  ADH.  The  pituitary  gland  is  affected.  
b. Nephrogenic  DI-­‐  Kidney  does  not  respond  to  ADH.  

Causes  

For  central  DI-­‐  

• 50%  cases  are  idiopathic  

• Trauma  –  surgery  
• Sarcoidosis,  syphilis  or  TB  in  brain  
• Eosinophilic  granuloma  
• Viral  encephalitis  

For  nephrogenic  DI  

• Pyelonephritis  
• Hypokalemia  
• Hypercalcemia  
• Lithium/  Demiclocycline  –  They  block  ADH  effect  on  collecting  tubules  of  kidney.  

Signs  and  symptoms    

1. Polyurea  –  They  can  urinate  from  5  to  15  liters  a  day.  Their  urine  is  colorless  because  of  low  
urine  osmolality.  
2. Polydipsea  –  They  feel  very  thirsty  as  they  have  to  replace  the  water  that  they  have  lost  
through  urination.  
{  polydipsea  can  be  seen  in  –  
a. Diabetes  mellitus  I  and  II  
b. Diuretics  
c. Diabetes  insipidus  
d. Primary  polydipsea}  
3. Mild  hypernatremia  

Diagnosis  

-­‐ Check  the  specific  gravity  of  urine,  whether  it  is  below  1.010  or  not.  
-­‐ Urine  osmolality  will  also  be  low.  
-­‐ Plasma  osmolality  is  250-­‐290m  osm/kg  
-­‐ The  formula  for  calculation  is  2  (Na+)  +  glucose/18  +  BUN/2.8  +  ethanol/1.6  
-­‐ Water  deprivation  test-­‐  Patient  is  deprived  from  drinking  water.  Urine  osmolarity  is  checked  
every  hour  until  it  becomes  stable.  
-­‐ Desmopressin-­‐  a  drug  just  like  ADH  (vasopressin)  
 
Urine  osmolarity   Central  DI   Nephrogenic  DI  
Before  vasopressin   Low     Low    
After  vasopressin   ↑↑↑     ↓↓  
 

Treatment  

For  central  DI  

-­‐ Desmopressin  (DDVAP)-­‐  Administartion  of  desmopressin  is  the  primary  therapy.  It  can  be  
administered  in  the  form  of  nasal  or  oral  spray  or  even  injectable  form.  
-­‐ Chlorpropamide-­‐  It  increases  the  ADH  production  and  enhances  the  effects  on  kidney  

For  nephrogenic  DI  

-­‐ Thiazide  –  It  increases  the  re-­‐absorption  of  sodium  which  in  turn  causes  absorption  of  water  
making  the  urine  concentrated.  

 
Title:  Diabetes  mellitus  

Diabetes  is  a  growing  epidemic  and  is  becoming  a  leading  cause  for-­‐  

• Blindness  
• Chronic  renal  failure  
• Peripheral  neuropathy  
• Below  the  knee  amputation.  

Definition  

It  is  a  disorder  in  carbohydrate  metabolism  that  causes  elevated  levels  of  glucose  in  circulation  due  
to  problems  in  maintenance  of  homeostasis  in  sugar  level.    

Types  

  Diabetes  Type  I  (juvenile)   Diabetes  Type  II  

Prevalence     5%   90-­‐95%  
Age  group   Less  than  30  years   More  than  40  years  
Body  habitat   Thin     Obese  
Obesity  and  family  history  are  
the  risk  factors    
Pathogenesis     Autoimmune  destruction  of   Insulin  resistance  
Beta  cells  of  islets  of   Down  regulation  of  insulin  
Langerhans  in  pancreas.   receptors  
It  is  associated  with  HLA  DR4  
and  DR3  
Clinical  presentation   Polyurea  –  glucose  is  being   Hyperglycemia    
excreted  and  glucose  causes   Polyurea  
osmotic  dieresis  and  takes   Polydipsea  
along  with  a  lot  of  water.   Polyphagea  
Polydipsea  –  The  loss  of  water   Less  number  of  ketone  bodies  
due  to  polyurea  needs  to  be   produces  (key  difference  from  
compensated  so  the  patient   typeI)  as  they  have  some  
feels  thirsty  and  consumes  a  lot   amount  of  insulin  within  them.  
of  water.  
Polyphagea  –  the  food  is  not  
being  used  in  the  body  as  the  
glucose  molecules  are  excreted  
in  urine  so  there  is  always  a  
hunger  for  food.  
Weight  loss-­‐  this  is  due  to  the  
fact  that  the  body  shifts  to  
starvation  mode.  
Fruity  smell  in  breath-­‐  body  
cannot  use  glucose  so  it  starts  
utilizing  fatty  acids  which  break  
down  to  form  ketone  bodies  
like  acetone  and  acetoacetate.  
Hyperglycemia    
Treatment     Administration  of  insulin   Education-­‐  Diet  and  Exercise  to  
 manage  obesity.  
Medications  like  
1. Sulphonylurea  
-­‐ Glyburide  
-­‐ Glipizide  
-­‐ Glimeperide  
They  act  on  pancreas  to  
produce  insulin.  
Side  effects-­‐  hypoglycemia  and  
weight  gain  
2. Metformin-­‐  increases  
insulin  sensitivity.  It  
cannot  be  used  in  
patients  with  renal  
insufficiency  (patients  
with  createnine  level  
more  than  1.5)  as  that  
may  cause  lactate  
acidosis.  
3. TZDs-­‐  
thiazolidinediones-­‐  
reduce  insulin  
resistance.  
Side  effects-­‐  
heparotoxic  so  need  to  
check  liver  function  test  
 
 
Diagnosis  

• Usually  patients  can  have  problems  like  blurry  vision,  which  might  bring  them  to  a  doctor.  
They  may  have  cataract.  This  is  due  to  the  excess  of  glucose  in  circulation.  

Glucose  →  sorbitol  (in  the  presence  of  aldose  reductase)  

The  lens  gets  swollen  due  to  the  excess  water  reabsorption  caused  by  the  sorbitol  deposited  
within  the  lens.  

• Patients  may  come  up  with  a  lot  of  fungal  infections  like  vaginitis  or  oral  fungal  infection.  
They  are  seen  as  reddish  white  lesions  with  a  lot  of  itching.  The  main  causative  agent  is  
candida  albicans.  
• Patients  may  have  peripheral  neuropathy-­‐  numbness  and  tingling  sensation  of  hands.  
• Normal  glucose  level  is  70-­‐100mg/dl.  
• First  test  –  FBG-­‐  fasting  blood  glucose  test-­‐  it  needs  a  fasting  of  8  hours  midnight.  
-­‐ It  should  not  be  more  than  126mg/dl  
• Second  test  –  RBG-­‐  random  blood  glucose  test-­‐  from  finger  prick  test-­‐  if  it  is  more  than  
200mg/dl  and  there  are  symptoms  (3Ps)  
• If  the  blood  glucose  is  100-­‐125mg/dl  in  RBG  ask  he  patient  to  carry  out  FBG.  
• Third  test-­‐  75g  oral  glucose  tolerance  test    
  

 
5.  Diabetes  mellitus:  complications  

Title:  DM  complications  

Two  types  of  complications  

(a) Micro-­‐vascular  complications  
(b) Macro-­‐vascular  complications  
 
Pathogenesis  
(a) Poor  glycemic  control  
-­‐ leads  to  Hyperglycemia  (glucose)  
-­‐ Key  to  diabetes  is  Non-­‐enzymatic  glycosylation  of  amino  acids  on  proteins      
-­‐ Sugar  binding  to  aminoacids  
-­‐ Stimulates  process  of  Atherosclerosis  
-­‐ Increase  permeability  of  blood  vessels  to  proteins  
-­‐ Increase  process  of  atherogenesis  
-­‐ Inside  the  blood  vessel,  the  glycosylated  proteins  get  deposited  into  the  tunica  media  of  
the  blood  vessel  forming  a  plaque.      
-­‐ Blood  vessels  get  thickened.  
 
Macro  vascular  complications    
-­‐ Coronary  artery  disease  (CAD)  
Myocardial  infarction  is  the  most  common  cause  of  death  in  patients  with  diabetes.  
This  happens  due  to  their  increased  predisposition  to  atherosclerosis.  A  sclerotic  plaque  in  
the  coronary  artery  may  get  dislodged  and  cause  MI.  
Stroke  –  due  to  the  ischemia  caused  by  sclerotic  plaque,  the  brain  undergoes  
damage  and  that  is  known  as  stroke.  
Peripheral  artery  disease  –  3rd  most  important  macrovascular  complication.  
Ischemia  to  lower  extremities.  
 
The  glyosylation  of  heme  group  of  hemoglobin  can  act  as  a  marker  for  diagnosis.  While  checking  the  
level  of  HbA1c  it  should  not  be  more  than  7.    
 
Microvascular  complications  
 
1. Diabetic  Nephropathy-­‐    
Physiology  of  glomerulus-­‐  
-­‐ Heparin  sulphate  on  the  basement  membrane  has  a  high  negative  charge  on  them.  
When  albumin  molecules  enter  the  glomerulus  the  filteration  does  not  take  place  due  to  
repulsion  between  similar  charges  and  the  molecules  move  from  afferent  (A-­‐  comes  first  
so  afferent  first)  arteriole  to  efferent  (  E-­‐  can  be  remembered  as  Exit)  arteriole.  
-­‐ In  case  of  diabetic  nephropathy  there  is  hyaline  deposition  causing  thickening  which  are  
called  as  Kiemosteil  Wilson’s  nodules.  This  is  called  nodular  glomerular  
nephropathy/sclerosis.  
-­‐ This  can  be  found  out  in  a  pathology  side  
 -­‐  Microalbuminuria  –  in  normal  cases,  albumin  molecules  are  not  able  to  eak  through  the  
basement  membrane  of  glomerulus  due  to  the  negative  charges  on  both  of  them.  With  
time,  the  basement  membrane  thickens  due  to  the  forceful  deposition  of  glycosyated  
proteins  on  to  the  basement  membrane.  This  reduces  the  negative  charge  and  hence  
makes  way  for  microalbumin  to  leak  through.  This  way  microalbumin  is  excreted  in  urine  
causing  microalbuminuria.  
-­‐ Hypoglycemia  →  ↑GFR→  microalbuminuria  
-­‐ Diagnosis-­‐  normally  the  microalbumin  ratio  is  30-­‐300mg/dl.  
-­‐ Another  sure  test  for  microalbuminuria  is  albumin/creatnine  ratio  which  if  more  than  
0.20,  confirms  diabetic  nephropathy.  
-­‐ If  microalbuminuria  is  left  untreated  there  will  be  albumin  excretion  in  urine  which  is  
even  more  dangerous  as  it  leads  to  problems  like  oedema.  
-­‐ After  some  time  of  increased  GFR  the  GFR  will  become  low  because  of  arteriosclerosis  of  
afferent  arteriole.  There  will  be  hypertension  as  well.  
-­‐ Treatment-­‐  
ACE  inhibitors-­‐  we  try  to  decrease  GFR  by  inhibiting  the  vasoconstrictive  effect  of  
vasopressor  on  efferent  arteriole.  This  way  loss  of  proteins  can  be  controlled.  
 
2. Diabetic  Retinopathy  
-­‐ Diabetes  is  the  leading  cause  of  blindness  in  the  U.S.  
-­‐ Two  kinds  of  pathologies  
1. Background  (non-­‐proliferative)  retinopathy    
-­‐ Ischemia  caused  due  to  deposition  in  blood  vessels.  
-­‐ Scar  formation  takes  place.  Ischemic  blood  vessels  do  not  proliferate.  
-­‐ There  are  other  problems  like  a  lot  of  exudates,  haemorrhage,  microaneurysms  at  the  
back  of  the  eye.  
-­‐ Generally  asymptomatic  till  it  affects  the  central  macular  oedema.  This  causes  vision  
loss.  
2. Proliferative  retinopathy  
-­‐ Due  to  ischemia,  new  blood  vessels  are  produced-­‐neovascularisation  
-­‐ Scar  due  to  ischemia  
-­‐ Retinal  detachment  and  vitreous  haemorrhage  can  be  there.  
Advise  your  patient  to  go  for  an  eye  examination.  The  doctor  may  suggest  laser  coagulation  to  
destroy  the  blood  vessels.  
 
3. Diabetic  Neuropathy    
Pathogenesis:  
Hyperglycemia-­‐  narrowing  of  capillaries  due  to  NEG  proteins  deposition-­‐  
vasoconstriction-­‐  ischemia-­‐  death  of  nerve  or  tissue.    
Symptoms:  
1. Sensory  and  vibration-­‐  loss  of  sensory  reflexes-­‐  since  they  don’t  have  sensation  
in  their  lower  extremities  they  may  develop  diabetic  foot.  
2. Paraesthesia  
3. Loss  ofVibration  
4.  Loss  of  propioception.  
 5. Pain  –  They  may  be  extremely  sensitive  to  even  a  touch  because  they  may  have  
excruciating  pain  even  while  we  touch.  
6. Charcot  joint  in  their  foot-­‐  Disfigured  joints  on  ankle  and  knees.  
The  symptoms  follow  a  stock  glove  pattern-­‐  start  from  the  toe  and  then  proceed  to  the  ankle,  knee  
and  upwards.  
 
Autonomic  neuropathy  
The  autonomic  nervous  system  consists  of  sympathetic  and  parasympathetic  nervous  system.  
Symptoms  are-­‐  
-­‐ Orthostatic  hypertension-­‐  due  to  damage  to  nerves  caused  due  to  ischemia-­‐  person  goes  
to  syncope.  
Neurogenic  bladder  
Patients  develop  urinary  retention  because  of  nerve  damage.  The  alpha  1  nerves  at  the  urethra  and  
the  cholinergic  nerves  of  the  bladder  have  undergone  damage  due  to  which  no  message  is  passed  to  
contract  and  the  bladder  remains  full.  
Gastroparesis  
Delayed  gastric  emptying.  
Nerves  working  on  stomach  for  peristalsis  may  not  be  working.  
They  can  get  hypoglycemic  coma.  
Symptoms  
-­‐ Constipation  or  diarrhoea    
-­‐ Nausea  and  vomiting  
Severe  autonomic  neuropathy  can  cause  impotence  in  men  as  S2,  S3  and  S4  are  affected.  
Mono  neuropathy  
-­‐ Ulnar  nerve-­‐  If  this  nerve  is  affected  patient  will  have  claw  like  hands  where  they  are  not  
able  to  flex  the  last  2  digits.  
-­‐ Radial  nerve-­‐  the  hand  may  just  drop  at  the  level  of  the  wrist  due  to  neuropathy  of  radial  
nerve.  
-­‐ Common  perineal  nerve-­‐  foot  drop  due  to  damage  to  common  perineal  nerve.  They  are  
not  able  to  dorsiflex  their  foot.  
Cranial  nerve  palsy  
-­‐ Occulomotor  nerve  is  the  most  affected.  
-­‐ It  innervates  all  the  muscles  of  the  eye  except  the  inferior  oblique  and  the  lateral  rectus  
muscles  of  the  eye  
-­‐ Pupils  are  innervated  by  parasympathetic  branch  of  cranial  nerve.  Pupils  are  spared.  
Pupils  have  parasympathetic  nerves  which  are  the  last  to  get  affected.  The  motor  nerves  
which  are  in  the  inner  circle  get  affected  first  and  hence  there  are  problems  with  the  
eyelids.  Pupils  will  constrict  but  will  not  be  able  to  adduct.    
-­‐ They  will  have  symptoms  like  diplopia,  ptosis  and  pain.  
 
Treatment  
1. Gastroparesis  
-­‐  metachlopramide  
-­‐  erythromycin  
 
 2. Peripheral  neuropathy-­‐  pregobulin  
-­‐ Gaba  pentin  
-­‐ Duloxetin    
3. Diabetic  foot  ulcers  
-­‐ They  can’t  feel  anything  on  their  toes  hence  they  develop  a  lot  of  foot  ulcers.  They  apply  
pressure  on  their  nerves  causing  pressure  necrosis.  This  can  cause  foot  infections  like  
cellulitis  and  osteomyelitis.  They  develop  hammer  toes.  
-­‐ This  is  the  leading  cause  for  below  the  knee  amputation  in  the  U.S.  
4. Delayed  wound  healing  
5. Immunocompromised    
 
Management  
1. Check  HbA1c  every  3  months  (life  span  of  RBC  is  120  days).  Check  if  it  is  below  7.0  or  not.  
2. Check  for  microalbuminuria  in  urine.  
3. BUN/  creatnine  
4. Yearly  eye  examination  
5. Podiatrist  consultation  every  year  for  foot  exams  
6. Cholesterol  level-­‐  Check  if  the  LDL  is  less  than  100.  For  diabetics  it  should  be  below  70mg/dl.  
7. Check  the  B.P.  it  is  good  if  it  is  below  than  130/80-­‐85.  
 
 
 
 
 
 
 
 
 
6.  Diabetic  ketoacidosis  

Definition  

It  is  a  type  of  metabolic  acidosis  seen  in  diabetic  patients  in  which  the  ketone  bodies  are  
produced  excessively.  

Causes  

The  main  cause  is  stress  and  stress  can  be  caused  due  to-­‐  

• Sepsis  
• Myocardial  infection  
• GI  bleeding  
• Infections    

Pathophysiology    

↓insulin→↑  blood  sugar  

glycogen→  glucose  (in  presence  of  glucagon)  

↑↑↑  blood  sugar  as  a  result,  but  body  cannot  use  the  glucose  and  is  still  starving,  

Fatty  acids→  acetyl  coA→  beta  hydroxylate,  acetylcetate,  acetone  (  the  ketone  bodies  or  
ketoacids  )  

The  cycle  can  be  written  as-­‐  

 ↓insulin  and  ↑glycogen  →  ↑blood  sugar→  Tmax  →  osmotic  dieresis  →water  is  lost→  
dehydration  (volume  depletion)  →labs  →  high  BUN/creatnine  and  presence  of  glucose  in  
urine.  

Signs  and  symptoms  

• Nausea  and  vomiting  

• Acetone  breath  
• Hyperventilation-­‐  rapid  short  breath  to  eliminate  the  excess  of  CO2  in  their  body    
• Dry  mouth  due  to  dehydration    

Diagnosis  

1. Blood  glucose  ≥ 250mg/dl- They are diabetic  

2. ABG  
3. Low pH which shows acidosis  
pH=HCO3−(if less than 15)/ Pa  CO2 .
the  pH  is  lower  than  7.3  
4. Beta  hydroxybutrate  and  acetylacetate  levels  will  be  high.  Nitroprusside  agent  is  
used  to  measure  the  levels.  Test  the  urine  and  the  serum  as  it  will  be  seen  in  both.  

Labs  

1. Hyperosmolality  
2. Hyponatremia-­‐  If  the  blood  glucose  rises  by  100mg/dl  the  sodium  lowers  by  
1.6mEq/l  
3. Hyperkalemia-­‐  Patients  look  hyperkalemic  but  they  are  actually  not.    

Treatment  

1. Plenty  of  fluids  because  patient  is  dehydrated  

2. Insulin  administration  
3. Potassium  is  given  to  counter  the  lowering  of  potassium  level  due  to  insulin  
administration  

 
Title  :  Acromegaly  

Definition  –  

It  is  a  condition  that  occurs  due  to  excess  of  growth  hormone.  In  children,  excess  of  growth  hormone  
causes  gigantism.  In  adults,  it  causes  acromegaly  as  the  growth  plates  have  got  already  fused.  The  
adults  start  manifesting  the  features  of  acromegaly  at  the  age  of  40  to  50  years  usually.  

{Mnemonic  for  hormones  produced  from  anterior  pituitary-­‐  FLAT  PiG  

F  –  FSH  

L-­‐  LSH  

A  –  ACTH  

T  –  TSH  

P  –  PROLACTIN  

G  –  GROWTH  HORMONE}    

Causes  

Macro-­‐adenoma  is  the  cause  for  acromegaly.  This  adenoma  is  more  than  1  cm  in  dimension.  

Clinical  features  

• They  have  skeletal  and  soft  tissue  changes  mainly  

• Big  and  thick  hands  and  feet  
• Very  coarse  voice  
• Enlarged  mandible  
• Obstructive  sleep  apnea-­‐  They  snore  heavily  due  to  enlargement  of  soft  tissues  of  the  larynx.  
They  may  even  choke  to  death  due  to  excessive  enlargement.  
• Enlarged  heart  so  they  develop  restrictive  cardiomyopathy.  They  may  develop  systolic  or  
diastolic  dysfunction  or  both.  
• Develop  hypertension  
• Enlarged  liver,  kidney  and  spleen.  
• Impaired  glucose  tolerance-­‐  They  are  not  able  to  clear  their  glucose  level  so  they  become  
hyperglycemic  and  develop  diabetes.  

Diagnosis  

• Biochemical-­‐  Check  IGF-­‐1  (insulin  growth  like  factor-­‐1)  level.  Growth  hormone  is  
processed  in  the  liver  to  produce  IGF-­‐1.  
• If  you  find  the  level  elevated,  it  indicates  acromegaly.  
• To  confirm,  give  100gm  of  glucose  and  check  the  level  of  GH.  If  GH  is  high,  it  means  that  
the  person  has  acromegaly.  
• Imaging  technique-­‐  MRI  to  check  macro-­‐adenoma  inside  the  brain.  
 Treatment  

Medical  management  

1. Octreotide-­‐    
• A  somatostanin  analogue  
• Inhibits  the  release  of  growth  hormone  releasing  hormone.  The  release  of  growth  
hormone  is  inhibited.    
2. Peguisonent-­‐  
• Growth  hormone  receptor  blocker  
 
Surgical  management  
• Transphenoidal  resection  of  the  tumor.  

Complications  

• Cardiac  arrhythmias  
• Diabetes    

                   

 
Pheochromocytoma  
Definition  

It  is  a  rare  tumour  of  adrenal  medulla  which  affects  chromaffin  cells  formed  from  neural  
crest  cells  primarily.  They  produce  a  lot  of  catecholmines.  

Formation  of  catecholamines    

Tyrosine  →L-Dopa→ dopamine → norepinephrine → epinephrine

↓ ↓ mao ↓ mao

HVA VMA Metanephrine mao=mono

mao=mono amino oxidase

Symptoms

5 Ps

1. Pressure  (high  B.P.)  

2. Palpitations-­‐  tachycardia  
3. Perspiration  
4. Pallor  
5. Pain-­‐  headaches    

Diagnosis  

1. Urine  screen-­‐  check  urine  metanephrine/  normetanehrine  (Vaniller  Mendelic  Acid-­‐

VMA)  
2. Urine  epinephrine/  norepinephrine  level-­‐  this  test  is  done  to  confirm  if  the  urine  
epinephrine  is  coming  from  adrenal  medulla  or  other  external  agents  like  oragn  of  
Zukerlandl  (which  is  seen  next  to  aorta).  
3. Imaging-­‐  CTscan  or  MRI  of  abdomen  to  locate  the  tumor.  
4. I-­‐metaiodobenzylguanidine  scan  to  locate  the  tumor.  
5. I-­‐131  can  be  used  as  the  tumour  takes  it  up.  

Treatment  

-­‐ Administration  of  non-­‐selective  alpha  blockers  which  can  reduce  adrenergic  
response-­‐  phenoxybenzamine.  
-­‐ Surgical  resection  of  tumour  after  giving  phenoxybenzamine  

Rule  of  ten  

10%  -­‐  bilateral  

10%  -­‐  malignant    

10%  -­‐  extra-­‐adrenal  

10%-­‐  calcify  

10%  -­‐  kids  

10%  -­‐  familial  

Neuroblastoma-­‐  a  tumour  found  in  children.  It  affects  the  adrenal  medulla  but  it  can  also  
happen  anywhere  in  sympathetic  chain.  Check  for  HVA.  It  can  be  the  reason  for  
hypertension  in  children.    
Title:-­‐Cushing  syndrome  
Cushing  syndrome  is  related  to  ACTH  which  is  produced  by  the  anterior  pituitary  gland  under  the  
influence  of  CRH  (corticotrophin  releasing  hormone-­‐  produced  in  hypothalamus).  The  function  of  
ACTH  is  to  produce  cortisol  so  it  moves  to  the  adrenal  cortex  and  acts  on  desmolase  to  start  the  
process  of  conversion  of  cholesterol  to  cortisol.  Cortisol  is  also  called  glucocorticoid.  This  is  because  
cortisol  is  involved  in  gluconeogenesis  in  liver  when  the  body  is  under  stress.  Under  stress  or  
starvation,  our  body  needs  energy  in  the  form  of  glucose.    

Definition  

Cushing  syndrome  is  defined  as  the  state  of  the  body  caused  by  an  elevated  amount  of  cortisol.  

Cushing  disease  occurs  due  to  pituitary  adenoma  that  leads  to  excess  production  of  ACTH  which  in  
turn  leads  to  excess  of  cortisol.  

Causes  

1. Iatrogenic  Cushing  Syndrome-­‐  For  almost  all  types  of  inflammations  like  COPD,  dermatitis,  
lupus  or  asthma,  steroids  like  prednisolone  are  the  drug  of  choice.  Steroids  are  just  like  
cortisol  so  the  patient  starts  manifesting  symptoms  of  Cushing  Syndrome.  
2. ACTH  producing  adenoma-­‐  The  pituitary  gland  adenoma  causes  increased  secretion  of  ACTH  
and,  therefore,  increased  level  of  cortisol.  
3. Adrenal  gland  adenoma-­‐  The  adrenal  gland  itself  starts  producing  excess  of  cortisol.  
4. Ectopic  source-­‐  Usually,  it  is  ATCH-­‐producing  cancer  like  small  cell  lung  carcinoma,  bronchio-­‐
carcinoma  or  thymoma.  

{Adrenal  gland  is  called  so  as  it  is  an  added  component  of  the  renal  gland  or  kidney.}  

Symptoms  

1. Central  obesity-­‐  Fat  deposition  on  abdomen  

2. Purplish  striae  on  abdomen-­‐  Cortisol  thins  out  collagen  fibers  and  allows  them  to  stretch  
making  the  dermis  thin  and  the  blood  vessels  beneath  prominent  in  the  form  of  purple  
striae.  
3. Moon-­‐like  faces  
4. Buffalo-­‐hump  
5. Easy  bruising  due  to  defective  collagen  fibers.  
6. Muscle  loss  in  extremities  –  Person  may  have  skinny  hands  as  cortisol  causes  muscle  
breakdown.  
7. Glucose  intolerance-­‐  Cortisol  causes  gluconeogenesis  and  produce  excess  of  glucose.  They  
are  predisposed  to  diabetes.  
8. Masculanization  in  females-­‐  This  is  due  to  excess  of  testosterone.  
9. Hirsutism-­‐  Excess  of  facial  hair.  
10. Oligomenorrhea  or  amenorrhea  
11. Osteoporosis  
12. Depression-­‐  They  may  even  go  manic.  
13. Immunosuppresion-­‐  Impaired  immunity  due  to  neutrophil  dysfunction.  
 Case  

A  22-­‐year  old  female,  with  Cushing  syndrome  had  her  vital  signs  taken.  Her  B.P,  was  148/90,  RBS  
was  250mg/dl.    

-­‐ The  high  blood  sugar  is  due  to  gluconeogenesis  caused  by  cortisol.  
-­‐ The  high  B.P.  is  due  to  the  activation  and  conversion  of  epinephrine  into  norepinephrine  and  
due  to  the  mineralocorticoid  like  activity  of  cortisol.  

Diagnosis  

1mg  of  dexamethasone  administered  in  the  night  and  the  level  of  cortisol  is  checked  in  the  
morning.  

-­‐  In  normal  cases,  dexamethasone  causes  inhibition  of  ACTH  secretion  from  pituitary  leading  
to  normal  level  of  cortisol.  24  hour  urine  cortisol  level  can  also  be  checked.  
 
-­‐ If  the  cortisol  level  is  abnormally  high,  check  the  level  of  ACTH.  
 
 
-­‐ If  the  level  of  ACTH  is  high,  it  can  be  due  to  pituitary  adenoma  or  small  cell  carcinoma  of  
lung.  Administer  a  high  dose  of  Dexamethasone.  If  the  ACTH  level  drops  down,  there  is  
pituitary  adenoma  which  can  be  confirmed  by  MRI  but  if  it  remains  the  same,  it  is  small  cell  
carcinoma  of  lung  which  can  be  confirmed  by  CT  scan,  X-­‐ray  and  biopsy  (best  way).  
 
-­‐ If  the  level  of  ACTH  is  low,  it  can  be  due  to  adrenal  gland  adenoma.  To  confirm,  carry  out  an  
abdominal  CT.  
 

Treatment  

1. Iatrogenic  
Taper  the  dose  of  steroid.  Abrupt  discontinuation  can  be  fatal.  No  hyperpigmentation  in  
cases  if  iatrogenic  induced  Cushing  Syndrome.  
2. Pituitary  adenoma  
POMC  (pro-­‐opio-­‐melano-­‐corticotropin)  is  produced  in  patients  with  pituitary  adenoma  
which  causes  hyperpigmentation  of  skin.  
Medical  treatment-­‐  ketoconazole  (inhibits  desmolase  activity),  metapyrone  (inhibits  11  beta  
hydroxylase)  
Surgical  treatment  –  transphenoidal  resection  of  adenoma  (best  for  patient)  
3. Adrenal  tumor  
Surgical  resection  
4. Small  cell  carcinoma  of  lung  
Radiotherapy  
 

 
  

 
 10. Diseases  of  the  Parathyroid  Glands:  Hyperparathyroidism  

Definition  

It  is  the  elevated  level  of  parathormone.  

Causes  

-­‐ Adenoma  -­‐80%  of  the  cases  have  parathyroid  adenoma  as  the  cause  
-­‐ Hyperplasia-­‐  All  4  parathyroid  glands  produce  excess  of  PTH.  
-­‐ Carcinoma-­‐  RARE  cause  like  1%  only.  

Clinical  features  

Mnemonic  used  is  ‘stones, bones, abdominal groans and psychiatric moans’.

-­‐ Bone  pain-­‐  due  to  destruction  of  bone    

-­‐ Osteitis  Fibrosis  Cystica-­‐  also  called  Brown  Tumors.  They  have  pathological  fractures.  
-­‐ Nephrolithiasis  (kidney  stones)  
-­‐ Nephrocalcinosis  
-­‐ Abdominal  groans  due  to  hypercalcemia  due  to  constipation,  radiating  to  the  back  
-­‐ Predisposition  to  peptic  ulcer  and  pancreatitis.  
-­‐ Psychiatric  overtones  
-­‐ Lethargic  
-­‐ Confused  
-­‐ Sleeping  problems,  anxiety  
-­‐ Polyuria  and  polydipsea-­‐  symptoms  of  D.  Insipidus  

Lab  

-­‐ High  PTH  

-­‐ High  Ca  
-­‐ Low  phosphate  
-­‐ Hypercalciuria  
-­‐ Chloride/phosphate  ratio-­‐  33:1-­‐  very  sensitive  

X-­‐Ray  

Sub-­‐periosteal  resorption-­‐  mainly  on  the  radial  aspect  of  2nd  and  3rd  upper  phalanges  

Treatment  

1.  Surgical    
-­‐ PTH  adenoma-­‐  surgical  removal  
-­‐ Hyperplasia-­‐  take  all  4  out.  Bury  one  gland  in  your  muscle  so  that  PTH  production  continues.  
2. Medical    
-­‐ Increase  fluids  to  treat  high  Ca  
-­‐ Loop  diuretic  like  furosemide  
-­‐ Thiazides  should  not  be  given  for  hypercalcemic  patients.  
-­‐ Medical  treatment  is  for  non-­‐symptomatic  patients.  
Hypoparathyroidism  

Definition  

The  parathormone  level  is  less.  

Causes  

-­‐ Thyroidectomy  
-­‐ Radical  surgery  for  thyroid  cancer  on  head  and  neck.  

Case  

39  year  old  female  comes  into  the  emergency  complaining  of  Grand  mal  seizures.  First  
benzodiazepines  were  administered.  Lab  reports  show  that  calcium  level  is  6.0  which  is  quite  low  or  
hypocalcemia.    

In  EKG  prolonged  QT  seen  which  is  about  500  which  normally  should  be  440.  

Low  calcium,  magnesium  and  potassium-­‐  prolonged  QT  

Clinical  features  

-­‐ Prolonged  QT  on  EKG  it  will  cause  Torsades,  and  later  ventricular  fibrillation  or  cardiac  
arrhythmia.  
-­‐ Grand  mal  seizures  due  to  hypocalcemia  
-­‐ Tetany  –  
1. Chvostek’s  sign-­‐  tapping  the  facial  nerve  causes  spasm  on  that  side  
2. Trousseau  sign-­‐  Put  a  BP  cuff  and  pump  it  over  patient’s  systolic  pressure  and  hold  it  for  
3  minutes  there  will  be  carpo-­‐petal  spasm.  It  is  not  practised  in  the  hospital  generally.  
3. Tingling  sensation  and  numbness  

Physical  examination  

-­‐ The  signs  of  tetany  are  tested.  

-­‐ Hyperactive  Deep  tendon  reflexes  

Diagnosis  

1. Level  of  PTH-­‐  it  will  be  low.  

2. Low  calcium  level  
3. Hyperphospotamia  
4. Low  urine  cyclic  AMP  

Treatment  

1. IV  Calcium  gluconate.  
2. Vitamin  D-­‐  calcium  reabsorption  
 
Hyperthyroidism  
Definition  

Abnormal  excessive  production  of  thyroid  hormones  (T3  and  T4)  due  to  hyperactivity  of  thyroid  
gland  is  hyperthyroidism.  

What  are  the  causes?  

1) Graves  disease-­‐  It  is  the  most  common  cause.  It  is  actually  diffuse  thyrotoxicosis  or  toxic  
diffuse  goiter  (hypoplasia  of  thyroid  gland  in  which  the  entire  gland  is  hyperfunctioning  
causing  excess  hormone  production).  This  disease  is  an  autoimmune  disorder  where  
numerous  antibodies  (TSI-­‐  Thyroid  Stimulating  Immunoglobulins)  bind  to  the  TSH  (Thyroid  
Stimulating  Hormone)  receptors.  TSH  receptors  respond  to  TSH  under  the  action  of  which  
the  gland  keeps  on  producing  more  and  more  of  thyroid  hormones.  TSI  are  actually  IgG  
immunoglobulin.  These  immunoglobulins  cause  a  lot  of  damage  to  the  gland  and  cause  the  
condition  thyrotoxicosis  as  there  is  a  toxic  production  of  thyroid  hormones.  
2) Toxic  adenoma-­‐  Only  a  small  mass  of  cells  of  the  thyroid  gland  produces  thyroid  hormones  
abnormally.      
3) Drugs  like  Amiodarone  –  it  is  given  when  a  person  undergoes  Ventricular  tachycardia.  This  
causes  hyperthyroidism  as  there  is  an  excess  consumption  of  iodine.  
4) Toxic  multinodular  adenoma  –  There  are  multiple  nodules  within  the  gland  which  act  as  
separate  factories  that  produce  thyroid  hormone  excessively.  This  disease  is  also  called  
Plummer’s  disease  and  these  patients  are  at  an  increased  risk  of  having  CHF  and  
arrhythmias.  As  thyroid  hormones  increase  the  beta1  receptors  in  the  heart,  there  will  be  
increase  in  heart  contractility  due  to  sympathomimetic  effect.  This  leads  to  CHF.  Atrial  
fibrillation,  which  leads  to  arrhythmias,  is  because  of  increased  thyroid  hormones.  
 
Clinical  manifestations-­‐  
• Exophthalmos  and  pretibial  myxedema-­‐  The  most  common  and  prominent  feature  is  
exophthalmos  and  pretibial  myxedema.  These  are  the  classic  signs  of  Graves  
disease.  Exophhalomos  is  the  bulging  of  eyeballs  and  widening  of  pupils.  The  
patients  seem  to  be  staring  at  a  particular  object.  It  is  caused  by  the  phenomenon  of  
proptosis  that  is  caused  by  glycosaminoglycans  (produced  by  the  antibodies  that  
cause  hyperthyroid)  deposition  in  the  eyelids.    The  leg  has  edema  in  front  of  the  
tibia  so  there  will  be  indentations  when  the  finger  is  pushed  on  that  part  of  the  leg.  
The  same  can  appear  on  the  dorsum  of  the  hands.  
• Lack  of  sleep.  
• Develop  tremors  and  have  a  shaking  or  trembling  hand.  
• Frequent  bowel  movements  
• Excessive  sweating  
• Palpitations  
• Weight  loss  in  spite  of  having  a  good  appetite-­‐  the  increased  level  of  T3  and  T4  cause  
increased  rate  of  metabolism.  
• Osteoporosis-­‐  the  osteoclasts  break  down  bone  under  the  action  of  thyroid  
hormones.  This  leads  to  hypercalcemia.  
 Diagnosis  

o TSH  test-­‐  The  level  of  TSH  will  be  low  because  of  negative  feedback  to  
the  pituitary  gland.  The  body  senses  that  the  level  of  thyroid  hormones  
is  high  so  there  is  no  need  for  TSH.  Hence  the  level  will  be  low.  
o The  level  of  T3  and  T4  will  be  high.  
o The  uptake  of  radioiodine  will  be  high.  
o Antimicrosomal  antibodies  
o Antithyroglobulin  antibodies  

Treatment  

1. Propiothiouracil/  methimazole-­‐  inhibit  the  coupling  and  organification  of  T4  or  T3  by  acting  
on  Iodide  Peroxide  
Side  effects-­‐  skin  rashes,  agranulocytosis  
Propiothiouracil  is  safe  during  pregnancy.  
2. Propanolol-­‐  Beta  blocker  
3. Radioablation  therapy-­‐  I131  can  be  used  to  destroy  the  tissue  when  used  in  Grave’s  disease.  
In  case  of  a  single  nodule,  the  nodule  gets  eliminated  under  the  action  of  I-­‐131  isotope.  
4. Surgical  removal  of  the  gland-­‐  In  that  case,  levothyroxine  hs  to  be  given,  otherwise,  the  body  
can  go  into  hypothyroidic  state.  

 
13.  Hypothyroidism    

Definition  

In  this  case,  there  is  low  level  of  T4  and  T3  and  there  is  increased  level  of  TSH.  It  is  primary  type.  
Secondary  is  when  TSH  is  not  produced.  Tertiary  is  when  TRH  is  not  produced.  

Causes  

1. Hashimoto’s  disease  (chronic  thyroiditis)-­‐  order  antimicrosomal  antibodies  to  know  if  they  
have  this  disorder  or  not.  
2. Surgery/  Radioiodine  therapy  
3. Drugs-­‐  lithium,    

Symptoms    

i. In  newborns-­‐  thyroid  hormone  is  important  for  brain  development.  Order  TSH  level  to  
find  if  it  is  low  or  normal.  Absence  of  thyroid  hormone  causes-­‐  
1.  cretinism  (mentally  retarded)  
2. Dwarfism  is  another  problem    
3. Flat  noses  
4. Poor  dentition  
5. Wide  spaced  eyeballs  
6. Pot  belly  
7. Umbilical  hernia  
8. Dry  skin  
9. Delayed  bone  development  
ii. In  adults-­‐  
1. Lethargy  
2. Constipation  
3. Depression  
4. Carpal  tunnel  syndrome  
5. Hyponatremia/anemia  
6. Decreased  deep  tendon  reflex  
7. Cold  intolerance  

Diagnosis  

1. TSH  level-­‐  increased  level  

2. T3  and  T4  free  levels  are  low  

Treatment  

1. Levothyroxine  

Complications  

1. Myxedema  coma-­‐  respiratory  depression-­‐  CO2  retention-­‐  respiratory  acidosis  

Thyroid  storm  

Definition  

This  is  a  decompensated  state  of  thyroid  hormone  induced  severe  hypermetabolism.  This  is  an  
extreme  case  of  thyrotoxicosis.  

-­‐ They  usually  have  a  history  of  hyperthyroidism.  They  have  high  T3  and  T4  but  low  TSH.  

Pathophysiology  

-­‐  Not  fully  understood.  

-­‐  increased  adrenergic  receptor  activation  because  sympathetic  nerves  innervate  thyroid  gland.  

-­‐  elevated  thyroid  hormone  so  high  metabolism  

History-­‐  thyrotoxicosis  

Clinical  features  

-­‐ Voracious  appetite  but  no  gain  in  weight  

-­‐ Anxiety,  seizures,  trembling,  tremors  
-­‐ Agitation,  palpitations  
-­‐ Excess  sweating  
-­‐ Heat  intolerance  
-­‐ Hyperpyrexic  –  38.5-­‐41  degree  Celsius  
-­‐ Increase  in  oxygen  and  energy  consumption.  
-­‐ Poor  attention  span  
-­‐ Hypertension  
-­‐ Heart  failure  
-­‐ Pulmonary  oedema  
-­‐ Tachycardia-­‐  may  proceed  to  supraventricular  arrhythmia-­‐  atrial  fibrillation  
-­‐ Nausea,  vomiting,  diarrhoea,  abdominal  pain,  jaundice  

Physical  examination  

-­‐ Sweaty  patient  

-­‐ Feverish  
-­‐ Orbitary  signs-­‐  Grave’s  Disease  
-­‐ Neck  –  goitre  

Causes  

-­‐ Hyperthyroidism  (Grave’s  disease-­‐  thyroid  stimulating  immunoglobulins)  

-­‐ Stress  from    
1. Sepsis  
2. Surgery  
3. Anaesthetic  induction  
4. DEA  
 5. Drugs-­‐  anticholinergic  
6. Direct  trauma  to  thyroid  
-­‐ Pregnant  women  transfer  through  placenta  and  affect  the  baby.  

Diagnosis  

-­‐ purely  clinical  diagnosis  

-­‐ thyroid  studies  –  increased  T3  and  T4  but  low  TSH  
-­‐ CBC-­‐  mild  leucocytosis  with  a  small  left  shift.    
-­‐ Change  in  LFTs  ,  LDH,  Creatinine,  increased  bilirubin  

Imaging  

-­‐ Chest  X-­‐ray-­‐  big  heart-­‐  CHF  

-­‐ EKG-­‐  due  to  Atr.  Fibrillation  

Treatment  

1. Beta  blockers-­‐they  prevent  the  peripheral  conversion  of  T4  to  T3.  Eg.  Propanolol-­‐  decrease  
heart  rate  and  contractility.  
2. Antithyroid  medications-­‐  propiothiouracil  (prevents  organification  and  coupling)  and  
methimazole  (prevents  organification  and  coupling).  PTU  inhibits  peripheral  conversion.  
3. Glucocorticoids-­‐  prevent  transformation  of  T4  to  T3  
4. Iodides  like  potassium  iodide-­‐  inhibit  the  release  of  thyroid  hormone  from  the  thyroid  gland.  
5. Acetaminophen  and  Tylenol  to  bring  down  fever.  
6. Fluids  to  control  diarrhoea  

 
15.  Thyroiditis  
Definition  

It  is  the  inflammation  of  the  thyroid  gland.    

Forms:  

i)  Subacute  viral  thyroiditis  or    subacute  granulomatous  thyroiditis.  

ii) Subacute  lymphocytic  thyoiditis  
iii) Fibrous  thyroididtis  (Riedel’s  thyroiditis)  

I.  Subacute  viral  thyroiditis  or    subacute  granulomatous  thyroiditis    

Causes:  

It  is  caused  by  virus.  

Symptoms  

-­‐ Fever,  flu  like  symptoms  or  illness  

-­‐ Transient  hyperthyroidism  due  to  excess  production  of  T3  and  T4  due  to  inflammation.  
-­‐ After  some  time,  they  become  euthyroid  and  then  due  to  draining  out  of  thyroid  hormones  
they  become  hypothyroid.  
-­‐ They  have  painful  tender  thyroid  gland  

Diagnosis  

Give  radioiodine  which  is  I  123  

-­‐the  uptake  is  quite  low  as  they  are  inflamed  

-­‐  TSH  level  is  low  

-­‐  T3  and  T4  is  going  to  be  high  

-­‐  The  ESR  will  be  high.  

Treatment  

-­‐ Mild  cases-­‐  NSAIDS  like  aspirin  can  be  given  

-­‐ Severe  cases-­‐  corticosteroids  like  prednisone  has  to  be  given.  

II.  Subacute  lymphocytic  thyroiditis  

It  is  painless  or  silent  in  nature.  

Symptoms    

-­‐ Transient  thyrotoxicosis    

-­‐ Hyperthyroid  
 Diagnosis    

-­‐ Radioiodide  uptake  is  low  

-­‐ Hypothyroid  –  will  be  the  only  difference.  

III.  Fibrous  thyroiditis  (  Riedel’s  thyroiditis)  

-­‐ Fibrous  collage  tissue  replaces  the  thyroid  gland  tissue  

-­‐ Thyroid  becomes  firm  
-­‐ Hypothyroid  
 
Hyperosmolar  hyperglycaemic  non-­‐ketotic  syndrome  HHNS  

Definition  

One  of  the  acute  complications  of  diabetes  mellitus.    

Cause  

 They  have  elevated  blood  sugar  which  causes  osmotic  dieresis  and  so  dehydration.  

Population  affected  

It  is  seen  in  type  II  DM  

Pathogenesis  

1. Low  insulin-­‐  this  causes  hyperglycemia-­‐so  dehydration  

2. Thirst  response  decreased-­‐  worsens  dehydration  

Symptoms  

-­‐ Thirsty/Oliguria  
-­‐ Decreased  intravascular  volume-­‐  low  BP,  (hypotension,  tachycardia)  
-­‐ Predisposed  to  seizures    
-­‐ Lethargic  
-­‐ Confused  
-­‐ May  go  to  coma  

Diagnosis  

-­‐ Finger  stick  and  check  RBS>  600mg/dl  

-­‐ Osmolality>320mg/dl  (normal-­‐290)  
-­‐ Check  pH.  If  pH  is  7.4,  it  means  the  person  is  not  acidotic.  Check  bicarb>15  then  the  person  
is  not  acidotic  
-­‐ Elevated  BUN  

Treatment  

-­‐ Replace  fluids-­‐  normal  saline  in  1st  water  and  then  I  litre  in  next  2  hours.  
-­‐ 2-­‐4  units  of  Insulin  for  high  blood  sugar  
-­‐ If  glucose  becomes  low  as  much  as  250mg/dl  then  we  give  5%  glucose  (B5  1/2    NSS).  
-­‐ Careful  about  CHF  and  renal  insufficiency  
Hypoglycaemia  

Definition  

Low  level  of  glucose  in  blood  is  called  hypoglycaemia.  

Causes  

1. Drugs  like  insulin  

2. Factitious  hypoglycaemia-­‐  due  to  exogenous  insulin-­‐  high  insulin  and  low  blood  glucose  
-­‐ C  peptide  is  low  
3. Sulfonylureas  like  glimeparide,  gliburide-­‐  check  urine  to  find  drug  metabolite  
4. Insulinoma  
5. Ethanol  ingestion-­‐  no  glycogen  storage  –  they  undergo  glycogenolysis-­‐  they  don’t  have  
enough  NADH  required  for  gluconeogenesis  
6. Surgery    
7. Adrenal  insufficiency-­‐  under  stress-­‐  reactive  hyoglycemia  
8. Liver  failure  

Clinical  features  

1. Glucose  level<  50  mg/dl  

2. Tachycardia  
3. Palpitations  
4. Anxiety                                                      epinephrine  activation  of  alpha1  and  beta1  receptors  
5. Sweating  
6. Tremors  
7. Brain  symptoms-­‐  confusion,  lethargy,  drowsy,  coma  and  death  

Diagnosis  

1. Finger-­‐stick  test  to  know  the  blood  sugar<50mg/dl  

2. C-­‐  peptide  
3. Serum  insulin  
4. Anti-­‐insulin  antibody  levels    

Treatment  

1. Eat  good  food  

2. D50W  through  IV-­‐  then  D10  if  it  reaches  to  a  level  of  100mg/dl  
3. Wernicke  encephalopathy  has  to  be  avoided.  
4. Thiamine  (B1)  has  to  be  given  first  and  then  glucose.  
Insulinoma  
Definition  

It  is  the  tumour  of  beta  cells  of  the  pancreas.  It  is  mostly  benign.  

It  is  associated  with  MEN  1(multiple  endocrine  nuclear-­‐1)  

Clinical  features:  

-­‐ Due  to  increased  insulin  there  is  hypoglycaemia  

-­‐ The  epinephrine  is  also  high  so  there  will  be  symptoms  like  –  
-­‐ Sweating/diaphoresis  
-­‐ Tachycardia  
-­‐ Tremors  
-­‐ Palpitations  
-­‐ The  CNS  symptoms  like-­‐  
-­‐ Headache  
-­‐ Confusion  
-­‐ Lethargy  
-­‐ Coma  
-­‐ Death  in  severe  cases  

Diagnosis  

1. Fasting  blood  sugar-­‐  hypoglycaemia  and  elevated  levels  of  insulin  in  serum  
2. Whipple’s  triad-­‐  i)  decreased  glucose  due  to  fasting  
ii)  Blood  sugar<  50  mg/dl-­‐  symptoms  start  
iii)  glucose-­‐  on  giving  glucose  they  feel  normal.  

Treatment  

Surgical  resection  of  the  tumour  is  done.  The  prognosis  is  quite  good  generally.  

  Insulin     C-­‐peptide   Glucose   Pro-­‐insulin  

Insulinoma     ↑↑↑   ↑↑↑   ↓↓   ↑  
Factitious   ↑↑   ↓   ↓   ↓  
insulin  used    
 
 MULTIPLE  ENDOCRINE  NEOPLASIA(MEN)  

MEN  I  -­‐Werner’s  syndrome  

Associated  with  the  3P’s  
Pituitary  tumour  (prolactinoma)  
Parathyroid  tumour  
Pancreatic  tumour  
Symptoms  
  Chronic  peptic  ulcer  
  Gastrinoma  (Zolliger  Ellison  syndrome)  
   Parathyroid  hyperplasia  (Hyper  PTH)  
 
MEN  IIA-­‐  Sipple’s  syndrome  (MPH)  
Associated  with  
  Pheochromocytoma  
  Hyperparathyrodism  
  Medullary  thyroid  carcinoma  
Symptoms-­‐  
High  blood  pressure  180/100  
Palpitation    
Hypercalcemia  
High  PTH  level    
 
 
 MEN  IIB  (MMMP)  
They  have  
  Pheochromocytoma  
  Marfenoid    habitus  (tall  and  lanky)  
Mucosal  neuromas  (nasopharynx/oropharynx/  larynx)  
Medullary  thyroid  carcinoma    
Symptoms-­‐  
  High  blood  pressure  220/100  
 
Parathyroid  gland  physiology  
Location-­‐  they  are  located  behind  the  thyroid  gland  and  are  4  in  number.  

-­‐ Produce  parathormone  

-­‐ Acts  on  bone  and  kidneys  

On  taking  Vit.  D  (endogenous)  it  moves  to    

-­‐ liver  where  it  is  converted  to  25-­‐OH2  Vit.D  

-­‐ In  kidney,  it  is  converted  to  1,  25-­‐OH2  Vit.D  in  the  presence  of  1,  alpha  hydroxylase.    
-­‐ This  way  1,25  dihydroxycholecalciferol  is  formed  which  is  the  active  form  of  Vitamin  D.  
-­‐ The  active  form  moves  to  duodenum  to  reabsorb  calcium  and  phosphate.  
-­‐ 400mg  of  calcium  absorbed.  
 

Functions  

-­‐ Parathormone  stimulates  osteoclasts  to  cause  bone  destruction  and  release    Ca  ions  
-­‐ Increases  production  of  1,25  (OH)2  
-­‐ Decreases  phosphate  reabsorption  by  kidneys  
-­‐ Increases  the  distal  convoluted  tubule  reabsorption  of  calcium.  

Vitamin  D  functions  

-­‐ Increases  reabsorption  of  calcium  and  phosphate    

-­‐ Increase  proximal  tubular  reabsorption  of  phosphate  

Calcium  regulation-­‐  occurs  in  bone,  kidney  and  intestine  

Too  low/hypocalcemia   Too  high/  hypercalcemia  

Parathyroid  hormone  is  released   Calcitonin  (made  by  parafollicular  cells  of  thyroid  
gland)  is  released  
Activate  Vit.  D  for  calcium  reabsorption    
Osteoclast  destroy  bone  to  release  Ca   Osteoblasts  are  stimulated  causing  bone  
deposition  
 
Pituitary  gland  physiology  

Anterior  lobe  of  pituitary  produces  FLAT  PIG  

-­‐ FSH  
-­‐ LH  
-­‐ ACTH  
-­‐ TSH  
-­‐ Prolactin  
-­‐ Growth  hormone  

Posterior  lobe  produces  

-­‐ Vasopressin,  ADH-­‐  supraoptic  

-­‐ Oxytocin-­‐  paraventricular  

Prolactinoma  

A  tumour  producing  too  much  prolactin.  

Microadenoma     Macroadenoma    
<1cm   >1cm  
Women     Men    
 

Case  

23  year  old  female  missed  her  periods  from  the  past  3  months  and  has  a  milky  secretion  
from  her  breasts.  

1.  b-­‐HCG-­‐  not  pregnant  

2. TSH-­‐  normal  
3. No  drugs  
4. This  might  be  a  prolactinoma  

Causes  

1. Pregnant  
2. Stressed  out  
3. Seizures  –  increased  prolactin  level  

 
Dopamine                          Hypothalamus                                              thyroid  releasing  hormone  

tubular  infundibular        prolactin  releasing  hormone  

   pathway                                                                                                                                                                                                                                                                                                                                  

                                                               Prolactin    

Drugs  to  block  dopamine  action  causing  from  increased  release  of  prolactin  

Phenothiazine  

Metoclopromide  (drug  given  for  diabetics)-­‐  hyperprolactinemia  is  side  effect    

They  are  dopamine  antagonist  blockers  

Patients  with  hypothyroidism  have  hyperprolactinemia.  

History  

C/o  of  galactorrhea  and  amenorrhoea  

This  is  because  of  the  prolactin  inhibitory  effect  on  hypothalamus  in  producing  GnRH  whic  in  
turn  is  responsible  for  the  release  of  LH  and  FSH.  This  is  the  reason  for  amenorrhoea.  

Clinical  features  

-­‐ Osteoporosis/  osteopenia-­‐due  to  lack  of  FSH  which  is  responsible  for  oestrogen  
production  
-­‐ In  men,  lowered  libido  
-­‐ Lowered  erectile  dysfunction  
-­‐ Gynecomastia    

Diagnosis  

1. Check  pregnancy-­‐  beta  HCG  

2. TSH  level  if  she  is  hypothyroid  or  no  
3. Rule  out  drugs  
4. Check  prolactin  level>100mg/ml  (normal  is  <20mg/ml)  
5. MRI-­‐  to  check  if  it  is  micro  or  macro  adenoma  

Treatment  

1. Bromocriptene  or  Cabergoline  (dopamine2  agonists)  

2. Transphenoidal  resection  surgery  
Primary  aldosteronism  
Definition  

There  is  a  tumour  producing  increased  levels  of  aldosterone.  This  will  cause  increased  activation  of    
Na+/K+ATPase  pump-­‐  increased  Na  reabsorption-­‐  increased  K  excretion-­‐  metabolic  alkalosis  and  
hypokalemic.  

Causes  

1. Single  adrenal  adenoma-­‐  Conn’s  syndrome  

2. Bilateral  adrenal  hyperplasia  
3. Adrenal  carcinoma  

Symptoms  

1. High  blood  pressure-­‐  due  to  increased  intravascular  volume  

2. Headache  due  to  hypertension  
3. Fatigue  and  weakness  due  to  hypokalemia  
4. Polydipsia/  polyuria  
5. Do  not  have  peripheral  oedema.    

Diagnosis  

1. Check  plasma  aldosterone  level/plasma  rennin  ratio>30    plasma  aldosterone  is  very  very  
high  
2. Saline  infusion  test  (NaCl)-­‐  in  normal  cases  the  level  of  aldosterone  should  decrease  but  in  
case  of  primary  aldosteronism  it  increases.  
3. Imaging-­‐  CT/MRI  may  show  adrenal  tumour.  
4. Adrenal  venous  sampling-­‐  if  the  aldosterone  level  is  high  on  one  side  only  then  it  is  adrenal  
adenoma,  if  both  the  sides  then  bilateral  hyperplasia  

Treatment  

1. Isolated  adrenal  adenoma-­‐  surgical  excision  

2. B/L  hyperplasia-­‐  spiranalactone  is  given  
 
SiADH  
POSTERIOR  PITUITARY  LOB  E  DISORDERS  

                                                                                                                                             Anti-­‐diuretic  hormone  

                                           Syndrome  of  inappropriate  ADH/  SiADH                                                    Diabetes  Insipidus                        

                                                                                                                                                                                 Central  DI                                                                                          Nephrogenic  DI  

Definition  

It  is  the  excess  production  of  ADH  which  causes  excess  water  absorption  form  collecting  tubule  of  
nephron.    This  causes  volume  expansion/hypervolumic  and  hyponatremia.  In  the  atrium,  ANP  (atrial  
natriuretic  peptide)  is  reeased  which  acts  on  kidneys  to  eliminate  sodium  ions.  This  worsens  the  
hyponatremic  condition.  

They  do  not  have  oedema.  So  SiADH  is  different.  

Causes  

1.  Cancer  (neoplasm)-­‐  lung  cancer  (small  cell/oat  cell  carcinoma)  

2. Stroke    
3. Trauma  
4. Infections  like  meningitis  or  encephalitis  
5. Drugs  like  Vincristin,  SSRIs,  Morphine,  Desmopressin  
6. TB,  pneumonia  

Clinical  features  

1. Acute  state-­‐  swelling  in  brain  due  to  hyponatremia-­‐  causes  lethargic,  weak,  seizures,  coma,  
somnolent  

Diagnosis  

1. Diagnosis  of  exclusion-­‐  labs  

i. Hyponatremia<135  
ii. Decreased  BUN/Cr  

Treatment  

Treat  the  underlying  cause  

Asymptomatic       Symptomatic      
Water  restriction   Water  restriction  
Normal  saline  +  loop  diuretic  (furasemide)   Isotonic  saline    
Lithium  bicarbonate  (inhibit  ADH)or   Hypertonic  saline  3%-­‐  titrate  it  at  0.5  
demicocycline   meQ/hr.  If  too  much  concentration  is  given-­‐  
central  pontine  myelolysis-­‐  it  can  cause  brain  
damage  
 
 18.Insulinoma  

Hyperthyroidism  

-­‐ Excess  of  T3  and  T4  are  produced.  

-­‐ Perchlorate/  petechnate-­‐  They  are  anion  inhibitors  which  block  the  iodide  pump  
by  blocking  the  re-­‐uptake  of  iodine  into  thyroid  gland.  
-­‐ Methimazole  or  propythiouracil  –  They  inhibit  the  activity  of  IPO  (iodine  
peroxidase)  which  is  responsible  for  organification  and  coupling.  Propythiouracil  
differs  from  methimazole  because  it  goes  outside  and  prevents  the  peripheral  
conversion  of  T3  and  T4  
-­‐ Side  effects  of  these  drugs-­‐  skin  rashes,  agranulocytosis  (low  WBC  count).  Such  
patients  need  to  get  their  CBC  (complete  blood  count)  checked  quite  often  to  
ensure  that  they  don’t  have  neutropenia.  If  they  have  neutropenia,  a  slight  fever  
can  cause  their  death.  
 

 
Thyroid  gland  physiology  
Thyroid  releasing  hormone  TRH  produced  by  hypothalamus-­‐  induces  pituitary  gland  to  form  thyroid  
stimulating  hormone  TSH-­‐  which  stimulates  thyroid  gland  to  produce  T4/T3/thyroxine  

Inside  the  follicular  cells  of  thyroid  gland    

-­‐ Iodine  molecules  trapped  by  follicular  epithelium-­‐  iodide  pump  

-­‐ Iodide  peroxidase-­‐  oxidation  of  I  molecules  to  form    I2      
-­‐ In  the  cell  membrane  I2    is  added  to  tyrosine  in  the  presence  of  iodide  peroxidise-­‐  
organification  
-­‐ MIT  and  DIT  are  formed.      
-­‐ 1MIT  +  2DIT=  T3                      Coupling  process  
-­‐ 2DIT  +  2DIT  =  T4  
-­‐ IPO  catalyses  organfication  and  coupling  
-­‐ Thyroid  globulin  stores  T3  and  T4  
-­‐ Under  the  impact  of  TSH    ,  T4  and  T3  are  released  
-­‐ T4  forms  T3  in  the  presence  of  5’iodase.  
-­‐ T3  is  the  most  active  form  and  reverse  T3  is  less  active  form  of  T4.  
-­‐ They  are  bound  to  thyroxine  binding  globulin  formed  by  liver  

Functions  of  T3  

1. Metabolism  –  catabolic  hormone  

2. Growth  hormone  +  T3  for  bone  formation  
3. CNS-­‐  mental  retardation  if  there  is  no  T4  and  T3  
4. Autonomic  nervous  system-­‐  stimulate  the  increase  of  Beta1  receptors  of  heart.  So  beta  
blockers  are  given  for  hyperthyroidism  
5. BMR  maintenance-­‐  Na-­‐K  ATPase  pump  does  not  function  in  the  absence  of  Oxygen  
6. Metabolism-­‐    
i. Glycogenolysis  
ii. Gluconeogenesis  
iii. Lipolysis  
iv. Protein  synthesis  

Mainly  required  for  growth  and  metabolism.  

VIP-­‐oma  
Definition-­‐  It  is  a  malignant  pancreative  tumour  that  produces    vaso-­‐active  intestinal  
peptide  in  excess.  It  is  extremely  rare.  Another  name  is  Verner  Morrison  syndrome  or  
WDHAS  (  watery  diarrhoea  hypokalemia  with  achlohydria  syndrome)  

Symptoms  

-­‐ Watery  diarrhoea  –  this  can  lead  to  hypokalemia.  

-­‐ Dehydration  
-­‐ Achlohydria-­‐  the  person  is  unable  to  produce  HCl.  VIP  inhibits  gastric  acid  production  
so  no  HCl  produced.  
-­‐ Hypoglycaemia  and  hypercalcemia  

Treatment  

Surgical  resection  of  the  tumor.  

Zollinger  Ellison  syndrome  

It  is  also  known  as  gastrinoma.  It  is  a  tumor  of  pancreatic  islet  cells  which  produce  excess  gastrin.  

It  is  associated  with  MEN  I  syndrome.  

Gastrinoma  triangle  points  are  

-­‐ Cystic  duct  

-­‐ Neck  of  pancreas  
-­‐ 2nd  and  3rd  portion  of  duodenum  

Symptoms  

-­‐ Peptic  ulcer  disease-­‐    

i. epigastric  pain  and  burning  sensation,    
ii. GI  bleed  (hemorrhage),    
iii. GI  perforation,    
iv. stricture  formation  due  to  fibrosis,    
v. metastasis  into  liver.  
-­‐ Abdominal  pain  
-­‐ Diarrhoea  
-­‐ Weight  loss  

Diagnosis  

i. Gastrin  level-­‐  fasting  gastrin  level.  

ii. Secretin  inhibitory  test-­‐  secretin  inhibits  gastrin.  If  the  level  of  gastrin  is  high  even  after  
administration  of  secretin,  it  is  due  to  adenoma.  
iii. Stomach  Basal  Acid  Output-­‐    Normal  level  is  <10mEq/hr.  In  case  of  these  patients  it  will  
be  higher  than  15mEq/hr.  

Treatment  

-­‐ PPI-­‐  proton  pump  inhibitors-­‐  H  K  ATPase  pump  is  inhibited.  Omeperazole  can  be  given.  
-­‐ Surgical  resection