Sugar = GLUCOcorticoid action -- cortisol Minerals (Na and K) = MINERALcorticoid action --- aldosterone and cortisol
Symptoms and signs of Hypoadrenalism (lack of cortisol and aldosterone) Low cortisol:
Low aldosterone:
Causes of Hypoadrenalism
Negative feedback
Secondary (pituitary) Panhypopituitarism Tumour Removal of pituitary ACTH is LOW CORTISOL IS LOW
Primary (adrenal) Addisons disease (autoimmune destruction of the adrenal cortex) Removal of adrenal gland due to a tumour ACTH IS HIGH CORTISOL IS LOW
Investigating cause of hypoadrenalism 1) If in doubt, draw it out!
Negative feedback
2) Confirm that you have low cortisol/ low aldosterone 3) Find the Cause Confirm Random plasma cortisol is …………………. If you suspect low levels of hormone, use a STIMULATION test to prove they are abnormally low. ACTH stimulation test (synacthen) = synthetic ACTH.
Confirm: Synacthen (stimulation) test Normal stimulation Normal patient
No stimulation
primary or secondary hypoadrenalism Find Cause: Measure ACTH level
High ACTH: primary (Addisons)
Low ACTH: secondary
Cushings Syndrome In this syndrome there is excess cortisol. This leads to: Fluid retention Sodium retention Potassium excretion High glucose Initially high white cells then low white cells. Increases fat stores Based on what you know about the adrenal hormones Draw (or write) the signs and symptoms of Cushing’s Syndrome
Important!! Cushings Syndrome: Signs and Symptoms Cushings Disease: a specific cause of Cushings Syndrome. Causes of Cushings Syndrome ACTH stimulates Cortisol but not aldosterone Aldosterone is stimulated by the R-A-A pathway (renin-angiotensin I- angiotensin II)
Secondary – ACTH HIGH CORTISOL HIGH
Negative feedback
1) From pituitary gland A tumour (usually benign) secreting ACTH. “Cushing’s Disease” 2) From ectopic tumour. Often a small cell lung cancer. Tumour secretes ACTH. Primary: CORTISOL LOW ACTH HIGH From an adrenal tumour which secretes cortisol NOTE: a tumour that secretes aldosterone causes Conn’s Syndrome.
Investigating Cushings Syndrome 1) If in doubt draw it out 2) Confirm that you have high levels of cortisol 3) Find the cause Plasma Cortisol is ….. If you suspect a high level of hormone do a suppression test to prove that it’s the level is abnormally high. Suppression test = using Dexamethasone (a synthetic steroid) to suppress ACTH.
Confirm: high levels of cortisol low dose dexamethasone suppression test
No suppression confirmed Cushing's Syndrome
Normal suppression
Pituitary, ectopic or Adrenal cause
Normal patient
Find the cause (1): Measure ACTH
Low ACTH: primary (adrenal) High ACTH: Pituitary or ectopic Find the cause (2) High Dose Dexamethasone Suppression Test
No Suppression
Suppression achieved
No feedback control exists
Some remnants of feedback control exist
Cause = ectopic tumour
cause = pituitary (Cushing's Disease)
Summary of flow chart 1) Low dose suppression to confirm abnormality 2) Measuring ACTH differentiates between primary and secondary 3) High dose suppression differentiates ectopic from pituitary
MedSoc Teaching – LFTs by Hellen Collier
13/05/15
LFTs Non-specific, so how can they be useful? 1. Reflect hepatocellular damage 2. Reflect cholestasis 3. Calculate serum bilirubin 4. Reflect synthetic function 1) HEPATOCELLULAR DAMAGE a) AST (aspartate transaminase) [5-35 iU/L] Found in liver, skeletal and cardiac muscle, kidney and brain High levels seen with liver cell inflammation
b) ALT (alanine transaminase) [5-35 iU/L] More liver specific
2) CHOLESTASIS a) Alkaline Phosphatase [30-150 iU/L] Increased alk phos may originate from the placenta, kidney, intestine, and leukocytes Liver isoenzyme located on bile canalicular region of hepatocyte membrane, therefore sensitive indicator of bile duct obstruction (within or outside the liver)
b) ƔGT (gamma glutamyltransferase) [10-55 iU/L] More liver specific than Alk Phos Reflects cholestasis but is also sensitive to enzyme inducing drugs (phenytoin, alcohol) in the absence of liver disease. c) Serum bilirubin [3-17 iU/L] RBC break down haemoglobin released bilirubin Becomes conjugated in the liver and excreted into the bile
MedSoc Teaching – LFTs by Hellen Collier
13/05/15
3) SYNTHETIC FUNCTION a) Serum albumin [35-50g/L] measures synthetic activity of liver may be normal in acute liver disease due to long half-life
b) PT measures synthetic activity Clotting factors synthesised in the liver include fibrinogen and Vit K dependent factors
TRANSAMINASES Causes of mild and severe abnormality of aminotransferases: Mild (1000) Common Chronic viral hepatitis (B, C) Acute viral hepatitis (A-E) Alcohol Ischaemic hepatitis Haemochromatosis Medications and toxins (aspirin, paracetamol) Autoimmune Autoimmune Steatohepatitis (NASH) Rare Drugs/toxins Acute bile duct obstruction Wilson’s disease Wilson’s disease α1-antitrypsin deficiency Acute viral hepatitis (CMV, EBV)
Patterns of abnormality Hepatocellular damage Cholestatic jaundice Liver failure Alcoholism
Case 1 Bili 180 (3-17 µmol/l) AST 1300 (5-35 IU/l) ALT 1900 (5-35 IU/l) Alk P 370 (30-150 IU/l) GGT 480 (10-55 IU/l) alb 35 (35-50 g/l) INR 1.2
Case 5 Mrs SB, 40yrs ALT 34 Alk P 245 GGT 110 Bili 14 Anti-mitochondrial antibody: positive (1:400)
Case 2 AST 80 ALT 110 Alk P 760 GGT 630 Bili 87 alb 41 INR 1.1
Case 6 Mrs GB, 50yrs, cholecystectomy 1 week ago AST 950 ALT 2034 Alk P 120 GGT 400 Bili 30
Case 3 AST 130 ALT 60 Alk P 145 GGT 300 Bili 300 Alb 34 PT 22 (11-23 sec)
Case 7 Mr PC, 70yrs, history of weight loss and increasing urinary frequency. He does not drink alcohol and has previously been well. He takes no regular medication ALT 36 Alk P 636 GGT 35 Bili 9
Case 4 Mr ST, 21yr medical student, has exams in a few weeks time ALT 23 Alk P 112 GGT 20 Bili 36
