Assessing endocrine disorders

Question 1

Describe radioimmunoassay

Answer 1

Radioimmunoassay is a lab technique used to measure concentrations of specific substances, e.g. hormones. Antigen being measured is labelled with radioactive isotope

• Number binding sites limited, all binding sites occupied in eqm
• Binding sites occupied with labelled hormone
• Calculate how much hormone is in sample
• Total hormone assays and free hormone assays = Different
  
  • Total - Dependent on binding protein levels, not always reflective of free hormone lvls, cheap
  • Free - Representative of active hormone fraction, not binding protein dependant, complex and expensive (separation step), poor reproducibility

Question 2

Describe immunometric assays

Answer 2

2 antibodies, 1 at 1 end, 1 at the other end

Question 3

Describe the investigations for thyroid dysfunction

Answer 3

• Overproduction:
  
  • Thyroid function
  • Autoantibodies
  • Technesium Scanning
• Underproduction:
  
  • Thyroid function
  • Autoantibodies
• Thyroiditis:
  
  • Thyroid function
  • ESR
  • Technesium Scanning
• Thyroid nodule: Toxic nodules tend to secrete T3
  
  • Ultrasound Scan
  • FNA
  • CT neck
• Goitre:
  
  • Thyroid Function
  • US
  • CXR
  • CT/MRI
  • Flow Volume Loop

Question 4

Describe the 3 stages of Cushing’s syndrome investigation

Answer 4

• Screening:
  
  • Urinary free cortisol
  • Diurnal rhythm
  • Overnight dexamethasone suppression test
• Confirmation of diagnosis
  
  • Low dose dexamethasone suppression testing
• Differentiation of the cause
  
  • High dose dexamethasone suppression testing - Rules out pituitary disease
  • ACTH - Differentiate b/w ectopic ACTH and adrenal
  • CRH - Alternative method
  • Localisation - Only done after by chemistry has confirmed diagnosis, scanning:
    
    • Pituitary - MRI, linferior petrosa; sinus sampling IPSS
    • Adrenal - CT or MRI
    • Extopic - Octreotide scan, ACTH sampling

Question 5

Describe the synacthen test

Answer 5

To diagnose primary adrenal failure:

• Blood taken over 1 hour (short synacthen, 250mg)

To diagnose secondary adrenal failure:

• Blood taken over 24 hrs (long synacthen test, 1mg)

Question 6

Describe the insulin tolerance test

Answer 6

• GOLD standard for assessing adrenal reserve
• Insulin adminstered to achieve hypoglycaemia (<2.1mmol/L)
• Hypoglycaemia stimulates stress response, mediated by compensatory hormones for hypoglycaemia
• Glucagon, catecholamines, GH, PRL
• Test contraindicated in:
  
  • Ischemic heart disease
  • Epilepsy
  • Severe panhypopituitarism
  • Very old or very young
  • Pregnancy
• Where insulin test contraindicated, glucagon test used

Question 7

Describe the test for acromegaly

Answer 7

Oral glucose tolerance test:

• Take blood sample for GH and IGF-1
• 75g oral glucose
• Take blood for GH and glucose at t= 30, 60, 90, 120 minutes
• Synacthen test can be carried out at end of this test
• In normal individuals, GH levels fall following oral glucose, and at least one of the samples during the test should have undetectable GH levels.
• Failure of suppression or a paradoxical rise in GH suggests acromegaly.
• Following treatment safe level of GH < 1.0mU/l (0.4ng/ml)

Question 8

Describe the physiology of the control of the hypothalamus, pituitary and peripheral organs

Answer 8

• Hypthalamus secretes hypothalmic factor onto pituitary gland
• Pituitary gland secretes pituitary hormone
• Pituitary hormone induces end organ hormone release, end organ hormone release has negative feedback effect, causes decreased release of hypothalmic and pituitary factor secretion

Question 9

Describe the ACTH response to CRH

Answer 9

• Normal response doubling of ACTH
• Adrenal disease ACTH remains low throughout test
• Ectopic ACTH and ACTH lvl is high and remains steady through test
• Cushing’s disease (pituitary) exaggerated ACTH response to 4 times baseline