HPA axis disorders

HPA axis disorders

Ectopic tumours=Cushing's syndrome
1. Clinical presentaions
  1. can have classincal cushing's syndrome symptoms
  2. may present with electrolyte disturbances – low potassium levels (hypokalaemia).
  3. pneumonia or other infections due to general immune suppression
  4. ectopic tumour can progress very rapidly and the patient can die very soon after presentation
  5. hyperpigmentation
Diagnosis of Cushing's syndrome
1. imaging techniques
  1. CT or MR imaging of Pituitary
  2. to detect pituitary tumours
    1. plain radiology
      Nota:
      - •can reveal large pituitary tumours which account for 10 - 20% of pituitary tumours causing CS.
    2. High resolution CT scanning
      Nota:
      - •reveals only about 50% microadenomas
    3. Magnetic resonance imaging (MRI)
      Nota:
      - •better than CT at distinguishing pituitary adenomas
    4. problems
      1. Imaging may not identify pituitary microadenoma
        12-27% false positive
        20-30% false negative
  3. to detect adrenal tumours
    1. High resolution CT scan
  4. Ectopic tumours
    1. high resolution CT scan
      Nota:
      - pin point tumour
      1. problem- imaging doesnt identify if the ectopic tumour is causing the ectopic ACTH
2. Measurement of Circulating Hormone Levels
  1. cortisol level
    1. mass spec
    2. immunoassay based on a single antibody
    3. day=200-550nmol/l
    4. midnight= less than 5nmol/l
    5. affected by stress,meals and pulsatile release
  2. analyse diurnal rythm
  3. ACTH levels
    1. 2 antibody based ELISA
    2. normal levels
      1. day= 5-50ng/l
      2. midnight= less than 5ng/l
      3. altered by stress, meals and pulsatile nature
  4. POMC levels
  5. measurement of CRH levels in the plasma is pointless
    Nota:
    - CRH is only present between hypothalmus and pituitary- no point measuring its levels in the blood
3. Measurement of Urinary metabolites of Hormones
  1. metabolites of cortisol and adrenal steroids
4. Detection of Metabolic Effects of Excess Hormone
  1. hyperglycaemia
5. Serum Potassium
  1. 30% false negative
    Nota:
    - normal potassium levels in patients with CS
  2. 10% false positive
6. Low dose dexamethasone test
  1. test to inhibit ACTH
  2. Dexamethasone is a synthetic glucocorticoid
  3. test
    Nota:
    - 0.5 mg dexamethasone administered every 6h for 48h measure ACTH and cortisol at 0h and 48h
    1. results
      Nota:
      - Normal response: ACTH suppressed to <5 ng/L Cortisol suppressed to <50nmol/LCushing’s syndrome Cortisol remains >50nmol/L (any cause)
7. High dose dexamethasone test
  1. used to distinguish between pituitary and ectopic tumours
  2. test
    Nota:
    - 2mg dexamethasone every 6h for 48h measure ACTH and cortisol at 0h and 48h
    1. result
      Nota:
      - Pituitary tumour - ACTH suppressed to 50% basalCortisol suppressed to 50% basal Ectopic tumour - No suppression
  3. 10% false positive
    Nota:
    - no suppression in the presence of pituitary tumour
  4. 10% false negative
    Nota:
    - suppression in ectopic tumours
8. CRH test
  1. test to stimulate ACTH
    1. collect baseline levels
      1. give 100ug of CRH- IV
        measure ACTH and cortisol levels
        results
        Nota:
        PITUITARY TUMOUR- Exaggerated or normal response ECTOPIC TUMOUR - No response ADRENAL TUMOUR- No response
  2. used to distinguish between pituitary and ectopic tumours
  3. 10-15% false negative
9. Petrosal sinus sampling
  1. Inferior Petrosal Sinus Sampling (IPSS)
    1. useful in cases where the source of ACTH is in doubt
    2. disadvantages
      1. only in specialised centres
      2. requires precise and reliable ACTH assay
      3. can cause mortality or morbidity
treatment of CS
1. adrenal tumour
  1. surgical removal
2. pituitary tumour
  1. surgical remoavl
  2. irradiation
  3. Treatment with metyrapone which blocks synthesis of cortisol.
  4. Bilateral adrenalectomy
3. Ectopic tumour
  1. chemotherapy for v.aggressive tumours
  2. metyrapone for more benign tumours to block the excessive production of cortisol.
  3. generally not removed surgically

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