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investigation and management of acromegaly by med student of unisza.

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  1. 1. Investigation and management of acromegaly Siti hamidah Med student UniSZA
  2. 2. Investigation 1) Assessment of GH: Random GH: often not diagnostic because of episodic secretion and short half-life of the hormone. Glucose tolerance test: GH is normally inhibited by glucose. If the glucose load fails to suppress the GH level below 1 mU/L and the IGF-1 level is elevated then the diagnosis of acromegaly can be confirmed.
  3. 3.  IGF-1: • long half-life and so is a useful measurement to assess GH secretion and therefore screen for acromegaly and monitor the effect of therapy. • A normal IGF-1 together with GH < 5 mU/L (2.5 ng/L) may be taken to exclude acromegaly if the diagnosis is clinically unlikely  IGF-binding protein-3 (IGFBP-3): is the main binding protein for circulating IGF and is increased in acromegaly. Can be useful in the diagnosis of acromegaly.
  4. 4. 2) Visual field examination – defects are common, e.g. bitemporal hemianopia (partial blindness where vision is missing in the outer half of both the right and left visual field) 3) MRI scan of pituitary if above tests abnormal. This will almost always reveal the pituitary adenoma. 4) Pituitary function – partial or complete anterior hypopituitarism is common. 5) Prolactin – mild to moderate hyperprolactinaemia occurs in 30% of patients. In some, the adenoma secretes both GH and prolactin.
  5. 5. • Pictures show the normal eyes view and bitemporal hemianopia view
  6. 6. • MRI scan:- pituitary adenoma
  7. 7. 6) chest and abdominal radiology: – to detect an ectopic source of growth hormone – may detect cardiomegaly due to cardiomyopathy 7) hands radiology reveals: – tufting of terminal phalanges – increased joint spaces due to cartilage hypertrophy
  8. 8. Complication of acromegaly • Heart disease acromegaly increases the risk of ischemic heart disease leading to a worsening of risk of heart attacks and angina. Risk of heart failure also rises with enlargement of the heart and imbalance between demands of the body to the capacity of the heart to pump blood.
  9. 9. • The risk of diabetes mellitus rises to a great extent among those with acromegaly. • Pregnant women with acromegalyhave a heightened risk of developing gestational diabetes and pregnancy induced hypertension. This may raise the risk of preterm birth or still birth.
  10. 10. • Those with acromegaly are at risk of arthritis and joint pains as well. This is called Acromegalic arthropathy and affects up to 70% of patients. Both the axial and peripheral skeleton may be affected. This involves the spine as well as the joints of the limbs. Due to compression of nerves of the hand, patient may develop Carpal tunnel syndrome.
  11. 11. • Due to overgrowth of structures of the back of the throat and tongue, there may be development of obstructive sleep apnoea and this leads to interrupted sleep. • There is a high risk of development of colonic polyps. These polyps, if not detected early and removed, may go on to form adenocarcinoma of the colon or bowel cancer. Those with acromegaly thus require early and regular screening for bowel cancer.
  12. 12. MANAGEMENT OF ACROMEGALY Aim= to achieve a mean growth hormone level below 5 mU/L (or 2.5 ng/L) Siti hamidah mahbud 030480
  13. 13. Surgery Trans-sphenoidal surgery is the appropriate firstline therapy. It will result in clinical remission in a majority of cases (60–90%) with pituitary microadenoma. Very high pre-operative GH and IGF-1 levels are also poor prognostic markers of surgical cure. Transfrontal surgery is rarely required except for massive macroadenomas.
  14. 14. Pituitary radiotherapy. External radiotherapy is normally used after pituitary surgery fails to normalize GH levels oftencombined with medium-term treatment with a somatostatin analogue or a dopamine agonist because of the slow biochemical response to radiotherapy. Stereotactic radiotherapy is used insome centres.
  15. 15. Medical therapy. • three receptor targets for the treatment of acromegaly pituitary somatostatin receptors, dopamine (D2) receptors and growth hormone receptors in the periphery.
  16. 16. Medical therapy. • Somatostatin receptor agonists. Octreotide and lanreotide are synthetic analogues of somatostatin used as a short-term treatment but now are sometimes used as primary therapy. They reduce GH and IGF levels in most patients. Both drugs are typically administered as monthly depot injections and are generally well tolerated but are associated with an increased incidence of gallstones
  17. 17. • Dopamine agonists. act on D2 receptors and can be given to shrink tumours prior to definitive therapy or to control symptoms and persisting GH secretion; most effective in mixed growth-hormone-producing and prolactin producing tumours. The doses are bromocriptine 10–60 mg daily or cabergoline 0.5 mg daily which should be started slowly. Given alone they reduce GH to ‘safe’ levels (only a minority of cases) but they are useful for mild residual disease or in combination with somatostatin analogues.
  18. 18. • Growth hormone antagonists Pegvisomant (a genetically modified analogue of GH) is a GH receptor antagonist which has its effect by binding to and preventing dimerization of the GH receptor. does not lower growth hormone levels or reduce tumour size but has been shown to normalize IGF-1 levels in 90% of patients. main role = treatment of patients in whom GH and IGF levels cannot be reduced to safe levels with somatostatin analogues alone, surgery or radiotherapy.
  19. 19. reference • Kumar & Clarks Clinical Medicine: 7th Edition