Cushing’s, Addison’s and Acromegaly

1. Cushing’s, Addison’s and Acromegaly Dr Edward Hutchison FY1 (Geriatrics)

2. Phase II Objectives • 3.21: Investigations– • Request appropriately the more common tests of thyroid, adrenal and pituitary gland function, seeking advice where necessary. • 3.23: Adrenal gland hormones • Recognise signs and symptoms of Addison’s disease, confirm diagnosis and initiate immediate management of Addisonian crisis. • Recognise symptoms and signs of Cushing’s syndrome, confirm diagnosis, participat in management of Addison’s disease and Cushing’s syndrome. • 3.24: Pituitary gland hormones • Recognise the circumstances when hypopituiarism might occur, recognise possibility of hypopituitism with ‘non-specific’ symptoms, investigate causes. • Initiate investigation for posterior pituitary function in patients with polyuria. • Recognise acromegaly, initiate investigation for acromegaly, outline to patients the possible treatments for acromegaly.

3. Aims • HPA Axis • Adrenal glands • Cushing’s syndrome/disease • Addison’s • Acromegaly

4. HPA Axis

6. Hypothalamus GnRH GHRH TRH Dopamine CRH

7. Pituitary Sphenoid sinus

10. Adrenal Glands Remember: GFR!

11. Functions of Cortisol? • Insulin resistance/gluconeogenesis • Protein catabolism • Immunosuppresion • CVS regulation – e.g. increasing BP • CNS actions – e.g. increased appetite, impaired memory • Increased bone turnover • Gastric acid secretion • Reduced skin collagen • Fluid retention

12. Right, now onto the stuff you actually want to know…

13. Cushing’s… …disease or syndrome?

14. Which is which? Syndrome Disease Excessive activation of glucocorticoid receptors. Excessive production of ACTH caused by a pituitary adenoma.

15. Classification

16. Clinical features Over to you…

19. Symptoms • Depression • Confusion • Weight gain • Poor glucose control (diabetics) • Weakness rising from a chair (proximal myopathy)

20. Investigation Bedside Blood Imaging

21. Not excluded Abstinence ?EtOH excess

22. ACTH level?

23. Management Untreated Cushing’s disease has a 50% 5 year mortality

24. Remember • Not only oral corticosteroids can cause Cushing’s syndrome, large amounts of topical and inhaled steroid may be absorbed into the systemic circulation. • Patients on large amounts of oral corticosteroids will require their dose to be tapered slowly to avoid an Addisonian-like crisis. • You also will need to manage the effect of long-term steroid therapy – e.g. diabetes, hypertension, thin skin, osteporosis.

25. Addison’s disease (Or adrenal insufficiency, to be more correct).

26. Definition? A syndrome resulting from inadequate secretion of corticosteroid hormones from progressive destruction of the adrenal cortex.

27. Causes A D D I SO N – autoimmune (90% of cases) – neoplasia (metastases) – degenerative (amyloid) – drugs (e.g. ketoconazole) – infective (TB, HIV) – secondary (ACTH, hypopituitism) – other (e.g. adrenal bleeding)

28. Clinical Features Over to you…

30. Investigations

31. The short synacthen test • Why do we do it? • How do we do it? • What result do we see in a positive test? (Ruling out Addison’s)

32. 250µg synacthen IM Positive test (ruling out Addisons): Plasma cortisol >460nmol/L at 30 minutes Serum cortisol at 0 minutes Serum cortisol at 30 minutes

33. Management • Glucocorticoid replacement • Hydrocortisone BD, usually 15mg on waking/5mg around 1800hrs • Excessive weight gain = over replacement • Educate patient – increase hydrocortisone when unwell • Mineralocorticoid replacement • Fludrocortisone 50-100µg daily • Titrate according to symptoms and U&Es

34. Addisonian Crisis • Features: • Severe shock – hypotension, tachycardia • Fever, abdominal pain, nausea & vomiting • Hyponatraemia/hyperkalaemia ±hypercalcaemia, hypoglycaemia • Management: • ABCDE assessment • Correct volume depletion • Replace glucocorticoids • Correct metabolic abnormalities • Treat underlying cause

35. Acromegaly

36. Definition? • A condition caused by excessive secretion of growth hormone

37. Most common cause? • Pituitary macroadenoma

38. Your turn!

41. Impress your examiner… Hypopituitism

42. Investigations

44. Management • Conservative: • Patient education • Medical (second line): • Somatostatin analogues (octreotide, lanreotide) • Dopamine agonists • GH receptor antagonists (pegvisomant) • Surgery (first line): • Trans-sphenoidal surgical debulking of pituitary adenoma • Radiotherapy: • Employed if acromegaly persists after surgery

45. References • Walker, BR., Colledge, NR., Ralston, SH., “Davidson’s Principles of Clinical Medicine” 21st edition, Churchill Livingstone, (2010). • Kumar, P., Clarke, M. “Clinical Medicine” 7th edition, Saunders, 2009. • Longmore, M. et al “Oxford Handbook of Clinical Medicine” 8th edition, Oxford University Press, 2010. • http://www.fipapatients.org/pictures/big/pituitary_normal.jpg • http://www.autismpedia.org/wiki/images/b/b9/Adrenal-core.gif • http://www.ghorayeb.com/files/Transsphenoid_Lateral_380x332.jpg • http://www.nosleeplessnights.com/wp-content/uploads/2013/03/dexamethasone.jpg • http://classconnection.s3.amazonaws.com/319/flashcards/1117319/jpg/addisons_disease1332524676283.jpg • http://upload.wikimedia.org/wikipedia/commons/2/2e/Addisons_hyperpigmentation.jpg • http://globalvoicesonline.org/wp-content/uploads/2012/05/syringe-drawing-320x300.jpg • https://lh5.googleusercontent.com/-qF8wwWfCtFI/TXRv47Ax4xI/AAAAAAAABR8/4jsTaDOngtc/s1600/Synacthen.JPG • http://www.gloshospitals.org.uk/SharePoint11/Pathology%20Web%20Images/Specimen%20containers/Gold_top_with_cap.jpg • http://www.sehha.com/diseases/endocrine/Addison12.gif • http://www.hdwallpapersinn.com/wp-content/uploads/2012/09/bigshow-img.jpg • http://www.examiner.com/images/blog/wysiwyg/image/andre-the-giant.jpg • http://upload.wikimedia.org/wikipedia/commons/1/15/Bitempvf.png • http://www.s2c8.co.uk/wp-content/uploads/2013/01/man-boob.jpg • http://www.physio-pedia.com/images/6/61/Moon_facies_in_Cushings.jpg • http://www.passpaces.com/images/acromegaly_MRCP.jpg