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Cushings, Addisons and Acromegaly Dr Edward Hutchison FY1 (Geriatrics)

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1 Cushings, Addisons and Acromegaly Dr Edward Hutchison FY1 (Geriatrics)

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

3 Aims HPA Axis Adrenal glands Cushings syndrome/disease Addisons Acromegaly

4 HPA Axis

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6 Hypothalamus GnRH TRHDopamineCRH GHR H

7 Pituitary Sphenoid sinus

8 Anterior Pituitary Hormones ACTHFSHPRLLHTSHGH

9 Posterior Pituitary Hormones ADHOxytocin

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 Cushings…

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

15 Classification ACTH-dependent Pituitary adenoma Ectopic ACTH production – e.g. small cell lung cancer, neuroendocrine tumours Iatrogenic – ACTH therapy ACTH-independent Iatrogenic – steroid therapy Adrenal adenoma/carcinoma Pseudo-Cushings EtOH excess Major depressive disorder Primary obesity

16 Clinical features

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

20 Investigation

21 Overnight dexamethasone suppression test/ 24hr urinary cortisol 48hr low-dose dexamethasone suppression test Confirmed ?EtOH excess Not excluded Abstinence

22 ACTH level? ACTH level High CRH test/48hr dexamethasone suppression test Suppressed MRI pituitary Not suppressed Ectopic source CXR, CT A/P, tumour markers Low/normalAdrenal cause CT adrenals ±adrenal venous sampling

23 Management ConservativeMedicalSurgical Patient education Reduce oral steroid therapy if possible Inhibit biosynthesis of corticosteroids – e.g. ketoconazole and metyrapone Trans-sphenoidal resection of pituitary (requires lifelong hormone replacement). Laparoscopic resection of adrenal tumour. Ectopic ACTH: treat underlying cause ±bilateral adrenalectomy. Untreated Cushings disease has a 50% 5 year mortality

24 Remember Not only oral corticosteroids can cause Cushings 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 Addisons 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 – neoplasia (metastases) – autoimmune (90% of cases) – degenerative (amyloid) – drugs (e.g. ketoconazole) – infective (TB, HIV) – secondary ( ACTH, hypopituitism) – other (e.g. adrenal bleeding)

28 Clinical Features

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30 Investigations Test BedsideLying/standing BP BloodsU&Es – low Na + /high K + Glucose – low Random serum cortisol Short synacthen test Plasma renin TFTs etc (?hypopituitism) FBC (?perncious anaemia) Gonadal function HIV test Plasma aldosterone ImagingAXR (?adrenal calcification CT or MRI of adrenals

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 Addisons)

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

33 Management Glucocorticoid replacement o Hydrocortisone BD, usually 15mg on waking/5mg around 1800hrs o Excessive weight gain = over replacement o Educate patient – increase hydrocortisone when unwell Mineralocorticoid replacement o Fludrocortisone µg daily o 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

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41 Impress your examiner… Hypopituitism

42 Investigations BedsideCollateral Hx Serial photographs BP ECG BloodsSerum GH (unreliable) Oral glucose tolerance test Serum IGF-1 TFTs/FSH/LH/PRL etc ImagingCT/MRI brain Echo OtherColonoscopy

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

45 References Walker, BR., Colledge, NR., Ralston, SH., Davidsons Principles of Clinical Medicine 21 st edition, Churchill Livingstone, (2010). Kumar, P., Clarke, M. Clinical Medicine 7 th edition, Saunders, Longmore, M. et al Oxford Handbook of Clinical Medicine 8 th edition, Oxford University Press, https://lh5.googleusercontent.com/- qF8wwWfCtFI/TXRv47Ax4xI/AAAAAAAABR8/4jsTaDOngtc/s1600/Synacthen.JPG https://lh5.googleusercontent.com/- qF8wwWfCtFI/TXRv47Ax4xI/AAAAAAAABR8/4jsTaDOngtc/s1600/Synacthen.JPG with_cap.jpg with_cap.jpg


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