Presentation on theme: "Cushing’s, Addison’s and Acromegaly"— Presentation transcript:
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 hormonesRecognise 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 hormonesRecognise 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.
6 Hypothalamus GnRH GHRH TRH Dopamine CRH The hypothalamus controls body temperature, hunger, important aspects of parenting behaviours, thirst, fatigue, sleep and circadian rhythms.GnRHGHRHTRHDopamineCRH
7 Pituitary Sphenoid sinus Pituitary gland communicates with the hypothalamus via the hypophyseal tract.Split into anterior and posterior.Blood supply: hypothalamo-hypophyseal portal systemSphenoid sinus
10 Adrenal Glands Remember: GFR! Cortex split into glomerulosa, fasciculata and reticularis aldosterones, cortisol and androgens respectively.Medulla secretes catecholamines under control of the sympathetic nervous system.
11 Functions of Cortisol? Insulin resistance/gluconeogenesis Protein catabolismImmunosuppresionCVS regulation – e.g. increasing BPCNS actions – e.g. increased appetite, impaired memoryIncreased bone turnoverGastric acid secretionReduced skin collagenFluid retention
12 Right, now onto the stuff you actually want to know…
23 Management Untreated Cushing’s disease has a 50% 5 year mortality ConservativeMedicalSurgicalPatient educationReduce oral steroid therapy if possibleInhibit biosynthesis of corticosteroids – e.g. ketoconazole and metyraponeTrans-sphenoidal resection of pituitary (requires lifelong hormone replacement).Laparoscopic resection of adrenal tumour.Ectopic ACTH: treat underlying cause ±bilateral adrenalectomy.Untreated Cushing’s disease has a 50% 5 year mortality
24 RememberNot 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 (Or adrenal insufficiency, to be more correct). 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 I SO N – autoimmune (90% of cases) – degenerative (amyloid) – drugs (e.g. ketoconazole)– infective (TB, HIV)– secondary (ACTH, hypopituitism)– other (e.g. adrenal bleeding)– neoplasia (metastases)
29 Which of these is most likely to prompt your investigations into possible adrenal insufficiency? Postural hypotension.Which are due to mineralocorticoid?Why do they get pigment changes? Pro-opiomelanocortin (POMC) gene synthesised by the anterior pituitary and is raised in response to low serum cortisol a ACTH production is increased.Associated autoimmune conditions: type 1 diabetes, pernicious anaemia, autoimmune thyroid disease, vitiligo ask about FHx.
30 Investigations Test Bedside Lying/standing BP Bloods U&Es – low Na+/high K+Glucose – lowRandom serum cortisolShort synacthen testPlasma reninTFTs etc (?hypopituitism)FBC (?perncious anaemia)Gonadal functionHIV testPlasma aldosteroneImagingAXR (?adrenal calcificationCT or MRI of adrenalsRandom serum cortisol is of no use in ill patients may be normal level but inappropriately low for the seriously ill patientMeasure aldosterone as part of short synacthen test to indicate primary or secondary insufficiency. (Secondary = low ACTH)
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)Uses: diagnosis of primary or secondary adrenal insufficiency, assessment of the HPA axis in patients taking long-term glucocorticoid therapy.NOTE: relies on ACTH-dependent adrenal atrophy and therefore may not detect acute ACTH deficiency.
32 Positive test (ruling out Addisons): 250µg synacthen IMPositive test (ruling out Addisons):Plasma cortisol >460nmol/L at 30 minutesSerum cortisol at 0 minutesSerum cortisol at 30 minutes
33 Management Glucocorticoid replacement Mineralocorticoid replacement Hydrocortisone BD, usually 15mg on waking/5mg around 1800hrsExcessive weight gain = over replacementEducate patient – increase hydrocortisone when unwellMineralocorticoid replacementFludrocortisone µg dailyTitrate according to symptoms and U&Es
34 Addisonian Crisis Features: Severe shock – hypotension, tachycardia Fever, abdominal pain, nausea & vomitingHyponatraemia/hyperkalaemia ±hypercalcaemia, hypoglycaemiaManagement:ABCDE assessmentCorrect volume depletionReplace glucocorticoidsCorrect metabolic abnormalitiesTreat underlying causeFludrocortisol is not needed during acute managementHyperkalaemia usually responds to fluid therapy but may need specific interventionCorrect volume depletion with 0.9% NaCl – avoid when Na <125mmol/l. May cause central pontine demyelination
35 Acromegaly Bonus points, can you name these wrestlers? Even more bonus points, can you name their signature move? Showstopper and no named special move (trick question!) but I believe he invented the tombstone…
36 Definition?A condition caused by excessive secretion of growth hormone
38 Your turn!Clinical features? What would you be looking for on examination?
39 Symptoms: headaches, sweating, hats/gloves too small, family commenting on change in appearance over years, Sx of carpal tunnel syndrome (night time paraesthesia and weakness associated with a median nerve injury).Sx of pituitary adenoma?
41 Impress your examiner… What would you ask about/examine for to show off you were thinking about a pituitary adenoma in a patient you suspected had acromegaly in finals?Large pituitary macroadenoma disrupts communication from the hypothalamus leading to loss of dopamine inhibition of PRL secretion leading to hyperprolactinaemia.Hypopituitism
42 Investigations Bedside Collateral Hx Serial photographs BP ECG Bloods Serum GH (unreliable)Oral glucose tolerance testSerum IGF-1TFTs/FSH/LH/PRL etcImagingCT/MRI brainEchoOtherColonoscopyBedside – collateral hx (counts as Ix), serial photographsAdministration of oral glucose should suppress GH of <0.5µg/L in normal subjects.In acromegaly, the GH does not suppress and paradoxically rises.Diagnosis difficult in diabetics because they do not have the insulin to respond to the glucose. You can measure IGF-1 (low in DM w/o acromegaly).Glucose stimulates IGF-1 that then suppresses GH
44 Management Conservative: Medical (second line): Surgery (first line): Patient educationMedical (second line):Somatostatin analogues (octreotide, lanreotide)Dopamine agonistsGH receptor antagonists (pegvisomant)Surgery (first line):Trans-sphenoidal surgical debulking of pituitary adenomaRadiotherapy:Employed if acromegaly persists after surgeryMedical therapy does not shrink macroadenomasMedical and radiotherapy together may provide symptomatic relief in inoperable cases.
45 ReferencesWalker, 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.https://lh5.googleusercontent.com/-qF8wwWfCtFI/TXRv47Ax4xI/AAAAAAAABR8/4jsTaDOngtc/s1600/Synacthen.JPG