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Definitions Aetiology Presentation Investigations Complications Management Prognosis Clinical scenario.

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Presentation on theme: "Definitions Aetiology Presentation Investigations Complications Management Prognosis Clinical scenario."— Presentation transcript:


2 Definitions Aetiology Presentation Investigations Complications Management Prognosis Clinical scenario

3 Definition Autoimmune destruction of the adrenal gland resulting in failure of adrenal steroid hormone production Cortisol & Aldosterone

4 Adrenal failure: 1. Primary adrenal failure Atrophy/destruction of the adrenal gland 2. Secondary adrenal failure Inadequate ACTH production 3. Tertiary adrenal failure Failure of CRH production

5 1. Primary adrenal failure Autoimmune Infection (TB, HIV) Invasion from mets (lymphoma, breast, lung) Haemorrhage (anticoagulants, Waterhouse- Friedrichsen Syndrome Infiltration (amyloid, sarcoid, haemochromatosis) Congenital adrenal hyperplasia Drugs (eg ketoconazole, phenytoin, rifampicin) ADDISONS

6 2. Secondary adrenal failure Acute steroid withdrawal 3. Tertiary adrenal failure Chronic high dose glucocorticoid therapy Sarcoidosis Tumour Cranial irradiation

7 Non-specific symptoms: Abdominal pain Nausea Diarrhoea Lassitude Dizziness Due to postural hypotension Pigmentation Buccal Scars Palmar creases Generalised Hypoglycaemia Cortisol is one of the main insulin antagonists

8 Bed side Lying and standing BP ECG Blood glucose Bloods U+Es Serum cortisol (best to be done in the morning) Adrenal autoantibodies Imaging MRI head CT abdo Special tests Short synacthen test (confirm the Dx) Long synacthen test (test response of adrenals)

9 Addisonian crisis Occurs when the physiological demand for these hormones exceeds the ability of adrenal glands to produce them ie, patients with chronic adrenal insufficiency when subject to an intercurrent illness or stress Major or minor infections Injury Surgery Burns Pregnancy General anaesthesia Abrupt withdrawal of steroids Waterhouse-Friedrichsen syndrome Present with hypovolaemic shock and profound hypoglycaemia MEDICAL EMERGENCY!

10 Chronic adrenal failure Glucocorticoid replacement Hydrocortisone Double dose if intercurrent illness, infection or surgery Mineralocorticoid replacement Fludrocortisone Addisonian Crisis IV fluids High dose hydrocortisone Dopamine (if hypotension persists) Treat precipitant Monitor U+Es and glucose

11 Hypothyroidism T1DM Pernicious anaemia Vitiligo Premature ovarian failure


13 Cushings Syndrome definition: The clinical condition resulting from prolonged exposure to glucocorticoids from an exogenous or endogenous cause. Cushings Disease definition: The clinical condition resulting from prolonged exposure to glucocorticoids from a pituitary adenoma.

14 Cortisol Endogenous ACTH dependent ACTH independent Exogenous Steroid use Pituitary adenoma 70% F>M Ectopic ACTH production 14% SCLC Carcinoid tumour Adrenal adenoma 10% Adrenal carcinoma 5% Adrenal hyperplasia 1%

15 Use whatever helps you remember! Myopathy Striae Bruising Osteoporosis Catabolic effects Diabetes Truncal obesity Supraclavicular fat pad Glucocorticoid effects Hypertension Hypokalaemia Mineralocorticoid effects

16 S – spinal tenderness W – weight (central obesity) E – easy bruising D – diabetes I – interscapular fat pad S – striae H – hypertension/hypokalaemia

17 Bedside 24 hour urinary free cortisol (to confirm Cushings syndrome) Bloods U+Es (<3.2 suggests ectopic ACTH production) Imaging MRI head (for pituitary adenoma) CT chest (for SCLC) Special tests to determine the cause Serum ACTH Dexamethasone suppression test Distinguishes the ACTH dependent causes

18 Same as complications of steroid use A common question in Finals! If struggling to remember dont panic! What can they lead on to? Eg Diabetes and its complications, cardiovascular disease, infections

19 Treat the cause! Conservative Stop medications! Exercise Diet Smoking cessation Medical Metyrapone (blocks cortisol synthesis) Ketoconazole (inhibits cytochrome P450) Mitotane (adrenolytic agent) adrenal carcinoma Radiotherapy (adjuctive therapy/for relapse/if surgery inappropriate/in children – when pituitary adenoma) Surgical Trans-sphenoidal adenomectomy Bilateral adrenalectomy (cant locate tumour/recurrence post-surgery) Removal of ACTH secreting tumour Distinction: Nelsons syndrome – post- adrenalectomy development of a locally aggressive pituitary tumour (corticotrophinoma) due to lack of negative feedback.

20 If treated very good prognosis Resolution of physical features and psychological disorders Follow up needed for osteoporosis, glucose intolerance, DM, HTN, subtle mood changes, obesity Untreated = <5 years Cardiovascular disease Infection

21 Definition: A hormonal disorder that develops when the pituitary gland produces too much growth hormone during adulthood

22 Pituitary adenoma (99%) Ectopic production (1%) Usually a carcinoid tumour Pancreas Lung Adrenals

23 Cause Pituitary adenoma Ectopic production GH secretion Insulin-like growth factors Arteriolar muscle hypertrophy Hypertension Anti-insulin effect Diabetes Soft tissue growth Big tongue Big lips Boggy palms Cardiomyopathy Colorectal cancer Sweat gland hypertrophy Excess sweating Bone growth Typical facies

24 Usually a spot diagnosis Typical facies Prominent supra-orbital ridges Big ears, nose, lips, tongue Prognathism Wide separation of teeth May complain of: Headache Numbness/tingling in hands Excessive sweating Vision problems Hoarse voice Obstructive sleep apnoea Muscle weakness

25 Observe: As previous slide Hands: Size – compare with your own Thenar eminence – wasting Check median nerve sensation Sweaty? Bogginess of palms Skinfold thickness – increased in active disease Ask for BP Neck Check for goitre JVP Visual fields and acuity Stand from seated position

26 Bedside BP Urine dip BM ECG Echocardiogram Bloods IGF levels Imaging MRI head Colonoscopy (if 50 years) Special tests Oral GTT with GH measurement Distinction: Random GH measurements not helpful because GH secreted in pulsatile manner. False positives for OGTT + GH Pregnancy Puberty Hepatic disease Renal disease Anorexia nervosa DM

27 Conservative Exercise Diet Smoking cessation Medical Octreotide & Lanreotide (somatostatin analogues) Bromocriptine & cabergoline (dopamine agonists) Metformin Pegvisomant (GH receptor antagonist) Radiotherapy (as adjuvant/when surgery inappropriate) Surgical Trans-sphenoidal adenomectomy Follow up: Yearly GH & IGF-1 measurement + OGTT, visual fields, CV assessment. IGF Insulin resistance

28 Hypertension (increased risk of stroke & IHD) Diabetes Cardiomyopathy LVH Colorectal cancer 5% associated with MEN-1 Remember 3Ps Parathyroid hyperplasia/adenoma Pancreatic endocrine tumours Pituitary adenoma Mortality increased 2-3x

29 28 year old woman is seen in outpatients. She has been referred by her GP who has been unable to find a cause for her symptoms. She has a 6 month history of intermittent abdominal pain which varies in site and intensity. She has also experienced some occasional diarrhoea. She feels generally weak and off her food. She has lost a stone over this period. On examination she has pigmented palmar creases and buccal mucosa but no other specific findings. Her BP is 100/70 lying down, you try to stand her to check it again but she feels dizzy and light headed and has to sit down. You check her BM and it is 2.9. Addisons disease

30 What are your differentials for this lady? How would you investigate her? How would you manage her? What are the complications of Cushings disease? What is the difference between Cushings syndrome and Cushings disease?


32 Medicine at a glance Ask Dr Clarke Oxford handbook of clinical medicine Special thanks to Dr Thomas Marshall

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