3 Addison’s Disease Definition Cortisol & Aldosterone Autoimmune destruction of the adrenal gland resulting in failure of adrenal steroid hormone productionCortisol & Aldosterone
4 Lets take a step back… Adrenal failure: Primary adrenal failure Atrophy/destruction of the adrenal glandSecondary adrenal failureInadequate ACTH productionTertiary adrenal failureFailure of CRH production
7 Presentation Non-specific symptoms: Dizziness Pigmentation Abdominal painNauseaDiarrhoeaLassitudeDizzinessDue to postural hypotensionPigmentationBuccalScarsPalmar creasesGeneralisedHypoglycaemiaCortisol is one of the main insulin antagonists
8 Investigations Bed side Bloods Imaging Special tests Lying and standing BPECGBlood glucoseBloodsU+EsSerum cortisol (best to be done in the morning)Adrenal autoantibodiesImagingMRI headCT abdoSpecial testsShort synacthen test (confirm the Dx)Long synacthen test (test response of adrenals)
9 Complications Addisonian crisis Occurs when the physiological demand for these hormones exceeds the ability of adrenal glands to produce themie, patients with chronic adrenal insufficiency when subject to an intercurrent illness or stressMajor or minor infectionsInjurySurgeryBurnsPregnancyGeneral anaesthesiaAbrupt withdrawal of steroidsWaterhouse-Friedrichsen syndromePresent with hypovolaemic shock and profound hypoglycaemiaMEDICAL EMERGENCY!
10 Management Chronic adrenal failure Addisonian Crisis Glucocorticoid replacementHydrocortisoneDouble dose if intercurrent illness, infection or surgeryMineralocorticoid replacementFludrocortisoneAddisonian CrisisIV fluidsHigh dose hydrocortisoneDopamine (if hypotension persists)Treat precipitantMonitor U+Es and glucose
13 Cushing’s Syndrome or Disease? Cushing’s Syndrome definition:The clinical condition resulting from prolonged exposure to glucocorticoids from an exogenous or endogenous cause.Cushing’s Disease definition:The clinical condition resulting from prolonged exposure to glucocorticoids from a pituitary adenoma.
15 Presentation Use whatever helps you remember! Catabolic effects MyopathyStriaeBruisingOsteoporosisGlucocorticoid effectsDiabetesTruncal obesitySupraclavicular fat padMineralocorticoid effectsHypertensionHypokalaemia
16 Acronyms S – spinal tenderness W – weight (central obesity) E – easy bruisingD – diabetesI – interscapular fat padS – striaeH – hypertension/hypokalaemia
17 Investigations Bedside Bloods Imaging 24 hour urinary free cortisol (to confirm Cushing’s syndrome)BloodsU+Es (<3.2 suggests ectopic ACTH production)ImagingMRI head (for pituitary adenoma)CT chest (for SCLC)Special tests → to determine the causeSerum ACTHDexamethasone suppression testDistinguishes the ACTH dependent causes
18 Complications Same as complications of steroid use A common question in Finals!If struggling to remember don’t panic!What can they lead on to?Eg Diabetes and its complications, cardiovascular disease, infections
19 Management Treat the cause! Conservative Medical Surgical Distinction: Stop medications!ExerciseDietSmoking cessationMedicalMetyrapone (blocks cortisol synthesis)Ketoconazole (inhibits cytochrome P450)Mitotane (adrenolytic agent) → adrenal carcinomaRadiotherapy (adjuctive therapy/for relapse/if surgery inappropriate/in children – when pituitary adenoma)SurgicalTrans-sphenoidal adenomectomyBilateral adrenalectomy (can’t locate tumour/recurrence post-surgery)Removal of ACTH secreting tumourDistinction:Nelson’s syndrome – post-adrenalectomy development of a locally aggressive pituitary tumour (corticotrophinoma) due to lack of negative feedback.
20 Prognosis If treated very good prognosis Untreated = <5 years Resolution of physical features and psychological disordersFollow up needed for osteoporosis, glucose intolerance, DM, HTN, subtle mood changes, obesityUntreated = <5 yearsCardiovascular diseaseInfection
21 Acromegaly Definition: A hormonal disorder that develops when the pituitary gland produces too much growth hormone during adulthood
22 Aetiology Pituitary adenoma (≈99%) Ectopic production (≈1%) Usually a carcinoid tumourPancreasLungAdrenals
23 Pathophysiology Cause Big tongue Big lips Boggy palms Cardiomyopathy Ectopic productionPituitary adenomaGH secretionInsulin-like growth factorsArteriolar muscle hypertrophyHypertensionAnti-insulin effectDiabetesSoft tissue growthBig tongueBig lipsBoggy palmsCardiomyopathyColorectal cancerSweat gland hypertrophyExcess sweatingBone growthTypical facies
24 Presentation Usually a spot diagnosis Typical facies May complain of: Prominent supra-orbital ridgesBig ears, nose, lips, tonguePrognathismWide separation of teethMay complain of:HeadacheNumbness/tingling in handsExcessive sweatingVision problemsHoarse voiceObstructive sleep apnoeaMuscle weakness
25 What should you do O/E? Observe: As previous slide Hands: Size – compare with your ownThenar eminence – wastingCheck median nerve sensationSweaty?‘Bogginess’ of palmsSkinfold thickness – increased in active diseaseAsk for BPNeckCheck for goitreJVPVisual fields and acuityStand from seated position
26 Investigations Bedside Bloods Imaging Special tests BP Urine dip BM ECGEchocardiogramBloodsIGF levelsImagingMRI headColonoscopy (if ≥50 years)Special testsOral GTT with GH measurementDistinction:Random GH measurements not helpful because GH secreted in pulsatile manner.False positives for OGTT + GHPregnancyPubertyHepatic diseaseRenal diseaseAnorexia nervosaDM
29 Clinical scenario28 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.Addison’s disease
30 What are your differentials for this lady What are your differentials for this lady? How would you investigate her? How would you manage her? What are the complications of Cushing’s disease? What is the difference between Cushing’s syndrome and Cushing’s disease?