PACES Station 5 Flashcards
Clinical Features of Acromegaly
Large, sweaty hands Thickened skin Prominent supraorbital ridges, enlarged nose and lips Prognathism Interdental separation Macroglossia Hypertrichosifs Gynaecomastia Bitemporal hemianopia (10%) Carpel tunnel HTN Cardiomegaly Diabetes Arthropathy Skin tags and colonic polyps Headaches, change in ring size/show size
Pathophysiology of Acromegaly
Most commonly caused by a growth hormone secreting adenoma of the anterior pituitary. 75% are macro adenomas
Rarer causes include ectopic GH release from carcinoid or small cell tumours
Complications of Acromegaly
HTN Cardiomegaly Arthritis IGGT/DM Visual field defects Cranial nerve palsies Tumours: fibroids and colonic polyps with risk of developing into malignancy
Investigating possible Acromegaly
Oral glucose tolerance test - should suppress GH
Serum insulin-like growth factor 1
MRI pituitary
Management of Acromegaly
Surgical - transphenoidal hypophysectomy with attempt to leave remaining pituitary intact to preserve function
Medical - somatostatin analogues (ocreotide) inhibit GH release. Cause gallstones.
Bromocriptin (Dopamine)agonist
Radiotherapy if surgery contraindicated is an option but also effects other pituitary hormones and visual loss
Differential Diagnosis for lump in Neck
Congenital - thyroglossal cyst, branchial anomalies
LNs - bacterial, viral, granulomatous, malignancy
Vascular - aneurysm
Salivary - tumour
Neurogenic - schwannoma, neurofibroma
Thyroid…
Management of Thyroid Nodule
- Functioning or not?
- serum TSH, if low suggests need scintigraphy to delineate hot nodule or not
- if TSH normal or high then FNA
Histology may be indeterminate but generally still remove
Types of Thyroid Cancer
Papillary carcinoma - most common and most favourable prognosis. Radio iodine /surgical management
Follicular carcinoma
Anaplastic carcinoma - highly aggressive undifferentiated
Medullary thyroid carcinoma - associated with MEN2a (phaeo and primaryPTH), MEN2b (phaeo + marfanoid)
Complications of Large Goitre
Dyspnoea and airway obstruction Dysphagia Recurrent laryngeal nerve palsy Horners Jugular vein compression Cerebrovascular steal syndrome
Clinical Features of Thyrotoxicosis
Goitre (usually non-tender), smooth diffuse in graves
Heat intolerance, sweating, agitation, stress
Weight loss, palpitations
AF
Brisk reflexes
Eyes - proptosis, ophthalmoplegia, lid lag
Specific to graves - proptosis, thyroid acropachy, pretibial myxoedema
Investigations of Thyrotoxicosis
TSH/T4
Thyroid autoantibodies
Radioisotope scanning
Management of Graves Thyrotoxicosis
Beta blocker - propranolol
Carbiomazole or propylthiouracil
Titrate dose
Stop at 18months (1/3 will remain euthyroid)
IF returns consider:
- repeat course
- radioiodine
- subtotal thyroidectomy
High dose steroids/surgical decompression for severe ophthalmoplegia
Progression of Eye Signs in Graves
NOSPECS No signs Only lid lag Soft tissue involvement Proptosis Extraoccular muscle involvement Chemosis Sight loss due to optic nerve compression/atrophy
Common causes of Hyperthyroidism
Graves Hashimotos (thyrotoxicosis before hypothyroid) Toxic adenoma Iodine induced TSH secreting tumour (rare) Infective thyroiditis Post-partum thyroiditis
Causes of Hypothyroidism
Primary
- autoimmune (hashimotos)
- iodpathic atrophy
- previous radio iodine
- antithyroid drugs
- infiltrative: sarcoid, systemic sclerosis
Secondary
-hypothalamic, pituitary disease
Drugs causing Hypothyroidism
Iodine contrast
Lithium
Sunitinib (tyrosine kinase inhib) used in renal cell carcinoma
Features of Cushings
Cushingoid facies Centripetal obesity Inter scapular fat pad Acne vulgaris Purpuric and petechial rashes Bruising Violaceous striae Proximal myopathy
Pathophysiology of Cushings Disease
Hyper secretion of ACTH from pituitary adenoma
Causes of Cushings Syndrome
ACTH dependent:
- Cushings disease (pituitary adenoma)
- Ectopic ACTH from SCLC or carcinoid
ACTH independent
- exogenous steroid administration
- adrenocortical adenoma/carcinoma
Investigations for cortisol excess
24hr urinary free cortisol (x3)
Midnight salivary/serum cortisol
Dexamethasone suppression test (no ACTH suppression)
Low dose dexamethasone suppression test can help distinguish between bushings and pseudocushings
Consider inferiors petrosal sinus sampling in ACTH dependent Cushings with no clear pituitary source
Check Calcium - hyperPTH in MEN1
Complications of Cushings
Diabetes
Osteoporosis
HTN
Cataracts
Management of Cushings Syndrome
If adenoma - surgical transphenoidal/adrenalectomy
If adjunct needed then ketoconazole used to inhibit steroid genesis
Nelsons Syndrome
Enlargement of a pituitary corticotroph adenoma due to absence of negative feedback from adrenal cortisol following removal of both adrenals.
Also get hyper pigmentation as high ACTM stimulated melanocyte stimulating hormone
May get bitemporal hemianopia
What is MEN1?
Autosomal dominant
- Pituitary adenoma (cushings)
- hyperparathyroidism
- pancreatic gastrinoma
Clinical Features of Addisons Disease
Widespread pigmentation - buccal mucosa, skin creases and pressure areas
Calcification of auricular cartilage
No adrenelectomy scars (would be present in Nelsons)
Postural hypotension
Other autoimmune conditions: vitiligo, T1DM, Pernicious anaemia, RA, SLE, Sj
Causes of Primary Adrenal Failure
Autoimmune (Addisons) TB Bilateral adrenelectomy Amyloidosis Haemochromatosis HIV Haemorrhagic infarcts - meningococcal Adrenal Mets Congenital Adrenal Hyperplasia
Diagnostic Tests for Adrenal Insufficiency
9 am serum cortisol
Synacthen test
Management of Adrenal Failure
Adrenal crisis - rapid steroid, fluid replacement and reversal of electrolyte abnormalities (low Na, high K)
Causes of Pituitary Failure
Pituitary mass Previous pituitary surgery/radiotherapy Infiltrative disease Pituitary infarct (Sheehans) Pituitary apoplexy Trauma/ SAH
Causes of Gynaecomastia
Hypogonadism Testicular tumour Chronic Liver Disease CKD Klinefelters Thyrotoxicosis Carcinoma of lung Drugs: digoxin, spironolactone Puberty
Klinefelters Syndrome
Tall Gynaecomastia Other features of hypogonadism including small, firm testes Autoimmune disease Mitral valve prolapse Varicose veins
Genetics: XXY or mosaicism XXY:XY
Turners Syndrome
XO
Short stature, square chest Widely spaced nipples Webbed neck Nail dysplasia High arch palate Short fourth metacarpals Numerous naevi Wide carrying angle
Associated: Coarctation, DM, renal malformations, cataracts, ptosis
Physiological Actions of Parathyroid Hormone
Stimulated by low Calcium
Bone: increase bone resorption
Kidneys: stimulates calcium reabsorption and inhibits phosphate (unlike vitD which promotes uptake of both)
Stimulates vitD synthesis
Clinical Features of RA
Symmetrical deforming polyarthropathy Involves PIPs and MCPs Palmar subluxation and ulnar deviation Swan neck, boutonnieres and Z deformity Rheumatoid nodules (firm, non-tender) May be vasculitic nail fold infarcts/pupura Risk of nerve entrapments
Then: MSK, ears, eyes, c-spine, lungs, heart, spleen, kidneys
Diagnostic Criteria for RA
ACR - at least 4 of the following: -morning stiffness >1hr -symmetrical joint involvement -arthritis in >3 joints involves small joints of hand -postive RF -rheumatoid nodules -radiographic evidence
Rheumatoid Factor
IgM against Fc of IgG. Present in 75% of RA and occurs in other autoimmune connective tissue disease e.g. SLE.
Suggests more aggressive joint disease than seronegative disease and extra-articular manifestations more common
AntiCCP also a poor prognostic marker
Possible causes of anaemia in RA
Anaemia of chronic disease Iron deficiency -GI loss due to NSAIDs Folate deficiency - methotrexate Pernicious anaemia BM suppression - gold, methotrexate, sulphasalazine Feltys Anaemia of renal disease
Eye involvement in RA
Episcleritis (painless) Scleritis (painful) Cataracts - steroids Sjogrens Extraoccular muscle tenosynovitis
Renal disease in RA
Membranous glomerulonephritis - gold
Mesangioproliferative glomerulonephritis
Acute tubulointerstitial nephritis - NSAIDs
Renal amyloidosis
Principles of Management of RA
MDT
General: education, physio, OT, bone protection, pneumovax
Analgesia
DMARDS
Biologicals - antiTNF (infliximab/adaluminab)
Corticosteroids
DMARDS in RA
Sulphasalazine - risk of nausea, rash neutropenia - 3 monthly FBC, LFT
Methotrexate - need baseline CXR and monitor LFT, FBC
Leflunomide- risk of HTN, neutropenia
Azathioprine - check TPMT prior to starting (predicts BM toxicity)
Ciclosporin - causes HTN and renal impairment
Clinical Features of Psoriatic Arthropathy
Nails - pitting, onycholysis, transverse ridging
Psoriatic plaques
Koebners phenomenon - plaques over sites of trauma
Other things to examine:
- MSK association with gout
- CVS: Aortitis and AR
- Resp: apical lung fibrosis
- Eyes: conjunctivitis, uveitis
Patterns of Psoriative Arthropathy
Asymmetrical, oligoarthritis involving DIP
Symmetrical polyarthritis involving PIP and MCP (rheumatoid pattern)
DIP arthritis
Arthritis mutilans - aggressive deforming disease with bone resorption leading to telescoping
Spondylitis/sacroilitis - asymmetrical unlike AnkSpond
Enthesitis
Inflammation of tendon insertion
Dactylitis
Inflammation of tendon sheath leading to sausage like swollen fingers
Management of Psoriatic arthropathy
MDT…
Analgesia
Corticosteroids
DMARDs - methotrexate, sulfasalazine, cyclosporin
Adverse effects of antiTNF alpha
Serious infection e.g. TB Haematological malignancy Nausea Hypersensitivity Worsens heart failure
Contraindications for antiTNF alpha
Pregnancy/breastfeeding Active bacterial infection Active TB (need 2 month therapy before initiating) Septic arthritis CCF Demyelinating disease
Clinical Features of Ankylosing Spondylitis
Severe kyphosis with protuberant abdomen Decreased cervical movement Decreased spinal movement Reduced chest expansion Schobers test positive - 10 above, 5 below dimples of venus should increase by 5cm
Extra bits: anterior uveitis, aortic regard, apical fibrosis, AV block (check pacemaker)
Definition of Ankylosing Spondylitis
Symptomatic sacroilitis for > 3 months with morning stiffness and improvement with exercise, worsening with rest
Systemic Manifestations of Ankylosing Spondylitis
Eyes: anterior uveitis Aortic regurg AV block Apical fibrosis Atlantoaxial subluxation Achilles tendonitis Amyloidosis
Diagnosing Ank Spond
Clinical hx
Raised inflammatory markers
evidence of sacroilitis on XR/MRI
Management of Ank Spond
MDT... Education Physio/OT Analgesia Corticosteroids DMARDs - gold, penicillamine (methotrexate and sulphasalazine help peripheral disease but not spine) Biologicals such as adalimumab
Clinical Features of Gout
Asymmetrical joint deformity and swelling
Tophi, hands, feet, ears
Olecranon bursa
Differential Diagnosis for single inflamed joint
Gout/pseudogout Septic arthritis Spondyloarthritis OA Lyme disease/stills disease
Pathophysiology of Gout
Uric acid produced by breakdown of purines in liver by enzyme xanthine oxidase - eliminated by kidneys and GI tract
Causes:
- reduced excretion: HTN, CKD, drugs (ACEi, aspirin, thiazides)
- Increased purine production: diet, lymphoproliferative disorders, secondary polycythaemia, glycogen storage disease
Management of Gout
Acute: rest, rehydrate, NSAIDs, colchicine
Recurrent: lifestyle advise, allopurinol
What is pseudogout
Crystal arthropathy of calcium pyrophosphate deposition - postivitely bifringent crystals in polarised light
Chondrocalcinosis on radiograph
Occurs in haemochromatosis, hypothyroidism and CKD
Classification of Systemic Sclerosis
Diffuse: involvement of skin, trunk and extremities, early involvement of lung, kidney, gut and heart
Limited: skin only at extremities and face, late lung involvement including pHTN, renal crisis is rare
Diagnostic Criteria for Systemic Sclerosis
1 major or 2+ minor
Major - skin involvement
Minor - sclerodactyl, finger pulp atrophy, bilateral pulmonary fibrosis
Organ involvement in systemic sclerosis
Skin - raynauds, sclerodactyly, pulp atrophy, calcinosis, nail dystrophy, ulceration, telangiectasia, vitiligo
MSK - arthritis, myositis, myopathy, intraairticular calcification
GI - dysphagia, GORD, intestinal hypo motility leading to bacterial overgrowth and malabsorption
Renal - malignant HTN, glomerulonephritis, renal crises
Resp - ILD, pleural effusions
CVS - restrictive cardiomyopathy, pericarditis, pulmonary HTN
Antibodies in Systemic Sclerosis
Limited - ANA, RF, antiCentromere
Diffuse - anti Scl 70, anti RNA pol
Management of Systemic Sclerosis
General: education, PT/OT, analgesia, MDT
Raynauds: smoking cessation, hand warmers, vasodilators (calcium antagonists, ACEi, prostacyclin), sympathectomy
GI: low residue diet, nutritional supplements, Abx, PPI for reflux, pro kinetics
Renal: ACEi
Rs: vasodilator therapy for pHTN, antifibrotis therapy - D penicillamine, interferon gamma
Clinical features of psoriasis
Erythematous plaques with silvery white scales on extensor surfaces, behind ears and scalp
Asymmetric arthropathy and nail changes
Koebner phenomenon
Auspitz sign - visible bleeding points over plaques from enlarged dermal capillaries and intense scratching
CVS - aortic regard
Rs - apical lung fibrosis
Eye - uveitis
Pathophysiology of Psoriasis
Inflammatory skin condition
Receive abnormal epidermal proliferation
T cell mediated
Associated with HLA-B13, B17 and Cw6, also susceptibility gene on chr 6
Genetics and environmental factors involved
Exacerbating factors in Psoriasis
Trauma Sunburn Stress Alcohol Smoking Beta haemolytic strep - guttate psoriasis Drugs - lithium, beta blockers, Acei, antimalarials Withdrawal of steroids HIV
Cardinal histopathological features of psoriasis
Acanthuses (skin thickening) Parakeraotisis Absence of granular cell layer Polymorphonuclear abscess of munro Dilated capillary loops in upper epidermis
Variants of Psorias
Chronic plaque psoriasis Pustular psoriasis Guttate psoriasis Palmoplantal psoriasis Erythrodermic psoriasis
What skin conditions demonstrate Koebners phenomenon?
Psoriasis Lichen planus Vitiligo Viral warts Pemphigus Pemphigoid Molloscum contagiosum
Management of psoriasis
General: patient education, avoid exacerbating factors
Topical: emollients, steroids, UVB, tar, dithranol
Systemic: methotrexate, azathioprine, cyclosporin, tacrolimus, retinoids
Clinical Features of Neurofibromatosis
Neurofibromas along course of peripheral nerves > 6
Axillary freckling
Cafe au last spots >6
HTN - secondary to renal artery stenosis
Acoustic neuroma ? hearing aid
Eyes - cataracts, optic glioma, lisch nodules (hamartomata on iris) on slit lamp
Pulmonary fibrosis, pneumothorax
Heart - cardiomyopathy
MSK: Kyphoscoliosis, bowing of legs, rib notching, charcot joints
Kidney - RAS
Phaeochromocytomas
Genetics of Neurofibromatosis
NF1 (peripheral) - AD, chr 17, tumour suppressor gene (neurofibromin normally binds and inhibits Ras)
NF2 (central) AD chr 22 also tumour suppressor gene
Clinical features of HHT
Telangiectasis of face, mouth, lips, tongue, buccal mucosa
NO features of Systemic sclerosis
Conjunctival pallor (iron deficiency anaemia)
Resp: AVMs, may be clubbed as a result
CVS: high output cardiac failure
GI: iron def anaemia, hepatosplenomegaly, portal HTN
Eyes - retinal haemorrhage
Neuro: SAH, central vascular lesions, ischaemic stroke - paradoxical emboli from pulmonary AVM
What are telangiectasia?
Enduring dilation of small blood vessels, capillary or venules (venules in HHT)
What is HHT
Autosomal dominant condition, multiple genes associated on different chromosomes
Telangiectasia effect multiple organs
Management of HHT
Anaemia - iron sups, transfusion Skin - cosmetic/laser ablation Epistaxis - cauterise, laser ablation PAVM - embolisation, surgical resection/ligation GI - photocoag therapy,
Clinical Features of Dermatomyositis
Heliotrope rash around eyes
Violaceous scaly papule over knuckles, elbows, knees - Gottron papule
Erythema + Poikiloderma in photosensitive distribution
Proximal muscle weakness and tenderness
Associated ILD, dysphagia, arthritis
Drugs causing dermatomyositis like skin changes
Hydroxyurea
Penicillamine
Statin
Quinidine
Investigations in Dermatomyositis
raised CK
EMG - spontaneous fibrillation
Muscle biopsy - necrosis, phagocytosis of muscle fibres
Causes of Purpura
Platelet defect - idiopathic, CLD
Capillary defect - age, steroids, vasculitis, ehlers-danlos, HHT, scurvy
Coag defect - warfarin, vWF, DIC, amyloidosis
Lichen Planus
Flat topped, violaceous polygonal papule on fleecers surfaces
Fine white striae - wickhams - on surface of lesions
Koebners phenomenon
Scalp involvement with scarring alopecia
Lace like white lines on buccal mucosa
Dystrophic nails
Associated drugs - ACEi, beta blockers, NSAIDs, antimalarials
Hep C association
Underlying causes of Erythema nodosum
Streptococcal throat infection TB Sarcoidosis IBD Behcets Drugs - OCP, penicillin, tetracyclines, sulphonamides
Clinical Features of SLE
Erythematous, maculopapular rash in butterfly distribution, sparing nasolabial folds with scaling and follicular plugging
May have vasculitis lesions, livedo, photosensitivity, alopecia
Symmetrical non-erosive polyarthritis
Hands - palmar erythema, arthritis, raynauds, dermatomyositis
Nails - splinter haemorrhages, nail-fold capillaries, periungal infarcts
Mouth - ulcers
Scalp - scarring alopecia
Rs - ILD, pleural effusions,
CVS - pericarditis, pHTN
CNS - hemiparesis, mononeuritis multiplex
Renal - HTN, oedema,
Haem - splenomegaly, lymphadenopathy
Eyes - sjogrens, retinal infarcts
Diagnostic Criteria for SLE
4 of the following: -malar rash -discoid rash -photosensitivity -oral ulcers -arthritis -serositis -renal involvement -neurological involvement -haematologial involvement ANA positive
Causes of Drug Induced Lupus
Procainamide Hydralazine Quinidine Chlorpromazine Methyldoxpa Phenytoin Carbamazepine OCP
Differentiating SLE with drug induced lupus
SLE - more females, renal and CNS involvement more common, positive antidsDNA
Drug induced - equal male to female, rare renal and CNS involvement, positive anti-histone
Autoantibodies of SLE
ANA in 95% antihistone in drug induced antidsDNA - high specificity for SLE Anti-ro, antiLa antiphospholipid
Management of SLE
Non-pharm
- avoid over exposure
- avoid high dose OCP
- remove offending drugs
- smoking cessation
Pharm
- NSAIDs
- antimalarials - hydroxychloroquine
- corticosteroids
- cytotoxics: azathioprine, mycophenalate, cyclosporin
Clinical Features of Tuberous Sclerosis
Salmon papule and nodules over face in butterfly distribution - adenoma sebaceous
Periungal fibroma - smooth, firm nodules adjacent to nails
Shagreen patches - irregular, green-brown patches over lumbosacral region
Ash leaf macules - hypopigmented areas over trunk and buttocks
Cafe au last spots
Eyes - angiofibromata of eye lid, retinal hamartomata
Oral - bifid uvula, high arch palate
Resp - pneumothorax, cysts
Abdo - hepatic and renal hamartoma
Neural - focal deficit depending on location of tubers
Genetics of Tuberous sclerosis
Autosomal dominante - 2 loci identified
Chr 9 and Chr 16 (hamertin and tuberin tumour suppressor genes)
65% spontaneous
Pemphigus vulgaris
Flaccid blisters with clear fluid Fragile Involved buccal mucosa\ Blisters just above basal cell layer IgG autoantibodies against desmogleins
Drugs implicated: penicillamine, benzylpenicillin, ACEi
Treat with barrier nursing, corticosteroids, avoid dehydration
Pemphigoid
Tense blisters
IgG against hemidesmosomes in basement membrane
Mucosal involvement rare
Treat with steroids/steroid sparing agents
Pseudoxanthoma elasticum
folds of loose skin in neck, popliteal fossa, axilla and groin
Plucked chicken appearance
Due to abnormal mineralisation and calcification of elastic fibres
Associated with:
- aortic regurg
- mitral regurgitation
- mitral valve prolapse
- peripheral vascular disease
- restrictive cardiomyopathy
- renovascular disease
- HTN
- angioid streaks
Causes of Angioid Streaks
Irregular red-brown lines radiating from optic disc
Ehlers danlos Pseudoxanthoma elasticum marfans sickle cell disease lead poisoning
Ehlers Danlos Syndrome
11 different forms, some AD some AR
Collage defect
Features:
skin - broad nasal bridge, wide eyes, thin hyper extensible skin, impaired wound healing
MSK -kyphoscoliosis, hyper extensible joints, hallus valgus, pes planes
GI: diverticula, diaphragmatic hernia, megacolon
CVS - MVP, AR, aneurysms, dissections
Causes of Blue sclerae
Pseudoxanthoma Marfans OI Ehlers Danlos Alkaptonuria
Causes of Acanthosis Nigricans
Obesity Diabetes/insulin resistance Cushings Acromegaly Thyroid disease PCOS Familial Malignancy - adenocarcinoma of GI tract
Pretibila myxodema
Firm, non pitting pink/purply brown plaques on anterolateral aspect of lower legs
peau d’orange texture
Diabetic Retinopathy
Background: blot haemorrhages, hard exudate
Preprolifeative: large blot haemorrhages, cotton wool spots, venous dilatations/beading
Proliferative: leashes of new vessels with evidence of photocoag scars
Eye problems in Diabetes
Cataracts Glaucoma Mononeuritis multiplex Infections Diabetic retinopathy (25%)
Pathophysiology of Diabetic Retinopathy
Hyperglycaemia’s structural and physiological effect on retinal capillaries
Increased sorbitol results in increased vessel permeability and weakness
Retinal ischaemia (small vessel disease) triggers VEGF
Production of vasoprolierative factors e.g. VEGF leads to new vessel formation
Indications to refer to Opthalmology
Non-proliferative with macular involvement
Pre-proliferative
Proliferative - urgent
Complications of laser photocoag
Vitreous haemorrhage
Visual field constriction
Headaches
Retinal vein occlusions
Hypertensive retinopathy
1 - Arteriolar narrowing
2 - AV nipping
3 - micro aneurysms, blot haemorrhages, flame haemorrhage, exudates
4 - papilloedema
Retinitis Pigmentosa
Black-brown pigmentation resembling bone spicules
Constricted visual fields
Night blindness
Photopsia - flashes of light
Associated with alports syndrome, bardett-biedel (polydactyly)
