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Addison’s Disease
 

Addison’s Disease

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    Addison’s Disease Addison’s Disease Presentation Transcript

    • Addison’s Disease Ali Chakera
    • Focus for Discussion
      • A general update on Addison’s disease
        • Diagnostic pathway
        • Treatment regimes
      • Monitoring Addison’s disease?
      • Surgical guidelines.
      • Is there a good screening test?
        • For us or for primary care.
    • Start with a case
      • 26 year old, VE
        • Nursery school teacher
          • Gets lots of bugs
        • D&V. Iv fluids, Δ gastroenteritis. Home
        • Begins to feel a bit dizzy and weak.
        • Five more admissions with the same.
    • VE, 26F
        • Eventually someone did a SST
          • 0 ΄ <20
          • 30 ΄ <20
          • 60 ΄ <20
      • However, still having problems
        • Turned up to A&E, vomiting
        • Waiting for 2 hours before being told to call Devon Docs!
    • Addison’s Disease
      • Primary vs secondary adrenal insufficiency
        • Concentrate on primary
      • Diagnosis
        • Clinical suspicion
        • SST + ACTH
        • Then look for underlying cause
      • Lifelong hydrocortisone +/- fludrocortisone treatment
    • Clinical Suspicion
      • Hyponatraemia
      • Hyperkalaemia
      • Hypoglycaemia
      • Raised urea
      • Metabolic acidosis
      • Hypercalcaemia
      • Raised thyroid stimulating hormone
      • Normocytic anaemia
      • Hyperpigmentation of skin & mucous membrane
      • Low blood pressure
      • Postural hypotension
      • Fatigue
      • Malaise
      • Loss of appetite
      • Nausea & vomiting
      • Abdominal pain
      • Weight loss
      • Postural dizziness
      • Myalgia
      • Joint pain
      • Salt craving
      • Loss of libido (women)
      Laboratory results Signs Symptoms
    • Testing for Addison’s disease
      • SST
        • 250mcg synacthen test
        • 1mcg synacthen test
      • ITT
        • More laborious and potentially dangerous
        • Gold standard
    • Causes of Addison’s disease
      • Autoimmune adrenalitis
        • Isolated adrenal insufficiency
        • Autoimmune polyglandular syndromes (APS) – type 1 and type 2
      • Infective
        • Tuberculosis
        • Fungal (histoplasmosis, Cryptococcosis, coccidioidomycosis)
        • HIV
      • Bilateral adrenalectomy
      • Haemorrhage / infarction
      • Malignant infiltration (metastasis, lymphoma)
      • Non-malignant infiltration (sarcoidosis, haemochromatosis, amyloidosis)
      • Drugs (ketaconazole, etomidate, aminoglutethimide, mitotane)
      • Genetic
        • Adrenoleucodystrophy
        • Congenital Adrenal hyperplasia
        • Familial ACTH resistance syndromes
        • Adrenal hypoplasia congenita
        • Kearns-Sayre syndrome (Mitochondrial cytopathy)
    • Causes of Addison’s disease
        • Adrenoleucodystrophy
        • Congenital Adrenal hyperplasia
        • Familial ACTH resistance syndromes
        • Adrenal hypoplasia congenita
        • Kearns-Sayre syndrome (Mitochondrial cytopathy)
      • Genetic
        • ketaconazole, etomidate, aminoglutethimide, mitotane
      Drugs
        • Malignant – mets, lympoma
        • Non-malignant - sarcoid, haemochromotosis, amyloid
      Infiltration Haemorrhage / infarction Bilateral adrenalectomy
        • Tuberculosis
        • Fungal (histoplasmosis, Cryptococcosis, coccidioidomycosis)
        • HIV
      Infective
        • Isolated adrenal insufficiency
        • Autoimmune polyglandular syndromes (APS) – type 1 and type 2
      • Autoimmune adrenalitis
    •  
    • Optimum treatment?
      • Some evidence that tds hydrocortisone is better than bd
        • No RCT’s
        • Non-randomised/retrospective data
        • ? Intuitive
      • Latest literature suggesting starting dose of 15mg/24hrs.
      • Most suggest 20-25mg/24hrs
    • Monitoring?
      • No optimum test.
      • ACTH
        • Respond quickly to cortisol, so no time period that you could count as normal
      • Day Curves
        • Hydrocortisone doesn’t have a smooth release so what are we really checking
      • 24 hour urine cortisol
        • To check if they are taking it
    • Clinical monitoring?
      • Signs
      • Symptoms
        • Patient well-being
      • Blood Pressure - postural
      • U&E’s
      • Plasma Renin (best measure of vol. status)
    • On the Horizon
      • Delayed release hydrocortisone
      • Slow release hydrocortisone
      • Hydrocortisone pump
    • Any Questions?
    • Treatment in Surgery
      • No consensus
      • No clinical evidence
      • General principles:
        • Larger doses traditionally given generally not needed.
        • Amounts should correlate to physiological increases in cortisol according to degree of stress.
        • Over-treatment may have wound healing consequences
    • Treatment in surgery
    • Any comments?
    • Is there a good screening test?
    • Is a baseline cortisol of value?
      • Is a morning cortisol a good screening test?
      • Evidence:
            • Hagg E, Asplund K, Lithner F. Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency. Clin Endocrinol (Oxf) 1987; 26: 221–26.
            • Lee MT, Won JG, Lee TI, Yang HJ, Lin HD, Tang KT. The relationship between morning serum cortisol and the short ACTH test in the evaluation of adrenal insufficiency. Zhonghua Yi Xue Za Zhi (Taipei). 2002 Dec;65(12):580-7.
        • Both suggest that a cutoff of 300nmol/l rules out Addison’s
    • Our results over the past year
      • 220 SST’s over the past year
      • 18 results consistent with adrenal insufficiency
      • Everyone with a baseline cortisol >300 had a normal SST
    • Synacthen Tests for Ali Chakera.xls   18 202   21.9 NNV 88.9 Specificity 73 16 57 Negative 98.6 PPV 71.8 Sensitivity 147 2 145 Positive Test > 250   No Yes     Normal Adrenals       18 202   16.7 NNV 100.0 Specificity 108 18 90 Negative 100.0 PPV 55.4 Sensitivity 112 0 112 Positive Test > 300   No Yes     Normal Adrenals    
    • Our results for the past 3 years
      • 648 SST’s over the past year
      • 60 results consistent with adrenal insufficiency = 53 patients
      • All bar one patient with a baseline cortisol >350 had a normal SST
    • 3 years of synacthen results.xls   57 591   15.0 NNV 98.2 Specificity 374 56 318 Negative 99.6 PPV 46.2 Sensitivity 274 1 273 Positive Test > 350   No Yes     Normal Adrenals       58 590   12.8 NNV 98.3 Specificity 445 57 388 Negative 99.5 PPV 34.2 Sensitivity 203 1 202 Positive Test > 400   No Yes     Normal Adrenals    
    • Conclusions
      • Addison’s disease needs a high index of suspicion.
      • There is no clear biochemical marker of adequate treatment.
      • There is no clear cut-off in terms of baseline cortisol – but perhaps GP’s could consider SST’s in primary care
    • Any Questions?
    •