Addison’s DiseaseAddison’s Disease

Ali Chakera

Focus for DiscussionFocus 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 caseStart 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, 26FVE, 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 DiseaseAddison’s Disease

Primary vs secondary adrenal insufficiency– Concentrate on primary

Diagnosis– Clinical suspicion– SST + ACTH– Then look for underlying cause

Lifelong hydrocortisone +/- fludrocortisone treatment

Symptoms Signs Laboratory results

Fatigue Malaise Loss of appetite Nausea & vomiting Abdominal pain Weight loss Postural dizziness Myalgia Joint pain Salt craving Loss of libido

(women)

Hyperpigmentation of skin & mucous membrane

Low blood pressure Postural hypotension

Hyponatraemia Hyperkalaemia Hypoglycaemia Raised urea Metabolic acidosis Hypercalcaemia Raised thyroid

stimulating hormone Normocytic anaemia

Clinical SuspicionClinical Suspicion

Testing for Addison’s diseaseTesting for Addison’s disease

SST– 250mcg synacthen test– 1mcg synacthen test

ITT– More laborious and potentially dangerous– Gold standard

Causes of Addison’s diseaseCauses 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

Infiltration Malignant – mets, lympoma

Non-malignant - sarcoid, haemochromotosis, amyloid

Drugs ketaconazole, etomidate, aminoglutethimide, mitotane

Genetic Adrenoleucodystrophy

Congenital Adrenal hyperplasia

Familial ACTH resistance syndromes

Adrenal hypoplasia congenita

Kearns-Sayre syndrome (Mitochondrial cytopathy)

Optimum treatment?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?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?Clinical monitoring?

SignsSymptoms

– Patient well-being

Blood Pressure - posturalU&E’sPlasma Renin (best measure of vol. status)

On the HorizonOn the Horizon

Delayed release hydrocortisone

Slow release hydrocortisone

Hydrocortisone pump

Any Questions?Any Questions?

Treatment in SurgeryTreatment 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 surgeryTreatment in surgery

Any comments?Any comments?

Is there a good screening test?Is there a good screening test?

Is a baseline cortisol of value?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 for the past Our results for the past 33 years years

648 SST’s over the past year60 results consistent with adrenal

insufficiency = 53 patients

All bar one patient with a baseline cortisol >350 had a normal SST

    Normal Adrenals

    Yes No  

Test > 400

Positive 202 1 203 Sensitivity 34.2 PPV 99.5

Negative 388 57 445 Specificity 98.3 NNV 12.8

  590 58  

    Normal Adrenals

    Yes No  

Test > 350

Positive 273 1 274 Sensitivity 46.2 PPV 99.6

Negative 318 56 374 Specificity 98.2 NNV 15.0

  591 57  

3 years of synacthen results.xls

ConclusionsConclusions

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?Any Questions?