Addison’s Disease

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?

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Addison’s Disease

by PeninsulaEndocrine on May 07, 2009

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Addison’s Disease — Presentation Transcript