Addison's disease

Definition: Primary adrenal failure

Clinical features

Nonspecific! Early: fatigue, weight loss, vomiting, pigmentation. Pigmentation affects sun exposed areas, palmar creases, buccal mucosae, axillae, new scars. May be associated vitiligo.

Addisonian crisis: Low-grade fever, shock, ↓glucose. May be precipitated by stress (infection, surgery).

Incidence

0.8 per 100,000.

Causes

Autoimmune
Tuberculosis
Metastases (lung Ca esp.)
Lymphoma
Amyloid
Haemorrhage (Waterhouse-Friederichsen syndrome)
Bilateral adrenalectomy (Nelson's syndrome)

Causes of 2° hypoadrenalism:

iatrogenic (sudden withdrawal of glucocorticoids)
pituitary
1. hypophysectomy (for adenoma)
2. large pituitary adenoma
3. Sheehan's syndrome
4. pituitary apoplexy
hypothalamus
1. craniopharyngioma/surgery to remove craniopharyngioma
2. cranial irradiation
3. 3 ventricle tumours
4. metastases
5. granulomatous disease

Pathophysiology

1° hypoadrenalism: glucocorticoid + mineralocorticoid deficiency.

2° hypoadrenalism: glucocorticoid deficiency only.

Pigmentation is due to increased ACTH secretion by pituitary. Precursor molecule is pro-opiomelanocortin (POMC), from which melanocyte stimulating hormone (MSHs) and MSH-like molecules are also produced in equimolar amounts.

Diagnosis

FBC: eosinophilia (Thorn's sign).
U&E: ↓Na⁺ ↑K⁺ ↓glucose.
plasma cortisol, urinary free corticol may be low or normal.
Short Synacthen test: 250 µg tetracosactrin IV. Plasma cortisol at 0, 30, 60 min.
Normal if peak > 550 nmol/l.
Abnormal in both 1° and 2° hypoadrenalism.
Long Synacthen test: 1 mg tetracosactrin IM. Plasma cortisol at 0, 4, 24 h.
Normal if coritsol > 1000 nmol/l at 4 h and 24 h.
1° hypoadrenalism: no response.
2° hypoadrenalism: 24 h > 4 h.

Treatment

Acute: hydrocortisone 100 mg iv qds. 1 l dextrose-saline iv in 1 h. Clinical improvement in 6 h.
Day 2: hydrocortisone 50 mg iv qds.
Day 3: hydrocortisone 40 mg po mane, 20 mg po nocte.
Day 4: hydrocortisone 20 mg po mane, 10 mg po nocte.

Chronic: hydrocortisone 20 mg mane, 10 mg nocte. (If required) fludrocortisone 100 µg od.
Issue MedicAlert bracelet & steroid card.

Surgery: 100 mg hydrocartisone po in pre-medication. Then as for acute crisis.