Key words

A. Clinical clues

• Someone known to have Addison’s disease/hypoadrenalism

• Someone on long-term steroids

• Postural hypotension or hypotension

• Generalised weakness

• Tachycardia

• Vomiting

• Abdominal pain

• Confusion

• Coma

B. Precipitating factors

• Infection, myocardial or cerebral infarction, trauma, parturition, metabolic stress, meningococcal septicaemia

C. Laboratory Findings

• Low serum Na (<130mmol/L)

• High serum K (>5mmol/L)

• Low blood glucose (<50 mg/dL or <2.8mmol/L)

• Decreased plasma bicarbonate (<28mmol/L)

• Elevated blood urea

• Low serum cortisol

• X-ray:

Calcifications or enlargement of the adrenals Pulmonary or miliary TB

D. Management of addisonian crisis 1. Steroid replacement:

• If adrenal crisis is suspected, corticosteroids must be given without delay.

The results of cortisol levels will not be available before starting

corticosteroid therapy. The short ACTH test may be undertaken together with treatment, provided that there is no undue delay in giving the required drugs. Blood is taken for baseline cortisol levels, and other hormone and electrolyte estimates. Dexamethasone 10mg is given IV, together with tetracosactrin (Synacthen). Dexamethasone begins replacement therapy rapidly without interfering with the cortisol assay.

Cortisol levels are taken at 30 and 60 mins. Corticosteroid treatment is continued as hydrocortisone.

NB. Dexamethasone has negligible mineralocorticoid activity.

• The initial bolus dose for hydrocortisone may be 200mg IV if the short ACTH test is omitted followed by 100mg IV q6h for 1 day, 8hourly on day 2 and is tapered during recovery by decreasing one third of the daily dose

every day until a replacement dose is reached within 5 days unless the precipitating cause has not been treated fully.

2. Volume repletion should be started immediately (eg. 1 litre of normal saline over 2h and then dextrose saline).

• Set up CVP line if necessary. Monitor glucose closely and to give IV or oral glucose is usually necessary.

• Further fluid replacement will depend on how much salt and water depletion has occured.

3. Fludrocortisone 0.05-0.3mg daily should be given when the hydrocortisone dose is below 100mg/day and IV fluids are discontinued in primary addisonism.

4. Consider the cause:

• Do ECG, CXR, blood C&S, urine microscopy etc.

• Since bacterial infection frequently precipitates acute adrenal crisis, broad-spectrum antibiotics can be administered empirically while waiting for the results of initial cultures.

# CAUTION

Delay in instituting corticosteroid therapy may result in mortality.

Water intoxication can easily occur in these patients if hypotonic saline is given.

E Treatment of chronic adrenal insufficiency

1. Primary adrenal insufficiency:

a. Glucocorticoid replacement:

• Average replacement steroid dosages for adults with primary hypoadrenalism are shown.

Drug (oral) Replacemant Dose

Hydrocortisone 30 mg daily- 20mg on waking, 10mg at 1800h Cortisone Acetate 37.5mg daily- 25mg on waking, 12.5mg at 1800h Dexamethasone 0.75mg daily-0.5mg on waking, 0.25mg at 1800h Prednisolone7.5mg daily- 5mg on waking, 2.5mg at 1800h

* Dexamethasone is less frequently used due to higher incidence of Cushing's syndrome.

• Cortisol secretion correlates with body surface area and cortisol turnover is increased in obesity.

• Increased doses are also required if drugs known to enhance the metabolism of glucocorticoids are concomitantly used eg barbiturates, phenytoin, rifampicin.

• Lower doses are indicated in significant liver disease (slow metabolism of glucocorticoids), geriatric patients, diabetes mellitus, peptic ulcer and hypertension.

• Reliable indices in assessment of glucocorticoid replacement doses include appropriate weight gain and regression of pigmentation. Urine free cortisol or serum cortisol measurement are not reliable indicators of adequate cortisol replacemet.

b. Mineralocorticoid replacement:

• Mineralocorticoid replacement is neccesary in primary adrenal insufficiency, and dose requirements can be variable.

• Fludrocortisone is given as a single daily dose of 0.05-0.30mg (Usual dose 0.1mg/d). Dose changes are in increments of 0.05mg/day of

fludrocortisone.

• Persistent hypotension, orthostatic hypotension, and hyperkalaemia are indicators that increased doses are needed, whereas hypertension, hypokalaemia and oedema indicate dose reduction.

c. Intercurrent illness or stress:

• Intercurrent illness or stress requires an adjustment of glucocorticoid therapy but not of mineralocorticoid therapy.

• For minor illnesses eg respiratory tract infection, dental extraction, glucocorticoid dosage is doubled until the condition has resolved.

• During major stress the maximum daily glucocorticoid requirement is equivalent to 300mg hydrocortisone.

• Vomiting and diarrhoea require hospitalization because they preclude oral intake of replacement therapy and result in rapid dehydration.

• Elective major surgery requires 100mg hydrocortisone administered IV during the night preceding the surgery, and subsequently 100mg 8 hourly until the patient has stabilized postoperatively. Medication is tapered rapidly (3-5 days) to the previous dosage.

• Major catastrophies or emergencies eg trauma, major emergency surgery, sepsis, MI require treatment as in acute adrenal crisis.

2. Secondary adrenal insufficiency.

• Secondary adrenal insufficiency does not require mineralocorticoid replacement.

F. Footnotes

Short ACTH (Synacthen) test 1. Procedure:

• A blood sample is taken for plasma cortisol at 9am. 250ug of tetracosactrin (synacthen) is given IV and further blood samples are taken at 30, and 60 mins.

• Baseline ACTH level should also be taken.

2. Interpretation:

• In normal subjects:

_ The basal cortisol should exceed 160nmol/l (6ug/dl).

_ The increment rise should be at least 190nmol/l (7ug/dl).

_ A cortisol level of 550nmol/l (20ug/dl) should be achieved during the test.

# A normal response effectively rules out primary adrenal insufficiency.

• In primary adrenocortical failure cortisol levels will remain low throughout the test.

• In patients with severe secondary adrenal insufficiency, plasma cortisol increases little or not at all after the administration synacthen.

• In patients with secondary adrenal insufficiency that is mild or of recent onset, however, the test may be normal.

• When secondary insufficiency is strongly suspected on clinical grounds with a normal response to ACTH, other tests such as the metyrapone test or long ACTH stimulation can be done.

_ HYPERNATRAEMIA