Introduction
Results from inadequate secretion of cortisol and/or aldosterone.
It is potentially fatal and notoriously variable in its presentation.
Acute adrenal crisis is more commonly seen in primary adrenal insufficiency (Addison disease) than in disorders of the pituitary gland causing secondary adrenocortical hypofunction.
Adrenal crisis may occur in the following situations:
(1) following stress, eg, trauma, surgery, infection, or prolonged fasting in a patient with latent insufficiency;
(2) following sudden withdrawal of adrenocortical hormone in a patient with chronic insufficiency or in a patient with temporary insufficiency due to suppression by exogenous corticosteroids or megestrol;
(3) following bilateral adrenalectomy or removal of a functioning adrenal tumor that had suppressed the other adrenal;
(4) following sudden destruction of the pituitary gland (pituitary necrosis), or when thyroid hormone is given to a patient with hypoadrenalism;
(5) following injury to both adrenals by trauma, hemorrhage, anticoagulant therapy, thrombosis, infection or, rarely, metastatic carcinoma; and
(6) following administration of etomidate, which is used intravenously for rapid anesthesia induction or intubation.
Etiology
The most common is ACTH deficiency (i.e. secondary adrenocortical failure), usually because of inappropriate withdrawal of chronic glucocorticoid therapy or a pituitary tumour.
In Addison's disease, either glucocorticoid or mineralocorticoid deficiency may come first, but eventually all patients fail to secrete both classes of corticosteroid.
Addison's disease results from progressive destruction of the adrenals, which must involve >90% of the glands before adrenal insufficiency appears.
Causes of adrenocortical insufficiency
Secondary (↓ACTH)
Withdrawal of suppressive glucocorticoid therapy
Hypothalamic or pituitary disease
Primary (↑ACTH)
Common causes
Tuberculosis
HIV/AIDS
Metastatic carcinoma
Autoimmune
Sporadic
Polyglandular syndromes
Rare causes:
Lymphoma
Intra-adrenal hemorrhage (Waterhouse-Friedrichsen syndrome following meningococcal septicemia)
Amyloidosis
Hemochromatosis
Corticosteroid biosynthetic enzyme defects:
Congenital adrenal hyperplasia
Drugs: Aminoglutethimide, metyrapone, ketokonazole, etomidate.
Clinical features
The patient complains of headache, lassitude, nausea and vomiting, abdominal pain, and often diarrhea.
Confusion or coma may be present.
Adrenocortical insufficiency caused by gradual adrenal destruction is characterized by an insidious onset of fatigability, weakness, anorexia, nausea and vomiting, weight loss, cutaneous and mucosal pigmentation, hypotension, and occasionally hypoglycemia.
Depending on the duration and degree of adrenal hypofunction, the manifestations vary from mild chronic fatigue to fulminating shock associated with acute destruction of the glands, as described by Waterhouse and Friderichsen.
The clinical features can be the manifestation of glucocorticoid deficiency and adrenal androgen deficiency with or without mineralocorticoid insufficiency and ACTH access.
Or all glucocorticoid and mineralocorticoid insufficiency with ACTH access without Adrenal androgen insufficiency.
The specific causes according to these features are:
Withdrawal of exogenous glucocorticoid: features of glucocorticoid insufficinecy is presnet, mineralocorticoid insufficiency is abscent, ACTH access abscent and adrenal androgen insufficiency is present.
Hypopituitarism: glucocorticoid and adrenal androgen insufficiency present and rest is absent.
Addision’s disease: features of absence of all the hormones of adrenal cortex.
Congenital adrenal hyperplasia (21hydroxylase deficiency): features of absence of all hormones of adrenal cortex but there is features of excess of adrenal androgen.
Features due to glucocorticoid insufficiency
Weight loss
Malaise
Weakness
Anorexia
Gastrointestinal- diarrohea or constipation
Postural hypotension
Shock
Hypglycemia
Hyponatremia (Dilutional)
Hypercalcemia
Features due to mineralocorticoid insufficiency:
Hypotension
Shock
Hyponatremia (depletional)
Hyperkalemia
Features due to ACTH access
Pigmentation in the:
Sun exposed areas
Pressure areas eg elbows and knees
Palmer creases, knuckles
Mucus membreane
Conjunctiva
Recent scars
Features due to adrenal androgen insufficiency:
Decreased body hair
Loss of libido especially in female.
Investigations
In patients with suspected acute adrenal crisis treatment should not be delayed pending results.
Assessment of glucocorticoid, mineralocorticoid and other non-specific test can be done to come to the diagnosis.
Assessment of glucocorticoid:
A random blood sample should be stored for measurement of cortisol.
A short ACTH stimulation test may be appropriate before administering hydrocortisone. Diagnoses primary or secondary adrenal insufficiency.
If an ACTH assay is unavailable, then a long ACTH stimulation test can be used (1mg depot ACTH i.m. daily for 3 days)
In secondary adrenal insufficiency there is a progressive increase in plasma cortisol with repeated ACTH administration.
In Addison’s disease cortisol remains less than 700 nmol/l (25.4ug/dl) at 8 hours after the last injection.
Assessment of mineralocorticoids
Plasma electrolyte measurements are insufficient to assess mineralocorticoid secretion in patients with suspected Addison's disease.
Hyponatraemia occurs in both aldosterone and cortisol deficiency.
In mineralocorticoid deficinecy plasma aldosterone is reduced or in low normal with high plasma renin activity.
Other tests
Blood glucose may be low, with symptomatic hypoglycaemia.
Adrenal antibodies are present in many cases of autoimmune adrenalitis.
Chest and abdominal X-rays may show evidence of tuberculosis and/or calcified adrenals.
Management
Adrenal crisis is a medical emergency and requires urgent treatment:
Emergency Management of acute hypoadrenalism:
Clinical context:
hypotension, hyponatraemia, hyperkalaemia, hypoglycaemia, dehydration, pigmentation often with precipitating infection, infarction, trauma or operation.
The major deficiencies are of salt, steroid and glucose.
Assuming normal cardiovascular function, the following are required:
One litre of 0.9% saline should be given over 30-60 minutes with 100 mg of intravenous bolus hydrocortisone.
Subsequent requirements are several litres of saline within 24 hours (assessing with central venous pressure line if necessary) plus hydrocortisone, 100 mg i.m., 6-hourly, until the patient is clinically stable.
Glucose should be infused if there is hypoglycaemia.
Oral replacement medication is then started, unless unable to take oral medication, initially hydrocortisone 20 mg, 8-hourly, reducing to 20-30 mg in divided doses over a few days.
Fludrocortisone (9 alpha-fluoro-hydrocortisone: a mineralocorticoid) is unnecessary acutely as the high cortisol doses provide sufficient mineralocorticoid activity - it should be introduced later.
Adequacy of glucocorticoid dose is judged by:
clinical well-being and restoration of normal, but not excessive, weight gain
normal cortisol levels during the day while on replacement hydrocortisone (cortisol levels cannot be used for synthetic steroids).
Fludrocortisone replacement is assessed by:
restoration of serum electrolytes to normal
blood pressure response to posture (it should not fall > 10 mmHg systolic after 2 minutes' standing)
suppression of plasma renin activity to normal.
Patient advice All patients requiring replacement steroids should:
know how to increase steroid replacement dose for intercurrent illness
carry a 'Steroid Card‘
wear a Medic-Alert bracelet (or similar), which gives details of their condition so that emergency replacement therapy can be given if found unconscious
keep an (up-to-date) ampoule of hydrocortisone at home in case oral therapy is impossible, for administration by self, family or GP.
Replacement dose of Glucocorticoid in adults:
Hydrocortisone 20-30 mg daily e.g. 10 mg on waking, 5 mg at 1200 h, 5 mg at 1800 h or
Prednisolone 7.5 mg daily 5 mg on waking, 2.5 mg at 1800 h
