primary adrenal insufficiency

Question 1

definition

Answer 1

addison’s disease

disorder that affects the adrenal glands, causing decreased production of adrenocortical hormones (cortisol, aldosterone, and dehydroepiandrosterone). This may be caused by a destructive process directly affecting the adrenal glands or by a condition that interferes with hormone synthesis. Approximately 90% of the adrenal cortex needs to be destroyed to produce adrenal insufficiency. Addison’s disease may be either acute (adrenal crisis) or insidious. If untreated, it is a potentially life-threatening condition.

Question 2

aetiology

Answer 2

In developed countries, most cases of the disease (80% to 90%) are caused by dysfunction of the autoimmune system, with antibodies directed against the adrenal cortex and/or 21-hydroxylase present in 60% to 90% of people with autoimmune dysfunction.[5] These antibodies are specific for autoimmune Addison’s disease; identification in a healthy person indicates an increased risk for development of adrenal failure. Disease can present as an isolated condition or can be associated with other autoimmune disorders (autoimmune polyglandular syndromes).[6]

Tuberculosis is the most prevalent cause in many countries in which it is endemic.

Question 3

types of adrenal insufficiency in general

Answer 3

Types of adrenal insufficiency
Primary: destruction or dysfunction of the adrenal gland
Secondary: inadequate pituitary adrenocorticotrophic hormone (ACTH) release and subsequent cortisol production
Tertiary: inadequate hypothalamic corticotropin-releasing hormone and subsequent ACTH release.

Question 4

symptoms and signs

Answer 4

fatigue
anorexia
weight loss
hypotension
vomiting 
hyperpigmentation
(arthralgia and myalgia)
(salt craving)

Question 5

risk factors

Answer 5

strong:
- female
- adrenocortical antibodies
- adrenal haemorrhage (patients on antiplatelets, or with antiphospholipid syndrome etc.)

weak:

• autoimune diseases
• TB
• non-TB bacterial infection
• fungal infection
• HIV
• drugs that inhibit cortisol production
• metastatic malignancy
• coeliac disease
• sarcoidosis (prone to developing autoimmune diseases)

Question 6

investigations

Answer 6

IN EMERGENCY:
- just take random serum cortisol if diagnosis not known and give treatment. do not wait for blood test results.

1st investigations:

• serum electrolytes => low sodium; elevated potassium; rarely, elevated calcium
• blood urea
• FBC => eosinophilia, anemia
• morning serum cortisol

next:

• syncACTH test => serum cortisol <497 nanomols/L (<18 micrograms/dL)
• serum ACTH (to differentiate primary (adrenal) from secondary (pituitary) and tertiary (hypothalamic) adrenal insufficiency)
• plasma renin => elevated to try to compensate for low aldosterone (but doesn’t change much)
• plasma aldosterone => low
• plasma DHEA + DHEAS
• adrenal antibodies
• adrenal CT and MRI
• insulin tolerance (hypoglycaemia) test (gold standard to test integrity of HPA axis, but contraindicated in older patients, cardiovascular diseases and epilepsy.) (in normal patient, should see high ACTH, high cortisol)
• overnight single-dose metyrapone test (to see if inhibiting cortisol production will increase ACTH levels)

Question 7

treatment

Answer 7

adrenal crisis:

• hydrocortisone sodium succinate
• saline for hypotension and dehydration
• glucose for hypoglycaemia

ongoing treatment:

• cortisone/hydrocortisone/prednisolone + fludrocortisone
• ++ temporary switch to stress dosing when needed
• ++ (for women with decreased libido) androgen replacement -> dehydroepiandosterone

Question 8

complications

Answer 8

(mostly due to steroid use)

• secondary cushing’s syndrome (too much glucocorticoid given)
• osteoporosis and hypertension (long term steroid use)

Question 9

prognosis

Answer 9

treatment adherence usually quite good because of fear of uncomfortable symptoms. Although the replacement doses try to replicate physiological glucocorticoid and mineralocorticoid secretion, some patients complain of persistent fatigue and decreased well-being.