Adrenal insufficiency, Addison's disease

Question 1

Adrenal insufficiency - inadequate production of glucocorticoids, mineralcorticoids (or both) by the adrenal gland

This can occur due to:
1. Primary insufficiency - dysfunction or destruction of adrenal cortex
2. Secondary insufficiency - inadequate ACTH production (by pituitary)
3. Tertiary insufficiency - inadequate CRH production (by hypothalamus)

Question 2

What are the causes of adrenal insufficiency?

Answer 2

• denotes important to know causes

Primary - adrenal gland disease
*1. Autoimmune adrenalitis (Addison’s disease)
*2. Bilateral adrenal haemorrhage or thrombosis (coagulopathy, meningococcal sepsi)
3. Metastasis (lungs, breast, renal, GI, lymphoma)
4. Infectious (PTB, HIV, CMV, fungal)
*5. Congenital adrenal hyperplasia
6. Adrenalectomy
7. Infiltrative (amyloidosis, haemochromatosis)
8. Drugs

Secondary - pituitary disease
*1. Pituitary tumours and craniopharyngioma
*2. Pituitary surgery or irradiation
3. Lymphocytic hypophysitis
4. Infiltrative (as per primary - to pituitary)
5. Infection (as per primary - to pituitary)
*6. Sheehan’s syndrome (peripartum blood loss)
7. Traumatic brain injury to pituitary

Tertiary - hypothalamus disease
*1. Withdrawal of long term steroids
*2. Hypothalamic tumours and metastasis
3. Infiltrative (as per primary - to hypothalamus)
4. Infection (as per primary - to hypothalamus)
5. Cranial irradiation
6. Traumatic brain injury

Question 3

Symptoms of adrenal insufficiency

Answer 3

A. Non-specific features
1. Weakness
2. Fatigue
* 3. Anorexia and wight loss
* 4. Orthostatic hypotension

B. Gastrointestinal disturbance
* 5. Vague abdominal pain
6. Nausea, vomiting
7. Constipation

C. Musculoskeletal and skin
8. Arthralgia and myalgia
* 9. Hyperpigmentation of buccal mucosa and gums
10. Darkened palmar crease, nail beds, scars

D. Neuropsychiatric symptoms
9. Salt craving
10. Psychiatric disturbance, confusion, stupor

Question 4

The histology of adrenal gland and endogenous cortisol secretion

Answer 4

Zona glomerulosa: mineralocorticoids
Zona fasciculata: glucocorticoids (cortisol)
Zone reticularis: glucocorticoids (androgen)
Medulla: cathecholamines

Question 5

What are the functions of mineralocorticoids and glucocorticoids?

Answer 5

Mineralocorticoids
1. Regulates electrolyte balance
2. Regulates blood volume and blood pressure

Glucocorticoids - stress response
1. Increases blood sugar level
2. Increase protein catabolism
3. Mobilises fatty acids from adipose

Question 6

Regulation of adrenal hormonal secretion
- Hypothalamus-Pituitary-Adrenal (HPA) axis
- Renin-angiotensin-aldosterone (RAAS) axis

Answer 6

HPA axis - glucocorticoid
1. CRH -> ACTH -> cortisol production
2. Cortisol exerts negative feedback to reduce stimulation
3. Cortisol usually highest in the morning on waking up (diurnal peak)

RAAS axis - mineralocorticoids
1. Response to triggers: RAAS, hyperkalaemia, ACTH
2. Aldosterone action increases sodium reabsorption and potassium exretion, leading to water retention