Addisons Disease + Secondary Adrenal Insufficiency

Question 1

Definition

Answer 1

Destruction of the cortex - results in mineralocorticoid (aldosterone), glucocorticoid (cortisol) and gonadocorticoid (androgen) deficiency

Question 2

Epidemiology

Answer 2

FEMALE

Question 3

Risk factors

Answer 3

Adrenocortical antibodies
Other autoimmune diseases
- Autoimmune polyendocrinopathy syndrome (APS)
Warfarin
TB
HIV

Question 4

Aetiology

Answer 4

Primary causes: In developed countries - autoantibody mediated adrenal destruction (21-hydroxylase present in 60-90% of people) = ADDISONS and has skin hyperpigmentation
In developing countries - TB (+sarcoidosis)

Question 5

Pathology

Answer 5

Destruction of the entire adrenal cortex = reduced glucocorticoid (cortisol), mineralocorticoid (aldosterone) + androgen
In Addison’s the reduced cortisol levels lead, through feedback to increase CRH + ACTH production.
ACTH stimulates POMC (melanocytes) resulting in hyperpigmentation

Question 6

Symptoms

Answer 6

Lethargy
Fatigue
Wt loss
Change in body hair (decrease androgens)
Reduced libido
Abdo pain + vomiting

Question 7

Signs

Answer 7

Hyperpigmentation,
hypoglycaemia,
Vitiligo
Tachycardia
POSTURAL HYPOTENSION (decrease aldosterone)

Question 8

Diagnosis

Answer 8

• FIRST LINE: 8-9am cortisol: (cortisol is normally highest here, if low v. Abnormal)
  <100nmol/L = highly suggestive of Addison’s
  100-500 mmol/L = refer to the patient to ACTH stimulated test
  > 500nmol/L: Addisons = unlikely = normal
• GOLD STANDARD: ACTH stimulation test (short synacthen test): Plasma cortisol measures before + after 30 mins
• Auto 21-d-hydroxylase Ab
• Bloods
• CXR for TB is suspected
• ACTH INCREASED (9am)

Question 9

Treatment

Answer 9

Corticosteroid replacement supportive therapy
-HYDROCORTISONE (cortisol replacement)
-FLUDOCORTISONE (aldosterone replacement)
* if trauma/infection = DOUBLE DOSE OF HYDROCORTISONE (Cortisol needed for stress response)

Question 10

Risk Factors (Secondary Adrenal Insufficiency)

Answer 10

Systemic glucocorticoid administration
High potency or dose of exogenous glucocorticoids

Question 11

Pathophysiology (Secondary Adrenal Insufficiency)

Answer 11

Occurs in patients with pituitary hypothalamic involvement = decreased ACTH secretion which ultimately results in adrenal failure
In hypothalamic pituitary disease mineralocorticoid and androgen secretion remain largely intact due to their relative independence from the pituitary
Low ACTH, Low Adrenal Hormones + NO Hyperpigmentation

Question 12

Aetiology (Secondary Adrenal Insufficiency)

Answer 12

HPA SUPRESSION -
- Iatrogenic (suppression of HPA axis) - steroids
- Hypothalamic pituitary disease = Decrease ACTH
- Adrenal mets (lung, liver, breast)
- Waterhouse-Friderichsen syndrome (WFS) = Adrenal insufficiency due to adrenal haemorrhage = MAJOR CAUSE OF MENINGOCOCCAL MENINGITIS

Question 13

Diagnosis (Secondary Adrenal Insufficiency)

Answer 13

FIRST LINE = 9 am cortisol
GOLD STANDARD = Short synATCHen test = Low ACTH