IRAE

Question 1

Testing for adrenal insufficiency? How would you actually do this on the ward?

Answer 1

Early morning cortisol level.

<100 nmol/L is diagnostic of adrenal insufficiency.

>400 rules it out

In between → needs Short SynACTHen + ACTH.

• 250mcg of co-syntropin [ACTH 1-24]: baseline before, 30min, 60min post injection. If cortisol level is >500 either before or after: patient do not have adrenal insufficiency.
• If SynACTHen is positive (i.e. <300), ACTH determines whether adrenal insufficiency is primary (ACTH high) or secondary (ACTH low)

Question 2

What are the biochemical / clinical difference between primary vs. secondary/tertiary adrenal insufficiency?

Answer 2

Primary: both corticosteroid + mineralocorticoid are affected → hyponatraemia, hyperkalaemia, hypotension is prominent. Patient has hyperpigmentation as there is increased ACTH.

Secondary: there is no hyperpigmentation. in ACTH deficiency, there is no salt wasting, volume contraction or hyperkalaemia, as it does not result in Aldosterone deficiency.

Question 3

What are the long-term impact of hypopituitarism in a long case patients therefore important to monitor? (3)

Answer 3

1. Adrenal insufficiency - so falls prevention, steroid replacement, hence all it’s side effects
2. Sex hormones - hypogonadotrophic hypogonadism: low energy, libido, infertility, Osteoporosis
3. GH: decreases BMD, increased risk of dyslipidaemia and cardiovascular disease

Question 4

DDx for IRAE hypophysitis in check-point inhibitor patients?

Answer 4

Causes of hypopituitarism includes (many, hence don’t just get fixated on hypophysitis)

Hypothalamic disorders: SOL, MS, stroke, infection, infiltration

Pituitary disorders: SOL (adenoma and other malignancies), infarction (Sheehan’s), bleeding (pituitary apoplexy), IRAE, infection,

Question 5

Investigation for hypopituitarism?

Answer 5

1. Morning serum cortisol. If low (<100), do ACTH level. If low or inappropriately not high, this establishes the diagnosis. If cortisol is >500, there is no difficiency, so no need to do ACTH.
   - If level is between 100-500, SynACTHen. Normal response (i.e. >500 establishes that there is no ACTH deficiency). Alternative is Metyrapone test.
2. Thyroid: do free T4 level and T3. TSH, is actually not usually low in hypopituitarism.
3. Sex hormones:
   - Men: serum testosterone + LH. If 8am testosterone is low, LH not elevated, patient has 2ndary hypogonadism.
   - Women: FSH, LH (low or inappropriately normal) + low estradiol.
4. GH: do IGF-1 level.

Question 6

Management of hypophysitis IRAE?

Answer 6

1. High-dose steroids - reverses acute inflammatory process
2. Long-term supplements: usually needs
   - Hydrocortisone 20mg mane, 10mg nocte
   - Thyroxine: s_hould not be given until adrenal function has normalised_, including ACTH level. Treatment of hypothyroidism in patient with hypoadrenalism → increases clearance of cortisol → worsens adrenal crisis.
3. Sex hormones
   - Men: testosterone if not interested in fertility. If wants to become fertile, tx with Gonadotropins.
   - Women: estradiol + progestin if not interested in fertility. If not, tx Gonadotropins.