Table 1.

Summary of checkpoint inhibitor-induced endocrinopathy.

Endocrinopathy	Incidence + timing of onset	Precipitating therapies	Symptoms	Investigations	Indications for treatment	Treatment
Pituitary	11-24% (8, 9, 81) (with anti-CTLA4)	Predominantly anti-CTLA4 (8, 9, 81)	Headache, fatigue, weakness nausea, weight loss, temperature intolerance, arthralgia	Pituitary hormone profile, sodium level, visual fields	Severe headache, hyponatraemia, hypopituitarism or pituitary enlargement seen on MRI (18, 19, 20, 21, 22)	High dose glucocorticoids if pituitary enlargement (24, 25)
	<1% (8, 9, 44, 49) (with anti-PD-1)	Rarely seen with anti-PD-1 – mostly cause ACTH deficiency (8, 9, 44, 49)		Pituitary MRI		Hormone replacement (24, 25) (hydrocortisone or prednisolone ± levothyroxine/oestrogen/testosterone)
	Usually 6–14 weeks after treatment
Thyroid dysfunction	5.2–8% overall (8, 9, 49, 50)	More commonly seen in anti-PD-1 or anti-PD-L1 therapies (49, 50)	May present with hyperthyroidism symptoms prior to becoming hypothyroid (lethargy, constipation, cold intolerance, etc.)	Thyroid hormone profile	Hypothyroidism	Thyroid hormone replacement
	5.2–5.9% (8, 9) (with anti-CTLA4)				Thyrotoxicosis	Consider beta blockers for palpitations (23)
	5–8% (49) (with anti-PD-1)	Seen less commonly in anti-CTLA-4 therapy (8, 9)				Anti-thyroid drugs only in Graves’ disease (51, 52, 53, 54, 55)
	14–20% (combined therapy) (49, 50)					High dose steroids if severe thyroiditis seen (49)
	Usually 1–3 months after treatment
Hyperglycaemia and new-onset diabetes	Approximately 1% (59)	Anti-PD-1/PD-L1 (58, 61, 62)	Polydipsia, polyuria, weight loss	Hyperglycaemia on fasting and random glucose samples, HbA1c	Persistent hyperglycaemia, diabetic ketoacidosis	Exogenous insulin replacement (usually lifelong) (62)
	Presents usually within 3 months of therapy	Not reported with anti-CTLA therapies (58)
Primary Adrenal insufficiency	Very rare, only a few case reports published (16, 23, 36, 40)	Anti-CTLA-4 therapy or Anti PD-1 (16, 40)	Typical Addisonian symptoms	Cortisol, ACTH, plasma renin	Treatment indicated in all cases	Hydrocortisone + Fludrocortisone (23, 27)