Table 2.

Summary of the adverse endocrine effects of immune checkpoint inhibitors

GlandIncidence15,16Most commonly associated checkpoint inhibitors 3,16Typical time from treatment onset16Symptoms16,45Screening advised?Suggested Investigations3,17Treatment3,17Prognosis16
ThyroidHypothyroid: overall 8%, combination up to 13%
Hyperthyroid: overall 2.9%, combination 8%
Anti PD-1 mAb or combination6 weeks
(range 4–10 weeks)
Hypothyroid: fatigue, dry skin, constipation, depression, cold sensitivity, weight gain
Hyperthyroid: fatigue, palpitations, diarrhoea, anxiety, insomnia, weight loss
TSH with every cycle or monthly, and 4–6 weeks after final cycleTSH, T4, T3
Consider pituitary screen if abnormal
If thyrotoxicosis: anti-TPO Ab, anti-TSHR Ab, cortisol, glucose
If clinical uncertainty: thyroid uptake scan
Hypothyroid: Continue immunotherapy
Hyperthyroid: continue immunotherapy if asymptomatic, hold if symptomatic and restart when symptoms resolve
See Fig 2
Typical disease course 3–6 weeks hyperthyroid, then prolonged hypothyroid
Two-thirds required long-term thyroid replacement
Hyperthyroidism rarely persists
PituitaryOverall 1.3%, combination 6.4%Anti-CTLA-4 mAb or combination12 weeks
(range 3–72 weeks)
General: fatigue, nausea
Hormone deficiency: hypothyroid (see thyroid), low cortisol (see adrenal) and sex hormone deficiency (erectile dysfunction, menstrual disturbance, loss of libido)
Mass effect: headache, visual loss
Low threshold for screening
Cortisol (ideally 9am, random if unwell), ACTH, TSH, T4, LH/FSH, oestradiol (if premenopausal), testosterone (men), IGF-1, prolactin
MRI pituitary
Hold immunotherapy until symptoms controlled, then most can restart
Continue if asymptomatic
See Fig 3
Secondary adrenal insufficiency (ACTH deficiency) mainly irreversible
Thyroid and sex hormones tend to recover within 3 months
PancreasOverall 0.5%, 1% with anti-PD-1/anti-PD-L-1Anti-PD-1 or Anti-PD-L-1 mAb7 weeks (range 1–52 weeks)Thirst, polyuria, fatigue, weight loss
Two-thirds present with DKA
Regular blood glucose monitoringGlucose, ketones, Hba 1c, C-peptide, anti-GAD Ab, ICA Ab
No imaging advised
Hold while blood glucose uncontrolled, restart once insulin initiated or stable
Most need insulin therapy. If mild, trial oral antihyperglycaemic agents
AdrenalMonotherapy 1%
Combination 5–7%
Anti-PD-1 or Anti-CTLA-4 mAb or combination10 weeks
(range 1–36 weeks)
Fatigue, dizziness, weakness, nausea, abdominal painNil
Low threshold for 9am cortisol
Cortisol, ACTH, TFT
CT adrenals
High-dose steroids initially, wean to hydrocortisone 20–30 mg/day
Fludrocortisone if postural hypotension persists
  • ACTH = adrenocorticotrophic hormone; CTLA-4 = cytotoxic T-lymphocyte antigen 4; FSH = follicular stimulating hormone; GAD = glutamic acid decarboxylase; ICA = islet cell antigen; IGF-1 = insulin-like growth factor 1; LH = luteinising hormone; mAb = monoclonal antibody; PD-1 = programmed cell death protein 1; PD-L-1 = programmed cell death protein ligand 1; T4 = thyroxine; T3 = triiodothyronine; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone; TSHR = thyroid-stimulating hormone receptor.