Immune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
Thyroid dysfunction affects 10-20% of patients on PD-1/PD-L1 antibodies, usually a transient thyroiditis followed by permanent hypothyroidism managed with levothyroxine without stopping immunotherapy; hypophysitis is characteristic of ipilimumab (5-10%) and causes headache, fatigue and low cortisol requiring permanent hydrocortisone; fulminant type 1 diabetes and primary adrenal insufficiency are rare but acute. Unlike most immune-related adverse events, endocrinopathies are generally irreversible because the gland is destroyed, but they are also compatible with continued treatment, and some data link them to better response. Kinase inhibitors (lenvatinib, sunitinib) cause hypothyroidism by a different mechanism.
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