Table 2: Targeted anticancer therapies causing hyponatraemia and their probable underlying causal mechanisms.

Anticancer agent	Underlying causal mechanism	Comments
Immune checkpoint inhibitors	Hypophysitis-induced hypocortisolism and secondary hypothyroidism96,97 Primary hypothyroidism100,101 Adrenalitis-induced primary adrenal insufficiency97	Ipilimumab causes hypophysitis96 Nivolumab and pembrolizumab cause primary hypothyroidism100,101
Cetuximab	Unknown mechanism107	–
Alemtuzumab	SIADH108	Very rare
Trastuzumab, ado-trastuzamab emtansine	CSWS111,112	Reported in presence of brain metastasis112
IFNα, IL-2	SIADH113,114	Limited clinical use in view of safer alternatives
Thalidomide analogues (thalidomide, lenalidomide)	SIADH117,118	Very rare
CAR-T therapy (axicabtagene ciloleucel, tisagenlecleucel)	IL-6-induced ADH secretion (cytokine release syndrome)119	Reported incidence of hyponatraemia, 51%119
TKIs (imatinib, dasatinib, nilotinib, bosutinib, axitinib, sorafenib, brivanib, gefitinib, erlotinib, afatinib)	SIADH107,121,123–126	Worsened by proton pump inhibitors128,129
mTOR inhibitors (temsirolimus, everolimus)	Unknown mechanism138	–
Proteasome inhibitors (bortezomib)	SIADH139	Severe hyponatraemia reported
HDAC inhibitors (vorinostat, romidepsin, belinostat)	Unknown mechanism140,142,144	–
Gonadotropin-releasing hormone agonists (goserelin, leuprorelin, leuprolide, triptorelin)	Pituitary apoplexy (with undiagnosed pituitary macroadenoma) causing secondary adrenal insufficiency, hypothyroidism, SIADH145	Typically occurs on first day after the first dose, warranting vigilance in this period146

ADH = antidiuretic hormone; CAR-T = chimeric antigen receptor T cell; CSWS = cerebral salt-wasting syndrome; HDAC = histone deacetylase; IFNα = interferon α; IL-2 = interleukin-2; IL-6 = interleukin-6; mTOR = mammalian target of rapamycin; SIADH = syndrome of inappropriate secretion of antidiuretic hormone; TKI = tyrosine kinase inhibitor.