Table 3. Ipilimumab-induced side effects of the endrocrine system.

side effect	onset (weeksafter start ofipilimumab)	treatmenta ofside effect	outcome ofside effect	age(years)	gender	primarytumor	stageb,c	previoussystemictherapies	metastasesbeforeipilimumab	remissionafteripilimumab	clinicalresponse
Hypophysitis*	7	steroids	permanentchanges	74	M	skin	IV	limb perfusiond	adrenal glands	none	SD
hypophysitis with symptoms ofbrain edema*	14	steroids	permanentchanges	M	67	skin	IV	IFN-α, cisplatin+vindesine+DTIC,DTIC+sorafenib,paclitaxel+carboplatin	skin, liver,lung, brain,LN	none	PD
amenorrhea, hyperprolactinemia, hypophysitis, with normal TSH/cortisol, pancreatitis	8	none	resolved	41	F	skin	adjuvant	n/a	n/a	n/a	SD
elevated TSH	24	none	ongoing	38	M	skin	adjuvant	n/a	n/a	n/a	SD
decreased TSH	12	steroids	resolved	68	F	skin	adjuvant	n/a	n/a	n/a	SD
generall hypophysal insufficiency (hypophysitis, hypothyreosis, hypogonadism)	15	steroids	ongoing	59	F	skin	IV	IFN-α, allovectin, DTIC, nilotinib	soft tissue, LN, lung	skin	PR
hypophysitis	10	steroids	resolved	57	M	skin	IV	temozolomide	brain	none	PD
hypophysitis	8	steroids, levothyroxine	resolved	56	F	skin	IV	DTIC	skin, peritoneal,	none	PD
hypophysitis	9	steroids	ongoing	60	F	mucosal	IV	IFN-α, DTIC, paclitaxel,docetaxel	parotis, LN, skin, lung	none	PD
hypophysitis	10	steroids, levothyroxin	permanent changes	31	M	skin	IV	DTIC, MEK-inhibitor	LN, skin	LN, skin	PR
hypophysitis	12	steroids, levothyroxine, testosterone	ongoing	72	M	skin	IV	DTIC, limb perfusiond	LN, spleen, lung, liver, muscle, skin	none	PD
hypophysitis+hepatitis	12	steroids	permanent changes	M	54	skin	adjuvant	n/a	n/a	n/a	SD
hypophysitis, pronounced fatigue, flu like symptoms	23	steroids	resolved	M	64	skin	adjuvant	n/a	n/a	n/a	SD
hypophysitis (hyperprolaktinaemia, low IGF-1, hyponatraemia), hypokaliaemia, hypophosphataemia	11	steroids	resolved	F	49	skin	IV	bevacizumab, temozolomide, DTIC, eldesine, platinol, paclitaxel, sorafenib	lung, liver, soft tissue, pancreas, LN, bone, skin, GIT	liver, LN	MR

^*case is detailed in the result section.

^alisted treatments are systemic treatments unless otherwise specified.

^btumor-free high-risk stage III melanoma (AJCC 2009); adjuvant administration of ipilimumab.

^cstage IV metastatic disease (AJCC 2009).

^dlimb perfusion with melphalan.

M indicates male; F, female; LN, lymph nodes; IFN-α, interferon-α; DTIC, dacarbazine; GIT, gastrointestinal tract; IGF-1, insulin-like growth factor-1; TSH, thyroid-stimulating hormone; PR, partial response; SD, stable disease; PD, progressive disease; MR, mixed response.