Hyponatremia associated with Ipilimumab-induced hypophysitis

Barnard, Zachary R.; Walcott, Brian P.; Kahle, Kristopher T.; Nahed, Brian V.; Coumans, Jean Valery

doi:10.1007/s12032-010-9794-7

Cited by 64 publications

(37 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The incidence of hypophysitis due to ipilimumab has been reported to range from 0 to 17 % in clinical trials for melanoma and for renal cell carcinoma. Anatomic evaluation of the pituitary gland with MRI in conjunction with serial biochemical evaluations may be helpful in monitoring therapy-induced hypophysitis and preventing life-threatening side effects [19,20]. It may also be helpful in the differential diagnosis of melanoma to consider both brain metastasis and hypophysitis as autoimmune reaction.…”

Section: Discussionmentioning

confidence: 99%

Ipilimumab, not just another anti-cancer therapy: hypophysitis as side effect illustrated by four case-reports

et al. 2014

View full text Add to dashboard Cite

Ipilimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4 (CTLA-4), an inhibitory molecule typically expressed on T cells. Blockade of CTLA-4 induces an overall activation of T cells, including an immune-mediated anti-tumour response. Unfortunately, this broad T cell stimulation also causes immune-related adverse events (irAEs), such as dermatitis, colitis, hepatitis and hypophysitis. Ipilimumab is currently available in Belgium as a second line of treatment for patients with advanced melanoma, and is used at a dose of 3 mg/kg of body weight, although higher doses were previously used (up to 10 mg/kg). We performed a retrospective analysis to identify melanoma patients treated with ipilimumab at the Ghent University Hospital between 2010 and 2013. Data on symptoms, stage and timing of ipilimumab, response and adverse events were collected with a special attention to endocrine disturbances, going from a limited involvement of one endocrine axis to development of a hypophysitis. We identified a total of 39 patients with stage III (No. = 7) or stage IV (No. = 32) melanoma, who received a dose of 3 (No. = 31) or 10 (No. = 8) mg/kg. Six patients developed a severe form of irAEs, including one case of colitis (2 %), one case of sarcoidosis (2 %) and 4 cases (10 %) of hypophysitis. Hypophysitis developed between the second and fourth cycle of ipilimumab administration and was independent of the dose used. We describe four cases of involvement of the pituitary gland during treatment with ipilimumab. When managed with vigilant monitoring and high-dose corticosteroids, the acute symptoms resolve, but lifelong hormone substitution therapy can be necessary. Involvement of the pituitary axes is a severe side effect of treatment with ipilimumab with an urgent need for the correct medical intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Ipilimumab, not just another anti-cancer therapy: hypophysitis as side effect illustrated by four case-reports

et al. 2014

View full text Add to dashboard Cite

show abstract

“…At magnetic resonance imaging (MRI), a pituitary swelling appears in most cases (up to 60-100% of baseline size), sometimes with thickening of the stalk (15). The height of the gland in the sagittal view increases from 3.4-6 to 7.7-11.8 mm (15,54,57). Contrast enhancement of the pituitary may or may not be homogeneous (58).…”

Section: Clinical Features Of Anti-ctla4-hmentioning

confidence: 99%

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

Torino

Barnabei

Paragliola

et al. 2013

European Journal of Endocrinology

109

103

View full text Add to dashboard Cite

mAbs are established targeted therapies for several diseases, including hematological and solid malignancies. These agents have shown a favorable toxicity profile, but, despite their high selectivity, new typical side-effects have emerged. In cancer patients, pituitary dysfunction may be mainly due to brain metastases or primary tumors and to related surgery and radiotherapy. Anticancer agents may induce hypopituitarism in patients cured for childhood cancers. These agents infrequently affect pituitary function in adult cancer patients. Notably, hypophysitis, a previously very rare disease, has emerged as a distinctive side-effect of ipilimumab and tremelimumab, two mAbs inhibiting the cytotoxic T-lymphocyte antigen-4 receptor, being occasionally seen with nivolumab, another immune checkpoint inhibitor. Enhanced antitumor immunity is the suggested mechanism of action of these drugs and autoimmunity the presumptive mechanism of their toxicity. Recently, ipilimumab has been licensed for the treatment of patients affected by metastatic melanoma. With the expanding use of these drugs, hypophysitis will be progressively encountered by oncologists and endocrinologists in clinical practice. The optimal management of this potentially life-threatening adverse event needs a rapid and timely diagnostic and therapeutic intervention. Hypopituitarism caused by these agents is rarely reversible, requiring prolonged or lifelong substitutive hormonal treatment. Further studies are needed to clarify several clinical and pathogenic aspects of this new form of secondary pituitary dysfunction.European Journal of Endocrinology 169 R153-R164

show abstract

“…The majority of male patients (83-87%) had hypogonadotrophic hypogonadism; in addition, in the recent report by Min et al (8), three out of five patients had low levels of serum IGF1. There is also a single case report describing diabetes insipidus (11) and one case of hyponatraemia secondary to SIADH (13). Serum prolactin may be elevated (two out of eight cases from the NCI data) or low (two out of eight patients from the case series reported by Blansfield et al (12)).…”

Section: Ipilimumab and Hypophysitismentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review

Juszczak

Gupta

Karavitaki

et al. 2012

European Journal of Endocrinology

112

View full text Add to dashboard Cite

Ipilimumab (Yervoy; Medarex and Bristol-Myers Squibb) is a human MAB against cytotoxic T-lymphocyte antigen 4, which enhances co-stimulation of cytotoxic T-lymphocytes, resulting in their proliferation and an anti-tumour response. It is licensed for the treatment of unresectable or metastatic malignant melanoma, while multiple clinical trials using this medication in the treatment of other malignancies are ongoing. As a clinical response to ipilimumab results from immunostimulation, predictably it generates autoimmunity as well, causing immune-related adverse events in the majority of patients. Of those, endocrinopathies are frequently seen, and in particular, autoimmune lymphocytic hypophysitis with anterior panhypopituitarism has been reported a number of times in North America. We present a case of a male referred to our department with manifestations of anterior panhypopituitarism after his third dose of ipilimumab for metastatic malignant melanoma, and we discuss the management of his case in the light of previous reports. We also review the published literature on the presenting symptoms, time to presentation, investigations, imaging, treatment and follow-up of ipilimumab-induced autoimmune lymphocytic hypophysitis.

show abstract

Hyponatremia associated with Ipilimumab-induced hypophysitis

Cited by 64 publications

References 19 publications

Ipilimumab, not just another anti-cancer therapy: hypophysitis as side effect illustrated by four case-reports

Ipilimumab, not just another anti-cancer therapy: hypophysitis as side effect illustrated by four case-reports

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

MECHANISMS IN ENDOCRINOLOGY: Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review

Contact Info

Product

Resources

About