Ipilimumab-induced autoimmune hypophysitis: a differential for sellar mass lesions

Abstract

SummaryAutoimmune hypophysitis (AH) has been previously described in a typical demographic population, primarily women in the reproductive age group and perinatal period. The era of immune modulation using anti-cytotoxic T-lymphocyte-associated antigen 4 biological therapy (ipilimumab) against advanced cancers like metastatic melanomas has now resulted in a new form of hypophysitis being increasingly recognised under a spectrum of immune-related adverse events. Drug-related AH often presents with subtle symptoms and a pituitary mass, with the potential for fatality necessitating wide awareness and a high index of clinical suspicion given that it is usually treatable. We describe below two cases of AH within the last three months at our centre, which were treated with different regimens and produced good endocrine outcomes.Learning points AH is a new and defined clinical entity occurring as a side effect of ipilimumab, which enhances immune-mediated destruction of metastatic melanoma.It can present insidiously and have life-threatening complications related to hypocortisolism, hence a high index of clinical suspicion must be exerted by treating physicians, and seems to result in resolution of pituitary masses and variable improvements of pituitary function.Clinical improvement, radiological resolution of pituitary masses and variable normalisation of pituitary function are possible with early treatment with high-dose oral or i.v. steroids and hormone replacement therapy, although duration and dosing protocols are unclear at this stage.Ipilimumab should continue to be prescribed as treatment for metastatic melanoma; however, close clinical observation of patient's progress must be maintained while they are on this drug.Predictive factors for onset of AH remain unclear and it is imperative that AH is distinguished from pituitary metastases.Further studies are required to determine the safety of continuing therapy with ipilimumab in patients who have developed AH while on treatment.

Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects

“…A secondary form of autoimmune drug-related hypophysitis has been recently described and related to the treatment with cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) blocking antibodies [115][116][117][118][119][120][121][122][123]. A recent review by Faje summarized the clinical presentation, treatment and biological insight of hypophysitis secondary to immunotherapy [124].…”

“…Among these, immune-targeted cancer therapyrelated hypophysitis has been recently recognized as an endocrine IRAE [124,125]. In fact, recent reports observed that patients developed LYH and other autoimmune diseases during the treatment with the CTLA-4-blocking agent ipulimumab, suggesting a possible correlation between CTLA4 and LYH [115][116][117][118][119][120][121][122][123][124]. It has been suggested that these blocking antibodies may act by depleting T-regulatory cells [120].…”

“…In some cases an electrolytic alteration with hyponatremia has also been described [121]. Usually, following cessation of therapy, a normalization of pituitary morphology at follow-up MRI and return to clinical baseline conditions can be observed spontaneously or after early treatment with high-dose of corticosteroids [122]. Predictive factors for onset of hypophysitis in patients treated with this immunotherapy remain at present unknown.…”

“…Predictive factors for onset of hypophysitis in patients treated with this immunotherapy remain at present unknown. It often presents insidiously with subtle symptoms and can have life-threatening complications, especially related to possible acute hypocortisolism [121][122][123][124]. Thus, it is imperative that this form is distinguished from pituitary metastases of melanoma or other malignancies and that a close clinical observation of patient's progress must be made by physicians.…”

A case of multiple immune toxicities from Ipilimumab and pembrolizumab treatment

“…6 The majority of clinicians have used intravenous steroids like dexamethasone but some centers have reported successful treatment with oral prednisone. 7 Re-treatment with the same CTLA-4 mAb seems to be safe whenever indicated. 1 Through this letter we report the case of a previously fit and healthy 55-year old man who was referred by his GP with an asymptomatic skin lesion on the lower back which had been growing in size for about six months.…”