Endocrine Abstracts

Background: There are increasing number of reports on immune checkpoint inhibitors induced adverse events including hypophysitis. Hypophysitis tends to occur more with CytotoxicT-lymphocyte-associated protein 4 inhibitors (12-15% of cases) which is a different entity compared to those associated to anti-program death 1 (anti-PD1) inhibitors.

Aim: We describe a case of pembrolizumab-associated hypophysitis and conduct a discussion based on a systematic review of the literature.

Case presentation: A 55-year-old woman presented with headache, nausea and fatigue 3.5 months (5 cycles) after initiation of adjuvant pembrolizumab for a stage 3b (TNM) melanoma. Endocrine profile was consistent with secondary adrenal failure, thyrotropic insufficiency and defective gonadotrophin secretion. Progressive decline of thyroid stimulating hormone and free tetraiodothyronine occurred three months prior to diagnosis. Imaging study showed an enlarged pituitary gland with homogeneous enhancement of the gland and pituitary stalk. After interruption of anti-PD1 therapy and administration of adrenal and thyroid hormonal substitutions improvement was observed. Magnetic resonance study showed declining pituitary mass three months later.

Discussion: Systematic search of literature identified 16 studies reporting 19 patients with single use pembrolizumab-associated hypophysitis. Most patients were treated for melanoma (n=7, 35%) and urogenital or breast neoplasia (n=7, 35%). Time to onset of pituitary insufficiency was most frequently 6 months (range 1.5 to 39.0 months) after treatment initiation. The most prevalent hormonal defect was isolated adrenocorticotropic hormone deficiency. Two studies reported multiple central hormonal defects. In those patients and in our case, increased pituitary mass was observed.

Conclusion: In contrast with the majority of other cases of pembrolizumab monotherapy associated hypophysitis, our case has distinct features. These include early disease onset, after pembrolizumab initiation, panhypopituitarism and increased pituitary mass. Whether or not this is a new clinical entity warrants further investigation. Until then, clinicians should be aware that pembrolizumab monotherapy associated hypophysitis might cover a heterogeneous clinical spectrum.