Pituitary macroadenoma apoplexy following treatment with pembrolizumab

Stephanie Andrade Lopes; Lucie Sciotto-Canel; Shahan Momjian; Assma Ben Aissa; Elise Brocco; Ondine Becquart; Kristof Egervari; Doron Merkler; Francois Jornayvaz; Sophie Leboulleux; Maria Mavromati

doi:10.1530/endoabs.90.EP705

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Endocrine Abstracts (2023) 90 EP705 | DOI: 10.1530/endoabs.90.EP705

ECE2023 Eposter Presentations Pituitary and Neuroendocrinology (234 abstracts)

Pituitary macroadenoma apoplexy following treatment with pembrolizumab

Stephanie Andrade Lopes ¹ , Lucie Sciotto-Canel ¹ , Shahan Momjian ² , Assma Ben Aissa ³ , Elise Brocco ⁴ , Ondine Becquart ⁴ , Kristof Egervari ⁵ , Doron Merkler ⁵ , François Jornayvaz ¹ , Sophie Leboulleux ¹ & Maria Mavromati ¹

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Author affiliations

¹Hôpitaux Universitaires de Genève (HUG), Endocrinology, Genève, Switzerland; ²Hôpitaux Universitaires de Genève (HUG), Neurosurgery, Genève, Switzerland; ³Hôpitaux Universitaires de Genève (HUG), Oncology, Genève, Switzerland; ⁴Hôpitaux Universitaires de Genève (HUG), Dermatology, Genève, Switzerland; ⁵Hôpitaux Universitaires de Genève (HUG), Pathology, Genève, Switzerland

A 70-year old man was referred to the endocrinology department for the evaluation of a pituitary macroadenoma which was diagnosed during work-up for a malignant melanoma. Pituitary MRI showed a 20×21×25 mm adenoma with supra-sellar extension and no compression of the optic chiasma. Hormonal work-up revealed central hypogonadism and slight hyperprolactinemia due to stalk compression, while pituitary function was otherwise normal. MRI follow-up was scheduled in six months. The patient had surgery for the melanoma, and started immunotherapy with pembrolizumab. After the third dose of pembrolizumab, treatment was complicated by grade 3 polyarthralgia and grade 2 diarrhea and was temporarily stopped. Two-months later, the patient was admitted to the hospital due to violent headaches. MRI revealed apoplexy of the pituitary macroadenoma. Hormonal work-up showed new onset central hypothyroidism and central adrenal insufficiency. The patient was not on anticoagulation. Due to the absence of visual complications, conservative management was initially decided and treatment with glucocorticoids and levothyroxine was started. One week later, the patient came back to the hospital with worsening headache, motivating surgery. Histologic examination showed necrotic fragments of a pituitary neuroendocrine tumor, with SF-1 immunostaining. Possible metastasis of malignant melanoma was excluded. Central hypogonadism, adrenal insufficiency and central hypothyroidism persisted at 3 months-follow-up. Immune check-point inhibitors have radically improved cancer management. However, they are linked to endocrine adverse events related to pituitary, thyroid and adrenal damage. Pituitary complications include hypophysitis or simple anterior pituitary hormonal dysfunction. Pituitary apoplexy is an uncommon, potentially serious complication of pituitary macroadenomas. The pathophysiology is poorly understood, but some risk factors have been identified, such as coagulation disorders, abrupt increase or decrease in blood flow or pituitary stimulation. Here we describe the case of a patient who experienced apoplexy of a pituitary macroadenoma after pembrolizumab treatment. The link between immunotherapy and apoplexy has not been described so far. Only one case of apoplexy has been described in a patient on anti-PD1. With the increase in numbers of patients treated with immunotherapy, more research is needed to assess whether pituitary apoplexy can be caused by immune checkpoint inhibitors and determine whether pituitary surgery should be performed before starting immunotherapy.