Pituitary apoplexy induced by gonadotropin-releasing hormone agonist administration: a rare complication of prostate cancer treatment

Abstract

Summary Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described as a rare cause of pituitary apoplexy, a potentially life-threatening clinical condition. We report the case of a 69-year-old man with a known pituitary macroadenoma who was diagnosed with prostate cancer and started treatment with GnRH agonist leuprorelin (other hormones were not tested before treatment). Few minutes after drug administration, the patient presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Pituitary MRI revealed tumor enlargement and T1-hyperintense signal, compatible with recent bleeding sellar content. Laboratory endocrine workup was significant for low total testosterone. The patient was managed conservatively with high-dose steroids, and symptoms significantly improved. This case describes a rare phenomenon, pituitary apoplexy induced by GnRH agonist. We review the literature regarding this condition: the pathophysiological mechanism involved is not clearly established and several hypotheses have been proposed. Although uncommon, healthcare professionals and patients should be aware of this complication and recognize the signs, preventing a delay in diagnosis and treatment. Learning points: Pituitary apoplexy (PA) is a potentially life-threatening complication that can be caused by gonadotropin-releasing hormone agonist (GnRHa) administration for the treatment of advanced prostate cancer. This complication is rare but should be taken into account when using GnRHa, particularly in the setting of a known pre-existing pituitary adenoma. PA presents with classic clinical signs and symptoms that should be promptly recognized. Patients should be instructed to seek medical care if suspicious symptoms occur. Healthcare professionals should be aware of this complication, enabling its early recognition, adequate treatment and favorable outcome.

Pituitary apoplexy induced by gonadotropin-releasing hormone (GnRH) agonist administration for treatment of prostate cancer: a systematic review

“…We identified a total of 66 published articles between 1995 and 2020 on database search and 21 cases fulfilled inclusion criteria (Ando et al 1995;Chanson and Schaison 1995;Morsi et al 1996;Reznik et al 1997;Eaton et al 2001;Spengos et al 2002;Blaut et al 2006;Davis et al 2006;Massoud et al 2006;Hands et al 2007;Guerra et al 2010;Sinnadurai et al 2010;Ito 2011;Huang et al 2013;Babbo et al 2014;Guerrero-Pérez et al 2015;Sasagawa et al 2015;Fabiano and George 2016;Keane et al 2016;Tanios et al 2017;Barbosa et al 2020). The mean age of the patients was 70 years.…”

“…Treatment of prostate cancer after PA was not described in 11 patients. Among the five patients treated conservatively, one patient received radiation treatment for prostate cancer following PA and the management of prostate cancer was not described in the rest (Barbosa et al 2020).…”

Pituitary Apoplexy After Leuprolide Therapy in a Breast Cancer Patient: A Case Report

“…This report documents a PA case of a GnRH-releasing pituitary adenoma in a breast cancer patient treated with leuprolide. First reported in 1995, PA has been reported in more than 20 patients treated with GnRH agonists [ 4 6 7 ]. Most cases involved prostate cancer patients, who were treated with GnRH agonists.…”

“…The acute phase, which occurs within minutes or hours after the administration of a GnRH agonist, reportedly resulted from metabolic hyperactivity and cell degranulation/shrinking in adenomas with reduced perfusion. However, in the subacute phase, LH secretion increases tumor size and causes ischemia/hemorrhage [ 7 ].…”

Ovarian protection and safety of gonadotropin-releasing hormone agonist after cervical cancer surgery: systematic review and meta-analysis

“…During the cytotoxic process of chemotherapy for cervical cancer, the cytotoxic effects of chemotherapeutic drugs can lead to the premature decline of ovarian function (21), reducing the number of follicles and leading to the fibrosis of ovarian tissue, and thus affecting the fertility of patients (22)(23)(24)(25). The GNRH-a is an artificial GnRH derivative agent, which is mostly used in the treatment and recurrence prevention of endometriosis (26).…”