Pituitary apoplexy: a rare complication of leuprolide therapy in prostate cancer treatment

Abstract

Gonadotropin-releasing hormone agonists, used widely in the treatment of metastatic prostate cancer and hormone receptor-positive breast cancer, are associated with a rare but potentially fatal outcome of pituitary apoplexy (PA). An 85-year-old man presented with sudden onset of headache, left eye pain, sensitivity to light, nausea and vomiting. The symptoms started 4 hours after initiation of leuprolide therapy for treatment of recently diagnosed metastatic prostate carcinoma. Radiological imaging of the brain demonstrated a heterogeneously enlarged pituitary gland measuring 19×16×13 mm and T1-hyperintense signal compatible with pituitary haemorrhage. Hormone function tests were indicative of panhypopituitarism, confirming the diagnosis of PA. Due to age, the patient was started on hormonal replacement therapy and eventually symptoms improved.

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

“…The first case recording this condition was reported by Ando et al . in 1995 and since then 20 other cases have been published ( 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ) – Table 2 . Literature analysis of these reports revealed clinical features consistent with PA, highlighting pituitary MRI as the gold standard for diagnosis.…”

“…In fact, our patient, despite the presence of a neuro-ophthalmic deficit, presented an excellent outcome with only medical treatment, possibly due to prompt evaluation and management. Histological findings with adenomatous tissue immunohistochemical staining were available in only 13 reports, all of them compatible with gonadotrophinomas (six positive for both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), four positive for FSH and three positive for LH) ( 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ).…”

“…On the other hand, in the group of patients with a later start of symptoms (subacute phase), it was suggested that the stimulation of LH secretion leading to cell growth and protein synthesis could have an effect on tumor size and intrasellar pressure, promoting generalized ischemia and consequent bleeding ( 8 , 10 ). Moreover, it has also been proposed that gonadotroph adenomas are the most common adenomas associated with the occurrence of PA. GnRHa binding to GnRH receptors on pituitary gonadotropin-secreting cells causes levels of LH and FSH to increase dramatically and this hormonal stimulation of gonadotrophs may be related to tumor growth, perpetuating tissue infarction ( 3 ). In fact, to our knowledge, only gonadotrophinomas were reported (both functioning and non-functioning ( 10 )), despite co-staining for growth hormone (GH) in one case and thyroid-stimulating hormone (TSH) in another ( 3 , 7 ).…”

“…Moreover, it has also been proposed that gonadotroph adenomas are the most common adenomas associated with the occurrence of PA. GnRHa binding to GnRH receptors on pituitary gonadotropin-secreting cells causes levels of LH and FSH to increase dramatically and this hormonal stimulation of gonadotrophs may be related to tumor growth, perpetuating tissue infarction ( 3 ). In fact, to our knowledge, only gonadotrophinomas were reported (both functioning and non-functioning ( 10 )), despite co-staining for growth hormone (GH) in one case and thyroid-stimulating hormone (TSH) in another ( 3 , 7 ).…”

“…Androgen deprivation therapy, including gonadotropin-releasing hormone agonists (GnRHa), is administered as primary systemic therapy for regional or advanced prostate cancer and as neoadjuvant/concomitant/adjuvant therapy in combination with radiation in localized or locally advanced disease (2). GnRHa administration for prostate cancer has been reported to induce PA in patients with a concurrent pituitary adenoma, but there are only 21 cases described in the literature to date (3,4,5,6,7,8,9,10). Although it is a rare complication, and since diagnosing PA requires high suspicion index, healthcare professionals should be aware of this association in order to enable an early recognition and adequate treatment.…”