ReviewPituitary apoplexy associated with cabergoline therapy
Introduction
Pituitary apoplexy is an uncommon but life-threatening condition. It usually occurs in a pre-existing adenoma, although a normal pituitary gland can also develop apoplexy, especially during pregnancy. Patients usually present with severe headache, visual disturbances, cranial nerve palsies, nausea, vomiting, altered consciousness, and impaired pituitary function. The majority of patients do not have a particular cause but predisposing factors include radiotherapy, thrombocytopenia, pituitary dynamic testing, trauma, recent surgery, diabetes mellitus, hypertension, and medications such as anticoagulants and dopamine agonists. Most reports of pituitary apoplexy in patients with adenomas are related to treatment with bromocriptine. We report a patient with prolactinoma who developed apoplexy 6 weeks after cabergoline treatment.
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Illustrative case report
A 20-year-old Chinese man presented to a neurologist with a 5 year history of chronic right sided headache requiring intermittent analgesia for pain relief. MRI of the brain revealed a intrasellar lesion extending to the suprasellar region resulting in compression of the optic chiasm. He was referred to our endocrinology service for assessment of tumor functionality.
He was an otherwise healthy individual and not taking any regular medications. He had no complaints of polyuria, polydipsia,
Discussion
The use of dopamine agonists has been listed as one of the risk factors for pituitary apoplexy. They cause apoptosis of lactotroph cells and this in turn decreases the metabolic demands. At the same time, the angiogenesis is inhibited but an imbalance between the two leads either to infarction with hemorrhage or hemorrhage only.
A literature search for patients reported between 1985 and 2011 revealed 10 patients1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and two case series11, 12 of pituitary apoplexy with
Conclusions
Pituitary apoplexy is a rare condition, and can be associated with treatment of adenomas with dopamine agonists. Although the dopamine agonists precipitate apoplexy, therapy can be continued after the apoplexy for biochemical and anatomical remission of prolactinoma. Whilst apoplexy is more widely reported with the use of bromocriptine, physicians should also be aware that it can also occur with cabergoline.
Conflicts of interest/disclosures
The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
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Cited by (29)
Prolactinoma: Medical and Surgical Considerations
2022, Otolaryngologic Clinics of North AmericaCitation Excerpt :For patients with macroprolactinomas and extrasellar extension or persistent hyperprolactinemia, it is not advisable to stop DA therapy. Rarely, pituitary apoplexy may occur spontaneously or during DA therapy and can require surgical intervention.26 In addition, rapid tumor shrinking on DAs can lead to cerebrospinal fluid (CSF) leak, which could necessitate surgical repair.27
Pituitary Apoplexy in Long-Term Cabergoline User During Thrombocytopenia Due to Chemotherapy for Chronic Myelocytic Leukemia
2018, World NeurosurgeryCitation Excerpt :Hemodynamic stress, pituitary stimulation, and coagulation disturbance are reported as risk factors.4 Pregnancy, diabetes mellitus, head trauma, lymphocytic leukemia, anticoagulant therapy, and the usage of DAs such as bromocriptine or cabergoline for pituitary prolactinoma have also been considered to be predisposing factors for PA.3,4,6-22 Following apoptosis of lactotroph cells by DA in pituitary prolactinoma, the necrosis and fibrous change in pituitary prolactinoma can result in tumorous size shrinkage with hemorrhagic complications.6,9,11,14 PA related to the usage of DAs commonly occurs within 1.5 years from the initiation of therapy,8 but the onset of PA after the long-term usage of cabergoline is yet to be described.
Surgical Management of Pituitary Apoplexy
2017, Primer on Cerebrovascular Diseases: Second EditionPost-traumatic pituitary apoplexy: Case presentation and review of literature
2017, Interdisciplinary Neurosurgery: Advanced Techniques and Case ManagementCitation Excerpt :PA can be asymptomatic and recognizable only after performing neuroimaging, and is therefore called subclinical or subacute apoplexy [14]. Pituitary adenomas can develop silently, enlarge and then suddenly become symptomatic after triggering events such as head trauma, radiation therapy, sudden changes in intracranial pressure, dopamine agonists administration, hormone stimulation tests, lumbar puncture or spinal anesthesia [1,5,13]. Some authors argue that pituitary apoplexy is more prone to occur in large pituitary tumors (e.g. macroadenoma) whereas microadenomas (< 1 cm in diameter) are less susceptible to bleeding [14].
Approach to the management of rare clinical presentations of macroprolactinomas in reproductive-aged women
2015, Case Reports in Women's HealthCitation Excerpt :Pituitary apoplexy is a rare complication of prolactinomas (prevalence, 0.08%) [8]. Hemorrhage within a prolactinoma during pregnancy is exceedingly rare, with 5 cases reported in macroadenomas and 2 in microadenomas [9,10]. Given the paucity of cases of pituitary apoplexy during pregnancy, most data are from case series of nonpregnant patients.
Pituitary tumor apoplexy
2015, Journal of Clinical NeuroscienceCitation Excerpt :In a review of 34 cases of PTA associated with endocrine stimulation testing, the most common tumors were non-functioning, growth hormone secreting and prolactinomas [61]. Other precipitants that have been reported include head trauma, radiotherapy, diabetes mellitus, diabetic ketoacidosis and the initiation or withdrawal of dopamine agonist therapy [46,62–65]. PTA after transsphenoidal resection has been reported and tends to be in the context of incomplete resection of very large (>4 cm) pituitary macroadenomas [66].