Giant Prolactinoma Presenting With Facial Nerve Palsy and Hemiparesis

Aleksandra Sliwinska; Fatima Jalil; Lori De La Portilla; Michael Baldwin; Joseph Lorenzo; Ketan R. Bulsara; Faryal S. Mirza

Disclosures

J Endo Soc. 2021;5(9) 

In This Article

Discussion

Giant prolactinomas are relatively rare pituitary tumors and management of these patients can be quite challenging. Clinical presentation can be misleading, mimicking other intracranial tumors or neurological disorders. Giant prolactinomas usually cause mass effect, compressing surrounding tissues and the optic chiasm.[6] The most common symptoms are vision changes (54.9%) and headaches (42.3%). Hormonal derangements are frequent, the most common one being low testosterone levels with hypogonadotropic hypogonadism, causing decreased libido and erectile dysfunction.[6–9] Less common presentations include cranial nerve palsy, seizures, cognitive decline, and psychiatric disturbances and pituitary apoplexy has been described in up to 9.8% of cases.[6] These patients have been reported to present with cranial nerves III, IV, V, and VI palsies.[4] Our patient is unique in that he presented with facial nerve palsy that reversed after CAB was started. Hemiparesis has rarely been reported with large pituitary adenomas in the setting of concurrent stroke or apoplexy was diagnosed.[10] In our case, we suspect that the enormous prolactinoma and its mass effect resulted in distortion of critical brain motor pathways and the corticobulbar fibers of the VII nerve, causing impaired motor function and weakness. These findings resolved with the reduction in size of the tumor with CAB therapy.

Giant prolactinoma can present with very high PRL level.[6,7,9] However, no consistent correlation has been reported between PRL level and tumor size.[5,6,9,11,12] Dopamine agonists, including bromocriptine and CAB, are effective first-line therapy and generally well tolerated. CAB, a long-acting D2-agonists, is favored over bromocriptine as it causes a greater decline in PRL levels.[8,13] Surgical management is sometimes needed to rapidly decompress the optic chiasm due to visual impairment[14,15] or can be a part of multimodal therapy due to continued growth and worsening symptoms despite dopamine agonist therapy or medication intolerance.[6,15] Long-term dopamine agonist therapy is usually necessary for management.[14–16] Due to concern about the neurological symptoms at presentation, the treating team decided to start the patient on a higher dose of CAB to see if the neurological symptoms improve and surgical intervention can be avoided. This was done with close observation and understanding that such large tumors have increased risk of apoplexy because of their large size, which can sometimes be precipitated by CAB treatment. The patient was followed closely and a follow up MRI of the brain a week after starting CAB, confirmed tumor shrinkage and lack of apoplexy. Hence, CAB dose was reduced to 0.5 mg every other day, on which he has been maintained.

Giant prolactinomas are very sensitive to dopamine agonists.[17,18] Acute symptoms arising from mass effect improve dramatically within days.[5,8] Other symptoms may resolve later during therapy, which often occurs before PRL levels normalize.[5] Gonadal dysfunction is reversed in 67% to 80% of men in the literature.[5,8] CAB dosage should be adjusted individually to avoid adverse effects and doses varying from 1.5 mg to 17.5 mg/week have been reported in various series.[6,8] In resistant giant prolactinomas, PRL level may not normalize despite a fairly high weekly dose of CAB (2.0 mg/day) or bromocriptine (15 mg/day).[19] Prolactin level may stay elevated in 20% to 40% of patients despite therapy and the nadir of PRL level seen between 10 and 20 months of therapy.[5,6,16,19] Patients with higher initial levels of PRL demonstrated a more significant response to dopamine agonist, suggesting that highly active tumors are more likely to respond to dopamine agonist monotherapy. The biochemical response does not correlate with tumor size and initial PRL level.[6] Our patient had an excellent response with a significant drop in PRL level just 2 days after starting CAB, suggesting high activity of lactotrophs. Dopamine agonists also facilitate tumor shrinkage and several studies have reported 60% to 80% reduction in tumor size over time,[6,8,17,19] with shrinkage in size usually reported at 6 to 20 months after starting treatment.[5,8,11,16] Although our patient has had an incomplete PRL response at 22 months of follow-up, he continues to show gradual improvement in PRL level and gradual shrinkage in the tumor size. Therefore, CAB dose has not yet been increased due to concern about side effects from higher CAB therapy.

Giant prolactinoma require long-term follow-up to monitor for structural response and for possible complications. Prolactin level, pituitary function tests, visual fields, and tumor size need to be followed regularly. Cohort study of massive (larger than 60 mm) and aggressive prolactinomas revealed that 39% of patients did not reach full resolution of hyperprolactinemia (17% reached partial response [PRL < 3 × upper limit of normal]) although most patients reported disappearance or improvement of their symptoms.[16] In our patient, given resolution of symptoms and successive decline in PRL and increase in testosterone, patient was observed clinically with frequent hormonal evaluation and repeat imaging.

Novel pharmacological regimens like pasireotide, a new somatostatin receptor ligand, and temozolomide, an alkylating agent, have been used successfully for aggressive and resistant prolactinomas and may become promising adjuncts.[20,21] Aggressive giant prolactinomas have been also linked to familial germline mutations including multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 4, Carney complex, familial isolated pituitary adenoma, and mutations in genes encoding succinate dehydrogenase, thus genetic testing may be pursued when there is high clinical suspicion or suggestive family history.[22,23] Our patient has continued to show gradual improvement both in tumor size and PRL levels. Hormonal testing for calcium level, and parathyroid and thyroid function has been normal and testosterone level continues to improve with full resolution of erectile dysfunction. We are planning to up-titrate CAB therapy as the next step and to pursue genetic evaluation. If the adenoma starts to behave more aggressively, surgical intervention and pasireotide or temozolamide treatments may also be considered.

Dopamine agonists may not prevent tumor re-expansion once they were discontinued.[24] Hence, patients with giant prolactinomas may never be a candidate for dopamine agonist withdrawal.[25,26] The most important predictors for prolactinoma recurrence are maximum tumor diameter and baseline PRL levels.[26] CAB up-titration should be managed cautiously as rapid shrinkage of the invasive tumor may cause unplugging of the eroded area and induce cerebrospinal fluid leakage[27] and can cause pituitary apoplexy or chiasmal herniation.[8,26] In our patient, initially high dose CAB (0.5 mg daily) was used due to urgency of the presentation, however patient was monitored closely by Neurosurgery and had repeat brain imaging to assure none of the complications have occurred. Patients on high-dose CAB or long-term therapy should be monitored by echocardiography for a possible valvular adverse effect.[28]

Conclusions

Giant prolactinoma is a rare entity that occurs mostly in men and presents with a significant mass effect on surrounding tissue. At diagnosis, clinical features may be mistaken for other neurological conditions like stroke. Giant prolactinoma may present with unique symptoms of facial nerve palsy and hemiparesis. Most giant prolactinomas are sensitive to dopamine agonists; however, PRL normalization may not happen and although the adenoma may shrink in size, it may not disappear. Long-term therapy and surveillance are required to monitor symptoms, decline in PRL, tumor shrinkage, and complications from dopamine agonist therapy.

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