Neuroendocrine and Pituitary
Tumor Clinical Center (NEPTCC) Bulletin
Winter 2018/2019 | Volume 24, Issue 2
CASE RECORDS OF THE MGH NEUROENDOCRINE AND PITUITARY TUMOR CLINICAL CENTER: When Do Prolactinomas Require Surgery?-Pamela S. Jones, MD, MS, MPH
A 22-year-old man presented to MGH Neurosurgical and Neuroendocrine and Pituitary Tumor Clinical Center with headaches and visual loss. He was referred by his ophthalmologist, who documented a temporal field defect with a dense right central scotoma.? He had first noted near blindness in his right eye 2 months prior to presentation at his annual physical when he decided to test himself on the eye chart.? He was then seen by an ophthalmologist who found right optic neuropathy and visual field testing consistent with severe right junctional scotoma and right afferent pupillary defect (Figure 1).
Besides decreased vision, he reported headaches attributed to migraines for the prior 6 months.? He endorsed limited libido, he did have facial hair, but did not think his voice had deepened with puberty.? He had been overweight and hypertensive since childhood.
On exam, he was obese but did not appear acromegalic or Cushingoid. There was a dense right central and superior temporal defect, and no detectable visual field abnormality on the left. Acuity was 20/15 on the left but he was unable to read an eye chart or count fingers with the right eye and left pupil did not react to light shone into right eye, consistent with afferent pupillary defect.
Endocrine testing revealed a 5pm cortisol of 6.3ug/dL (normal 5-15 ug/dL), an elevated prolactin at 465.9 ng/ml (normal <20), TSH 2.62 uIU/ml (normal 0.4-5.0), free T4 1.1 ng/dl (normal 0.9-1.8). Total testosterone was low at 44 ng/dL (normal 249-836 ng/dL).
Pre-operative visual field test demonstrating dense right eye junctional scotoma
A pituitary-protocol MRI with and without contrast revealed a 2.2 x 2.3 x 3.1 cm sellar mass with suprasellar extension that resulted in mass effect on the right prechiasmatic optic nerve, optic chiasm, and optic tract. The lesion was intrinsically T1 hyperintense and had a fluid layer on axial T2 imaging, suggesting a largely cystic component to the lesion (Figure 2).
A) Coronal post-contrast T1 sequence MRI showing homogenously enhancing mass with chiasmal compression.
B) Axial T2 sequence MRI demonstrates significant fluid level within the lesion.
C) Sagittal pre-contrast T1 sequence MRI showing inherent T1 hyperintensity of the lesion, consistent with cystic content.
Given the lab findings of a markedly elevated prolactin level and MRI findings of a large cystic tumor with significant optic nerve and chiasm compression, we had an interdisciplinary discussion about the next management steps of medical management versus surgery. Ultimately, given the cystic nature of the lesion and the significance of the patient?s visual disturbance, we offered both options to the patient and he elected surgical decompression.
Four days after initial consultation, he was brought into the hospital for a transsphenoidal surgery for resection of the tumor. The tumor was found to be mostly cystic, with solid tumor along the left sella. Intraoperative MRI was obtained that did not show any obvious residual (Figure 3). His prolactin level on the morning of post-operative day 1 was lower at 112.6 ng/mL, but remained abnormal. Vision in right eye improved to 20/50. His fasting morning cortisol was low at 6.3 ug/dL and he was discharged on prednisone 5mg daily.
A) Intra-operative coronal T1 post-contrast sequence MRI showing enhancement of pituitary stalk and gland within the right side of sella; no obvious remaining tumor
B) Intra-operative coronal T2 sequence MRI showing significant decompression of the optic chiasm
At his 4-week post-operative endocrine visit the prolactin was 139.3 ng/mL. He was started on cabergoline 1mg weekly. He tolerated the medicine well and, after 3 months, prolactin down trended to 21 ng/mL. The dose was increased to 1.25mg weekly and his prolactin was normalized to 9 ng/mL.? Testosterone increased spontaneously to 255 ng/dL, the lower limit of the normal range. His thyroid hormones remained normal and he was weaned off of prednisone at 2 months after surgery following a normal cosyntropin stimulation test. His right eye vision had improved to 20/30, and his afferent pupillary defect and visual field defect had both resolved. He denied headaches, and reported more energy and an increase in his physical activity.
Prolactinomas are the most common of the functional pituitary tumors, comprising 51-66% of adenomas. Patients with these tumors typically present with hypogonadism, infertility or, in the case of macroadenomas, symptoms related to mass effect, such as visual field defects and headache. Medical management with dopamine agonists (DAs) has been the mainstay of treatment for several decades, with normalization of serum prolactin levels achieved in 75% of patients using bromocriptine and 85?90% using cabergoline.
Despite the effectiveness of DAs in achieving normal prolactin levels and shrinking the adenoma, with improvement in visual field defects within 24 hours in some patients, surgery for prolactinomas should be considered for a few scenarios. The most common role for surgery is in cases where patients are intolerant to medication, with side effects of nausea, dizziness, or even psychosis. Patients may also have a contraindication to DAs, such as psychiatric conditions. Another role for surgery includes drug resistance of the tumor?a failure to normalize prolactin and/or shrink tumor?that may be recognized with initial treatment or occur over time. Female patients with macroprolactinomas who are seeking pregnancy may be candidates for surgical resection over medical therapy given the need for expeditious restoration of fertility and the contraindication to taking DAs in pregnancy.
Largely cystic prolactinomas, as discussed above, were historically assumed to be resistant to DAs and therefore thought to be a surgical condition. Our group?s research has shown that medical therapy can be an effective and durable option, even in cases of large cystic tumors with chiasmal compression. In this patient?s case, we presented him with the data that DAs could be effective in treating his tumor, however the time course for shrinkage is variable, ranging from weeks to several months. Given his significant visual disturbance, our patient opted for surgery. After an informed, multidisciplinary discussion, patient preference is another reason for surgical intervention of prolactinomas, whether it is for visual concerns, as with our patient, or for the potential of avoiding or at least requiring a lower dose of DAs after significant tumor debulking.
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3. Faje AT, et al. J Clin Endocrinol Metab. 2016; 101:3709?15