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Show ORIGINAL CONTRIBUTION Delayed Visual Loss Following Pergolide Treatment of a Prolactinoma Hideki Chuman, MD, PhD, Wayne T. Cornblath, MD, Jonathan D. Trobe, MD, and Stephen S. Gebarski, MD A patient who had achieved marked improvement in vision and shrinkage of a prolactinoma following treatment with pergolide ( 0.1 mg/ day) suffered a marked worsening of vision 7 months after continued treatment at the same dose. Brain magnetic resonance imaging ( MRI) at the time of visual loss showed further shrinkage of the tumor and prolapse of the chiasm into the pituitary fossa. The dose of pergolide was cutinhalf ( 0.05 mg/ day); 12months later, vision had completely recovered. Brain MRI at the time of visual recovery showed no change in the position of the prolapsed chiasm. This is the 11th reported case of delayed visual loss following dopaminergic treatment of prolactinoma. Recovery of vision always occurs with reduction of the medication dosage. Many patients whose prolactinomas are treated in this fashion display chiasmal prolapse, and few suffer visual loss. Considering that visual recovery occurs without a visible change in the position of the chiasm, traction is an unlikely cause of delayed visual loss. Therefore, the term chiasmal traction syndrome, used to describe visual loss with prolapsed chiasm following surgical and radiation treatment of sellar tumors, should not be applied in this setting lest it prompt consideration of surgical chiasmapexy. The proper management is reduction of the dopaminergic agonist dosage. ( JNeuro- Ophthalmol 2002; 22: 102- 106) Pergolide ( Permax; Athena Neurosciences, San Francisco, CA), a dopaminergic agonist, reduces prolactin synthesis, decreases the size of prolactinomas, and improves visual field defects resulting from chiasmal compression ( 1). Its more common side effects of nausea, orthostatic hypotension, nasal congestion, and depression rarely limit its use ( 1). We describe a patient whose prolactinoma- induced bitemporal hemianopia disappeared with standard doses of Kellogg Eye Center, Departments of Ophthalmology ( HC, WTC, JDT), Neurology ( WTC, JDT), and Radiology ( Neuroradiology) ( SSG), University of Michigan Medical Center, Ann Arbor, Michigan, USA. Address correspondence to Jonathan D. Trobe, MD, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105, USA pergolide but recurred 6 months later with continued treatment at the same pergolide dose. Cutting the pergolide dose in half reversed the visual field defect. Delayed vision loss has previously been reported in ten patients treated with bromocriptine or cabergoline ( 2- 5). We present our case to document that this phenomenon may also occur with pergolide treatment and to emphasize that the mechanism of the delayed visual loss is unlikely to be traction on the optic chiasm. CASE REPORT A 64- year- old woman had a 1- year history of progressively blurred vision in the OD. She had had diabetes mellitus for 32 years and had been taking insulin for 5 years. She denied galactorrhea. Visual acuity was 20/ 50 OD and 20/ 25 OS. There was a right afferent pupillary defect. Visual fields performed on the Humphrey Field Analyzer showed a temporal hemian-opic defect in the OD and an arcuate defect in the OS ( Fig. I A). The optic discs and the rest of the neuro-ophthalmologic examination were normal. Brain magnetic resonance imaging ( MRI) showed an intrasellar mass with lateral, infrasellar, and suprasellar extension severely deforming the optic chiasm ( Fig. IB). A prolactin level was 3,894 ng/ mL ( normal = less than 23). She was diagnosed as having a prolactin- secreting pituitary adenoma and began taking oral pergolide 0.1 mg/ day. Within several weeks, she noted a marked improvement in her vision. Seven months after starting pergolide treatment, her prolactin level had fallen to 63 ng/ mL. Visual acuity was 20/ 20 OU. Pupillary reactions were now normal. Visual fields had nearly normalized ( Fig. 2A). A brain MRI showed marked reduction in the size of the pituitary tumor with reduced deformity of the optic chiasm, which had descended into the sella turcica ( Fig. IB). She continued to take pergolide 0.1 mg/ day. Six months later ( 13 months after starting the pergolide treatment), she noted that the letters on the temporal side of OU visual field were missing. Visual acuity was 20/ 30 OD and 20/ 25 OS. Pupils were normal. Visual fields n 1 0 2 . DOT: lp. l097/ 01. WNQ. gnn0018241.84472.7A . J Neuro- Ophthalmol. Vol. 22, No. 2,. 2Q02 , Copyright © Lip pincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. CHUMAN ET AL. JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 FIG. 1. Before pergolide treatment. A: Visual fields ( Humphrey, gray scale) show temporal hemianopic defect in the OD, arcuate defect in the OS. B: T1- weighted coronal enhanced magnetic resonance imaging shows homogeneous mass ( M) displacing and severely distorting the optic chiasm ( arrow), which is barely visible above the mass. showed that the original defects had returned ( Fig. 3A). The discs were normal. Serum prolactin was 14 ng/ mL. Brain MRI showed further shrinkage of the pituitary tumor and marked prolapse of the optic chiasm into the sella turcica ( Fig. 3B). The pergolide dose was cut in half to 0.05 mg/ day. Six months after halving the pergolide dose, visual acuity had improved to 20/ 20 OD and 20/ 25 OS. Pupils were normal. Visual fields showed marked improvement ( Fig. 4A). Brain MRI showed no change in the degree of chiasmal prolapse ( Fig. 48). Twelve months after lowering the pergolide dose, visual fields had returned to normal. The prolactin level was 14 ng/ mL. DISCUSSION In our patient, treatment of a prolactinoma with pergolide in standard doses ( 0.1 mg/ day) for 7 months caused tumor shrinkage and relief of field loss attributed to chiasmal compression. However, continued treatment for an additional 6 months at that dose led to marked worsening of the visual fields. Imaging showed prolapse of the optic chiasm into the pituitary fossa. Reduction of the pergolide dose to 0.05 mg/ day led 12 months later to full recovery of the visual field loss, but MRI showed no change in the position or contour of the prolapsed chiasm. Our patient represents the 11th reported case of delayed visual loss after dopamine agonist treatment of prolactinoma ( 2- 5). Taxel et al. ( 2) reported a similar patient whose bitemporal hemianopia resolved almost completely on bromocriptine 5.0 mg/ day but returned slightly 3 months after bromocriptine treatment at 7.5 mg/ day. As in our case, MRI at the time of visual loss showed further tumor shrinkage and now showed chiasmal prolapse. The bromocriptine dose was reduced to 5.0 mg/ day, and within 2 months, the visual field defects had recovered, but MRI showed no change in the position of the prolapsed chiasm. In a series of ten dopaminergic agonist- treated prolactinoma patients ( 4), Moster et al. ( 4) described one patient who was treated with bromocriptine at 15 mg/ day and suffered a late decline in vision, but the authors did not mention whether the chiasm was prolapsed. Kaufman et al. ( 5) listed one patient as suffering delayed visual loss with chiasmal prolapse, but no details were presented. Jones et al. ( 3) described seven prolactinoma patients in whom visual loss developed from 4 months to 10 years ( median, 10 months) after being treated with dopaminergic agonists. All patients eventually recovered vision fully with reduction in the dopaminergic agonist dosage, but the authors provided details on only two patients, both of whom were treated with relatively high bromocriptine doses ( 20 103 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 DELAYED VISUAL LOSS FOLLOWING PERGOLIDE TREATMENT < I . _ . ' ' i f - • i • • : . • • • • : * ; % • • • : • • ; • •. • M I FIG. 2. Seven months after pergolide treatment at 0.05 mg by mouth twice daily. A: Visual fields show nearly full recovery. B: T1- weighted coronal enhanced magnetic resonance imaging shows marked reduction in size of the pituitary mass ( M) with less deformity of the optic chiasm ( arrow). The chiasm is now retracted somewhat toward the sella due to shrinkage of the mass. mg/ day and 10 mg/ day). In one case, complete visual recovery occurred immediately after discontinuing the bromocriptine for 2 weeks and was maintained for 5 years at a bromocriptine dose of 5 mg/ day; in the other case, complete visual recovery occurred within 3 weeks after the bromocriptine dose was lowered from 10 mg/ day to 5 mg/ day. The prolactin levels doubled or tripled after a reduction in the bromocriptine dose, but the patients suffered no ill effects. Although follow- up imaging was not explicitly described, the authors mentioned that at the time of visual recovery, " there was no obvious reduction in the degree of chiasmal herniation." Although imaging failed to show any relief in chiasmal prolapse, Taxel et al. ( 2) and Jones et al. ( 3) presumed that the reduction in dopaminergic agonist dosage caused a regrowth of tumor that was simply too small to detect ra-diologically but enough to release tethering of the optic chiasm or its vascular supply. Their argument is based on previously reported cases in which visual field loss developed weeks to months after surgery or radiation of sellar ( usually pituitary) tumors and in which the chiasm or optic nerves were found on surgical re- exploration to be dragged down into the sella by scarred tissue ( 6,7) or tethered to the dia-phragma sellae ( 8). Lysis of adhesions and packing of the sellar floor to prop the chiasm up to its normal position ( chi-asmapexy) has, in some cases, restored normal vision, but documentation of visual recovery is not particularly convincing ( 6- 8). Whereas this reasoning might apply to postsurgical or postradiation empty sella syndromes, it may not pertain to dopaminergic agonist- treated prolactinomas. First, autopsies have failed to show any evidence of sellar adhesions in such cases ( 5). Second, chiasmal herniation is evidently common after dopaminergic agonist treatment of prolactinomas, yet visual loss is rare. Lundin et al. ( 9) found chiasmal herniation in eight ( 80%) often such patients, none of whom had any visual loss. The evidence that herniation of the chiasm is responsible for visual loss even in conditions known to cause sellar adhesions is actually quite weak. Kaufman et al. ( 5) found no relationship between the degree of chiasmal herniation and the severity of visual loss in seven patients with empty sella syndrome secondary to surgical or radiation treatment of pituitary adenomas. Chiasmapexy is often not successful in restoring vision and may cause visual worsening if the sella is packed too much. Given that vision recovered completely without any restitution in the position of the optic chiasm in our patient, in the patient of Taxel et al. ( 2), and in the seven patients of Jones et al. ( 3), the notion that traction causes visual loss in _ 104 . „ _ . . „ . . © 2002 Lippincott Williams & Wilkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. CHUMAN ETAL. JNeuro- Ophthalmol, Vol 22, No. 2, 2002 Im& mmi ":::::::: HSfc ~^ W' * 3£ r'-'' z FIG. 3. Thirteen months after pergolide treatment at 0.1 mg daily. A: Visual fields show marked worsening in the defect as compared with Figure 2. B: T1- weighted coronal enhanced magnetic resonance imaging: further shrinkage of the mass with worsened distortion of the chiasm ( arrow). Due to interval retraction of the mass, the chiasm is now prolapsed into the sella turcica. FIG. 4. Six months after pergolide treatment at 0.05 mg/ daily. A: Visual fields show nearly full return to normal. B: T1- weighted coronal enhanced magnetic resonance imaging shows no change in the size of the mass or the degree of chiasmal distortion and prolapse. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited JNeuro- Ophthalmol, Vol. 22, No. 2, 2002 DELAYED VISUAL LOSS FOLLOWING PERGOLIDE TREATMENT such cases should be questioned. An alternative possibility is that the dopaminergic agonist causes direct toxicity, va-sospasm- induced ischemia, or reversible perivascular fibrosis. Although no direct neurotoxicity has been found in experimental work with dopaminergic agonists, perivascular fibrosis has been noted as a distinctive feature of surgically removed bromocriptine- treated prolactinomas as compared with prolactinomas not treated with bromocriptine ( 10). The incidence of delayed visual loss following dopaminergic agonist treatment of prolactinomas is low but not negligible. In a series of eight patients treated with bromocriptine for prolactinomas, no visual loss was reported after follow- up periods of over 12 months ( 11). In another series often such patients ( 4), only one suffered a late decline in vision. That patient underwent a second transsphenoidal exploration, even though the chiasm was not herniated, and vision was worse after the procedure. In the series of Jones et al. ( 3), chiasmapexy was fortunately rejected as too risky a solution to delayed visual loss. As applied to delayed visual loss following dopaminergic agonist treatment of a prolactinoma, the terms chiasmal traction syndrome, tethered chiasm syndrome, and chiasmal herniation syndrome should be avoided. They imply a mechanism that may be incorrect and is likely to prompt a surgical maneuver- chiasmapexy- that may worsen vision ( 4). If imaging fails to disclose tumor enlargement as the cause of delayed visual loss, the correct approach is to lower the dopaminergic agonist dose. Patients apparently do not suffer this complication at doses equivalent to bromocriptine 5 mg/ day. Although higher doses may be necessary to normalize the prolactin level, they should be used only if the patient's endocrine status is clinically unsatisfactory. Visual acuity and visual fields should be monitored for several years after dopaminergic agonist treatment is begun, because delayed visual loss has been reported as long as 24 months later. REFERENCES 1. Molitch ME. Prolactinoma. In Melmed S, ed. The Pituitary. Cambridge: Blackwell Scientific Publications, 1995: 443- 77. 2. Taxel P, Waitzman DM, Harrington JF Jr, et al. Chiasmal herniation as a complication of bromocriptine therapy. J Neuroophthalmol 1996; 16: 252- 7. 3. Jones SE, James RA, Hall K, et al. Optic chiasmal herniation: an under recognized complication of dopamine agonist therapy for macroprolactinoma. Clin Endocrinol 2000; 53: 529- 34. 4. Moster ML, Savino PJ, Schatz NJ, et al. Visual function in prolactinoma patients treated with bromocriptine. Ophthalmology 1985; 92: 1332^ 11. 5. Kaufman B, Tomsak RL, Kaufman BA, et al. Herniation of the suprasellar visual system and third ventricle into empty sella: morphologic and clinical considerations. AJR Am J Roentgenol 1989; 152: 597- 608. 6. Welch K, Stears JC. Chiasmapexy for the correction of traction of the optic nerves and chiasm associated with their descent into an empty sella turcica. JNeurosurg 1971; 35: 760- 4. 7. Decker RE, Carras R. Transsphenoidal chiasmapexy for correction of posthypophysectomy traction syndrome of the optic chiasm. J Neurosurg 1977; 46: 527- 9. 8. Fischer EG, DeGirolami U, Suojanen JN. Reversible visual field deficit following debulking of a Rathke's cleft cyst: a tethered chiasm? J Neurosurg 1994; 81: 459- 62. 9. Lundin P, Bergstrom K, Nyman R, et al. Macroprolactinomas: serial MR imaging in long- term bromocriptine therapy. AJNR Am J Neuroradiol 1992; 13: 1279- 91. 10. Landolt AM, Osterwalder V. Perivascular fibrosis in prolactinomas: is it increased by bromocriptine? J Clin Endocrinol Metab 1984; 58: 1179- 83. 11. Lesser LL, Zheutlin JD, Boghen D, et al. Visual function improvement in patients with macroprolactinomas treated with bromocriptine. Am J Ophthalmol 1990; 109: 535- 43. ^ 1 0 6 . „ _ . . „ . . © 2002 Lippincott Williams & WUkins , Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. |
