Macroprolactinoma Early Detection Is A Vision Saving Strategy
Overview
Managing visual field damage in patients with macroprolactinomas presents significant therapeutic challenges. This study aimed to examine the visual impairments associated with macroprolactinomas and their outcomes following medical and surgical treatments, with a focus on identifying predictors of visual recovery.
A retrospective review of 150 patients with macroprolactinomas was conducted, analyzing clinical presentation, serial pituitary MRI scans, laboratory results, visual symptoms, neuro-ophthalmologic exams, visual field tests, and optical coherence tomography. The primary outcome measured was complete visual field recovery, with descriptive analyses and investigation of potential predictors.
At diagnosis, 26.7% of patients (40 out of 150) exhibited visual field defects. By the end of the follow-up period (median of 6.0 years), 61.5% of these patients with available visual field tests showed complete recovery. Predictors of complete visual recovery included smaller macroadenoma size at diagnosis, lower baseline serum prolactin levels, and lower incidences of central hypogonadism, central hypothyroidism, and compressive optic neuropathy. Additionally, patients with better initial visual acuity (better than 6/8 in both eyes) were more likely to achieve full visual recovery.
Among the cohort of 150 patients with macroprolactinomas, 26.7% presented with visual field defects at diagnosis. Following treatment, 61.5% of these patients experienced complete visual recovery. Key predictors of successful visual recovery included smaller tumor size, lower prolactin levels, reduced rates of related endocrine dysfunctions, and better visual acuity at presentation. This study highlights the importance of early detection and treatment in optimizing visual outcomes for patients with macroprolactinomas.
Introduction
Prolactin-secreting adenomas, or prolactinomas, are the most prevalent functional pituitary tumors, constituting about 40% of all pituitary tumors. Among these, macroprolactinomas (those ≥10 mm in diameter) can expand and impinge on adjacent structures. When a macroprolactinoma grows upwards, it may press against the optic chiasm or nerves, leading to significant visual impairments, often presenting as bitemporal visual field defects due to chiasmal compression. Occasionally, lateral growth of the tumor can compress cranial nerves in the cavernous sinus, resulting in ophthalmoplegia.
Visual field defects are observed in 29%–66% of patients with macroprolactinomas, with a higher incidence in those with giant prolactinomas (over 4 cm in size). Men are generally more affected than women, as they tend to present with larger, more aggressive tumors. Visual dysfunction linked to macroprolactinomas can notably impact functional outcomes and quality of life.
Although pituitary surgery is the most effective approach for immediate tumor reduction and relief of visual symptoms, both surgical and radiation treatments carry the risk of damaging the optic nerves and worsening visual function. Unlike other pituitary tumors, prolactinomas often respond quickly to medical treatment with dopamine agonists, which usually induce significant tumor shrinkage. However, in rare cases, dopamine agonist therapy may lead to pituitary apoplexy or herniation of the optic chiasm, jeopardizing visual pathways.
This study investigates the incidence and patterns of visual complications associated with macroprolactinomas, examining how these issues manifest during treatment and follow-up. The study aims to detail the presentation of macroprolactinoma, identify baseline characteristics linked to visual morbidity, and explore predictors of visual recovery in patients treated either medically or surgically.
Method
This study focused on patients with pituitary macroadenomas (≥10 mm) and hyperprolactinemia, defined as serum prolactin levels ≥95 mcg/L (2000 mIU/L). Secondary hyperprolactinemia, such as that caused by medication, was excluded. Patients were identified through a prolactinoma registry at the Rabin Medical Center, Israel, where they were either diagnosed or referred to the Pituitary Clinic. Treatment for all patients primarily involved cabergoline, with four patients initially receiving bromocriptine until cabergoline became available. Data collected included clinical presentations, therapeutic responses, visual symptoms, and ophthalmological assessments, as well as serial pituitary-directed MRI studies and various laboratory tests. Macroprolactin levels were not routinely measured.
The study protocol involved medical treatment, and in cases of inadequate response or visual impairment necessitating optic tract decompression, trans-sphenoidal surgery was considered. A treatment failure was defined as persistent hyperprolactinemia despite the maximum tolerated dose of cabergoline. MRI scans were performed at diagnosis and 12 months post-treatment, with additional imaging as needed for patients with ongoing issues.
Visual assessments included best corrected visual acuity (BCVA), visual field tests, and optical coherence tomography (OCT). Visual field tests were repeated as necessary, and OCT tests measured retinal nerve fiber layer (RNFL) thickness. These assessments were used to monitor visual changes and guide treatment.
Biochemical evaluations measured serum prolactin using an immunometric assay with sensitivity of 0.15 mcg/L, and normal ranges were defined according to established standards. Other hormonal levels assessed included testosterone, estradiol, cortisol, and thyroid function. Hypogonadism and hypocortisolism were defined by specific hormone levels, and central hypothyroidism was identified by low or inappropriately normal TSH levels.
The study was approved by the Rabin Medical Center institutional review board and adhered to the Helsinki Declaration, with no external funding provided.
Statistical Analysis
Statistical analyses were conducted using SPSS Software, Version 28. Comparisons were made between male and female patients, and the cohort was divided into three groups based on the proximity of the macroadenoma to the optic apparatus and the presence of visual field defects. The study compared medically versus surgically treated patients and used various statistical tests to analyze continuous and categorical variables. A p-value of <0.05 was considered statistically significant.
Result
From January 1993 to July 2023, a total of 150 patients with macroprolactinoma were studied, consisting of 121 men (80.6%) and 29 women (19.3%). The average age at diagnosis was 43.0 years, with a median prolactin level of 918 mcg/L and an average adenoma diameter of 21.5 mm. Patients were followed for a median of 6.0 years, and all received cabergoline treatment. Some also underwent multimodal therapies.
Patients were categorized into three groups based on MRI findings and visual field tests: Group A had no adenoma contact with the optic nerve or cranial nerves; Group B had adenomas in contact with the optic apparatus but no visual defects; and Group C had adenomas causing visual impairment. Group C patients exhibited larger adenomas, higher prolactin levels, and more frequent central hypothyroidism and hypocortisolism. Visual field defects varied according to the anatomical impact of the tumor, with certain patterns like nasal hemianopsia and homonymous hemianopsia noted.
Sex differences were evident: men were older at diagnosis, had larger adenomas, and higher prolactin levels compared to women. Men also had higher rates of visual field defects and diplopia. Among patients experiencing pituitary apoplexy, all affected men had visual field defects, while the single affected woman did not.
Treatment outcomes showed that 89.5% of patients with visual impairment experienced improvement within 12-18 months of starting cabergoline, and 61.5% achieved complete visual recovery by the end of follow-up. The median time to visual improvement was 4 months. Side effects of cabergoline were mild in most cases, with a small percentage experiencing issues like hypersexuality or cerebrospinal fluid leakage.
Surgical intervention was required for 27 patients, primarily due to resistance to medication or visual impairment. Post-surgery, no visual field deterioration was observed. Radiotherapy was administered to 7 patients, none of whom developed radiation optic neuropathy.
Pituitary apoplexy occurred in 4 patients during follow-up, with cases emerging within the first 3 years of treatment. Optic chiasm herniation into the empty sella was seen in 21 patients, with only 3 experiencing visual deterioration. Cystic transformation occurred in 3 patients, all with large adenomas, but did not affect visual recovery.
Factors influencing complete visual recovery included smaller adenoma size, lower prolactin levels, and fewer cases of central hypogonadism or hypothyroidism at baseline. Visual recovery rates did not significantly differ between surgical and medical treatments. Prolactin normalization within 6 months was similar in both treatment approaches. Overall, patients requiring urgent optic tract decompression showed approximately equal visual recovery rates whether treated surgically or medically.
Conclusion
Visual recovery is a critical aspect of managing patients with pituitary adenomas, particularly those with macroprolactinomas and associated visual disturbances. This study examined 150 patients with macroprolactinoma and found that 40 (26.7%) had visual field impairments at diagnosis. While previous research focused on visual outcomes following transsphenoidal surgery, this study specifically evaluated the effects of medical therapy on visual recovery.
The findings revealed that visual damage at diagnosis was more prevalent among men (30.6%) compared to women (10.3%), likely due to the typically larger and more invasive nature of prolactinomas in men. By the end of the follow-up period, 61.5% of patients with initial visual damage experienced complete recovery, which aligns with earlier studies reporting a 67% resolution rate of visual field defects following dopamine agonist treatment. Overall, 90% of patients showed improvement in their visual fields, consistent with the expected improvement rates of 85%-95% for male macroprolactinomas.
Predictors of visual improvement included smaller tumor size, lower serum prolactin levels, fewer instances of central hypogonadism and hypothyroidism, and better visual acuity. Patients with a retinal nerve fiber layer (RNFL) thickness of ≤75 μm in at least one eye had lower rates of visual recovery. Early identification of these factors can aid in managing patient expectations and guide treatment decisions.
Pituitary apoplexy, a complication occurring in 10 patients (6.7%), was associated with sudden visual deterioration in 8 cases. Apoplexy typically presents with headaches, visual impairment, and optic nerve issues, and should be closely monitored, especially during the initial three years of medical treatment.
Chiasmal herniation was observed in 21 patients (14.0%), but only 3 patients (2.0%) experienced late visual deterioration related to this issue. Although higher rates of symptomatic chiasmal traction have been reported in other studies, the impact on visual outcomes in this cohort was minimal.
No significant differences in visual recovery were found between patients treated surgically and those treated medically after 12–18 months. This suggests that medical therapy can be as effective as surgery in inducing tumor shrinkage and improving visual outcomes. However, preoperative treatment with dopamine agonists might complicate surgical procedures due to tumor fibrosis, though evidence on this is conflicting.
The study acknowledges limitations, including its retrospective design, small sample size, and missing data, which precluded detailed regression analysis. Additionally, newer technologies for predicting visual recovery were not utilized.
In conclusion, this study provides valuable insights into visual outcomes following medical therapy in patients with macroprolactinoma. Visual disturbances are relatively uncommon, and recovery rates are influenced by tumor size, prolactin levels, and other clinical factors. The study highlights the need for continued research into the optimal management strategies for visual disturbances associated with macroprolactinomas.
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