Diagnostic Approach: Prolactinoma with Neurological Complications
This constellation of diplopia, shuffling gait, depressed reflexes, and elevated prolactin strongly suggests a prolactinoma with mass effect causing cranial nerve palsies, and the shuffling gait may represent either dopaminergic medication side effects or compression of adjacent structures—urgent MRI with contrast is mandatory to rule out a compressive macroadenoma or giant adenoma.
Immediate Diagnostic Priorities
Urgent neuroimaging with MRI brain with and without gadolinium is mandatory to evaluate for prolactinoma with mass effect causing cranial nerve compression. 1, 2 The diplopia indicates cranial nerve involvement (likely CN III, IV, or VI), which requires immediate assessment for compressive lesions. 3, 4
Critical Imaging Protocol
MRI brain with and without contrast including high-resolution sequences of the pituitary and cranial nerves III-VI is the preferred initial imaging modality. 1 This will identify prolactinoma size and any suprasellar extension causing optic chiasm or cranial nerve compression.
Add MRA or CTA if third nerve palsy is suspected (particularly if pupil-involving), as posterior communicating artery aneurysm must be urgently excluded. 1, 4, 5, 2 Even though prolactinoma is likely given the elevated prolactin, aneurysm remains life-threatening and cannot be missed.
Include dedicated imaging of the cavernous sinus and orbital apex, as multiple ipsilateral cranial nerve palsies suggest lesions at these locations. 1 Large prolactinomas can invade the cavernous sinus and affect multiple cranial nerves simultaneously.
Characterizing the Diplopia
The pattern of diplopia helps localize the lesion and guides management:
Vertical diplopia with ptosis suggests third nerve palsy, which requires urgent evaluation for compressive aneurysm even in the setting of known prolactinoma. 4 Complete third nerve palsy with pupil involvement is a medical emergency. 3, 1
Horizontal diplopia worse at distance suggests sixth nerve palsy, which can result from increased intracranial pressure from a large pituitary mass. 3, 2 This is common with macroadenomas and giant adenomas.
Perform the Parks-Bielschowsky three-step test to identify superior oblique (fourth nerve) palsy if vertical diplopia is present. 3, 4 This helps distinguish between different cranial nerve involvement patterns.
Prolactinoma Evaluation
Once imaging confirms prolactinoma, the size determines prognosis and treatment approach:
Microprolactinomas (<10mm) have excellent surgical cure rates (64-98% total removal) but medical therapy remains first-line. 6 However, the presence of diplopia suggests this is likely a larger lesion.
Macroadenomas (≥10mm) have lower surgical cure rates (6.7% hormonal cure, 63.9% total removal) and higher recurrence rates (39%). 6 The presence of cranial nerve palsies strongly suggests macroadenoma or giant adenoma with cavernous sinus involvement.
Giant adenomas (>40mm) have very poor surgical outcomes (0% hormonal cure, 23.5% total removal) and medical therapy is critical. 6
Evaluating the Shuffling Gait and Depressed Reflexes
This combination requires careful consideration of multiple etiologies:
If the patient is already on dopamine agonist therapy (bromocriptine or cabergoline), the shuffling gait may represent medication side effects or paradoxical parkinsonism. 7 Bromocriptine is a dopamine receptor agonist that can cause motor dysfunction in some patients.
Large prolactinomas with suprasellar extension can compress the hypothalamus and cause various neurological deficits including gait disturbance. 8, 6 Depression, anxiety, and cognitive symptoms are well-documented even with smaller prolactinomas.
Depressed reflexes combined with gait abnormality may indicate peripheral neuropathy or spinal cord compression from metastatic disease if the prolactinoma is actually a manifestation of systemic malignancy. Consider additional workup if imaging shows atypical features.
Treatment Algorithm
Medical Management (First-Line)
Dopamine agonists are first-choice therapy for prolactinomas, with cabergoline preferred over bromocriptine due to better efficacy and tolerability. 9, 7, 10
Cabergoline should be used at the lowest effective dose with periodic reassessment of need for continuing therapy. 9 Start with 0.25-0.5mg twice weekly and titrate based on prolactin levels.
Baseline echocardiogram is mandatory before initiating cabergoline, as cardiac valvulopathy is a serious complication, particularly at doses >2mg/day. 9 Routine echocardiographic monitoring every 6-12 months is recommended during treatment.
Monitor for fibrotic complications including pleural, pericardial, and retroperitoneal fibrosis with attention to dyspnea, chest pain, renal insufficiency, and abdominal masses. 9 These can have insidious onset.
Discontinue cabergoline if echocardiogram reveals new valvular regurgitation, restriction, or leaflet thickening. 9
Surgical Indications
Surgery should be considered in specific circumstances:
Trans-sphenoidal microsurgery is indicated for patients resistant or intolerant to dopamine agonists, those who refuse long-term medical therapy, or when urgent decompression is needed for vision-threatening chiasmal compression. 10, 6
Patients with cranial nerve palsies from mass effect may require urgent surgical decompression if medical therapy does not rapidly reduce tumor size. 6 However, initiate medical therapy first unless there is acute vision loss.
Recurrence after surgery occurs in 39% of patients, requiring second-step treatment with repeat surgery, dopamine agonists, or radiotherapy. 6
Management of Diplopia During Treatment
While awaiting tumor shrinkage with medical therapy:
Prism glasses (press-on or ground-in) can temporize diplopia while waiting for tumor response to dopamine agonists. 3 Many patients require part-time occlusion for activities like driving.
Botulinum toxin injection of opposing extraocular muscles can reduce diplopia in select cases. 3 This is particularly useful if ptosis is complete and diplopia only emerges when the lid is elevated.
Strabismus surgery should be deferred until tumor size is stable and cranial nerve function has maximized recovery (typically 6 months). 3 Premature surgery may require revision as the tumor shrinks with medical therapy.
Critical Pitfalls to Avoid
Do not assume elevated prolactin automatically means benign prolactinoma—rule out medication-induced hyperprolactinemia first. 8, 10 Antipsychotics (including sulpiride/eglonil), metoclopramide, and other medications commonly cause hyperprolactinemia.
Do not delay imaging in patients with pupil-involving third nerve palsy even if prolactin is elevated—aneurysm must be excluded urgently. 1, 4, 5 Compressive aneurysm is life-threatening and requires immediate neurosurgical evaluation.
Do not attribute all neurological symptoms to the prolactinoma without considering alternative diagnoses. 8 Depression, anxiety, and cognitive symptoms can be direct effects of hyperprolactinemia, but ensure comprehensive neurological examination rules out other pathology.
Do not start cabergoline without baseline echocardiogram and counseling about cardiac risks. 9 Valvulopathy is a serious complication that requires ongoing monitoring.